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Sample records for rapidly progressive glomerulonephritis

  1. Rapidly progressive glomerulonephritis after immunotherapy for cancer.

    PubMed

    Parker, M G; Atkins, M B; Ucci, A A; Levey, A S

    1995-04-01

    Cytokines have been used in experimental and standard protocols for immune enhancement for cancer. The combination of interleukin-2 and interferon-alpha 2 beta has been used in experimental protocols for metastatic renal cell carcinoma. A man who developed rapidly progressive renal failure after receiving this combination therapy is reported. A renal biopsy revealed a pauci-immune crescentic glomerulonephritis. Antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were absent. The spectrum of renal disease and potentially related extrarenal manifestations associated with interleukin-2 and inteferon-alpha are reviewed. A pathogenesis of altered cell-mediated immunity, consistent with abnormalities in extrarenal organs after immune enhancement, is proposed.

  2. [Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

    PubMed

    Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

    2014-02-26

    Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.

  3. Treatment of nephrotic syndrome associated with idiopathic rapidly progressive glomerulonephritis and cyclosporin A.

    PubMed

    Maduell, F; Sánchez-Alcaraz, A; Sigüenza, F; Caridad, A; Sangrador, G

    1993-02-01

    Recent reports suggest that cyclosporin A is beneficial in inducing remission of idiopathic nephrotic syndrome. Nephrotic syndrome is seen in 10-30% of patients with rapidly progressive glomerulonephritis. We report a case of a 69-year-old man with nephrotic syndrome, associated with idiopathic rapidly progressive glomerulonephritis, who was treated initially with corticosteroid and cyclophosphamide. Three months later he developed thrombophlebitis and leucopenia and cyclophosphamide was suspended. Relapse of nephrotic syndrome associated with rapidly progressive glomerulonephritis developed and therapy with cyclosporin A was used with a good response.

  4. Simultaneous comprehensive multiplex autoantibody analysis for rapidly progressive glomerulonephritis.

    PubMed

    Sowa, Mandy; Trezzi, Barbara; Hiemann, Rico; Schierack, Peter; Grossmann, Kai; Scholz, Juliane; Somma, Valentina; Sinico, Renato Alberto; Roggenbuck, Dirk; Radice, Antonella

    2016-11-01

    Rapidly progressive glomerulonephritis (RPGN) is mainly caused by anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis, immune-complex or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides and leads to rapid loss of renal function. Detection of ANCA and autoantibodies (autoAbs) to GBM and dsDNA enables early diagnosis and appropriate treatment of RPGN aiding in preventing end-stage renal disease.Determination of ANCA on neutrophils (ANCA) as well as autoAbs to myeloperoxidase (MPO-ANCA), proteinase 3 (PR3-ANCA), GBM, and dsDNA was performed by the novel multiplex CytoBead technology combining cell- and microbead-based autoAb analyses by automated indirect immunofluorescence (IIF). Forty patients with granulomatosis with polyangiitis (GPA), 48 with microscopic polyangiitis (MPA), 2 with eosinophilic GPA, 42 with systemic lupus erythematosus (SLE), 43 with Goodpasture syndrome (GPS), 57 with infectious diseases (INF), and 55 healthy subjects (HS) were analyzed and findings compared with classical single testing.The CytoBead assay revealed for GPA, MPA, GPS, and SLE the following diagnostic sensitivities and for HS and INF the corresponding specificities: PR3-ANCA, 85.0% and 100.0%; MPO-ANCA, 77.1% and 99.1%; anti-GBM autoAb, 88.4% and 96.4%; anti-dsDNA autoAb, 83.3% and 97.3%; ANCA, 91.1% and 99.1%, respectively. Agreement with classical enzyme-linked immunosorbent assay and IIF was very good for anti-GBM autoAb, MPO-ANCA, PR3-ANCA, and ANCA, respectively. Anti-dsDNA autoAb comparative analysis demonstrated fair agreement only and a significant difference (P = 0.0001).The CytoBead technology provides a unique multiplex reaction environment for simultaneous RPGN-specific autoAb testing. CytoBead RPGN assay is a promising alternative to time-consuming single parameter analysis and, thus, is well suited for emergency situations.

  5. Simultaneous comprehensive multiplex autoantibody analysis for rapidly progressive glomerulonephritis

    PubMed Central

    Sowa, Mandy; Trezzi, Barbara; Hiemann, Rico; Schierack, Peter; Grossmann, Kai; Scholz, Juliane; Somma, Valentina; Sinico, Renato Alberto; Roggenbuck, Dirk; Radice, Antonella

    2016-01-01

    Abstract Rapidly progressive glomerulonephritis (RPGN) is mainly caused by anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis, immune-complex or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides and leads to rapid loss of renal function. Detection of ANCA and autoantibodies (autoAbs) to GBM and dsDNA enables early diagnosis and appropriate treatment of RPGN aiding in preventing end-stage renal disease. Determination of ANCA on neutrophils (ANCA) as well as autoAbs to myeloperoxidase (MPO-ANCA), proteinase 3 (PR3-ANCA), GBM, and dsDNA was performed by the novel multiplex CytoBead technology combining cell- and microbead-based autoAb analyses by automated indirect immunofluorescence (IIF). Forty patients with granulomatosis with polyangiitis (GPA), 48 with microscopic polyangiitis (MPA), 2 with eosinophilic GPA, 42 with systemic lupus erythematosus (SLE), 43 with Goodpasture syndrome (GPS), 57 with infectious diseases (INF), and 55 healthy subjects (HS) were analyzed and findings compared with classical single testing. The CytoBead assay revealed for GPA, MPA, GPS, and SLE the following diagnostic sensitivities and for HS and INF the corresponding specificities: PR3-ANCA, 85.0% and 100.0%; MPO-ANCA, 77.1% and 99.1%; anti-GBM autoAb, 88.4% and 96.4%; anti-dsDNA autoAb, 83.3% and 97.3%; ANCA, 91.1% and 99.1%, respectively. Agreement with classical enzyme-linked immunosorbent assay and IIF was very good for anti-GBM autoAb, MPO-ANCA, PR3-ANCA, and ANCA, respectively. Anti-dsDNA autoAb comparative analysis demonstrated fair agreement only and a significant difference (P = 0.0001). The CytoBead technology provides a unique multiplex reaction environment for simultaneous RPGN-specific autoAb testing. CytoBead RPGN assay is a promising alternative to time-consuming single parameter analysis and, thus, is well suited for emergency situations. PMID:27858870

  6. [Rapidly progressive glomerulonephritis in a 68-year-old man].

    PubMed

    Rubio, E; Acevedo, M

    2004-01-01

    A 68-year-old male with macroscopic hematuria and constitutional symptoms as fever and weight loss. There was nothing interesting in the anamnesis or in the physical exploration. The laboratory test had an elevation of creatinine of 4 mg/dL and ten days before it had been 1.4 mg/dL. In the urine analysis: proteinuria of 1.5 G/24 h, and hematuria. On the second day we made a renal biopsy where we could seen segmental glomerular necrosis and crescent fromation in 80% of the glomeruli. In the immune study c-ANCA anti-PR3 was positive. In the complementary studies we didn't find other organs affected. With the diagnosis of pauci-immune glomerulonephritis limited to the kidney we began treatment with corticosteroids and cyclophosphamide. As the renal function was severely affected the patient needed one dialysis session. We began with 1 g intravenous methylprednisolone daily for 3 days followed by oral prednisone 60 mg daily tapering to 10 mg daily by 3 months. This was combined with 150 mg oral cyclophosphamide daily. Seven plasma exchanges were performed. At the beginning of treatment creatinine was 7 mg/dL, it was decreasing rapidly and three week after cretinine was 3 mg/Dl and he was asymptomatic. One year after treatment, creatinine is 1.4 mg/dL and the urine analysis is normal, C-ANCA are negative.

  7. Predictors of outcome in idiopathic rapidly progressive glomerulonephritis (IRPGN)

    PubMed Central

    Alexopoulos, Efstathios; Gionanlis, Lazaros; Papayianni, Ekaterini; Kokolina, Elizabeth; Leontsini, Maria; Memmos, Dimitrios

    2006-01-01

    Background Small vessel vasculitides are known to follow a devastating course towards end-stage renal disease, unless treated with immunosuppressive regiments. We investigated the value of clinical, histological and immunohistochemical parameters as predictors of outcome at diagnosis in patients with pauci immune necrotizing glomerulonephritis. Methods In 34 patients the percentage and evolution stage of crescents, the presence of glomerular necrosis, the degree or severity of arteriosclerosis, as well as the extent of tubulointerstitial infiltration, interstial fibrosis and tubular atrophy were assessed. Monoclonal antibodies were used to identify infiltrating macrophages, α-SMA(+) and PCNA(+) cells, the expression of integrins α3β1 and LFA-1β, the adhesion molecule ICAM-1, the growth factor TGF-β1 and the terminal complement component C5b-9. Results 24 pts (70.6%) showed a complete or partial response to the treatment. The follow-up period was 20 ± 22 months. At multivariate analysis, serum CRP (p = 0.024), the intensity of tubular expression of C5b-9 (p < 0.0001) as well as the extent of glomerular and tubular expression of α3β1 integrin (p = 0.001 and 0.008 respectively) independently predicted the response to treatment. The response rate was better in ANCA(+) pts (p = 0.008). The extent of interstitial infiltrate (p < 0.0001), the severity of tubulointerstitial fibrosis (p < 0.0001) and the severity of tubular TGF-β1 expression (p < 0.0001) were independent predictors of long term outcome of renal function. Conclusion Patients with ANCA-associated renal vasculitis seem to respond better to the treatment. Acute phase reactants, such as CRP, implying a more intense parenchymal inflammatory reaction, as well as the intensity of the de novo expression of C5b-9 and the glomerular and tubular expression of α3β1 integrin predict the response to therapy. The severity of TIN lesions and of the tubulo-interstitial TGF-β1 and C5b-9 expression predict an

  8. Granulomatosis with polyangiitis: rapidly progressive necrotizing glomerulonephritis in a pediatric patient

    PubMed Central

    Luna, Mariana; Bocanegra, Victoria; Vallés, Patricia G

    2014-01-01

    Granulomatosis with polyangiitis (GPA) is associated with a broad range of clinical manifestations including renal disease. It is a systemic vasculitis that is rarely encountered in children. We present a 14-year-old girl who suffered from pharyngitis 1 week before admittance to hospital. She was admitted for macroscopic hematuria and oliguria, under the possibility of nephritic syndrome. Renal failure with rapidly progressive glomerulonephritis occurred within 24 hours. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies (c-ANCA with antiproteinase 3 specificity) and renal biopsy revealed pauci-immune crescentic focal necrotizing glomerulonephritis. Treatment including methylprednisolone and cyclophosphamide intravenous pulses allowed renal recovery after 3 weeks. The clinical, hematological, and biochemical parameters improved substantially, achieving remission. Granulomatosis with polyangiitis, although rare in children, should be considered in the above clinical scenario. This case underlines that knowledge of renal histology diagnosis and early aggressive immunosuppressive therapy are essential for the management of these patients. PMID:24790466

  9. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628

    PubMed Central

    Ma, Frank Y.; Han, Yingjie; Nikolic-Paterson, David J.; Kolkhof, Peter; Tesch, Greg H.

    2015-01-01

    Background/Aim Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Methods Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Results Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). Conclusions The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases. PMID:26700873

  10. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis

    PubMed Central

    Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir; Thorlund, Kristian; Bruchfeld, Annette; Guillevin, Loic; Haubitz, Marion; Merkel, Peter A.; Peh, Chen Au; Pusey, Charles; Jayne, David

    2011-01-01

    Background Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized control trials of plasma exchange for renal vasculitis. Study Design Systematic review and meta-analysis of manuscripts identified from electronic databases, bibliographies, and studies identified by experts. Data was abstracted in parallel by two reviewers. Setting & Population Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange Outcome Composite of end-stage renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model the pooled relative risk of end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared to standard care alone (95% confidence interval 0.65 to 0.99; p=0.04). No significant heterogeneity was detected (p=0.5; I2=0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (p=0.7) or number of plasma exchange treatments (p=0.8). The relative risk for end-stage renal disease was 0.64 (95% confidence interval 0.47 to 0.88; p=0.006) while the relative risk for death alone was 1.01 (95% confidence interval 0.71 to 1.4; p=0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliable determine if plasma exchange reduces the composite of end-stage renal disease or death. Conclusions Plasma exchange may reduce the composite endpoint of end-stage renal disease or death in renal vasculitis. Further trials are required given the limited data available. PMID:21194817

  11. Association of idiopathic retroperitoneal fibrosis, rapidly progressive glomerulonephritis and antiproteinase 3 antineutrophil cytoplasmic antibodies (anti PR3-ANCA).

    PubMed

    Martínez-Odriozola, P; Gutiérrez-Macías, A; Moina Eguren, I; Arrieta Lezama, J

    2008-09-01

    We report a case of idiopathic retroperitoneal fibrosis and rapidly progressive glomerulonephritis with serum antiproteinase 3 antineutrophil cytoplasmic antibodies (anti-PR3-ANCA), without clinical or histological signs of Wegener's granulomatosis, in a 46-year-old man. Our case and previously reported cases showing the same association support the hypothesis that the association is not fortuitous, but reflects a common immunological mechanism.

  12. [Anti-neutrophil cytoplasmic autoantibody-associated rapid progressive glomerulonephritis complicated with both limited and diffuse scleroderma].

    PubMed

    Miyata, Naoko; Kobayashi, Tomoko; Matsukawa, Yoshihiro; Sawada, Shigemasa; Nishinarita, Susumu; Horie, Takashi

    2002-12-01

    We report two patients with scleroderma, 73-year-old female and 67-year-old female, who developed anti neutrophil cytoplasmic autoantibody (ANCA) associated rapid progressive glomerulonephritis (RPGN). Both patients have had a long history of scleroderma (23 and 14 years, respectively) when ANCA-associated glomerulonephritis occurred. In the first patient, scleroderma was localized in both fingers. She has been followed-up as CREST syndrome rather than systemic sclerosis. The complaints on admission were leg edema and left chest pain in the first patient, and a pyrexia and dyspnea in the second patient. Both patients showed pulmonary manifestation (pleural effusion in the first patient, interstitial pneumonia and alveolar hemorrhage in the second patient, respectively) and rapid progressive glomerulonephritis. Both patients died in spite of corticosteroid therapy. Autopsy findings in the second patient demonstrated crescentic glomerulonephritis and alveolar hemorrhage. Our cases demonstrated that MPO-ANCA associated glomerulonephritis could be associated with limited scleroderma as well as systemic scleroderma. In these condition, the prognosis will be poor if scleroderma seemed to be stable.

  13. Post-reperfusion rapidly progressive glomerulonephritis in post-transplant IgA nephropathy.

    PubMed

    Tovbin, David; Shnaider, Alla; Kachko, Leonid; Basok, Anna; Vorobiov, Marina; Rogachev, Boris; Abramov, Dan; Zlotnik, Moshe

    2004-01-01

    Rapidly progressive glomerulonephritis (RPGN) is a rare occurrence in IgA nephropathy (IgAN) in renal transplant patients on immunosuppressive therapy. RPGN post ischemia-reperfusion has not been previously reported. We report a 62 year old male patient on azathioprine therapy, 9 years after left cadaveric renal transplantation due to end stage renal disease of unknown etiology, who presented with progressive deterioration in renal function and hematuria. Renal biopsy was consistent with IgAN. Duplex and CT scan demonstrated a decreased renal graft perfusion, due to severe atherosclerosis and stenosis of iliac arteries. The patient underwent left axilo-femoral bypass graft surgery with improvement in kidney graft perfusion and function. However, few weeks later, patient presented with pulmonary edema and advanced renal failure and he was initiated on hemodialysis. Repeated renal biopsy demonstrated crescentic GN. To the best of our knowledge, this is the first report of RPGN following reversal of ischemia and reperfusion. There was no evidence for atherembolic disease which is not uncommon after vascular surgery and it has been reported to be rarely associated to crescentic GN. Theoretical explanations for exacerbation of IgAN to crescentic GN, following successful reperfusion, could be enhancement of capillary damage, inflammation and oxidative stress. Putative mechanisms for these phenomena may be interaction of reperfusion-induced hyperfiltration, high intraglomerular capillary pressure, oxidative stress, increased polymorphonucler cells infiltration and inflammation; the presence of IgA immune deposits and azathioprine metabolites, both can also be associated to enhancement of oxidative stress.

  14. [A case of rapidly progressive glomerulonephritis in the course of Wegener's granulomatosis].

    PubMed

    Idasiak-Piechocka, I; Oko, A; Łochyńska, K; Woźniak, A; Czekalski, S

    2000-01-01

    Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in

  15. A case of IgA nephropathy associated with mycosis fungoides that developed into rapidly progressive glomerulonephritis.

    PubMed

    Hara, Masaki; Nemoto, Tetsuo; Hijima, Tsunekazu; Tsuchiya, Ken; Nitta, Kosaku; Ando, Minoru

    2013-02-01

    A 53-year-old Japanese male was diagnosed with atopic dermatitis and initiated treatment with a local dermatologist in February 2001. A routine medical check-up revealed proteinuria, microscopic hematuria and slight elevation of serum creatinine level in spring 2006. He was referred to our hospital for nephrology consultation and followup.In December 2009, he developed a sudden high fever of greater than 39 °C with sore throat. In addition, his serum creatinine level greatly increased to 4.6 mg/dl. His prevalent renal illness was thought to be rapidly progressive glomerulonephritis (RPGN). Soon after admission, kidney and skin biopsies were performed. The kidney specimens showed that the glomeruli had proliferative mesangial cells strongly positive for anti-IgA antibody, 75% of which manifested fibrocellular crescentic formation surrounding the Bowman's capsules. His skin disease was pathologically proven to be mycosis fungoides(MF). It is likely that his kidney disease was exacerbated by the upper respiratory tract infection and converted to RPGN. Ash is kidney function rapidly declined, hemodialysis therapy was initiated and he remains on chronic dialysis therapy. This is a serious case of IgA nephropathy associated with MF,which developed into RPGN and subsequent end-stage renal disease.

  16. Association between rapidly progressive glomerulonephritis and the properdin factor BfF and different HLA-D region products.

    PubMed

    Müller, G A; Gebhardt, M; Kömpf, J; Baldwin, W M; Ziegenhagen, D; Bohle, A

    1984-01-01

    Frequencies of the HLA antigens ABC, DR and MT, as well as of the properdin factor alleles were determined in 24 unrelated patients presenting with immune complex mediated idiopathic rapidly progressive glomerulonephritis (RPGN) type II. As in Goodpasture syndrome (RPGN type I with pulmonary hemorrhage), a significant association with the B-cell alloantigen HLA-DR 2 was demonstrated (relative risk for HLA-DR 2 positive individuals was 3.54; P less than 0.01). In addition a marked increase of the HLA specificity MT 3 was shown, which is supposed to belong to an antigen system of a second HLA-D region locus. The highest relative risk of 14.67 (P less than 0.00001), however, was calculated for all patients carrying the BfF phenotype. Increased numbers of patients positive for HLA-DR 2 and -MT 3, as well as BfF suggested immune response genes or disease-related mutations on different haplotypes responsible for a MHC (major histocompatibility complex) associated predisposition of RPGN type II.

  17. Presence of Anti-Glomerular Basement Membrane Antibodies and Myeloperoxidase Anti-Neutrophilic Cytoplasmic Antibodies in a Case of Rapidly Progressive Glomerulonephritis.

    PubMed

    Mavani, Gaurang P; Pommier, Max; Win, Sandar; Michelis, Michael F; Rosenstock, Jordan

    2015-01-01

    A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 μmol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative glomerulonephritis most likely due to ANCA vasculitis. He received three doses of pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U (normal <1). He was started on high-dose oral steroids; monthly intravenous cyclophosphamide and plasmapheresis were also initiated. His symptoms improved and creatinine is 247.5 μmol/L (2.8 mg/dL). His repeat anti-GBM antibody was negative. This is a rare case of rapidly progressive glomerulonephritis due to dual MPO-ANCA antibodies and anti-GBM antibodies (DAV).

  18. Presence of Anti-Glomerular Basement Membrane Antibodies and Myeloperoxidase Anti-Neutrophilic Cytoplasmic Antibodies in a Case of Rapidly Progressive Glomerulonephritis

    PubMed Central

    Mavani, Gaurang P.; Pommier, Max; Win, Sandar; Michelis, Michael F.; Rosenstock, Jordan

    2015-01-01

    A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 μmol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal <0.4). He was clinically diagnosed with rapidly proliferative glomerulonephritis most likely due to ANCA vasculitis. He received three doses of pulse methylprednisolone therapy. Kidney biopsy showed pauci-immune glomerulonephritis. Immunofluorescence was positive for faint linear IgG staining of glomerular basement membrane (GBM). Anti-GBM antibody was positive 2.1 U (normal <1). He was started on high-dose oral steroids; monthly intravenous cyclophosphamide and plasmapheresis were also initiated. His symptoms improved and creatinine is 247.5 μmol/L (2.8 mg/dL). His repeat anti-GBM antibody was negative. This is a rare case of rapidly progressive glomerulonephritis due to dual MPO-ANCA antibodies and anti-GBM antibodies (DAV). PMID:26301224

  19. Sjögren Syndrome-Related Membranous Glomerulonephritis Progressing to Membranoproliferative Glomerulonephritis.

    PubMed

    Yabuuchi, Junko; Suwabe, Tatsuya; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Hayami, Noriko; Oguro, Masahiko; Kunisawa, Kyohei; Kawada, Masahiro; Yamanouchi, Masayuki; Sumida, Keiichi; Mizuno, Hiroki; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2016-01-01

    We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis.

  20. Sjögren Syndrome-Related Membranous Glomerulonephritis Progressing to Membranoproliferative Glomerulonephritis

    PubMed Central

    Yabuuchi, Junko; Suwabe, Tatsuya; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Hayami, Noriko; Oguro, Masahiko; Kunisawa, Kyohei; Kawada, Masahiro; Yamanouchi, Masayuki; Sumida, Keiichi; Mizuno, Hiroki; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2016-01-01

    We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis. PMID:27904866

  1. Fibrillary glomerulonephritis presenting as crescentic glomerulonephritis

    PubMed Central

    Shah, H. H.; Thakkar, J.; Pullman, J. M.; Mathew, A. T.

    2017-01-01

    Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that commonly presents clinically with hypertension, proteinuria, microscopic hematuria, and varying degree of renal insufficiency. Histologically, FGN can present with different patterns of glomerular injury, more commonly mesangioproliferative, membranoproliferative, and membranous nephropathy. While crescent formation has been described in some kidney biopsy series of FGN, crescentic glomerulonephritis pattern of glomerular injury has been rarely described. Optimal therapy and outcomes in FGN presenting with crescentic GN is not currently known. We report an adult patient who presented with massive proteinuria and severe renal failure. The kidney biopsy revealed crescentic FGN (C-FGN). The patient remained dialysis dependent despite immunosuppressive therapy. We also briefly review FGN, and the few reported cases of C-FGN that presented as rapidly progressive or advanced renal failure in the literature. PMID:28356674

  2. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.; Shu, Huidy; Haman, Aissa; Sejvar, James J.; Miller, Bruce L.

    2009-01-01

    In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly. PMID:18668637

  3. Rapidly progressive Alzheimer disease.

    PubMed

    Schmidt, Christian; Wolff, Martin; Weitz, Michael; Bartlau, Thomas; Korth, Carsten; Zerr, Inga

    2011-09-01

    Different rates of progression have been observed among patients with Alzheimer disease. Risk factors that accelerate deterioration have been identified and some are being discussed, such as genetics, comorbidity, and the early appearance of Alzheimer disease motor signs. Progressive forms of Alzheimer disease have been reported with rapid cognitive decline and disease duration of only a few years. This short review aims to provide an overview of the current knowledge of rapidly progressive Alzheimer disease. Furthermore, we suggest that rapid, in this context, should be defined as a Mini-Mental State Examination score decrease of 6 points per year.

  4. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.

    2016-01-01

    Purpose of Review This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Recent Findings Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. Summary RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis. PMID:27042906

  5. Mesangial proliferative glomerulonephritis associated with progressive amyloid deposition in hamsters experimentally infected with Leishmania donovani.

    PubMed Central

    Oliveira, A. V.; Roque-Barreira, M. C.; Sartori, A.; Campos-Neto, A.; Rossi, M. A.

    1985-01-01

    In the present work, 42 golden hamsters (Mesocricetus auratus) were infected by intracardiac injection of 5 X 10(6) amastigote forms of Leishmania donovani. Another group of 28 animals served as uninfected controls. Six hamsters of the infected group and four hamsters of the control group were selected randomly and sacrificed at Days 7, 14, 21, 28, 35, 42, and 49 after inoculation. The kidneys were studied by light microscopy, immunofluorescence and electron microscopy. The levels of serum and urinary immunoglobulins were determined. None of the control hamsters had kidney lesions. Light-microscopically the kidneys of infected hamsters showed a marked mesangial proliferation from Day 7 after infection. These changes were more pronounced at Day 21, when a discrete infiltration of mononuclear cells was frequent. These glomerular changes diminished after Day 28 and were replaced by deposits of amyloid. In the beginning these deposits were in the mesangium and progressively became more extensive, involving capillary loops, Bowman's capsule, and interstitium. The immunofluorescence study showed L donovani antigens and hamster immunoglobulins, primarily in the mesangial areas, by Days 7-14 after infection. These deposits extended into contiguous loops from Day 21 to Day 28. In the last 2 weeks the fluorescent staining for L donovani antigens remained intensely positive, whereas the staining for hamster immunoglobulins became moderate to slightly positive. The ultrastructural study revealed mesangial proliferation, mesangial and paramesangial electron-dense deposits, and amyloidosis in the glomeruli of infected animals. The serum immunoglobulins increased from Day 7 after infection, reaching a peak at Day 21 and falling thereafter until Day 49 to near control values. Immunoglobulins were detected in the urine of infected hamsters at day 21, increasing in amount thereafter. Since L donovani antigens and immunoglobulins were identified in the glomerular lesions, it is

  6. Rapidly Progressing Alzheimer's: Something Else?

    MedlinePlus

    ... Something else? My mother has been diagnosed with Alzheimer's disease, but she seems to be declining rapidly. Doesn' ... Answers from Jonathan Graff-Radford, M.D. Yes, Alzheimer's disease usually worsens slowly. But its speed of progression ...

  7. Glomerulonephritis associated with tuberculosis: a case report and literature review.

    PubMed

    Solak, Yalcin; Gaipov, Abduzhappar; Anil, Melih; Atalay, Huseyin; Ozbek, Orhan; Turkmen, Kultigin; Polat, Ilker; Turk, Suleyman

    2013-06-01

    Rapidly progressive glomerulonephritis caused mycobacterium tuberculosis is rare; however, three case have been reported to date. Crescentic glomerulonephritis is a life-threatening disease and together with the presence of tuberculous infection is associated with a poor outcome if treatment is inadequate and delayed. We describe the case of a 31-year-old female patient with nephrotic syndrome and progressive renal failure secondary to pulmonary tuberculosis. Renal biopsy showed crescent formation in 14 out of 27 glomeruli, and there was diffuse linear staining of immunoglobulin G deposits. Treatment included corticosteroids in combination with antituberculosis drugs for 2 months, and resulted in a significant improvement in renal function, the disappearance of proteinuria and pulmonary symptoms. We also present a review of the pertinent literature and discuss the pathophysiology of tuberculosis-related acute postinfectious glomerulonephritis. Copyright © 2012. Published by Elsevier B.V.

  8. A Case of Concurrent MPO-/PR3-Negative ANCA-Associated Glomerulonephritis and Membranous Glomerulopathy

    PubMed Central

    Nakada, Yasuyuki; Tsuboi, Nobuo; Takahashi, Yasuto; Yoshida, Hiraku; Hara, Yoriko; Okonogi, Hideo; Kawamura, Tetsuya; Arimura, Yoshihiro; Yokoo, Takashi

    2015-01-01

    We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immunofluorescence examination of the patient's neutrophils showed a perinuclear pattern. Enzyme-linked immunosorbent assays revealed that the ANCA in this case did not target myeloperoxidase (MPO) or proteinase 3 (PR3) but bactericidal-/permeability-increasing protein, elastase, and lysosome. The relationship between these two etiologically distinct entities, MPO-/PR3-negative ANCA-associated glomerulonephritis and MGN, remains unclear. PMID:25648906

  9. Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

    PubMed

    Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

    2015-12-01

    The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  10. Crescentic glomerulonephritis in children.

    PubMed

    Jardim, H M; Leake, J; Risdon, R A; Barratt, T M; Dillon, M J

    1992-05-01

    Data on patients with crescentic glomerulonephritis (greater than 50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7-15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR less than 30 ml/min per 1.73 m2) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%-79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m2. In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P less than 0.05). Outcome was not, however, related to the percentage of glomeruli affected (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  11. α-1-Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression.

    PubMed

    Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio

    2016-06-01

    Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes.

  12. [Glomerulonephritis with IgA mesangial deposits].

    PubMed

    Pillebout, Evangéline; Nochy, Dominique

    2010-11-01

    IgA nephropathy is the primitive glomerulonephritis the most frequently encountered worldwide. In about one case out of three, it is responsible for the progression from progressive renal failure to end-stage renal failure. The pathophysiological mechanisms of this disease which is mediated by immune complexes remain unclear. The presentation, clinical progression and optical microscope aspect of the renal biopsy may widely vary, making any histological classification very difficult. Most therapeutic studies include the patients only on clinical criteria of severity. The only consensual management is that of patients with a nephropathy and mild glomerular lesions and a nephritic syndrome, or with an extracapillar glomerulonephritis and a rapidly progressive renal failure; corticoids are indicated in former cases while corticoids must be combined with immunosuppressive agents in the latter ones. Corticotherapy may be considered in patients with a proteinuria higher than 1g/day without renal failure. In any patient with primitive IgA nephropathy, the overall management used for chronic glomerulopathy must be initiated, including, in case of arterial hypertension or proteinuria, the renin-angiotensin system blockade.

  13. Activation of Src Mediates PDGF-Induced Smad1 Phosphorylation and Contributes to the Progression of Glomerulosclerosis in Glomerulonephritis

    PubMed Central

    Mima, Akira; Abe, Hideharu; Nagai, Kojiro; Arai, Hidenori; Matsubara, Takeshi; Araki, Makoto; Torikoshi, Kazuo; Tominaga, Tatsuya; Iehara, Noriyuki; Fukatsu, Atsushi; Kita, Toru; Doi, Toshio

    2011-01-01

    Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis. PMID:21445358

  14. A Case of Anti-Glomerular Basement Membrane Glomerulonephritis Complicated by Type 1 Diabetes Mellitus, Mimicking Urinary Tract Infection

    PubMed Central

    Aoki, Yoshihiro; Tanimoto, Izumi; Miyauchi, Yoshihiro; Suzuki, Yoshio; Shiojiri, Toshiaki

    2017-01-01

    Patient: Female, 44 Final Diagnosis: Anti-glomerular basement membrane glomerulonephritis Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Type 1 diabetes mellitus (DM) tends to complicate other autoimmune diseases. When considering renal dysfunction in patients with DM, diabetic nephropathy is a likely diagnosis. By contrast, anti-glomerular basement membrane (GBM) glomerulonephritis, an autoimmune disease, is one cause of rapidly progressive glomerulonephritis. Case Report: We report the case of a 44-year-old woman diagnosed with anti-glomerular basement membrane (GBM) glomerulonephritis. The diagnosis was made on the basis of serological test results and pathological findings of a renal biopsy. Five years before admission, she was diagnosed with type 1 DM. At admission, she presented with a fever, chills, nausea, low back pain, and malaise, which were followed by progressive renal dysfunction. The initial presentation mimicked a urinary tract infection, which delayed the correct diagnosis. Conclusions: Our patient’s course strongly suggests that rapidly progressive glomerulonephritis should be considered as an early differential diagnosis in cases of progressive renal dysfunction, especially when accompanied by fever, regardless of the underlying disease. PMID:28344312

  15. Antineutrophil cytoplasmic antibodies crescentic allograft glomerulonephritis after sofosbuvir therapy

    PubMed Central

    Gadde, Shilpa; Lee, Belinda; Kidd, Laura; Zhang, Rubin

    2016-01-01

    Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis (RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine (adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis. PMID:27872837

  16. Rapid Progression of Coronary Atherosclerosis: A Review

    PubMed Central

    Shah, Priyank; Bajaj, Sharad; Virk, Hartaj; Bikkina, Mahesh; Shamoon, Fayez

    2015-01-01

    Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis. PMID:26823982

  17. Glomerulonephritis mediated by antibody to glomerular basement membrane. Immunological, clinical, and histopathological characteristics.

    PubMed Central

    McPhaul, J J; Mullins, J D

    1976-01-01

    A prospective study was undertaken to establish the incidence of glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and its histopathological characteristics in a clinical group of patients presenting with renal disease. Biopsies from 43 of 409 consecutive patients technically satisfactory for direct immunofluorescent (IF) examination had diffuse and generalized linear localization of host immunoglobulin (Ig); two other badly scarred kidneys tested negative to IF although GBM antibodies were eluted. Confirmatory evidence of GBM antibody-mediated disease in these patients came from whole kidney or biopsy elutions (15 patients), serologic assays for circulating GBM antibodies by indirect IF (9 of 38 patients), radioimmunoassay (26 of 34), and hemagglutination (31 of 32). Although sera were not tested from six patients, circulating antibodies were demonstrated by some test in 36 of 39 of the remainder. Histologically, half of the patients had minor and nonspecific glomerular abnormalities or mild focal proliferative glomerulonephritis. More severely involved kidneys had focal necrotizing (17%), rapidly progressive (7%), and chronic, usually sclerosing, glomerulonephritis (27%). Clinical courses of these patients comparably were quite variable, ranging from indolent microhematuria and/or gross hematuric bouts to progressive renal failure; nephrotic syndrome was observed in 11 patients. GBM antibody-mediated glomerulonephritis may be a relatively mild disease with apparently stable renal function, although 16 patients have experienced functional deterioration, and 11 have progressed to dialysis, renal transplantation, or death. Images PMID:56340

  18. [An autopsy case of Goodpasture syndrome preceded with membranous glomerulonephritis].

    PubMed

    Takeuchi, K; Takeda, T; Sakai, I; Taneichi, K; Shibaki, H

    1997-12-01

    Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.

  19. Glomerulonephritis (For Parents)

    MedlinePlus

    ... salt, and potassium diuretics (medicines that increase urine production) medicines to lower blood pressure (if high blood pressure is a problem) antibiotics (if a bacterial infection is causing glomerulonephritis) steroids ...

  20. Hypertension in Chronic Glomerulonephritis

    PubMed Central

    2015-01-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  1. Rapidly Progressive Spontaneous Spinal Epidural Abscess.

    PubMed

    Aycan, Abdurrahman; Aktas, Ozgür Yusuf; Guzey, Feyza Karagoz; Tufan, Azmi; Isler, Cihan; Aycan, Nur; Gulsen, İsmail; Arslan, Harun

    2016-01-01

    Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation.

  2. Rapidly Progressive Spontaneous Spinal Epidural Abscess

    PubMed Central

    Aktas, Ozgür Yusuf; Guzey, Feyza Karagoz; Tufan, Azmi; Isler, Cihan; Aycan, Nur; Gulsen, İsmail

    2016-01-01

    Spinal epidural abscess (SEA) is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI) remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation. PMID:27688918

  3. Rapid progression of familial amyloidotic polyneuropathy

    PubMed Central

    Coelho, Teresa; Obici, Laura; Merlini, Giampaolo; Mincheva, Zoia; Suanprasert, Narupat; Bettencourt, Brian R.; Gollob, Jared A.; Gandhi, Pritesh J.; Litchy, William J.; Dyck, Peter J.

    2015-01-01

    Objectives: To assess the association between severity of neuropathy and disease stage, and estimate the rate of neuropathy progression in a retrospective cross-sectional analysis of a multinational population of patients with familial amyloidotic polyneuropathy (FAP). Methods: We characterize neuropathy severity and rate of progression in available patients with FAP in France, the United States, Portugal, and Italy. Neuropathy Impairment Scores (NIS), time from symptom onset to NIS measurement, polyneuropathy disability (PND) scores, FAP disease stage, and manual grip strength data were collected. We estimated neuropathy progression using Loess Fit and Gompertz Fit models. Results: For the 283 patients studied (mean age, 56.4 years), intercountry genotypic variation in the transthyretin (TTR) mutation was observed, with the majority of patients in Portugal (92%) having early-onset Val30Met-FAP. There was also marked intercountry variation in PND score, FAP stage, and TTR stabilizer use. NIS was associated with PND score (NIS 10 and 99 for scores I and IV, respectively; p < 0.0001) and FAP stage (NIS 14 and 99 for stages 1 and 3, respectively; p < 0.0001). In addition, there was an association between NIS and TTR genotype. The estimated rate of NIS progression for a population with a median NIS of 32 was 14.3 points/year; the corresponding estimated rate for the modified NIS+7 is 17.8 points/year. Conclusions: In a multinational population of patients with FAP, rapid neuropathic progression is observed and the severity of neuropathy is associated with functional scales of locomotion. PMID:26208957

  4. Pauci-immune glomerulonephritis in a captive chimpanzee (Pan troglodytes), and a review of spontaneous cases in animals.

    PubMed

    Neidig, Lauren E; Owston, Michael A; Ball, Erin; Dick, Edward J

    2016-08-10

    Crescentic glomeruli are the hallmark finding in rapidly progressive glomerulonephritis (RPGN) and are characterized by disruption and proliferation of the glomerular capsule and an influx of cells into Bowman's space. Pauci-immune-type RPGN is identified by a lack of immunoglobulins and immune complexes in the glomerular basement membrane. Complete necropsy and histology were performed on the affected chimpanzee. Electron microscopy was performed on kidney sections. A search of the literature was performed to identify spontaneous RPGN in animals. We report a case of crescentic glomerulonephritis of the pauci-immune-type in a hepatitis C virus-infected 28-year-old male chimpanzee (Pan troglodytes) who was humanely euthanized for a cardiac-related decline in health. To our knowledge, this is the first report describing pauci-immune crescentic glomerulonephritis in a non-human primate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Crescentic Glomerulonephritis in IgA Multiple Myeloma: A Case Report

    PubMed Central

    Moscoso-Solorzano, Grace T.; Madureira-Silva, Marcus V.; Balda, Carlos; Franco, Marcello F.; Mastroianni-Kirsztajn, Gianna

    2011-01-01

    Background There are few reports of glomerulonephritis (GN) with crescents and a rapidly progressive course that lead to a diagnosis of a previously unsuspected B-cell dyscrasia. Case Presentation: We report a case of rapidly progressive GN: the patient showed no evidence of etiology at the time of biopsy and was diagnosed as IgA multiple myeloma (MM) during investigation based on a renal biopsy. He presented diffuse proliferative and exudative GN and marked plasma cell infiltration of the kidney. Conclusion The present case raises the possibility that proliferative GN with crescents may be a rare mode of presentation of MM. PMID:22470380

  6. Quantitative morphometry of glomerulonephritis with crescents. Diagnostic and predictive value.

    PubMed

    Elfenbein, I B; Baluarte, H J; Cubillos-Rojas, M; Gruskin, A B; Coté, M; Cornfeld, D

    1975-01-01

    Histologic patterns in the glomerular tufts in "Glomerulonephritis with many crescents" take three main forms: (1) compression and sclerosis of glomeruli, (2) necrotizing glomerulitis, and (3) proliferation with or without exudation. In the third group, histologic differentiation between patients with poststreptococcal glomerulonephritis with many crescents (AGN) and those with nonstreptococcal rapidly progressive glomerulonephritis (RPGN) may be impossible. In a retrospective study, quantitative morphometry of glomeruli effectively separated three patients with AGN from two patients with RPGN after the usual histologic and electron microscopic observations had failed. Parameters studied were areas of tufts and crescents and total number of cells and granulocytes in tufts and crescents. Surface areas of tufts and crescents were separately determined by photographing glomeruli, projecting and tracing outlines of tufts and crescents, and cutting out and weighing the tracings. The cell density of glomerular tufts (cell per 1000-sq. mum. area) was significantly greater in AGN than in RPGN when either total cell densities (17.64 plus or minus 0.41 versus 13.63 plus or minus 0.30) or total cells minus granulocytes (16.39 plus or minus 0.50 versus 12.99 plus or minus 0.52) were compared. The cell density in the tufts was 120 and 70 per cent greater than controls in AGN and RPGN, respectively. Exudation of inflammatory cells is contributory but not the major cause of hypercellularity in AGN. Follow-up studies with biopsies showed marked resolution in two of three patients with AGN, with normal blood urea nitrogen levels and focal scarring in the third, whereas the two patients with RPGN had either extensive scarring and reduced renal function or required chronic hemodialysis.

  7. Fibrillary glomerulonephritis in Castleman's disease.

    PubMed

    Miadonna, A; Salmaso, C; Palazzi, P; Elli, A; Braidotti, P; Lambertenghi Deliliers, G

    1998-01-01

    Castleman's disease is an uncommon lymph node disorder which can be associated with renal disease. In this report we describe a patient with fever, weight loss, anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome. Castleman's disease, plasma cell type, was diagnosed by histologic analysis after surgical excision of a pelvic lymph node. The disease was considered localized, since further investigations did not show any other pathologic mass. After resection of the pelvic lymphoid mass, clinical remission of systemic symptoms and laboratory abnormalities was observed, with the exception of the nephrotic syndrome. Renal biopsy was performed and showed a pattern compatible with fibrillary glomerulonephritis. Progressive decline in renal function was observed, despite immunosuppressive therapy.

  8. A Molecular Signature of Proteinuria in Glomerulonephritis

    PubMed Central

    Reich, Heather N.; Tritchler, David; Cattran, Daniel C.; Eichinger, Felix; Boucherot, Anissa; Henger, Anna; Berthier, Celine C.; Nair, Viji; Cohen, Clemens D.

    2010-01-01

    Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. PMID:20976140

  9. A Case of Post-Streptococcal Glomerulonephritis with Diffuse Alveolar Hemorrhage

    PubMed Central

    Sung, Hye-Young; Lim, Chang Hoon; Shin, Mi-Jung; Kim, Young Ok; Song, Ho-Chul; Kim, Suk Young; Choi, Euy Jin; Chang, Yoon Sik; Bang, Byung Kee

    2007-01-01

    Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex ("hump"). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment. PMID:18162726

  10. Spectrum and outcome of primary glomerulonephritis.

    PubMed

    Al Wakeel, Jamal S; Mitwalli, Ahmed H; Tarif, Nauman; Alam, Awatif A; Hammad, Durdana; Abu-Aisha, Hassan; Memon, Nawaz; Sulimani, Fathia; Askar, Akram; Qudsi, Abdo

    2004-01-01

    Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the

  11. Recent progress on FFAGS for rapid acceleration

    SciTech Connect

    C. Johnstone; S. Koscielniak

    2002-12-10

    Muon acceleration is one of the more difficult stages to develop for a Neutrino Factory or Muon Collider. The large transverse and longitudinal admittances which must be designed into the system and the rapidity with which acceleration must take place because of muon decay preclude the use of conventional synchrotron design. The approach here employs fixed-field architectures for muon acceleration; specifically, a fixed-field alternating gradient or FFAG accelerator. This paper explores the FFAG option, in particular addressing an adjustment in the rf phase which, although characteristic of fixed-field machines, becomes problematic in the context of rapid acceleration.

  12. [Glomerulonephritis in diabetics].

    PubMed

    Mágori, A; Sonkodi, S; Lászik, Z; Mohácsi, G

    1989-10-01

    Diagnosis of glomerulonephritis (GN) is rare among diabetics and few data relevant to this issue can be found in literature. In Institute of Pathology of "Szent-Györgyi Albert" University of Medicine the presence of GN was found in cases during the examination of renal biopsy material of 36 diabetics. All patients have suffered from diabetes mellitus of 2nd type and of less than 10 year existence, requiring no insulin treatment. In 2 cases diffuse diabetic glomerulosclerosis associated with GN. It is emphasized that kidney biopsy and its complex--light and electronmicroscopic and immunhistological--examination are essential to the diagnosis of GN of diabetics.

  13. Treatment of Rapidly Progressive Systemic Sclerosis: Current and Futures Perspectives

    PubMed Central

    Mendoza, Fabian A.; Mansoor, Maryah; Jimenez, Sergio A.

    2016-01-01

    Introduction Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. Areas Covered This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification. Expert Opinion The extent, severity, and rate of progression of SSc skin and internal organ involvement determines the optimal therapeutic interventions for SSc. Cyclophosphamide for progressive SSc-associated interstitial lung disease and mycophenolate for rapidly progressive cutaneous involvement have shown effectiveness. Methotrexate has been used for less severe skin progression and for patients unable to tolerate mycophenolate. Rituximab was shown to induce improvement in SSc-cutaneous and lung involvement. Autologous bone marrow transplantation is reserved for selected cases in whom poor survival risk outweighs the high mortality rate of the procedure. Novel agents capable of modulating fibrotic and inflammatory pathways involved in SSc pathogenesis, including tocilizumab, pirfenidone, tyrosine kinase inhibitors, lipid lysophosphatidic acid 1, and NOX4 inhibitors are currently under development for the treatment of rapidly progressive SSc. PMID:27812432

  14. Rapidly Progressive Gas-containing Lumbar Spinal Epidural Abscess

    PubMed Central

    Bang, Jin Hyuk

    2015-01-01

    Gas-containing (emphysematous) infections of the abdomen, pelvis, and extremities are well-known disease entities, which can potentially be life-threatening. They require aggressive medical and often surgical treatment. In the neurosurgical field, some cases of gas-containing brain abscess and subdural empyema have been reported. Sometimes they progress rapidly and even can cause fatal outcome. However, gas-containing spinal epidural abscess has been rarely reported and clinical course is unknown. We report on a case of rapidly progressive gas-containing lumbar spinal epidural abscess due to Enterococcus faecalis in a 72-year-old male patient with diabetes mellitus. PMID:26512268

  15. Rapidly Progressive Gas-containing Lumbar Spinal Epidural Abscess.

    PubMed

    Bang, Jin Hyuk; Cho, Keun-Tae

    2015-09-01

    Gas-containing (emphysematous) infections of the abdomen, pelvis, and extremities are well-known disease entities, which can potentially be life-threatening. They require aggressive medical and often surgical treatment. In the neurosurgical field, some cases of gas-containing brain abscess and subdural empyema have been reported. Sometimes they progress rapidly and even can cause fatal outcome. However, gas-containing spinal epidural abscess has been rarely reported and clinical course is unknown. We report on a case of rapidly progressive gas-containing lumbar spinal epidural abscess due to Enterococcus faecalis in a 72-year-old male patient with diabetes mellitus.

  16. Diagnosis and Evaluation of a Patient with Rapidly Progressive Dementia

    PubMed Central

    Bucelli, Robert C.; Ances, Beau M.

    2014-01-01

    While the most common dementia is Alzheimer’s disease (AD), a detailed history is needed to rule out rapidly progressive dementias (RPDs). RPDs are less than two years in duration and have a rate of progression faster typical neurodegenerative diseases. Identification of RPDs is important as some are treatable. This review focuses on the spectrum of RPDs, with special emphasis on paraneoplastic disorders and Creutzfeldt-Jakob disease (CJD). PMID:24279195

  17. Myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis in autosomal dominant polycystic kidney disease

    PubMed Central

    2013-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder that is characterized by the development of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/day, and ADPKD is rarely associated with nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN). To date, myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis (CrGN) has not been reported in a patient with ADPKD. Case presentations We report two cases of MPO-ANCA positive ADPKD. A 60-year-old Japanese woman (case 1) and a 54-year-old Japanese woman (case 2) presented with RPGN featuring severe proteinuria and microscopic hematuria. In both patients percutaneous needle biopsy of the kidney revealed MPO-ANCA-associated CrGN with a paucity of glomerular immunoglobulin staining. Each patient received intravenous methylprednisolone for 3 days, followed by oral prednisolone. Case 1 showed gradual improvement and has not progressed to end-stage renal disease (ESRD), but case 2 developed ESRD requiring hemodialysis within one month despite treatment. Conclusion These are the first two reported cases of MPO-ANCA-associated CrGN in patients with ADPKD. Our experience suggests that serial measurement of the ANCA titer and renal biopsy should be considered for accurate diagnosis and appropriate treatment of ADPKD patients who present with proteinuria, hematuria, and rapid decline of renal function. PMID:23617397

  18. [Systemic enzyme therapy of experimental gout glomerulonephritis].

    PubMed

    Ignatenko, G A; Mukhin, I V

    2004-01-01

    Renal lesion deteriorates the course and prognosis of gouty glomerulonephritis. Current pathogenetic therapy is not sufficiently effective. Effects of different treatments on morphological and functional manifestations of renal disorders in experimental gouty glomerulonephritis are reviewed.

  19. [Two cases of rapidly progressive nephritic syndrome complicated with alcoholic liver cirrhosis].

    PubMed

    Kaneko, Tomohiro; Arima, Ryuji; Arakawa, Yusuke; Aoki, Michiko; Fukuda, Kumiko; Fukui, Megumi; Hirama, Akio; Fujita, Emiko; Mii, Akiko; Utsumi, Koichi; Shimizu, Akira; Iino, Yasuhiko

    2011-01-01

    It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA (IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR)were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three courses of steroid semi-pulse therapy and post therapy with steroids and MZR were combined, his proteinuria and serum Cre level decreased and stagnated ascites markedly decreased. The two cases were diagnosed as having secondary IgA nephropathy induced by the deposition of the IgA1 derived mainly from the intestinal tract, which had increased

  20. Antidopaminergic Medication is Associated with More Rapidly Progressive Huntington's Disease.

    PubMed

    Tedroff, Joakim; Waters, Susanna; Barker, Roger A; Roos, Raymund; Squitieri, Ferdinando

    2015-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder leading to progressive motor, cognitive and functional decline. Antidopaminergic medications (ADMs) are frequently used to treat chorea and behavioural disturbances in HD. We aimed to assess how the use of such medications was associated with the severity and progression of the motor aspects of the condition, given that there have been concerns that such drugs may actually promote neurological deterioration. Using multiple linear regression, supplemented by principal component analysis to explore the overall correlation patterns and help identify relevant covariates, we assessed severity and progression of motor symptoms and functional decline in 651 manifest patients from the REGISTRY cohort followed for two years. ADM treated versus non-treated subjects were compared with respect to motor impairment at baseline and progression rate by means of multiple regression, adjusting for CAG-repeat and age. Patients treated with ADMs had significantly worse motor scores with greater functional disability at their first visit. They also showed a higher annual rate of progression of motor signs and disability over the next two years. In particular the rate of progression for oculomotor symptoms and bradykinesia was markedly increased whereas the rate of progression of chorea and dystonia was similar for ADM and drug naïve patients. These differences in clinical severity and progression could not be explained by differences in disease burden, duration of disease or other possible prognostic factors. The results from this analysis suggest ADM treatment is associated with more advanced and rapidly progressing HD although whether these drugs are causative in driving this progression requires further, prospective studies.

  1. Progress in the rapid diagnosis of viral infections: a Memorandum*

    PubMed Central

    1978-01-01

    This Memorandum reports the progress that has been made over the past year in the development of laboratory techniques for the rapid diagnosis of viral infections. Progress is reported in the use of the immunoperoxidase and immunofluorescence techniques for detecting viruses in respiratory secretions, the use of the glutaraldehyde and periodate methods for peroxidase conjugation, the application of enzyme immunoassay techniques in the detection of viral antigens and antibodies, and training in the use of these techniques. A number of recommendations for further research are made. PMID:352567

  2. Rapid progression of hepatocellular carcinoma after Radiofrequency Ablation

    PubMed Central

    Ruzzenente, Andrea; de Manzoni, Giovanni; Molfetta, Matteo; Pachera, Silvia; Genco, Bruno; Donataccio, Matteo; Guglielmi, Alfredo

    2004-01-01

    AIM: To report the results of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in cirrhotic patients and to describe the treatment related complications (mainly the rapid intrahepatic neoplastic progression). METHODS: Eighty-seven consecutive cirrhotic patients with 104 HCC (mean diameter 3.9 cm, 1.3 SD) were submitted to RFA between January 1998 and June 2003. In all cases RFA was performed with percutaneous approach under ultrasound guidance using expandable electrode needles. Treatment efficacy (necrosis and recurrence) was estimated with dual phase computed tomography (CT) and alpha-fetoprotein (AFP) level. RESULTS: Complete necrosis rate after single or multiple treatment was 100%, 87.7% and 57.1% in HCC smaller than 3 cm, between 3 and 5 cm and larger than 5 cm respectively (P = 0.02). Seventeen lesions of 88(19.3%) developed local recurrence after complete necrosis during a mean follow up of 19.2 mo. There were no treatment-related deaths in 130 procedures and major complications occurred in 8 patients (6.1 %). In 4 patients, although complete local necrosis was achieved, we observed rapid intrahepatic neoplastic progression after treatment. Risk factors for rapid neoplastic progression were high preoperative AFP values and location of the tumor near segmental portal branches. CONCLUSION: RFA is an effective treatment for hepatocellular carcinoma smaller than 5 cm with complete necrosis in more than 80% of lesions. Patients with elevated AFP levels and tumors located near the main portal branch are at risk for rapid neoplastic progression after RFA. Further studies are necessary to evaluate the incidence and pathogenesis of this underestimated complication. PMID:15069713

  3. Rapidly progressive quadriparesis heralding disseminated coccidioidomycosis in an immunocompetent patient.

    PubMed

    Tan, Lee A; Kasliwal, Manish K; Nag, Sukriti; O'Toole, John E; Traynelis, Vincent C

    2014-06-01

    Coccidioides species are dimorphic fungi endemic to southwestern USA and northern Mexico. Disseminated coccidioidomycosis is rare with an estimated incidence of 1% in affected individuals and usually presents as meningitis when the central nervous system is involved. Spinal involvement with coccidioidomycosis, though not uncommon, predominantly manifests as osseous involvement leading to osteomyelitis and epidural abscess formation. Progressive quadriparesis as a presenting symptom secondary to intramedullary spinal cord coccidioidomycosis is very unusual and to our knowledge has not been described. We report a patient with disseminated coccidioidomycosis who presented with rapidly progressive quadriparesis due to cervical intramedullary spinal cord involvement. The absence of known coccidioidomycosis with atypical clinical presentation made the diagnosis elusive, requiring emergent cervical laminectomies with dural biopsy for decompression of the spinal cord and confirmation of the diagnosis. The patient eventually succumbed to the progressive course of the disease. Although rare, disseminated coccidioidomycosis can present as new, rapidly progressing quadriparesis in patients who have traveled to endemic areas. A high index of suspicion in such patients with appropriately directed laboratory investigations and consideration of early biopsy might unravel the diagnosis facilitating early antifungal treatment with the potential to minimize morbidity and mortality associated with disseminated coccidioidomycosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Pediatric case of crescentic post-streptococcal glomerulonephritis with myeloperoxidase anti-neutrophil cytoplasmic antibody.

    PubMed

    Kanai, Hiroaki; Sawanobori, Emi; Koizumi, Keiichi; Ohashi, Ryuji; Higashida, Kosuke

    2015-04-01

    Post-streptococcal glomerulonephritis (PSGN) generally has a good renal prognosis, and immunosuppressive therapies are not needed. However, a few patients present with severe acute kidney injury and extensive crescent formations. The etiology of such patients is not well known, and involvement of anti-neutrophil cytoplasmic antibodies is rarely reported. A 9-year-old girl with rapidly progressive nephritic syndrome was diagnosed with PSGN. A biopsy showed diffuse crescentic glomerulonephritis with immunoglobulin G and C3 deposits; moreover, humps were observed on electron microscopy. After she was administered methylprednisolone pulse therapy and intravenous cyclophosphamide, followed by prednisolone and azathioprine therapy, her urinary abnormalities improved and renal function normalized. However, the myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) titers gradually increased. We speculated that PSGN may be augmented by increased MPO-ANCA levels. Therefore, the patient is currently being treated with losartan, enalapril, azathioprine, and prednisolone. Although the MPO-ANCA titer remains high, urinary findings show mild proteinuria and her renal function has been norma for 18 months since onset. A progressive clinical course and severe histological findings may indicate the involvement of ANCA in deterioration of condition in patients with PSGN. Furthermore, in such cases immunosuppressive therapies should be considered even in pediatric PSGN.

  5. Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use.

    PubMed

    Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J

    1999-01-01

    We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.

  6. Do plaques rapidly progress prior to myocardial infarction? The interplay between plaque vulnerability and progression.

    PubMed

    Ahmadi, Amir; Leipsic, Jonathon; Blankstein, Ron; Taylor, Carolyn; Hecht, Harvey; Stone, Gregg W; Narula, Jagat

    2015-06-19

    There is a common misperception in the cardiology community that most acute coronary events arise from ruptures of mildly stenotic plaques. This notion has emanated from multiple studies that had measured the degree of angiographic luminal narrowing in culprit plaques months to years before myocardial infarction. However, angiographic studies within 3 months before myocardial infarction, immediately after myocardial infarction with thrombus aspiration or fibrinolytic therapy, and postmortem pathological observations have all shown that culprit plaques in acute myocardial infarction are severely stenotic. Serial angiographic studies also have demonstrated a sudden rapid lesion progression before most cases of acute coronary syndromes. The possible mechanisms for such rapid plaque progression and consequent luminal obstruction include recurrent plaque rupture and healing and intraplaque neovascularization and hemorrhage with deposition of erythrocyte-derived free cholesterol. Moreover, recent intravascular and noninvasive imaging studies have demonstrated that plaques which result in coronary events have larger plaque volume and necrotic core size with greater positive vessel remodeling compared with plaques, which remain asymptomatic during several years follow-up, although these large atheromatous vulnerable plaques may angiographically seem mild. As such, it is these vulnerable plaques which are more prone to rapid plaque progression or are those in which plaque progression is more likely to become clinically evident. Therefore, in addition to characterizing plaque morphology, inflammatory activity, and severity, detection of the rate of plaque progression might identify vulnerable plaques with an increased potential for adverse outcomes. © 2015 American Heart Association, Inc.

  7. Characterisation of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

    PubMed Central

    Maratou, Klio; Behmoaras, Jacques; Fewings, Chris; Srivastava, Prashant; D’Souza, Zelpha; Smith, Jennifer; Game, Laurence; Cook, Terence; Aitman, Tim

    2010-01-01

    Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity. PMID:21179115

  8. [A case of MPO ANCA associated glomerulonephritis with interstitial pneumonitis complicated with lung tuberculosis and pericarditis].

    PubMed

    Takahashi, K; Suda, S; Takayama, M; Deguchi, F; Matsuda, O; Tachibana, K; Yoshimura, A

    2000-10-01

    The main target organs of myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA)-related disease are the kidney and lung. This report describes a 71-year-old man with rapidly progressive glomerulonephritis (RPGN) and interstitial pneumonitis associated with MPO ANCA. The patient was admitted to our hospital because of bloody sputum, low grade fever and appetite loss on October, 1998. He was diagnosed as having interstitial pneumonitis from the findings of chest X-ray and CT examinations. Moderate proteinuria and hematuria, renal dysfunction(serum creatinine: 5.6 mg/dl, BUN: 58.0 mg/dl) and positivity for MPO ANCA were noted. He was negative for anti-glomerular antibody and PR3-ANCA. Renal biopsy was performed and revealed crescentic glomerulonephritis without deposition of immunoglobulins. Therefore, the diagnosis of pauci immune type RPGN was made. Pulse therapy with methylprednisolone(1.0 g/day x 3 days) following oral administration of prednisolone (60 mg/day) found marked improvement of renal function maintenance and interstitial pneumonitis, respectively. However, he died because of lung tuberculosis and acute tuberculous pericarditis during treatment with prednisolone. In this case, MPO ANCA might have been directly associated with both RPGN and interstitial pneumonitis. Furthermore, chronic lung disease, such as interstitial pneumonitis, is important as a preceding disease of RPGN. MPO ANCA-related disease is more frequent in aged persons, therefore particular attention should be paid during their treatment with an immunosuppressant.

  9. Characterization of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains.

    PubMed

    Maratou, K; Behmoaras, J; Fewings, C; Srivastava, P; D'Souza, Z; Smith, J; Game, L; Cook, T; Aitman, T

    2011-03-01

    Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. Wistar-Kyoto (WKY) rats show marked susceptibility to CRGN, whereas Lewis rats are resistant. Glomerular injury and crescent formation are macrophage dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterized Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% false discovery rate) for basal and LPS-stimulated macrophages. Moreover, we identified eight genes with differentially expressed alternatively spliced isoforms, by using an in-depth analysis at the probe level that allowed us to discard false positives owing to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7 and define groups of genes that play a significant role in differential regulation of macrophage activity.

  10. Rapid progression of glioblastoma multiforme: A case report

    PubMed Central

    Zhang, Yan Yan; Ruan, Ling Xiang; Zhang, Sheng

    2016-01-01

    Glioblastoma multiforme (GBM) tumors are intracranial lesions with varying shapes that grow rapidly. GBM tumors most commonly present as solitary lesions and multiple lesions are rare. The aim of the present case report was to investigate the imaging features of glioblastoma multiforme (GBM). In this study, the case of a 60-year-old patient who was hospitalized due to seizures is presented. Magnetic resonance imaging (MRI) revealed multiple lesions, heterogeneous in size, with peritumoral edema and ring-shaped enhancement. The lesions grew rapidly within 10 days of hospitalization and were initially misdiagnosed as either infections or intracranial metastatic tumors as a result of imaging examinations. The patient was subsequently administered mannitol, diazepam, Tegretol and ceftriaxone. After treatment, the patient recovered and regained full consciousness. However, MRI examination 23 days after hospitalization revealed that the multiple lesions in the left temporal and left occipital lobes had increased in size. Therefore, resection of the tumor in the left temporal occipital lobe was performed. Histopathological examination identified GBM (grade IV) in the left temporal and parietal lobes. The patient succumbed to the disease 7 months after surgery due to GBM recurrence. The findings of the present case indicate that GBM may progress rapidly with a doubling time of 10 days and multiple cystic alterations. Furthermore, if diagnosis of GBM is unclear, early biopsy is recommended. PMID:28105188

  11. An unusual case of Plasmodium vivax malaria monoinfection associated with crescentic glomerulonephritis: a need for vigilance.

    PubMed

    Patel, Mohan P; Kute, Vivek B; Gumber, Manoj R; Gera, Dinesh N; Shah, Pankaj R; Patel, Himanshu V; Trivedi, Hargovind L; Vanikar, Aruna V

    2013-01-01

    Plasmodium vivax infection is increasingly a major public health burden and the second most frequent human malaria. Higher levels of clinical severity and chloroquine resistance are major factors responsible for such increases. Malarial glomerular injury is uncommon and mainly observed in Plasmodium malariae-infected patients. Occasionally, transient immune complex-mediated glomerulonephritis is associated with Plasmodium falciparum infection. Coexistent crescentic glomerulonephritis and vivax malaria have not previously been reported. We report a fatal case of P. vivax malaria, who presented with acute renal failure. P. vivax monoinfection status was diagnosed with peripheral blood smear and rapid antigen test. Further evaluation for renal failure related to systemic illness and immunological markers were inconclusive. He was treated with antimalarial drugs, hemodialysis, and supportive therapy. Renal biopsy performed for nonrecovering renal failure reveled crescentic glomerulonephritis. This case highlights the need to thoroughly search for malaria-associated crescentic glomerulonephritis using renal biopsy after nonrecovering renal failure.

  12. The pattern of histologically-proven acute post-infectious glomerulonephritis in Tunisian adults seen in 1976-2004.

    PubMed

    Helal, Imed; Kaaroud, Hayet; Goucha, Rym; Ben Moussa, Fatma; Ben Maiz, Hedi; Kheder, Adel

    2012-05-01

    Acute post-infectious glomerulonephritis (APIGN) is uncommon in adults. It is widely recognized that the prognosis of APIGN is good in children. There is however little information about its long-term prognosis in adults. Between December 1976 and October 2004, 148 adult cases of APIGN were managed in our center. We retrospectively reviewed these patients' records and evaluated their clinical course and outcome. The mean age of studied patients was 36 ± 15 years, and the male to female ratio was 2.3. The most common site of preceding infection was the respiratory tract (68.8%). At presentation, 89.2% had nephritic syndrome and 9.4% had rapidly progressive glomerulonephritis. Proteinuria was observed in 99.3%, hematuria in 95.3%, peripheral edema in 89.2% and hypertension in 81.8%. Most patients (60.7%) had acute kidney injury and four patients (2.7%) required dialysis. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis in 88.8% of patients, associated with extracapillary proliferation in 12%. After a median follow-up of 2.5 year, only two patients died and 16.12% of patients had persistent clinical and/or biological abnormality. Chronic kidney disease was noted in 10 patients (6.75%) including four patients (2.7%) who progressed to end-stage renal disease. Poor prognostic factors included nephrotic range proteinuria, extracapillary proliferation in renal biopsy, acute kidney injury and the need for dialysis. In this cohort of patients, APIGN progressed to chronic kidney disease in less than 10% of patients.

  13. Rapidly progressive lupus nephritis and concomitant thrombotic microangiopathy.

    PubMed

    Gharbi, Chems; Bourry, Edward; Rouvier, Philippe; Hacini, Sabria; Letaief, Ahmed; Baumelou, Alain; Izzedine, Hassane

    2010-10-01

    Although uncommon, thrombotic microangiopathy (TMA) is one of the most serious complications in patients with systemic lupus erythematosus. A 30-year-old black woman admitted to our hospital because of fever, fatigue, 'dark' urine and rapidly progressive renal failure was found to have systemic lupus erythematous and atypical hemolytic uremic syndrome. Kidney biopsy showed WHO class IV lupus nephritis with crescents and TMA. Hemodialysis was initiated for worsening renal failure. The patient was treated with corticosteroids, monthly pulse intravenous Cyclophosphamide, plasmapheresis and Rituximab on a weekly basis for 4 weeks. The patient's blood pressure was aggressively controlled using antihypertensive agents. Despite this extensive therapy, she remained dialysis dependent although hematological parameters returned to normal values.

  14. C3 deposits worsens the prognosis in type iii extracapillary glomerulonephritis.

    PubMed

    Sánchez-Agesta Martínez, Marina; Rabasco Ruiz, Cristina; Sánchez Sánchez, Rafael; Ortega Salas, Rosa; López Andreu, María; Aljama García, Pedro; Espinosa Hernández, Mario

    2017-10-05

    Type iii extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN. The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. All patients diagnosed of PEGN from 1995 to 2015 (n=72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. Positive staining for C3 was observed in 22 out of the 72 patients (30.5%). At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85mg/dl, P=0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (P=0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Renal Biopsy Findings in Acute Renal Failure in the Cohort of Patients in the Spanish Registry of Glomerulonephritis

    PubMed Central

    López-Gómez, Juan M.; Rivera, Francisco

    2008-01-01

    Background and objectives: Renal biopsy in acute renal failure of unknown origin provides irreplaceable information for diagnosis, treatment, and prognosis. This study analyzed the frequency and clinicopathologic correlations of renal native biopsied acute renal failure in Spain during the period 1994 through 2006. Design, setting, participants, & measurements: Acute renal failure was defined as a rapid deterioration of glomerular filtration rate, with or without oligoanuria or rapidly progressive renal insufficiency, including acute-on-chronic renal failure. Patients who were younger than 15 yr were considered children, those between 15 and 65 yr adults, and those >65 elderly. Results: Between 1994 and 2006, data on 14,190 native renal biopsies were collected from 112 renal units in Spain. Of these, 16.1% (2281 biopsies) were diagnosed with acute renal failure. The prevalence of the main clinical syndromes was different in the three age groups: Biopsy-confirmed acute renal failure in children was 5.7%, in adults was 12.5%, and in elderly increased significantly to 32.9%. The prevalence of biopsy-confirmed acute renal failure according to cause was as follows: Vasculitis, 23.3%; acute tubulointerstitial nephritis, 11.3%; and crescentic glomerulonephritis types 1 and 2, 10.1%. The prevalence of the different causes differed significantly according to age group. Conclusions: The Spanish Registry of Glomerulonephritis provides useful information about renal histopathology in biopsy-confirmed acute renal failure. The prevalence of vasculitis and crescentic glomerulonephritis is high, especially in elderly patients. These data obtained from a national large registry highlight the value of renal biopsy in undetermined acute renal failure. PMID:18354075

  16. Rapidly progressive cryptogenic organising pneumonia presenting as a lung mass

    PubMed Central

    Akram, Saeed; Irfan, Muhammad; Aftab, Kanwal

    2009-01-01

    A very rare case of a rapidly progressive variant of cryptogenic organising pneumonia (COP) presenting as a focal mass-like lesion with compression of the large airways leading to respiratory failure is described. A 60-year-old lady presented to the Aga Khan University Hospital Emergency Department in hypoxaemic respiratory failure with a 6-day history of dyspnoea, productive cough and fever. Chest x ray showed a right upper lobe mass-like lesion compressing the large airways and right pleural effusion. She deteriorated in the Emergency Department and was intubated due to worsening hypoxaemic respiratory failure. The pleural fluid and bronchoscopic specimens were negative on microbiological and cytological examination. CT-guided right lung biopsy revealed chronic non-specific inflammation without granuloma and malignancy. COP was diagnosed on video-assisted thoracoscopic (VATS) lung biopsy. She was successfully treated with high dose steroids and discharged in a stable condition; her 3-month follow-up chest x rays showed complete resolution of the lung lesion with some residual fibrosis. PMID:21686529

  17. Pauci-immune crescentic glomerulonephritis in the Down's syndrome.

    PubMed

    Cherif, Mejda; Hedri, Hafedh; Ounissi, Mondher; Gergah, Taher; Goucha, Rim; Barbouch, Samia; Abderrahim, Ezzedine; Maiz, Hedi Ben; Kheder, Adel

    2013-11-01

    Kidney disease is a rare complication in patients with the Down's syndrome. However, with increased survival, it appears that a growing number of these patients present with glomerulonephritis. Most cases have been reported as case reports and include lesions such as mesangiocapillary glomerulonephritis with hypo-complementemia, crescentic glomerulonephritis with anti-neutrophil cytoplasmic antibodies (ANCA), amyloidosis and immunotactoid glomerulopathy. We report the observation of a 38-year-old man with the Down's syndrome who presented with severe renal failure, proteinuria and microscopic hematuria evolving over two months. There was no history of congenital heart disease or urinary symptoms. Percutaneous renal biopsy revealed fibrous crescents, rupture of Bowman's capsule and peri-glomerular granuloma; there were no deposits on immunofluorescence study. Thoracic computerized tomography scan showed alveolar congestion. The patient tested negative for ANCA. At the time of reporting, the patient is on regular chronic hemodialysis. Our case illustrates a distinct entity that further expands the spectrum of renal disease known to occur in the Down's syndrome. Early detection of the renal disorders may prevent or slow down the progression.

  18. Glomerulonephritis

    MedlinePlus

    ... seen, including: Nerve inflammation (polyneuropathy) Signs of fluid overload, including abnormal heart and lung sounds Swelling ( edema ) ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  19. Glomerulonephritis

    MedlinePlus

    ... of removing extra fluids and waste from your blood — typically by an artificial kidney machine. Chronic kidney disease. Your kidneys gradually lose their filtering ability. Kidney function that deteriorates to less than 10 percent of ... High blood pressure. Damage to your kidneys and the resulting ...

  20. Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats.

    PubMed

    Togashi, Yuko; Imura, Naoko; Miyamoto, Yohei

    2013-11-01

    The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.

  1. Sequential development of pulmonary hemorrhage with MPO-ANCA complicating anti-glomerular basement membrane antibody-mediated glomerulonephritis.

    PubMed

    Peces, R; Rodríguez, M; Pobes, A; Seco, M

    2000-05-01

    We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 67-year-old woman with diabetes. Intensive combined immunosuppressive therapy with methylprednisolone bolus, oral prednisone, and cyclophosphamide led to negativity of anti-GBM antibodies but was not able to restore renal function. After 28 months of hemodialysis, the patient suddenly presented with pulmonary hemorrhage. In this setting, high levels of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and negative anti-GBM antibodies were found. Therapy with oral prednisone and cyclophosphamide led to resolution of pulmonary hemorrhage and negativity of MPO-ANCA.

  2. Membranoproliferative glomerulonephritis and Pott's disease.

    PubMed

    Ram, Rapur; Sandeep, Peddi; Sridhar, Annapindi Venkatasatya Surya Naga; Rukumangadha, Nandyala; Sivakumar, Vishnubotla

    2014-08-01

    The reports of glomerular lesions of kidney due to tuberculosis are sparse. A 48-year-old gentleman, presented with swelling of feet of 3 months duration. As he had renal impairment, proteinuria and normal-sized kidneys, he was subjected to renal biopsy. The light microscopy and immunofluorescence revealed the diagnosis was membrano-proliferative glomerulonephritis. During hospital stay, the patient complained fever and stiffness at thoracic spine. The MRI of thoraco-lumbo-sacral spine revealed paravertebral abscess at D11-D12. The pus aspirated was positive for Mycobacterium tuberculosis. He was started on anti-tuberculous medication. After 8 weeks of therapy, the serum creatinine was 1.5 mg/dL and 24 h urine protein 250 mg.

  3. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: Protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo 1

    PubMed Central

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E.; Borza, Dorin-Bogdan

    2010-01-01

    The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport post-transplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM antibodies. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to antibody-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 cross-links, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys—a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by post-translational modifications of an autoantigen. PMID:20709951

  4. Crescentic glomerulonephritis in Wegener's granulomatosis: morphology, therapy, outcome.

    PubMed

    Grotz, W; Wanner, C; Keller, E; Böhler, J; Peter, H H; Rohrbach, R; Schollmeyer, P

    1991-06-01

    Fourteen patients with Wegener's granulomatosis (WG) and severe renal and extrarenal involvement were studied (serum creatinine on admission 5.8 +/- 3.4 mg/dl). Renal histology showed a necrotizing, crescentic glomerulonephritis in all patients. Despite advanced renal disease on admission cyclophosphamide, steroids (in 13 patients) and plasma exchange (in 9 patients) caused a rapid and sustained improvement of renal function. Four patients required intermittent hemodialysis over a period of one week. After 2 weeks of treatment serum creatinine values below 2 mg/dl (n = 4) indicated a nearly complete recovery of renal function in the long-term follow up (mean serum creatinine achieved after 12 months therapy: 1.1 +/- 0.1 mg/dl (n = 4). Therefore serum creatinine values observed after 2 weeks of therapy, appear to be of prognostic value with regard to renal outcome. No relapse of active WG or progressive renal deterioration was observed during follow-up (22 +/- 13 months) except in one patient with persisting renal impairment. Three patients died (staphylococcus sepsis, intracerebral hemorrhage during hypertensive crisis, pulmonary embolism) during the first two months of therapy. The decline of serum creatinine seemed to be a better indicator of successful therapy than the decrease of anticytoplasmatic antibody (ANCA), erythrocyte sedimentation rate (ESR) and hematuria. On admission ANCA titer neither correlated with serum creatinine, the degree of renal involvement, nor was it of prognostic value. ANCA, serum creatinine and hematuria normalized within 2 to 8 months, whereas ESR and proteinuria remained elevated. Our data indicate a good prognosis of WG even with advanced renal involvement and generalized vasculitis provided aggressive treatment is performed early.

  5. A case of a 6-year-old girl with anti-neutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis.

    PubMed

    Shimizu, Maki; Sekiguchi, Takanori; Kishi, Natsuko; Goji, Aya; Takahashi, Tomoko; Kozan, Hiroko; Sakaguchi, Zenichi; Kinoshita, Yukiko; Matsuura, Sato; Suga, Kenichi; Urushihara, Maki; Kondo, Shuji; Kagami, Shoji; Ohara, Katsuaki

    2011-08-01

    A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.

  6. Kartagener syndrome associated with mesangioproliferative glomerulonephritis.

    PubMed

    Krishnamurthy, Sriram; Choudhary, Bharat; Rajesh, Nachiappa Ganesh; Ramesh, Ananthakrishnan; Srinivasan, Sadagopan

    2012-05-01

    An 11-year-old girl with clinical features of Kartagener syndrome presented with signs of acute glomerulonephritis. Blood urea and creatinine were mildly elevated and anti-streptolysin O and C3 levels were normal. Renal biopsy demonstrated mesangial proliferation and direct immunofluorescence showed IgM and C3 deposits. This appears to be the first report of Kartagener syndrome in association with mesangioproliferative glomerulonephritis. The literature is reviewed and the possible mechanisms for this association are discussed.

  7. [Rapidly progressive compromise of cranial pairs as neurosyphilis manifestation].

    PubMed

    Baccaro, Fernando; Moldes, Sofía; Novelli Poisson, Paola; Arduin, Julieta; Valerga, Mario

    2012-01-01

    Syphilis remains a common disease throughout the world, being neurosyphilis a relatively common manifestation. A case of a 34 years old male with HIV and neurosyphilis is presented, characterized by a clinical course evidenced by progressive palsy of cranial nerves. This case is unusual and a rare presentation of progressive cranial involvement with swallowing deficit, have found no similar data in the literature.

  8. [Antioxidant effect of wobenzym applied for patients with chronic glomerulonephritis].

    PubMed

    Mukhin, I V

    2007-01-01

    There is formation of free radicals in mesangial cells in patients with chronic glomerulonephritis which increases destruction of renal tissue and enable autoimmune inflammation. The unbalance between activity of oxidizing and antioxidazing starts developing. It accelerates the progression of the disease. The article presents the assessment of influence of enzyme medication Wobenzym on main indices of oxidizing and antioxidazing systems. It was established the presence of antioxidant effect in Wobenzym medication. The use of this medication in combination with other drugs and without them enables restoration of the disturbed balance.

  9. Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

    PubMed

    Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

    2006-02-01

    The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

  10. Crescentic glomerulonephritis: a possible complication of streptokinase treatment for myocardial infarction.

    PubMed Central

    Murray, N; Lyons, J; Chappell, M

    1986-01-01

    Twenty days after a streptokinase infusion given for myocardial infarction, a patient developed a group G streptococcal throat infection. Thirteen days later he presented with a serum sickness type illness and progressive renal failure. Renal biopsy showed crescentic glomerulonephritis. Images Fig 1 Fig 2 PMID:3790385

  11. The lack of predictors for rapid progression in prostate cancer patients receiving sipuleucel-T.

    PubMed

    Ng, Laura; Heck, Wendy; Lavsa, Stacey; Crowther, David; Atkinson, Brad; Xiao, Lianchun; Araujo, John

    2013-05-06

    Sipuleucel-T is an immunotherapy indicated for the treatment of metastatic prostate cancer. It offers a new mechanism to treat prostate cancer without the side effects of hormone therapies and chemotherapies. In previous studies sipuleucel-T did not delay disease progression, but demonstrated an overall survival benefit compared to placebo. While clinical trials have evaluated the effects of sipuleucel-T on overall survival and progression, more studies are needed to evaluate its effectiveness and role in the management of prostate cancer. The objective of this study is to identify the incidence and possible predictors for disease progression in patients receiving sipuleucel-T. A retrospective review of patients who received sipuleucel-T between 1 September 2010 and 11 October 2011 was conducted (n = 36). Patients who changed therapy or died within 120 days were classified as experiencing rapid progression. Potential predictors of rapid progression were examined using logistic regression. Seven patients met criteria for rapid progression. Progression occurred in 72.2% of all patients. The median days to progression was 158. No significant predictors of rapid progression were identified. Currently no predictors have been found to be associated with rapid progression in prostate cancer patients on sipuleucel-T.

  12. Anti-glomerular basement membrane crescentic glomerulonephritis: A report from India and review of literature

    PubMed Central

    Gupta, A.; Agrawal, V.; Kaul, A.; Verma, R.; Pandey, R.

    2016-01-01

    Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disease that most commonly presents as rapidly progressive glomerulonephritis with or without pulmonary involvement. It is characterized by the presence of antibodies directed to antigenic targets within glomerular and alveolar basement membranes. This study was performed to evaluate the clinicopathological features and outcome in anti-GBM crescentic glomerulonephritis (CrGN) at a tertiary care center in North India over a period of 9 years (January 2004 to December 2012). A diagnosis of anti-GBM CrGN was made in the presence of >50% crescents, linear deposits of IgG along GBM, and raised serum anti-GBM antibody titer. Of 215 cases of CrGN diagnosed during this period, 11 had anti-GBM CrGN. Anti-GBM CrGN was found at all ages but was most common in the third to fifth decade with no gender predilection (mean age 48 +/- 15 years, 13–67 years). Patients presented with a mean serum creatinine of 10.2 +/- 5.3 mg/dl and sub-nephrotic proteinuria. Pulmonary involvement was present in two patients. Myeloperoxidase-antineutrophil cytoplasmic antibody was positive in two (2/11) elderly patients. Follow-up was available in four patients for a range of 30-270 (mean 99.5 ± 114.5) days, two remained dialysis dependent while two died due to uremia and sepsis. Our findings show that anti-GBM disease is a rare cause of CrGN in India, accounting for only 5% of patients. It usually presents as a renal-limited disease and is associated with a poor renal outcome. PMID:27795626

  13. Do food antigens play a role in the pathogenesis of some cases of human glomerulonephritis?

    PubMed Central

    van der Woude, F J; Hoedemaeker, P J; van der Giessen, M; de Graeff, P A; de Monchy, J; The, T H; van der Hem, G K

    1983-01-01

    Circulating immune complexes after a test meal were measured with three methods (PEG precipitation, Clq-ELISA and the indirect granulocyte phagocytosis test) in 10 controls, two symptomless persons with selective IgA deficiency and 14 patients with various types of glomerulonephritis, of which two patients (with idiopathic membranous glomerulopathy and local focal glomerulonephritis) also had selective IgA deficiency. The PEG and Clq-ELISA test did not show significant differences between the groups. In the two symptomless persons with selective IgA deficiency and in the patient with local focal glomerulonephritis and selective IgA deficiency the indirect granulocyte phagocytosis test (IGFT) showed a reproducible increase in IgG, IgM and complement containing immune complexes. In the last patient multiple food antigens were probably responsible for this phenomenon, a rapid amelioration of kidney function could be induced three times by giving an antigen free diet. PMID:6851247

  14. Progress towards rapid identification of phytochemicals in plant extracts

    USDA-ARS?s Scientific Manuscript database

    New mass spectrometry equipment is bringing closer to reality the rapid accurate assessment of chemical composition of extracts from a variety of plant materials. Using a variety of plant sources, we are using HPLC separation, UV-VIS spectrometry, ion trap mass fragmentation and accurate mass deter...

  15. Crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis.

    PubMed

    Enríquez, Ricardo; Sirvent, Ana Esther; Amorós, Francisco; Pérez, Miguel; Matarredona, Jaime; Reyes, Adolfo

    2005-01-01

    We describe the association of crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome. A 39-year-old woman presented edema and proteinuria and later a non-pruritic urticarial rash. Laboratory results showed nephrotic syndrome, hypocomplementemia and positive anti-C1q antibodies. Skin biopsy disclosed leukocytoclastic vasculitis. Acute renal failure developed. Renal biopsy revealed crescentic membranoproliferative glomerulonephritis. She was treated with corticosteroids and cyclosphosphamide with improvement of the renal function and partial remission of the nephrotic syndrome. Afterwards the nephrotic syndrome relapsed, mycophenolate mofetil in monotherapy was administered with reduction in proteinuria. As far as we know only 3 cases, 2 in children and one in an adult, of crescentic glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome have been reported. In our patient renal manifestations preceded urticarial lesions. We provide information on the evolution during a 42-month follow-up.

  16. Progress on high-performance rapid prototype aluminum mirrors

    NASA Astrophysics Data System (ADS)

    Woodard, Kenneth S.; Myrick, Bruce H.

    2017-05-01

    Near net shape parts can be produced using some very old processes (investment casting) and the relatively new direct metal laser sintering (DMLS) process. These processes have significant advantages for complex blank lightweighting and costs but are not inherently suited for producing high performance mirrors. The DMLS process can provide extremely complex lightweight structures but the high residual stresses left in the material results in unstable mirror figure retention. Although not to the extreme intricacy of DMLS, investment casting can also provide complex lightweight structures at considerably lower costs than DMLS and even conventional wrought mirror blanks but the less than 100% density for casting (and also DMLS) limits finishing quality. This paper will cover the progress that has been made to make both the DMLS and investment casting processes into viable near net shape blank options for high performance aluminum mirrors. Finish and figure results will be presented to show performance commensurate with existing conventional processes.

  17. Rapidly progressive and fatal neurocutaneous melanosis presenting as recurrent headache.

    PubMed

    Yamazaki, Yasuhiro; Matsuzawa, Tohru; Takasugi, Kazuo; Suzuki, Nozomu; Kanda, Makoto; Kobayashi, Ichiro

    2013-04-01

    Neurocutaneous melanosis is an extremely rare disease characterized by large or multiple congenital melanocytic nevi and benign or malignant proliferation of melanocytes in the central nervous system. Neurological manifestations usually develop during the first three years of life and the prognosis of patients with NCM who manifest neurological symptoms is very poor. Here we describe a 9-year-old girl who manifested neurological symptoms caused by communicating hydrocephalus and died of proliferation of melanocytes in the central nervous system 11 months after the initial symptoms. Serum and cerebrospinal fluid 5-S-CD levels could be a useful marker of disease progression, even in patients with NCM without apparent malignant findings at initial biopsy. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  18. Rapid progression of ocean acidification in the California Current System.

    PubMed

    Gruber, Nicolas; Hauri, Claudine; Lachkar, Zouhair; Loher, Damian; Frölicher, Thomas L; Plattner, Gian-Kasper

    2012-07-13

    Nearshore waters of the California Current System (California CS) already have a low carbonate saturation state, making them particularly susceptible to ocean acidification. We used eddy-resolving model simulations to study the potential development of ocean acidification in this system up to the year 2050 under the Special Report on Emissions Scenarios A2 and B1 scenarios. In both scenarios, the saturation state of aragonite Ω(arag) is projected to drop rapidly, with much of the nearshore region developing summer-long undersaturation in the top 60 meters within the next 30 years. By 2050, waters with Ω(arag) above 1.5 will have largely disappeared, and more than half of the waters will be undersaturated year-round. Habitats along the sea floor will become exposed to year-round undersaturation within the next 20 to 30 years. These projected events have potentially major implications for the rich and diverse ecosystem that characterizes the California CS.

  19. Necrobiotic xanthogranuloma-rapid progression under treatment with melphalan.

    PubMed

    Ziemer, Mirjana; Wedding, Ulrich; Sander, Christina S; Elsner, Peter

    2005-01-01

    Necrobiotic xanthogranuloma is a systemic disease associated in most cases with monoclonal paraproteinaemia. Although the causative role of the paraproteinaemia is supposed, the pathogenesis of this disease remains unknown. We report a 65-year-old woman with a 28-year history of disseminated indurated plaques involving her face, trunk and extremities. Since 1994 an IgG kappa paraproteinaemia was present. Current biopsies showed typical histological features of necrobiotic xanthogranuloma. We treated this extraordinary widespread condition with melphalan and prednisolone. Although the serum levels of IgG kappa light chains and gamma globulins decreased, the cutaneous plaques extended rapidly in size and number, which casts doubt on the causative significance of the paraproteinaemia in the pathogenesis of necrobiotic xanthogranuloma. The paraproteinaemia in patients with necrobiotic xanthogranuloma may rather reflect a secondary phenomenon than the originating cause. Pathogenetic and therapeutical concepts based thereon that have been proposed so far should be critically reconsidered.

  20. Bartonella Endocarditis and Pauci-Immune Glomerulonephritis

    PubMed Central

    Raybould, Jillian E.; Raybould, Alison L.; Morales, Megan K.; Zaheer, Misbah; Lipkowitz, Michael S.; Timpone, Joseph G.; Kumar, Princy N.

    2016-01-01

    Abstract Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis–associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti–neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone. PMID:27885316

  1. Pancreatic Cancer: Progress and Challenges in a Rapidly Moving Field.

    PubMed

    Collisson, Eric A; Olive, Kenneth P

    2017-03-01

    "Pancreatic Cancer: Advances in Science and Clinical Care," a Special Conference of the American Association for Cancer Research, was held in Orlando, FL, on May 12 to 15, bringing together more than 450 basic, translational, clinical, and epidemiologic pancreatic cancer researchers as well as pancreatic cancer patients, survivors, and advocates. Pancreatic cancer remains one of the great challenges in medicine, but the accelerating pace of research and early hints of clinical successes to come were palpable throughout the meeting. Prominent meeting themes included immunology and the tumor microenvironment, heterogeneity of both the epithelial and stromal compartments, personalized medicine efforts to integrate molecular information into clinical practice, new approaches to early detection, and clinical trials using a host of novel targeted therapies. Adding to the vibrant atmosphere of the meeting, a coalition of pancreatic cancer research and support foundations participated, with several innovative initiatives announced by individual organizations. We present here a summary of meeting highlights, a series of "success factors" that will benchmark the progress of the field over the next 2 years, and three challenges to the pancreatic cancer research community as it moves toward to the goal of extending patient survival. Cancer Res; 77(5); 1060-2. ©2017 AACR.

  2. Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

    PubMed Central

    2017-01-01

    Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed. PMID:28573137

  3. Poststreptococcal glomerulonephritis with pulmonary edema presenting as respiratory distress.

    PubMed

    Chiu, Chih-Yung; Huang, Yhu-Chering; Wong, Kin-Sun; Hsia, Shao-Hsuan; Lin, Chi-Jen; Lin, Tzou-Yien

    2004-11-01

    Acute poststreptococcal glomerulonephritis(PSGN) is characterized by an abrupt onset of edema,hypertension, and hematuria. Although the association of pulmonary edema with acute glomerulonephritis has been established, it is uncommon for children with PSGN to present with respiratory distress due to pulmonary edema. We encountered six such patients, aged 6-10 years, during a 10-month period. The demographic data, clinical manifestations, laboratory data, radiographic pictures, and clinical courses were collected. All patients presented to the primary pediatricians with dyspnea and alveolar infiltrates with bilateral pleural effusions on plain chest radiographs that were misinterpreted as pneumonia initially. The diagnosis of PSGN was de-layed until the awareness of the presence of pulmonary edema complicating PSGN. Subsequent urinalysis and blood pressure measurement all showed microscopic hematuria and hypertension. Elevated serum antistreptolysin 0 titers and depressed serum complement C3 levels confirmed the diagnosis of PSGN. Two patients progressed to respiratory failure because of a delayed diagnosis of PSGN. All patients recovered without sequelae following appropriate diuresis and antihypertensive therapy. We conclude that in preschool and school-age children who present with dyspneic respirations and a chest radiograph showing radiographic features of pulmonary edema, proper evaluation including blood pressure recording and urinalysis should be performed immediately. Prompt diagnosis and early therapy of PSGNmay avoid mortality and unnecessary therapeutic intervention.

  4. Experimental Progress Toward Multiple Adiabatic Rapid Passage Sequences

    NASA Astrophysics Data System (ADS)

    Miao, X.; Wertz, E.; Cohen, M. G.; Metcalf, H.

    2006-05-01

    Multiple repetitions of adiabatic rapid passage (ARP) sweeps with counterpropagating light beams can enable huge optical forces on atoms. The repetition rate of the ARP sweeps φsγ results in a force k φs/πk γ/2 ≡Frad where 1/γ≡τ is the excited state lifetime and Frad is the ordinary radiative force. This is because each pair of ARP-induced inversions can coherently transfer momentum ±2 k between the light beams, and thus 2 k to the atoms. In developing instruments for such experiments on the 2^3S1-> 2^3P2 transition at λ = 1083 nm in He, we exploit recent developments in the optical communications industry. We use commercial phase and intensity modulators of the LiNbO3 waveguide type having Vπ as low as 6 V and thus requiring relatively low rf power for the modulation. Synchronized driving of the two modulators can produce the necessary multiple ARP sequences of 10 ns chirped pulses that span several GHz, as needed for the experiment^3. We are also developing optical methods for characterizing these pulses. T. Lu, X. Miao, and H. Metcalf, Phys., Rev. A 71 061405(R) (2005).

  5. Serum Metabolomics of Slow vs. Rapid Motor Progression Parkinson’s Disease: a Pilot Study

    PubMed Central

    Roede, James R.; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H.; Rhodes, Shannon L.; Ritz, Beate; Jones, Dean P.

    2013-01-01

    Progression of Parkinson’s disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD. PMID:24167579

  6. TLR9 Differentiates Rapid from Slowly Progressive Forms of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Trujillo, Glenda; Meneghin, Alessia; Flaherty, Kevin R.; Sholl, Lynette M.; Myers, Jeffrey L.; Kazerooni, Ella A.; Gross, Barry H.; Oak, Sameer R.; Coelho, Ana Lucia; Evanoff, Holly; Day, Elizabeth; Toews, Galen B.; Joshi, Amrita D.; Schaller, Matthew A.; Waters, Beatrice; Jarai, Gabor; Westwick, John; Kunkel, Steve L.; Martinez, Fernando J.; Hogaboam, Cory M.

    2011-01-01

    Idiopathic pulmonary fibrosis is a generally progressive disorder with highly heterogeneous disease progression. The most common of the idiopathic interstitial pneumonias, idiopathic pulmonary fibrosis is characterized by a steady worsening of lung function and gas exchange cause by diffuse alveolar damage and severe fibrosis. We examined clinical features of patients with idiopathic pulmonary fibrosis to classify them as exhibiting rapid or slowly progressive over the first year of follow-up. We identified differences between the two groups in order to investigate the mechanism of rapid progression. Previous work from our laboratory has demonstrated that Toll-like receptor 9, a pathogen recognition receptor, promotes myofibroblast differentiation in lung fibroblasts cultured from biopsies of patients with idiopathic pulmonary fibrosis. Therefore, we hypothesized that TLR9 functions as both a sensor of pathogenic molecules and a profibrotic signal in rapidly progressive idiopathic pulmonary fibrosis. TLR9 was present at higher concentrations in surgical lung biopsies from rapidly progressive patients than in tissue from normal controls. Fibroblasts from rapid progressors were more responsive to the TLR9 agonist, CpG, than were fibroblasts from control patients. We used a humanized SCID mouse and demonstrated that there was increased fibrosis in murine lungs receiving human lung fibroblasts from rapid progressors than in mice receiving normal fibroblasts. This fibrosis was exacerbated by intranasal CpG challenges. Furthermore, CpG induced the differentiation of blood monocytes into fibrocytes and the epithelial-to-mesenchymal transition of A549 lung epithelial cells. These data suggest that TLR9 may drive the pathogenesis of rapidly progressive idiopathic pulmonary fibrosis and is a potential indicator of this subset of the disease. PMID:21068441

  7. Predictors of rapid disease progression in autosomal dominant polycystic kidney disease.

    PubMed

    Corradi, Valentina; Gastaldon, Fiorella; Caprara, Carlotta; Giuliani, Anna; Martino, Francesca; Ferrari, Fiorenza; Ronco, Claudio

    2017-02-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases with a reported prevalence of 1:400 to 1:1000. Since the intact kidneys can compensate for the loss of glomerular filtration in ADPKD patients, renal insufficiency usually remains undetected until almost the fourth decade of life. Hereafter, reliable diagnostic and prognostic biomarkers to identify ADPKD progression are urgently needed. Several studies and systematic reviews tried to identify markers or predictors of rapid disease progression of ADPKD. The aim of this study is to review predictors of rapid disease progression of ADPKD that can be useful to the clinician. We will describe several factors associated with rapid progression of ADPKD derived from retrospective or cross-sectional studies, suggesting the best and most useful predictors that may help to patients management in clinical practice. We will attempt to identify the most useful predictors of rapid disease progression of ADPKD: established TKV growth rate >5% per year, annual estimated glomerular filtration rate decline >5 mL/min/1.73 m2, truncating PKD1 mutations and elevated plasma copeptin level. The combination of several factors that can predict the rapid ADPKD progression is more accurate than a single-marker strategy. The "PRO-PKD" risk scoring system combined with TKV, can be useful in order to evaluate the ADPKD patients and they appear to be appropriate predictors of progression disease. Moreover levels of copeptin and some urinary markers can be matched to these factors for improved patient assessment in rapid progression.

  8. A Micro RNA Processing Defect in Rapidly Progressing Idiopathic Pulmonary Fibrosis

    PubMed Central

    Oak, Sameer R.; Murray, Lynne; Herath, Athula; Sleeman, Matthew; Anderson, Ian; Joshi, Amrita D.; Coelho, Ana Lucia; Flaherty, Kevin R.; Toews, Galen B.; Knight, Darryl; Martinez, Fernando J.; Hogaboam, Cory M.

    2011-01-01

    Background Idiopathic pulmonary fibrosis exhibits differential progression from the time of diagnosis but the molecular basis for varying progression rates is poorly understood. The aim of the present study was to ascertain whether differential miRNA expression might provide one explanation for rapidly versus slowly progressing forms of IPF. Methodology and Principal Findings miRNA and mRNA were isolated from surgical lung biopsies from IPF patients with a clinically documented rapid or slow course of disease over the first year after diagnosis. A quantitative PCR miRNA array containing 88 of the most abundant miRNA in the human genome was used to profile lung biopsies from 9 patients with rapidly progressing IPF, 6 patients with slowly progressing IPF, and 10 normal lung biopsies. Using this approach, 11 miRNA were significantly increased and 36 were significantly decreased in rapid biopsies compared with normal biopsies. Slowly progressive biopsies exhibited 4 significantly increased miRNA and 36 significantly decreased miRNA compared with normal lung. Among the miRNA present in IPF with validated mRNA targets were those with regulatory effects on epithelial-mesenchymal transition (EMT). Five miRNA (miR-302c, miR-423-5p, miR-210, miR-376c, and miR-185) were significantly increased in rapid compared with slow IPF lung biopsies. Additional analyses of rapid biopsies and fibroblasts grown from the same biopsies revealed that the expression of AGO1 and AGO2 (essential components of the miRNA processing RISC complex) were lower compared with either slow or normal lung biopsies and fibroblasts. Conclusion These findings suggest that the development and/or clinical progression of IPF might be the consequence of aberrant miRNA processing. PMID:21712985

  9. Rapid Progression of Solitary Plasmacytoma to Multiple Myeloma in Lumbar Vertebra

    PubMed Central

    Yang, Jin Seo; Kang, Suk Hyung; Choi, Hyuk Jai

    2013-01-01

    The prognosis of solitary plasmacytoma varies greatly, with some patients recovering after surgical removal or local fractional radiation therapy, and others progressing to multiple myeloma years later. Primary detection of progression to multiple myeloma is important in the treatment of solitary plasmacytoma. There have been several analyses of the risk factors involved in the early progression to multiple myeloma. We describe one case of solitary plasmacytoma of the lumbar vertebra that was treated with surgical decompression with stabilization and additional radiotherapy. The patient had no factors associated with rapid progression to multiple myeloma such as age, size, immunologic results, pathological findings, and serum free light chain ratio at the time of diagnosis. However, his condition progressed to multiple myeloma less than two months after the initial diagnosis of solitary plasmacytoma. We suggest that surgeons should be vigilant in watching for rapid progression to multiple myeloma even in case that the patient with solitary plasmacytoma has no risk factors for rapid progression to multiple myeloma. PMID:24379952

  10. The Rapid Recovery Progression Measure: A Brief Assessment of Biopsychosocial Functioning During Substance Use Disorder Recovery.

    PubMed

    Elison, Sarah; Dugdale, Stephanie; Ward, Jonathan; Davies, Glyn

    2017-07-29

    There is debate in the literature around how to measure outcomes in treatment and recovery from substance use disorder (SUD). Various constructs have been suggested as appropriate including "recovery capital" and "treatment progression."  To contribute to this debate, the construct of "recovery progression"  has been suggested by the authors, and a psychometric assessment, the Recovery Progression Measure (RPM). Although published psychometrics data have demonstrated the RPM to be reliable, at 36-item long, it may be too lengthy to complete in clinic environments. Therefore, a shorter version has been developed, the Rapid RPM. To examine reliability, validity, sensitivity and specificity of the Rapid RPM via data from 9208 service users. Data were collected from service users accessing the Breaking Free Online (BFO) treatment and recovery program, which has within its baseline assessment the six-item, 11-point Likert scale Rapid RPM. Psychometric properties were examined. Internal reliability of the Rapid RPM was excellent, α =.92. The Rapid RPM also had good concurrent and predictive validity, with baseline scores, and changes in scores to follow-up, being significantly associated with scores on standardized measures of common mental health sequela, severity of substance dependence and quality of life, and changes in self-reported substance use. The Rapid RPM was also able to differentiate between participants scoring above thresholds on these measures for clinically relevant substance dependence and mental health difficulties. This study provides data to support reliability, validity, sensitivity and specificity of the Rapid RPM, indicating potential as a clinical tool.

  11. Monoclonal gammopathy-associated proliferative glomerulonephritis.

    PubMed

    Sethi, Sanjeev; Rajkumar, S Vincent

    2013-11-01

    Monoclonal gammopathy is characterized by circulating monoclonal immunoglobulin owing to clonal proliferation of immunoglobulin-producing B lymphocytes or plasma cells. Clonal proliferation of B lymphocytes is seen in B-cell lymphoma/leukemia, and clonal plasma cell proliferation is seen in multiple myeloma and monoclonal gammopathy of undetermined significance. The monoclonal immunoglobulin in the setting of a B-cell or plasma cell disorder can cause a proliferative glomerulonephritis via 2 mechanisms: (1) glomerular deposition of the monoclonal immunoglobulin with activation of the classical pathway of complement (direct mechanism), resulting in an immunoglobulin-positive C3-positive glomerulonephritis, and (2) glomerular deposition of complement factors of the alternative and terminal pathway via inhibition of alternative pathway-regulating proteins by the monoclonal immunoglobulin (indirect mechanism), resulting in immunoglobulin-negative C3-positive glomerulonephritis (C3 glomerulopathy). Evaluation should include serum and urine electrophoresis and immunofixation as well as serum-free light-chain assay. If a monoclonal immunoglobulin is detected on these tests, bone marrow biopsy or imaging is needed to exclude more advanced plasma cell dyscrasia. Evaluation of alternative pathway of complement should be done in patients with Ig-negative C3-positive glomerulonephritis. If monoclonal gammopathy is due to an underlying malignant disease such as myeloma, lymphoma, or chronic lymphocytic leukemia, then specific treatment should be aimed at treating the malignant disease, with the goal of eradicating the clonal cells producing the immunoglobulin. In contrast, if monoclonal gammopathy is due to a monoclonal gammopathy of undetermined significance, treatment options include bortezomib, cyclophosphamide, and dexamethasone for a non-IgM monoclonal immunoglobulin and rituximab alone or in combination with cyclophosphamide and dexamethasone for an IgM monoclonal

  12. [Oligomeganephronic renal hypoplasia complicated by glomerulonephritis].

    PubMed

    Kan'shina, N F; Rykov, V A; Lakhno, P A

    1990-01-01

    Clinico-anatomical data of a rare condition congenital oligomeganephronic renal hypoplasia with a glomerulonephritis as a complication are available for a 13-year-old girl who died of chronic renal failure. Large aglomerular zones consisting of primitive canaliculi in a loose stroma were observed in kidneys that were decreased in size. The glomeruli were few in number, some of them of a large size (2-2.5-fold), firmly attached to the capsule, with pronounced extracapillary proliferation.

  13. Biopsy-proven childhood glomerulonephritis in Johor.

    PubMed

    Khoo, J J; Pee, S; Thevarajah, B; Yap, Y C; Chin, C K

    2004-06-01

    There has been no published study of biopsy-proven childhood glomerulonephritis in Malaysia. To determine the pattern of childhood glomerulonephritis in Johor, Malaysia from a histopathological perspective and the various indications used for renal biopsy in children. Retrospective study was done of all renal biopsies from children under 16 years of age, received in Sultanah Aminah Hospital, Johor between 1994 and 2001. The histopathological findings were reviewed to determine the pattern of biopsy-proven glomerulonephritis. The indications for biopsy, mode of therapy given after biopsy and the clinical outcome were studied. 122 adequate biopsies were received, 9 children had repeat biopsies. Of the 113 biopsies, minimal change disease formed the most common histopathological diagnosis (40.7%) while lupus nephritis formed the most common secondary glomerulonephritis (23.0%). The main indications for biopsy were nephrotic syndrome (50.8%), lupus nephritis (25.4%) and renal impairment (13.1%). The mode of therapy was changed in 59.8% of the children. Of 106 patients followed-up, 84 children were found to have normal renal function in remission or on treatment. 4 patients developed chronic renal impairment and 16 reached end stage renal disease. Five of the 16 children with end stage disease had since died while 11 were on renal replacement therapy. Another 2 patients died of other complications. The pattern of childhood GN in our study tended to reflect the more severe renal parenchymal diseases in children and those requiring more aggressive treatment. This was because of our criteria of selection (indication) for renal biopsy. Renal biopsy where performed appropriately in selected children may not only be a useful investigative tool for histological diagnosis and prognosis but may help clinicians plan the optimal therapy for these children.

  14. Diffuse proliferative glomerulonephritis after bone marrow transplantation.

    PubMed

    Suehiro, T; Masutani, K; Yokoyama, M; Tokumoto, M; Tsuruya, K; Fukuda, K; Kanai, H; Katafuchi, R; Nagatoshi, Y; Hirakata, H

    2002-09-01

    A 15-year-old boy developed nephrotic syndrome and acute renal failure 4 years after allogenic bone marrow transplantation (BMT) for lymphoid crisis of chronic myelocytic leukemia. On admission, he presented with clinical features of chronic GVHD including transient exacerbation of cholestatic liver injury. Renal biopsy showed diffuse proliferative glomerulonephritis with cellular crescents. The patient was treated with methylprednisolone pulse therapy (1 g/day, for 3 days) followed by oral prednisolone. Renal function gradually improved but nephrotic state was persistent. A second renal biopsy showed improvement of acute tubular necrosis and endocapillary proliferation and transformation of crescents into a fibrous form. After tapering of oral prednisolone, cyclophosphamide was started, which resulted in a gradual improvement of proteinuria. Several cases of nephrotic syndrome occurring after BMT have already been reported, but most cases had membranous nephropathy. In our case, renal biopsy revealed diffuse proliferative glomerulonephritis with findings of active cellular immunity, and aggressive treatment resulted in attenuation of these findings. Moreover, chronic GVHD-related liver injury was noted at the time of this episode. Our findings suggest that chronic GVHD may be complicated with diffuse proliferative glomerulonephritis through unknown cellular immune mechanism.

  15. NF-κB upregulates ubiquitin C-terminal hydrolase 1 in diseased podocytes in glomerulonephritis.

    PubMed

    Zhang, Hongxia; Mao, Xing; Sun, Yu; Hu, Ruimin; Luo, Weili; Zhao, Zhonghua; Chen, Qi; Zhang, Zhigang

    2015-08-01

    Podocyte injury is a pivotal factor during the progression of glomerular diseases. It has been demonstrated that the expression of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is increased in injured podocytes in a number of types of glomerulonephritis. However, its mechanism of regulation remains to be elucidated. A previous study by our group suggested that UCH-L1 is a downstream protein of nuclear factor (NF)-κB signaling. In the present study, the involvement of NF-κB in the regulation of the expression of UCH-L1 was investigated in diseased podocytes in vivo and in vitro. Increases in the expression of phosphorylated NF-κB at p65 and UCH-L1 were detected using immunohistochemical analysis of kidney biopsy tissues from 56 cases of nephritis, including immunoglobulin A nephropathy, membranous glomerulonephritis and lupus nephritis. The two indicators were also analyzed using western blot analysis in cultured murine podocytes stimulated by inflammatory factors. The results of the present study demonstrated that in human renal biopsies of several cases of immune complex-mediated glomerulonephritis, the increases of NF-κB and UCH-L1 were positively correlated with the number of diseased podocytes. By contrast, in non-immune complex-mediated glomerulonephritis, no clear activation of NF-κB and increase of UCH-L1 expression was observed. In vitro, immune stimulation also led to the upregulation of UCH-L1 through the NF-κB signaling pathway in mouse podocytes. In conclusion, the results of the present study suggested that the activation of NF-κB and upregulation of UCH-L1 in podocytes may be vital in podocyte injury associated with immune complex-mediated glomerulonephritis.

  16. Familial Mediterranean fever and membranous glomerulonephritis: report of a case.

    PubMed

    Ceri, Mevlut; Unverdi, Selman; Altay, Mustafa; Unverdi, Hatice; Ensari, Arzu; Duranay, Murat

    2010-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease characterized by recurrent attacks of fever and painful episodes of sterile polyserositis. Kidney involvement may occur as a result of secondary amyloidosis during the course of FMF. Previously, different types of glomerulopathies such as IgM and IgA nephropathy, crescentic glomerulonephritis, diffuse proliferative glomerulonephritis, minimal change disease, and membranoproliferative glomerulonephritis were rarely reported. We herein represent a first case of membranous glomerulonephritis who had complete remission with colchicine treatment in the course of familial Mediterranean fever.

  17. Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema

    PubMed Central

    Fujita, Kohei; Kim, Young Hak; Nakatani, Koichi; Mio, Tadashi

    2015-01-01

    Key Clinical Message Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET-CT may be helpful in establishing a precise diagnosis in such cases. PMID:26509028

  18. Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema.

    PubMed

    Fujita, Kohei; Kim, Young Hak; Nakatani, Koichi; Mio, Tadashi

    2015-10-01

    Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET-CT may be helpful in establishing a precise diagnosis in such cases.

  19. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

    SciTech Connect

    Zhang Zhiqiang . E-mail: zhiqiang_zhang@merck.com; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

    2007-05-10

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4{sup +} T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection.

  20. Clinicopathological Correlates in a PRNP P102L Mutation Carrier with Rapidly Progressing Parkinsonism-dystonia.

    PubMed

    Umeh, Chizoba C; Kalakoti, Piyush; Greenberg, Michael K; Notari, Silvio; Cohen, Yvonne; Gambetti, Pierluigi; Oblak, Adrian L; Ghetti, Bernardino; Mari, Zoltan

    2016-01-01

    Parkinsonism-dystonia is rare in carriers of PRNP P102L mutation. Severity and distribution of prion protein (PrP) deposition may influence the clinical presentation. We present such clinic-pathological correlation in a 56-year-old male with a PRNP P102L mutation associated with a phenotype characterized by rapidly progressing parkinsonism-dystonia. The patient was studied clinically (videotaped exams, brain MRIs); molecular genetically (gene sequence analysis); and neuropathologically (histology, immunohistochemistry) during his 7-month disease course. The patient had parkinsonism, apraxia, aphasia, and dystonia, which progressed rapidly. Molecular genetic analysis revealed PRNP P102L mutation carrier status. Brain MRIs revealed progressive global volume loss and T2/FLAIR hyperintensity in neocortex and basal ganglia. Postmortem examination showed neuronal loss, gliosis, spongiform changes, and PrP deposition in the striatum. PrP immunohistochemistry revealed widespread severe PrP deposition in the thalamus and cerebellar cortex. Based on the neuropathological and molecular-genetic analysis, the rapidly progressing parkinsonism-dystonia correlated with nigrostriatal, thalamic, and cerebellar pathology.

  1. [Central nervous system leukemia mimicking rapidly progressive HTLV-1 associated myelopathy].

    PubMed

    Haruki, Hiroyo; Tanaka, Shinichiro; Koga, Michiaki; Kawai, Motoharu; Negoro, Kiyoshi; Kanda, Takashi

    2009-03-01

    A 79-year-old woman was suffered from rapidly progressive paresthesia of lower limbs and gait disturbance. After one month, she showed flaccid paraplegia and hyperreflexia in the lower limbs with positive Babinski signs. Anti-HTLV-1 antibody titer was elevated in the serum, but negative in the cerebrospinal fluid (CSF). CSF examination showed mild pleocytosis, elevated protein, and normal glucose content. Adult T cell lymphoma (ATL)-like cells were seen in the CSF. MRI showed no abnormal intensity in the spinal cord and brain. Two months later, she showed rapid worsening of the paraplegia and she became unable to stand. A tentative diagnosis of rapidly progressive HTLV-1 associated myelopathy (HAM) was given, but intravenous methylprednisolone was ineffective. Six months later, she developed pneumonia, and abundant ATL cells were seen in the peripheral blood, suggesting a diagnosis of ATL. Direct infiltration of ATL cells to central nervous system was therefore suggested to have caused neurological abnormalities in this case. One may consider central nervous system leukemia when rapidly progressive HAM-like symptoms and signs are recognized, especially without positive anti-HTLV-1 antibody in the CSF.

  2. Post-infectious glomerulonephritis following infective endocarditis: Amenable to immunosuppression

    PubMed Central

    Mantan, M.; Sethi, G. R.; Batra, V. V.

    2013-01-01

    Glomerulonephritis develops in about 20% patients with infective endocarditis (IE), but is mostly asymptomatic. Heavy proteinuria or derangement of kidney functions is uncommon. We report here a child with IE and proliferative glomerulonephritis who manifested as significant proteinuria that recovered on treatment with immunosupressants. PMID:24049276

  3. Membranous glomerulonephritis and tuberculous peritonitis: a rare association.

    PubMed

    Ghosh, Biswadip; Pande, Arindam; Ghosh, Anirban; Banerjee, Arnab; Saha, Sandip

    2011-07-27

    Membranous glomerulonephritis is rarely associated with tuberculosis infection. We report a case of a 24-year-old female with tuberculous peritonitis associated with membranous glomerulonephritis causing subnephrotic range proteinuria. Histological examination confirmed both diagnoses. The patient showed improvement with anti-tubercular drugs over six months of follow-up.

  4. Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report.

    PubMed

    Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja

    2008-01-01

    We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.

  5. Forty Years Abuse of Baking Soda, Rhabdomyolysis, Glomerulonephritis, Hypertension Leading to Renal Failure: A Case Report

    PubMed Central

    Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja

    2008-01-01

    We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment. PMID:24179353

  6. Membranoproliferative glomerulonephritis associated with psoriasis vulgaris.

    PubMed

    Akoglu, Hadim; Dede, Fatih; Akoglu, Gulsen; Gonul, Ipek Isik; Odabas, Ali Riza

    2009-01-01

    Psoriasis is a hereditary, chronic inflammatory disorder of the skin. Generally, the psoriatic process is limited to the skin; however, internal organs such as the kidneys may be involved in the course. Several glomerular diseases have been distinguished due to renal histological findings of psoriatic patients to date. The underlying pathogenetic mechanisms of these associations remain unclear because of the limited number of cases. We report a case of primary membranoproliferative glomerulonephritis (MPGN) in a psoriatic patient. This is the first reported case that demonstrates the coexistence of MPGN and psoriasis.

  7. Malignant pigmented villonodular synovitis in the knee - report of a case with rapid clinical progression.

    PubMed

    Imakiire, Naoaki; Fujino, Takashi; Morii, Takeshi; Honya, Keita; Mochizuki, Kazuo; Satomi, Kazuhiko; Fujioka, Yasunori

    2011-01-07

    Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.

  8. Acute glomerulonephritis with bacteriuria: a probable etiologic relationship.

    PubMed

    El Said, W; Awad, S; Farid, F; Maged, Z; Fattah, F A; El Maghraby, M

    1979-01-01

    Twenty-one cases of acute glomerulonephritis in children with no previous history of renal disease were studied. Urinary infection with a rising titre of serum agglutinins against the organisms isolated from urine was found in 5 cases. No evidence of previous streptococcal infection was found in these cases. In the meantime all 8 cases with post-streptococcal glomerulonephritis remained without bacteriuria. In one case acute glomerulonephritis followed virus hepatitis, and in the remaining 7 cases the cause of glomerulonephritis was unknown. It is suggested that in predisposed patients the bacteria present in urinary infections might act as antigens starting immunologic reactions in the glomeruli, leading to glomerulonephritis. The final proof of this theory awaits immunofluorescence identification of these antigens in the glomeruli.

  9. Rapidly solidified ceramics: Processing, structure, and magnetic properties. Progress report, September 1984--January 1985

    SciTech Connect

    Kalonji, G.M.; O`Handley, R.C.

    1985-12-31

    Since its initiation in September 1984, work under this contract has progressed in two areas: construction of a gas atomizer for rapid solidification of ceramics; and characterization of rapidly solidified materials in the SrO-Fe{sub 2}O{sub 3}, BaO-Fe{sub 2}O{sub 3}, MnFe{sub 2}O{sub 4}-SiO{sub 2}, and CoFe{sub 2}O{sub 4}-SiO{sub 2} systems. This report summarize this work.

  10. Rapidly progressive cataract formation associated with non-small-cell lung cancer therapy.

    PubMed

    Liu, Erica; Kopani, Kamden

    2016-12-01

    We report 6 patients who developed rapidly progressive hypermature cataracts after starting treatment with rociletinib, a non-small-cell lung cancer therapy with known side effects of hyperglycemia, fatigue, and prolonged QT. Early cataract detection and surgery may prevent complications during future cataract removal. Although rociletinib development has been suspended, there are patients who have been treated and will continue to be treated with this medication based on their physician's judgment. These physicians should know about the potential for rapid vision loss due to cataracts as a manageable side effect.

  11. Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

    PubMed

    Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

    2015-03-01

    Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  12. Atypical presentation of Creutzfeldt-Jakob disease: a rare but important cause of rapidly progressive dementia.

    PubMed

    Taillefer, Marguerite S; Tangarorang, Glendo L; Kuchel, George A; Menkes, Daniel L

    2011-09-01

    We report an atypical presentation of sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old woman that illustrates the difficulty in diagnosing this rare, but important, cause of rapidly progressive dementia. Despite well-established criteria, this diagnosis is often missed or substantially delayed (Table 1). In this case, a precipitous cognitive decline associated with a urinary tract infection initiallysuggested delirium. Although atypical CJD was considered as a cause when symptoms persisted, a definitive diagnosis was established postmortem when the cerebrospinal fluid (CSF) prion protein 14-3-3 tested positive. Creutzfeldt-Jakob disease must be considered in the differential diagnosis of rapidly progressive dementia as Connecticut accounts for approximately three of the more than 200 cases diagnosed nationally.

  13. [Rapidly progressive puberty in a patient with mosaic Turner syndrome: a case report and literature review].

    PubMed

    Liang, Y; Wei, H; Yu, X; Huang, W; Luo, X P

    2017-02-02

    Objective: To explore the clinical characteristics of diagnosis and treatment in patients with Turner syndrome and rapidly progressive puberty. Method: A rare case of rapidly progressive puberty in Turner syndrome with a mosaic karyotype of 45, X/46, X, del(X)(p21)(80%/20%)was diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January. 2015. Clinical characteristics and the related literature were reviewed. Original papers on precocious puberty or rapidly progressive puberty in Turner syndrome, published until Apr. 2016 were retrieved at PubMed and CNKI databases by the use of the key words "Turner syndrome" , "precocious puberty" and "rapidly progressive puberty" . Result: The patient was born at term with birth weight of 2 450 g and was diagnosed with SGA at 3 years of age for the first evaluating of growth and development. Then recombined human growth hormone (rhGH )was given at 4 years of age due to short stature (height<3 percentile) and low growth velocity(<5.0 cm/year) as well. However, rhGH treatment was discontinued after 9 months because of economic burdens. Breast development was noted at 9 years and 3 months. The patient was followed up at 3 months intervals. Physical examination revealed a Tanner stage Ⅲ breast development at 10.33 years , the bone age was 11.6 years. Then, gonadotropin-releasing hormone analogs treatment was added to slow pubertal progression and to preserve maximum adult height. The growth rate decreased with therapy from 7.5 cm/year to 4.4 cm/year. The patient was reevaluated, and the chromosome analysis of peripheral blood revealed a mosaic karyotype 45, X/46, X, del(X)(p21)(80%/ 20%). To date, only 10 cases have been reported in the literature. Six of them showing mosaic TS, three karyotypes with structural abnormality of short arm of X chromosome, one with the karyotype 45, X. Conclusion: It is the first time that rapidly progressive puberty in a 45, X/46, X, del(X)(p21

  14. Botulism with Unusual Rapid Progression to Complete Paralysis in a Child.

    PubMed

    Tsai, Hui-Ju; Liang, Wen-Chen; Wang, Chien-Hua; Chou, Po-Ching; Hsu, Jong-Hau; Huang, Chia-Tsuan; Jong, Yuh-Jyh

    2015-12-01

    Botulism is a severe neuroparalytic illness which is difficult to diagnose accurately, especially in children. We report a child with type A botulism intoxication, with very rapid progression to coma-like consciousness and respiratory failure. Careful physical examinations led to the suspicion of botulism, and electrophysiologic examinations, including electroencephalogram and repetitive nerve stimulation tests, further supported the diagnosis. Hospitalization due to botulism had a great emotional impact on the patient and psychological support was crucial.

  15. Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome.

    PubMed

    Oh, Won Sup; Heo, Sang Taek; Kim, Sun Hyung; Choi, Won Jun; Han, Myung Guk; Kim, Ji Young

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. Although the increasing numbers of cases and deaths is of great concern, an effective treatment strategy for SFTS has not been established. We present the cases of two patients with rapidly progressing SFTS who were successfully treated with plasma exchange and ribavirin. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Lung Pathology in U.S. Coal Workers with Rapidly Progressive Pneumoconiosis Implicates Silica and Silicates

    PubMed Central

    Petsonk, Edward L.; Rose, Cecile; Young, Byron; Regier, Michael; Najmuddin, Asif; Abraham, Jerrold L.; Churg, Andrew; Green, Francis H. Y.

    2016-01-01

    Rationale: Recent reports of progressive massive fibrosis and rapidly progressive pneumoconiosis in U.S. coal miners have raised concerns about excessive exposures to coal mine dust, despite reports of declining dust levels. Objectives: To evaluate the histologic abnormalities and retained dust particles in available coal miner lung pathology specimens, and to compare these findings with those derived from corresponding chest radiographs. Methods: Miners with severe disease and available lung tissue were identified through investigator outreach. Demographic as well as smoking and work history information was obtained. Chest radiographs were interpreted according to the International Labor Organization classification scheme to determine if criteria for rapidly progressive pneumoconiosis were confirmed. Pathology slides were scored by three expert pulmonary pathologists using a standardized nomenclature and scoring system. Measurements and Main Results: Thirteen cases were reviewed, many of which had features of accelerated silicosis and mixed dust lesions. Twelve had progressive massive fibrosis, and 11 had silicosis. Only four had classic lesions of simple coal workers’ pneumoconiosis. Four had diffuse interstitial fibrosis with chronic inflammation, and two had focal alveolar proteinosis. Polarized light microscopy revealed large amounts of birefringent mineral dust particles consistent with silica and silicates; carbonaceous coal dust was less prominent. On the basis of chest imaging studies, specimens with features of silicosis were significantly associated (P = 0.047) with rounded (type p, q, or r) opacities, whereas grade 3 interstitial fibrosis was associated (P = 0.02) with the presence of irregular (type s, t, or u) opacities. Conclusions: Our findings suggest that rapidly progressive pneumoconiosis in these miners was associated with exposure to coal mine dust containing high concentrations of respirable silica and silicates. PMID:26513613

  17. [Immune complex glomerulonephritis associated with pulmonary tuberculosis].

    PubMed

    Villar, I; Hernández, E; Cozzi, J; Paletta, C; Mathurín, S

    1994-01-01

    A 32 year old man was admitted for dyspnea, hemoptysis, macroscopic hematuria, hypertension (140/100), peripheral edema and hemodynamic decompensation. Lung Xrays revealed pulmonary edema and a cavity in the left apex. Laboratory determinations revealed an altered renal function with increased creatinine and urea levels and nephrotic syndrome. There was leucocyturia, hematuria and cylindruria. The sputum showed a large number of acid-fast bacilli. The patient began anti-tuberculosis treatment with three drugs (isoniacid, rifampicin, pirazinamide). On ultrasonography, both kidneys revealed ecogenic lesions with size, shape and cortico-medular relationship preserved. The patient persisted with altered renal function, steady levels of urea nitrogen, creatinine and potassium, preserved diuresis and hypertension. Bidimensional echocardiogram: LVDD 55 mm, hypoquinetic septum, pericardic effusion, thickened pericardium, pleural effusion, shortening fraction decreased. He received treatment for this congestive cardiac failure and hypertension with enalapril, nifedipine and fursemide. A percutaneous renal biopsy was performed with anatomopathologic diagnosis of diffuse encocapillar proliferative glomerulonephritis with crescents (15%) and total glomerular sclerosis (33%). Immunofluorescence: positive, immune-complexes with IgM and C3. The patient gradually recovered his normal renal function, improved his pleural effusions and normalized his cardiac function. He was discharged in good clinical condition on the 69th day of anti-tuberculosis treatment. An association between pulmonary tuberculosis and glomerulonephritis is discussed. It is proposed that renal lesions might be the consequence of the tuberculosis due to the sedimentation of circulating immune-complexes.

  18. Progressive versus rapid rate of contraction during 7 wk of isometric resistance training.

    PubMed

    Maffiuletti, N A; Martin, A

    2001-07-01

    The aim of this study was to compare the effects of isometric training performed with progressive versus rapid rate of contraction on the knee extensor neuromuscular properties over a 7-wk period. Sixteen healthy male subjects trained quadriceps femoris muscle in a leg extension machine three times a week during 7 wk. The training sessions consisted of six sets of six maximal isometric contractions. A first group trained by performing progressive contractions lasting 4 s, whereas a second group performed contractions with a rapid rate of contraction (i.e., ballistic contractions) lasting about 1 s. Both groups significantly increased the isometric and isokinetic voluntary torque, and the respective absolute or relative gains were comparable. Isometric training performed with progressive rate of contraction affected the evoked action potential (M wave) of the vastus lateralis muscle and not the related twitch properties. On the other hand, the isometric training completed with ballistic contractions significantly modified the twitch contractile properties of the knee extensors and not the associated M waves of both vastus medialis and vastus lateralis. Knee extensors adapted specifically their neuromuscular properties to the type of rate of contraction performed during 7-wk isometric resistance training. Progressive isometric contractions produced modifications of the nervous system at peripheral level (i.e., muscle membrane electrical activity), whereas ballistic isometric contractions affected the knee extensor contractile muscle properties (i.e., excitation-contraction coupling).

  19. [Acute inflammatory polyradiculoneuropathy and membranous glomerulonephritis following Epbstein-Barr virus primary infection in a 12-year-old girl].

    PubMed

    Meyer, P; Soëte, S; Raynaud, P; Henry, V; Morin, D; Rodière, M; Rivier, F; Roubertie, A

    2010-11-01

    Acute inflammatory polyradiculoneuropathy, or Guillain-Barré syndrome (GBS), is characterized by peripheral nerve demyelination, which leads to rapidly progressive weakness, loss of sensation, and loss of deep tendon reflexes. It is a prototype of postinfectious autoimmune disease, whose pathophysiology is well described in the forms provoked by certain bacteria (molecular mimicry with Campylobacter jejuni), but remains unclear for the forms related to other organisms (cytomegalovirus, Epstein-Barr virus and other herpes group viruses, Mycoplasma pneumoniae). Glomerular lesions can be associated with the neurological symptoms and have also been described after various infections, independently of any signs of polyradiculoneuropathy. We report the observation of a 12-year-old girl who presented with Guillain-Barré syndrome with facial diplegia, ataxia, and intracranial hypertension following Epstein-Barr virus (EBV) primary infection. During the course of the neurological disease, membranous glomerulonephritis (MGN) was diagnosed. The neurological impairment was regressive within 6 months after intravenous immunoglobulin treatment followed by intravenous then oral corticosteroid administration. Viremia remained high more than 6 months after the onset of symptoms. Glomerulopathy progressed independently and finally required immunosuppressant medication with cyclosporine. EBV might be the factor that triggered the autoimmune disorders, as previously reported for systemic lupus erythematosus and multiple sclerosis in children. To the best of our knowledge, this association of 3 conditions (GBS, MGN, and EBV primary infection) has never been reported in the literature. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  20. Rapid clinical progression to diagnosis among African-American men with systemic lupus erythematosus.

    PubMed

    Arbuckle, M R; James, J A; Dennis, G J; Rubertone, M V; McClain, M T; Kim, X R; Harley, J B

    2003-01-01

    The initial clinical course of systemic lupus erythematosus (SLE) is variable, ranging from relatively minor manifestations progressing over years to rapid onset of fulminate disease. We sought to identify factors associated with the rapid manifestation of SLE. Chart review of military medical records was used to identify 130 patients who met the American College of Rheumatology classification criteria for SLE. Demographics, clinical criteria date of occurrence, and the date of SLE classification (at least four clinical criteria) met were documented. Prospectively stored serum samples prior to the diagnosis were evaluated for SLE autoantibodies. Median time from the first recorded criteria to diagnosis was significantly shorter in African-American (AA) males compared with AA females and European American (EA) females and males combined. AA males were more likely to have nephritis as their first clinical symptom. Also, less time transpired between the first clinical criterion and SLE diagnosis in AA males with nephritis than in other groups presenting with nephritis. Even when cases presenting with nephritis were excluded, a diagnosis of SLE was made more rapidly in AA males. African-American men progress from initial clinical manifestations to SLE diagnosis more rapidly than other ethnic or gender groups.

  1. [An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].

    PubMed

    Takeda, T; Takeda, T; Naiki, Y; Yonekawa, S; Sakaguchi, M; Iwamoto, I; Tanaka, H; Hasegawa, H; Imada, A; Kanamaru, A; Hiruma, S; Maekura, S; Hashimoto, S; Yamazumi, T

    1998-11-01

    A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.

  2. Monosomy 3 status of uveal melanoma metastases is associated with rapidly progressive tumors and short survival.

    PubMed

    Abdel-Rahman, Mohamed H; Cebulla, Colleen M; Verma, Vishal; Christopher, Benjamin N; Carson, William E; Olencki, Thomas; Davidorf, Frederick H

    2012-07-01

    The aim of the study was to investigate the molecular genetics of uveal melanoma (UM) metastases and correlate it with disease progression. Twelve pathologically confirmed UM metastases from 11 patients were included. Molecular genetic alterations in chromosomes 3 (including the BAP1 region), 8q, 6p, and 1p were investigated by microsatellite genotyping. Mutations in codon 209 of GNAQ and GNA11 genes were studied by restriction-fragment length polymorphism (RFLP). We identified monosomy of chromosome 3 in tumors from four patients with an average survival of 5 months (range 1-8 months) from time of diagnosis of metastatic disease. In contrast, tumors with either disomy or partial chromosome 3 alterations showed significantly slower metastatic disease progression with an average survival of 69 months (range 40-123 months, p = 0.003). Alterations in chromosomal arms 1p, 6p, and 8q and mutations in either GNAQ or GNA11 showed no association with disease progression. Prominent mononuclear inflammatory infiltrate was observed in tumors from patients with slowly progressive disease. In conclusion, in UM metastases, monosomy 3 is associated with highly aggressive, rapidly progressive disease while disomy or partial change of 3 and prominent mononuclear inflammatory infiltrate in the tumor is associated with better prognosis. These findings should be considered when designing clinical trials testing effectiveness of various therapies of metastatic UM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Bartonella henselae infection-associated vasculitis and crescentic glomerulonephritis leading to renal allograft loss.

    PubMed

    Chaudhry, A R; Chaudhry, M R; Papadimitriou, J C; Drachenberg, C B

    2015-06-01

    Bartonella henselae (BH) is the main cause of cat scratch disease (CSD), which more typically presents as a self-limited localized suppurative lymphadenopathy in immunocompetent individuals. In contrast, immunocompromised patients commonly have systemic disease with life-threatening complications. In addition to the angioproliferative lesions, such as bacillary angiomatosis, an increasing number of immune post-infectious complications are being recognized with BH infections, including glomerulonephritis, vasculitis, hemophagocytic syndrome, and neurological problems. We report the case of a renal transplant recipient who developed CSD in the second year post transplantation. In addition to prolonged fever and generalized lymphadenopathy and splenomegaly requiring differentiation from a post-transplant lymphoproliferative disorder, the course was complicated by the development of dermal leukocytoclastic vasculitis and pauci-immune necrotizing and crescentic glomerulonephritis, which led to failure of the renal graft. Glomerulonephritis as a complication of CSD has never been described in a kidney allograft, to our knowledge. Awareness of the diverse clinical symptoms associated with BH, including granulomatous/suppurative lesions and other less common complications can lead to more rapid and accurate diagnosis. Also, as recommended by the current guidelines, a thorough history of pet ownership should be part of the clinical evaluation before and after transplantation for all transplant recipients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    PubMed

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.

  5. Endostreptosin: isolation of the probable immunogen of acute post-streptococcal glomerulonephritis (PSGN).

    PubMed Central

    Cronin, W; Deol, H; Azadegan, A; Lange, K

    1989-01-01

    It is now generally accepted that acute post-streptococcal glomerulonephritis (PSGN) is the consequence of the formation of antigen-antibody-complement complexes on the basement membrane of the glomerulus and that the antigen is of streptococcal origin. In cases of acute PSGN a high titre of specific antibodies to a streptococcal cytoplasmic extract can be found at the very beginning of the disease. This cytoplasmic antigen which we called endostreptosin (ESS) is probably the pathogenetic antigen of glomerulonephritis. It is deposited on the subendothelial side of the basement membrane in the first few days of the disease and is rapidly covered by newly-formed and specific antibody and complement with resultant immune injury causing signs and symptoms of symptomatic but also frequently asymptomatic acute glomerulonephritis. To further characterize and isolate ESS we used immunoaffinity chromatography and Western blotting techniques. PAGE analysis of the affinity-isolated ESS revealed the major component to have a molecular weight of approximately 45 kD. Sera from patients with PSGN or sera of rabbits immunized with affinity-isolated ESS reacted by Western blotting with at least one antigenic component with a molecular weight of approximately 45 kD. Normal human sera or the sera of non-immunized rabbits failed to demonstrate activity against this antigen. The basement membranes of the glomeruli of patients with very early PSGN stain with fluorescein-labelled gammaglobulin of patients with glomerulonephritis. This staining can be prevented when these sera are pre-absorbed with ESS but not by pre-absorption with intact cells or cytoplasmic extracts of other bacteria. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:2667818

  6. [Autopsy case of Lissauer's general paresis with rapidly progressive left hemiparesis].

    PubMed

    Kato, Hiroko; Yoshida, Mari; Ando, Tetsuo; Sugiura, Makoto; Hashizume, Yoshio

    2009-06-01

    A 48-years-old man presented with slowly progressive bradykinesia, personality change and rapidly progressive left hemiparesis. On admission, he presented dementia, poor judgment, left hemiparesis. MRI revealed a widespread high intensity area in right hemisphere and MRA was almost normal. Serological tests of serum and CSF demonstrated high titers of antibodies to Treponema pallidum. He was treated for syphilis with daily penicillin injections without improvement. He died of sepsis eight months after admission. At autopsy, the brain weighed 1,100 g and the right cerebral hemisphere was atrophic, especially in frontal base, temporal, parietal, angular, and posterior regions covered by thickened, fibrotic leptomeninges. Microscopically, chronic meningoencephalitis was observed. Severe neuronal loss with gliosis was seen in the right cerebral cortices. Scattered rod-shaped microglia and inflammatory cell infiltration were visible in the cerebral parenchyma. The dorsal column of the spinal cord was not involved and meningovascular syphilis was unclear. The distribution of the encephalitic lesions was well correlated with the clinical and neuroradiological findings. This was a rare autopsy case presenting Lissauer's general paresis, clinically manifesting as rapidly progressive stroke-like episode.

  7. Rapid Disease Progression in HIV-1 Subtype C–Infected South African Women

    PubMed Central

    Mlisana, Koleka; Werner, Lise; Garrett, Nigel J.; McKinnon, Lyle R.; van Loggerenberg, Francois; Passmore, Jo-Ann S.; Gray, Clive M.; Morris, Lynn; Williamson, Carolyn; Abdool Karim, Salim S.

    2014-01-01

    Background. Whereas human immunodeficiency virus (HIV) subtype B–infected individuals generally progress to AIDS within 8–10 years, limited data exist for other clades, especially from Africa. We investigated rates of HIV disease progression of clade C–infected South African women. Methods. Prospective seroincidence cohorts in KwaZulu-Natal were assessed for acute HIV infection monthly (n = 245) or every 3 months (n = 594) for up to 4 years. Rapid disease progression was defined as CD4 decline to <350 cells/µL by 2 years postinfection. Serial clinical and laboratory assessments were compared using survival analysis and logistic regression models. Results. Sixty-two women were identified at a median of 42 days postinfection (interquartile range, 34–59), contributing 282 person-years of follow-up. Mean CD4 count dropped by 39.6% at 3 months and 46.7% at 6 months postinfection in women with preinfection measurements. CD4 decline to <350 cells/µL occurred in 31%, 44%, and 55% of women at 1, 2, and 3 years postinfection, respectively, and to <500 cells/µL in 69%, 79%, and 81% at equivalent timepoints. Predictors of rapid progression were CD4 count at 3 months postinfection (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.31–3.28; P = .002), setpoint viral load (HR, 3.82; 95% CI, 1.51–9.67; P = .005), and hepatitis B coinfection (HR, 4.54; 95% CI, 1.31–15.69; P = .017). Conversely, presence of any of HLAB*1302, B*27, B*57, B*5801, or B*8101 alleles predicted non–rapid progression (HR, 0.19; 95% CI, .05–.74; P = .016). Conclusions. Nearly half of subtype C–infected women progressed to a CD4 count <350 cells/µL within 2 years of infection. Implementing 2013 World Health Organization treatment guidelines (CD4 count <500 cells/µL) would require most individuals to start antiretroviral therapy within 1 year of HIV infection. PMID:25038116

  8. [Mechanisms of immune deposit formation in glomerulonephritis].

    PubMed

    Bussolati, B; Camussi, G

    1996-03-01

    Recent experimental studies allowed the identification of several mechanisms of immune deposit formation, which are able to reproduce the morphological and clinical pattern of human glomerulonephritis. Moreover, it was shown that most of the lesions considered, in the past, as due to circulating immune complexes (IC), are instead caused by the "in situ" formation of IC. As a result of these studies, the following schematic classification was proposed: 1) immune deposits formed by glomerular localization of IC primarily formed in the circulation; 2) immune deposits formed "in situ" by reaction of circulating antibodies with fixed structural antigens; 3) immune deposits formed "in situ" by antibodies reactive with movable structural antigens; 4) immune deposits formed "in situ" by antibodies reactive with sequestered antigens leaking out of tissues; 5) IC formed "in situ" by antibodies reactive with exogenous or non-glomerular endogenous antigens planted in the glomeruli; 6) ANCA-associated glomerular disease.

  9. Rapidly progressing, massive mitral annular calcification. Occurrence in a patient with chronic renal failure.

    PubMed

    Depace, N L; Rohrer, A H; Kotler, M N; Brezin, J H; Parry, W R

    1981-11-01

    Calcification of the mitral annulus developed in a patient while undergoing dialysis. The rapid onset of events corresponded to the onset of end-stage renal failure and uncontrolled secondary hyperparathyroidism. Sequential echocardiograms verified the progression of calcification of the annulus as well as the valve. A new systolic and diastolic murmur and reduced valve orifice on two-dimensional echocardiography suggested acquired nonrheumatic mitral stenosis and insufficiency. We propose that metastatic calcium deposition rather than long-term hypertensive and degenerative effects was the predominant mechanism for massive calcification of the annulus and valve. It is suggested that M-mode echocardiography be used sequentially to follow both the occurrence and progression of calcification of the mitral annulus or valve in patients with chronic renal failure, secondary hyperparathyroidism, or both.

  10. Rapidly progressive atherosclerosis after domino liver transplantation from a teenage donor with homozygous familial hypercholesterolemia.

    PubMed

    Golbus, Jessica R; Farhat, Linda; Fontana, Robert J; Rubenfire, Melvyn

    2017-07-22

    Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by impaired clearance of low-density lipoprotein cholesterol. Given limitations in pharmacologic therapy and the significant morbidity and mortality associated with this disease, liver transplantation may be offered to select homozygous FH patients in childhood in an effort to slow progression of atherosclerotic cardiovascular disease. In rare cases, domino liver transplantation can be performed, transplanting the livers of patients with various metabolic disorders into elderly recipients whose projected survival precludes prolonged waiting on the transplant list. Herein, we report a case of domino liver transplantation using the liver of a 14-year-old boy with homozygous FH into a 65-year-old man with primary sclerosing cholangitis and cirrhosis who developed rapidly progressive atherosclerotic cardiovascular disease involving the arteries of his proximal bilateral lower extremities, carotid arteries and superior mesenteric artery. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  11. Dural Arteriovenous Fistula Manifested as Rapid Progressive Dementia Successfully Treated by Endovascular Embolization Only

    PubMed Central

    Hwang, Heewon; La, Yun Kyung; Baek, Min Seok; Baik, Kyoungwon; Suh, Sang Hyun

    2017-01-01

    A 43-year-old male presented with daytime sleepiness at work and indifferent behavior like never before. Two weeks prior to hospital admission, he had episodic memory loss with well preserved remote memory. Brain MRI showed a dural arteriovenous fistula (DAVF) in the right lateral transverse sinus with a bilateral thalamic venous infarction. Cerebral angiography confirmed a right transverse sigmoid dural arteriovenous fistula with a feeding artery of the right occipital artery and left posterior meningeal artery. The DAVF was completely eliminated through multiple endovascular interventions. Recently, endovascular treatment has become one of the main therapeutic options to obliterate a fistulous site, which has led to a rapid diagnostic approach and management of DAVFs with high curative rates. We report a rare case of posterior fossa located at a dural arteriovenous fistula that caused rapid progressive dementia and was successfully eliminated through only endovascular treatment. PMID:28316870

  12. Rapidly progressing dual infection with Aspergillus and Rhizopus: when soil inhabitants become deadly invaders.

    PubMed

    Bhagat, Milind; Rapose, Alwyn

    2016-12-08

    We present a case report of a 61-year-old patient with acute pulmonary and cerebral infections with Aspergillus and Rhizopus. The only risk factor for invasive fungal disease was high-dose corticosteroids used to treat her chronic obstructive pulmonary disease exacerbation. She had rapid progression and succumbed to her infections within 2 weeks of diagnosis in spite of aggressive antifungal therapy and surgery. To the best of our knowledge, this is the first reported case of rapidly fatal dual infection with Aspergillus and Rhizopus Our case highlights the role of high-dose corticosteroids as a risk factor for invasive fungal disease in patients without traditional risk factors like haematological malignancies, solid organ transplantation or uncontrolled diabetes.

  13. Rapidly progressive intravascular primary effusion lymphoma in an HIV-positive renal transplant recipient.

    PubMed

    Cain, Owen; Yoong, Adrian; Lipkin, Graham; Huengsberg, Mia; Murray, Jim; Rudzki, Zbigniew; Vydianath, Bindu

    2017-08-16

    We describe the clinical and post-mortem findings of a case of rapidly progressive, ultimately fatal primary effusion lymphoma (PEL) arising in an HIV-positive man two years after renal transplantation. Disseminated multi-organ involvement associated with a peculiar intravascular pattern of growth, as seen in this case, has only been reported once previously. This is also, to our knowledge, the first detailed description of a lymphoma arising post-transplant in an HIV-positive patient. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. [Experimental systemic enzyme therapy of gouty and primary glomerulonephritis].

    PubMed

    Mukhin, I V; Nikolenko, V Iu

    2003-01-01

    The influence of a systemic enzymotherapy on the morphological, biochemical, and functional manifestations of the kidney damage during the experimental gouty and primary glomerulonephritis is described in comparison to the results obtained by traditional methods.

  15. Machine learning to predict rapid progression of carotid atherosclerosis in patients with impaired glucose tolerance.

    PubMed

    Hu, Xia; Reaven, Peter D; Saremi, Aramesh; Liu, Ninghao; Abbasi, Mohammad Ali; Liu, Huan; Migrino, Raymond Q

    2016-12-01

    Prediabetes is a major epidemic and is associated with adverse cardio-cerebrovascular outcomes. Early identification of patients who will develop rapid progression of atherosclerosis could be beneficial for improved risk stratification. In this paper, we investigate important factors impacting the prediction, using several machine learning methods, of rapid progression of carotid intima-media thickness in impaired glucose tolerance (IGT) participants. In the Actos Now for Prevention of Diabetes (ACT NOW) study, 382 participants with IGT underwent carotid intima-media thickness (CIMT) ultrasound evaluation at baseline and at 15-18 months, and were divided into rapid progressors (RP, n = 39, 58 ± 17.5 μM change) and non-rapid progressors (NRP, n = 343, 5.8 ± 20 μM change, p < 0.001 versus RP). To deal with complex multi-modal data consisting of demographic, clinical, and laboratory variables, we propose a general data-driven framework to investigate the ACT NOW dataset. In particular, we first employed a Fisher Score-based feature selection method to identify the most effective variables and then proposed a probabilistic Bayes-based learning method for the prediction. Comparison of the methods and factors was conducted using area under the receiver operating characteristic curve (AUC) analyses and Brier score. The experimental results show that the proposed learning methods performed well in identifying or predicting RP. Among the methods, the performance of Naïve Bayes was the best (AUC 0.797, Brier score 0.085) compared to multilayer perceptron (0.729, 0.086) and random forest (0.642, 0.10). The results also show that feature selection has a significant positive impact on the data prediction performance. By dealing with multi-modal data, the proposed learning methods show effectiveness in predicting prediabetics at risk for rapid atherosclerosis progression. The proposed framework demonstrated utility in outcome prediction in a typical

  16. Experimental glomerulonephritis is attenuated by CD8+ T cell chimerism and prevented by Mls-1-incompatible thymocytes.

    PubMed

    Sutmuller, M; Baelde, H J; Tysma, O M; de Heer, E; Bruijn, J A

    1998-07-01

    Chronic graft-versus-host disease (GvHD) in mice is a model resembling glomerulonephritis in human systemic lupus erythematosus. In the present study congenic mouse strains were used to investigate the pathogenetic role of (1) donor T cell subset chimerism and (2) donor thymocytes in this model. In GvHD employing minor lymphocyte-stimulating-1 (Mls-1)-compatible donors and recipients, full-blown immune complex glomerulonephritis was associated with a low-donor CD8(+) T cell chimerism. Injection of lymphocytes from Mls-1-negative donors (Mls-1(b)) into Mls-1-positive recipients (Mls-1(a)) induces a type of GvHD characterized by rapid self-limitation accompanied by the immediate inhibition of donor T cell chimerism and the absence of glomerulonephritis. However, omission of thymocytes from the donor inoculate does result in glomerular depositions containing immunoglobulins. These results suggest that donor CD8(+) T cell chimerism is associated with attenuation of immune complex glomerulonephritis, whereas Mls-1-incompatible donor T cell precursors prevent the disease. Copyright 1998 Academic Press.

  17. [Treatment of dyslipoproteinemia by systemic enzyme therapy in experimental glomerulonephritis].

    PubMed

    Mukhin, I V

    2002-01-01

    Patients with chronic glomerulonephritis (CG) develop disturbances of lipid blood spectrum leading to additional damage to renal structure. The existent methods of pathogenetic therapy have no effect on lipid imbalance. Recently, many autoimmune diseases have been treated with systemic enzyme therapy (SET). The authors studied SET effect in disturbed lipid metabolism in experimental glomerulonephritis. Experimental animals showed morphological and biochemical changes similar to those in CG of man. SET reduced renal tissue damage and symptoms of dyslipoproteinemia.

  18. Sjögren Syndrome and Cryoglobulinemic Glomerulonephritis.

    PubMed

    Anand, Ananya; Krishna, Gopal G; Sibley, Richard K; Kambham, Neeraja

    2015-09-01

    We report the case of a 53-year-old woman with Sjögren syndrome and cryoglobulinemia. The patient presented with nephrotic syndrome, hematuria, and reduced estimated glomerular filtration rate. The kidney biopsy revealed diffuse endocapillary proliferation and leukocyte exudation with focal intraluminal hyaline thrombi, prominent tubulointerstitial inflammation, and vasculitis. Diffuse granular mesangial and segmental to global capillary wall staining was observed on immunofluorescence with antisera to C3 and immunoglobulin M (IgM), with less intense staining indicative of IgG and κ and λ light chains. A biopsy diagnosis of Sjögren syndrome-related cryoglobulinemic membranoproliferative glomerulonephritis and vasculitis was rendered. Subsequent investigations revealed the presence of circulating type II cryoglobulins with cryocrit of 9%. Although rare, Sjögren syndrome is the most common cause of non-hepatitis C virus-related mixed cryoglobulinemia. We discuss the possible pathogenic mechanisms involved in the development of mixed cryoglobulinemia and its evolution to lymphoma, as best described in the setting of hepatitis C virus infection. Although the specific antigen involved is unknown, it is likely that the mixed cryoglobulinemia in Sjögren syndrome is triggered by the long-term B-cell stimulation, resulting in clonal proliferation of B cells. Additional chromosomal aberrations and cytokine milieu alterations, as seen in hepatitis C virus infection, may result in prolonged B-cell survival and progression to non-Hodgkin lymphoma. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Membranous glomerulonephritis associated with Mycobacterium shimoidei pulmonary infection.

    PubMed

    Kanaji, Nobuhiro; Kushida, Yoshio; Bandoh, Shuji; Ishii, Tomoya; Haba, Reiji; Tadokoro, Akira; Watanabe, Naoki; Takahama, Takayuki; Kita, Nobuyuki; Dobashi, Hiroaki; Matsunaga, Takuya

    2013-01-01

    Male, 83 FINAL DIAGNOSIS: Membranous glomerulonephritis Symptoms: Producting cough Medication: - Clinical Procedure: - Specialty: Nephrology. Rare disease. Membranous glomerulonephritis can occur secondarily from infectious diseases. There are no reports describing membranous glomerulonephritis caused by non-tuberculous mycobacterium infection. However, several cases with membranous glomerulonephritis due to Mycobacterium tuberculosis have been reported. Mycobacterium shimoidei is an uncommon pathogen, and less than 20 cases with this species have been reported. A therapeutic regimen for this infection has not been established yet. An 83-year-old Japanese man presented with productive cough for 6 months. Computed tomography scan showed multiple cavities in the bilateral pulmonary fields. Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing. Urine examination showed a sub-nephrotic range of proteinuria and histology of the kidney showed membranous glomerulonephritis. Antimycobacterial treatment with clarithromycin, rifampicin, and ethambutol dramatically improved not only the pulmonary disease, but also the proteinuria. To the best of our knowledge, the presented case is the first report showing non-tuberculous mycobacterium-induced secondary membranous glomerulonephritis. A combination with clarithromycin, ethambutol, and rifampicin might be effective for treatment of Mycobacterium shimoidei infection.

  20. Confetti-like depigmentation: A potential sign of rapidly progressing vitiligo.

    PubMed

    Sosa, Juan Jesús; Currimbhoy, Sharif D; Ukoha, Uzoamaka; Sirignano, Samantha; O'Leary, Ryan; Vandergriff, Travis; Hynan, Linda S; Pandya, Amit G

    2015-08-01

    Confetti-like depigmentation was noted in patients reporting recent worsening of vitiligo. We sought to determine if confetti-like depigmentation is a marker of rapidly progressing vitiligo. Review of patient records and images of patients from a vitiligo registry resulted in 7 patients with 12 images that fit inclusion criteria and were evaluated for percent depigmentation by 3 independent reviewers. The Vitiligo Disease Activity Score and the Koebner Phenomenon in Vitiligo Score in an additional cohort of patients with confetti-like lesions were compared with patients who had vitiligo without confetti-like lesions. The mean percentage of depigmentation at baseline was 19.2%, which increased to 43.9% in images obtained at a mean of 16 weeks of follow-up. Vitiligo Disease Activity Score and Koebner Phenomenon in Vitiligo Score were significantly higher in the patients with confetti-like lesions compared with those without confetti-like lesions. A skin biopsy specimen of a confetti-like lesion in 1 patient revealed an inflammatory infiltrate in the papillary dermis with CD8(+) T cells localized to the dermoepidermal junction. Small, single-center retrospective review and lack of full-body photographs are limitations. A confetti-like pattern of depigmentation may be a negative prognostic indicator for patients with rapidly progressing vitiligo. Further, prospective studies to evaluate this physical finding should be performed. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Can Home Monitoring Allow Earlier Detection of Rapid Visual Field Progression in Glaucoma?

    PubMed

    Anderson, Andrew J; Bedggood, Phillip A; George Kong, Yu Xiang; Martin, Keith R; Vingrys, Algis J

    2017-07-29

    Recent developments in electronic technology are making it possible to home monitor the sensitivity of the central visual field using portable devices. We used simulations to investigate whether the higher test frequency afforded by home monitoring improves the early detection of rapid visual field loss in glaucoma and how any benefits might be affected by imperfect compliance or increased variability in the home-monitoring test. Computer simulation, with parameter selection confirmed with a cohort study. A total of 43 patients with treated glaucoma (both open-angle and closed-angle), ocular hypertension or glaucoma suspects (mean age, 71 years; range, 37-89 years), were followed in the cohort study. We simulated series (n = 100 000) of visual fields for patients with stable glaucoma and patients with progressing glaucoma for 2 in-clinic (yearly and 6-monthly) and 3 home-monitoring (monthly, fortnightly, and weekly) schedules, each running over a 5-year period. Various percentages of home-monitored fields were omitted at random to simulate reduced compliance, and the variability of the home monitored fields also was manipulated. We used previously published variability characteristics for perimetry and confirmed their appropriateness for a home-monitoring device by measuring the device's retest variability at 2 months in a cohort of 43 patients. The criterion for flagging progression in our simulation was a significant slope of the ordinary least squares regression of a simulated patient's mean deviation (MD) data. The sensitivity for identifying rapid visual field loss (-2 decibels [dB]/year loss of MD). Although a sensitivity of 0.8 for rapid field loss was achieved after 2.5 years of 6-monthly testing in the clinic, weekly home monitoring achieved this by 0.9 years despite moderate test compliance of 63%. The improved performance of weekly home monitoring over 6-monthly clinical testing was retained even when home monitoring was assumed to produce more

  2. New trends of an old disease: the acute post infectious glomerulonephritis at the beginning of the new millenium.

    PubMed

    Stratta, Piero; Musetti, Claudio; Barreca, Antonella; Mazzucco, Gianna

    2014-06-01

    The association between acute renal disease and infection has been known since the mid '800s: acute post-infectious glomerulonephritis (PIGN) is a reactive immunological process against the kidney secondary to an infection, classically caused by a Streptococcus. The typical clinical presentation of PIGN is an acute nephritic syndrome with macro- or microscopic hematuria, proteinuria, hypertension, edema and renal function impairment of variable degree. The histology is characterized by an intracapillary glomerular proliferation, but may rarely be associated with an extracapillary proliferation. The classical childhood form is still present nowadays, even with severe cases, in developing countries, while in the last decades it almost disappeared in industrialized countries, where post-infectious GN are often found in elderly patients with multiple comorbidities. These clinical variants are usually related to other infective agents, like Staphylococcus aureus, both methicillin resistant (MRSA) and susceptible, and may be characterized by an IgA-dominant deposition. Kidney biopsy is rarely needed, especially in the child, while in the adult or old patient a biopsy is warranted if there is an atypical presentation or evolution, like rapidly progressive renal failure, absent or delayed function recovery, persisting low C3, nephrotic range proteinuria and persisting high proteinuria. Current therapy strategies rely on culture-guided systemic antibiotics, especially in the old patient, in which MRSA are relatively frequent, support therapy and only in very selected cases on steroids. These latter cases include the rare PIGN with crescents and those with a severe interstitial inflammation.

  3. C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases.

    PubMed

    Gupta, Ruchika; Sharma, Alok; Agarwal, Sanjay K; Dinda, Amit K

    2015-11-01

    C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN) has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH). Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman's capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

  4. Erythropoietin-producing cells in the liver of ICR-derived glomerulonephritis (ICGN) mice.

    PubMed

    Yamaguchi-Yamada, Misuzu; Akashi, Naotsugu; Goto, Yasufumi; Anan, Sayuri; Yamamoto, Yoshie; Ogura, Atsuo; Manabe, Noboru

    2006-01-01

    The ICR-derived glomerulonephritis (ICGN) mouse is an appropriate model for anemia associated with chronic renal disorder (CRD). Insufficient renal production of erythropoietin (EPO) induces the anemia associated with CRD. EPO mRNA is expressed in both kidneys and liver of progressing-stage ICGN mice. Hypoxic stimulation induced the EPO mRNA expression in the liver as well as in the kidneys of ICGN mice. The localization of EPO-producing cells in the liver remains controversial. Present study using an amplified in situ hybridization technique identified that nonparenchymal cells were the source of hepatic EPO production in ICGN mice under both normoxia and hypoxia.

  5. Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

    PubMed

    Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

    2015-01-01

    We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

  6. Membranous glomerulonephritis in the Iberian lynx (Lynx pardinus).

    PubMed

    Jiménez, Angeles; Sánchez, Belén; Pérez Alenza, Dolores; García, Pilar; López, Jose Vicente; Rodriguez, Alejandro; Muñoz, Alvaro; Martínez, Fernando; Vargas, Astrid; Peña, Laura

    2008-01-15

    The Iberian lynx is the most endangered felid species in the world, confined nowadays to two isolated metapopulations in the southwest of Spain, where less than 200 individuals survive. Little is known about the diseases that affect these animals in the wild or in captivity. Kidney samples from necropsies of 27 Iberian lynxes, wild and captive, were examined by histopathology, immunohistochemistry (IgG, IgM, IgA, laminin, type IV collagen, and fibronectin), electron microscopy (n=8) and immunogold labelling for IgM, IgG and IgA in one case, in order to characterize the glomerulopathy prevalent in this species. Urinalyses from records were available for 9 of the necropsied animals and blood and urine samples from 23 free ranging and captive Iberian lynxes were prospectively obtained in order to evaluate the renal function of the living population. A focal, diffuse membranous glomerulonephritis (MGN) that progressed with age was diagnosed in all but one of the animals in different stages not associated to concurrently known infectious diseases. Positive immunoexpression of IgM and IgG was observed in the glomerular capillary basement membranes and intramembranous electron-dense deposits, compatible with immune complexes (ICs) were seen with electron microscopy. The immunogold labelling was also positive for IgM and IgG in the electron-dense areas. The serum biochemistry and urinalyses also revealed signs of mild chronic kidney disease in 16 of the 23 animals evaluated. In conclusion, the membranous glomerulopathy affecting the Iberian lynx is a progressive disease of immune origin. We postulate a possible genetic predisposition towards the disease, enhanced by inbreeding and a possible connection to an immune-mediated systemic disease.

  7. Haematuria on the Spanish Registry of Glomerulonephritis

    PubMed Central

    Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel

    2016-01-01

    Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria’s overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome. PMID:26818712

  8. Haematuria on the Spanish Registry of Glomerulonephritis.

    PubMed

    Yuste, Claudia; Rivera, Francisco; Moreno, Juan Antonio; López-Gómez, Juan Manuel

    2016-01-28

    Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.

  9. Brucellar spondylodiscitis with rapidly progressive spinal epidural abscess showing cauda equina syndrome.

    PubMed

    Hu, Tan; Wu, Ji; Zheng, Chao; Wu, Di

    2016-01-01

    Early diagnosis of Brucellosis is often difficult in the patient with only single non-specific symptom because of its rarity. We report a patient with Brucellar spondylodiscitis, in which the low back pain was the only symptom and the magnetic resonance imaging (MRI) showed not radiographic features about infection at initial stage. He was misdiagnosed as a lumbar disc herniation for inappropriate treatment in a long time. The delay in diagnosis and correct treatment led to rapid progression of the disease and severe complications. The patient was treated successfully with triple-antibiotic and surgical intervention in the end. Brucellar spondylodiscitis should always be suspended in the differential diagnosis specially when the patient comes from an endemic area or has consumed dairy products from animals in such an area and comprehensive examination should be done for the patent to rule out some important diseases like Brucellosis with sufficient reasons.

  10. Brucellar spondylodiscitis with rapidly progressive spinal epidural abscess showing cauda equina syndrome

    PubMed Central

    Hu, Tan; Wu, Ji; Zheng, Chao; Wu, Di

    2016-01-01

    Early diagnosis of Brucellosis is often difficult in the patient with only single non-specific symptom because of its rarity. We report a patient with Brucellar spondylodiscitis, in which the low back pain was the only symptom and the magnetic resonance imaging (MRI) showed not radiographic features about infection at initial stage. He was misdiagnosed as a lumbar disc herniation for inappropriate treatment in a long time. The delay in diagnosis and correct treatment led to rapid progression of the disease and severe complications. The patient was treated successfully with triple-antibiotic and surgical intervention in the end. Brucellar spondylodiscitis should always be suspended in the differential diagnosis specially when the patient comes from an endemic area or has consumed dairy products from animals in such an area and comprehensive examination should be done for the patent to rule out some important diseases like Brucellosis with sufficient reasons. PMID:28053732

  11. Rapid progression of pulmonary blastomycosis in an untreated patient of chronic lymphocytic leukemia.

    PubMed

    Sarkar, Pralay K; Malhotra, Paras; Sriram, P S

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is associated with a state of immunosuppression characterized by hypogammaglobulinemia as well as B and T lymphocyte dysfunction. Though opportunistic infections are common in CLL patients, particularly after treatment, reports of infections by endemic dimorphic fungi are very few. Here we report a case of pulmonary blastomycosis in a CLL patient who initially presented with an indolent pulmonary mass lesion. The pulmonary lesions progressed rapidly over a two-week period. The diagnosis was established by transbronchial lung biopsy. He was treated with Amphotericin B lipid complex followed by oral itraconazole and recovered uneventfully. This case illustrates the importance of a timely diagnosis and treatment. The presentation of blastomycosis in immunocompromised patients, diagnosis, and treatment are discussed.

  12. A Challenging Case of Rapid Progressive Kaposi Sarcoma After Renal Transplantation

    PubMed Central

    Reuter, Stefan; Vrachimis, Alexis; Huss, Sebastian; Wardelmann, Eva; Weckesser, Mathias; Pavenstädt, Hermann

    2014-01-01

    Abstract De-novo malignancy is a serious posttransplant complication. While the incidence of Kaposi sarcoma (KS) is low, the time for its diagnosis is early after renal transplantation. Typically, it can be identified because of the classical skin lesion. We herein report an unusual case of rapid progressive KS without skin lesions in a 52-year-old patient leading to death within 8 months after kidney transplantation. This striking case illustrates the usefulness of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for demonstrating the cause of unexplained deterioration of patient’s condition. Early identification of KS is critical because early (modification of) therapy can substantially improve patient’s prognosis. PMID:25192485

  13. An unusual case of rapidly progressive contractures: Case report and brief review

    PubMed Central

    Subasree, R.; Panda, Samhita; Pal, Pramod Kumar; Ravishankar, S.

    2008-01-01

    An 8-year-old boy, diagnosed as cervical dystonia, was referred to our tertiary center. After a trivial trauma he had developed painful lumps in the axial region, which was followed by restricted movements of neck, shoulder, and abdominal muscles over 4 months. He had kyphoscoliosis, torticollis, rigid abdomen, and multiple muscle contractures. He also had short great toes. A detailed skeletal survey showed calcification in the soft tissues surrounding the shoulder anterior chest wall, thorax, and paraspinal muscles; there was also beaking of vertebrae, which was confirmed by CT thorax. This report showcases the diagnostic challenge posed by myositis ossificans progressiva, which can rarely cause rapidly progressing muscle contractures. A brief review of literature is also presented. PMID:19893652

  14. Male patients presenting with rapidly progressive puberty associated with malignant tumors

    PubMed Central

    Kim, Soo Jung; Ko, A Ra; Jung, Mo Kyung; Kim, Ki Eun; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

    2016-01-01

    In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm. PMID:27104181

  15. Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β

    PubMed Central

    Cohen, Mark L.; Kim, Chae; Haldiman, Tracy; ElHag, Mohamed; Mehndiratta, Prachi; Pichet, Termsarasab; Lissemore, Frances; Shea, Michelle; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Appleby, Brian S.; Surewicz, Krystyna; Surewicz, Witold K.; Sajatovic, Martha; Tatsuoka, Curtis; Zhang, Shulin; Mayo, Ping; Butkiewicz, Mariusz; Haines, Jonathan L.; Lerner, Alan J.

    2015-01-01

    Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but the cause of variable progression rates and phenotypes of sporadic Alzheimer’s disease is largely unknown. We aimed to investigate the relationship between diverse structural assemblies of amyloid-β and rates of clinical decline in Alzheimer’s disease. Using novel biophysical methods, we analysed levels, particle size, and conformational characteristics of amyloid-β in the posterior cingulate cortex, hippocampus and cerebellum of 48 cases of Alzheimer’s disease with distinctly different disease durations, and correlated the data with APOE gene polymorphism. In both hippocampus and posterior cingulate cortex we identified an extensive array of distinct amyloid-β42 particles that differ in size, display of N-terminal and C-terminal domains, and conformational stability. In contrast, amyloid-β40 present at low levels did not form a major particle with discernible size, and both N-terminal and C- terminal domains were largely exposed. Rapidly progressive Alzheimer’s disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30–100 monomers, and fewer particles composed of < 30 monomers. The link between rapid clinical decline and levels of amyloid-β42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer’s disease phenotypes. These findings indicate that Alzheimer’s disease exhibits a wide spectrum of amyloid-β42 structural states and imply the existence of prion-like conformational strains. PMID:25688081

  16. Rapidly progressive Alzheimer's disease features distinct structures of amyloid-β.

    PubMed

    Cohen, Mark L; Kim, Chae; Haldiman, Tracy; ElHag, Mohamed; Mehndiratta, Prachi; Pichet, Termsarasab; Lissemore, Frances; Shea, Michelle; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Appleby, Brian S; Surewicz, Krystyna; Surewicz, Witold K; Sajatovic, Martha; Tatsuoka, Curtis; Zhang, Shulin; Mayo, Ping; Butkiewicz, Mariusz; Haines, Jonathan L; Lerner, Alan J; Safar, Jiri G

    2015-04-01

    Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but the cause of variable progression rates and phenotypes of sporadic Alzheimer's disease is largely unknown. We aimed to investigate the relationship between diverse structural assemblies of amyloid-β and rates of clinical decline in Alzheimer's disease. Using novel biophysical methods, we analysed levels, particle size, and conformational characteristics of amyloid-β in the posterior cingulate cortex, hippocampus and cerebellum of 48 cases of Alzheimer's disease with distinctly different disease durations, and correlated the data with APOE gene polymorphism. In both hippocampus and posterior cingulate cortex we identified an extensive array of distinct amyloid-β42 particles that differ in size, display of N-terminal and C-terminal domains, and conformational stability. In contrast, amyloid-β40 present at low levels did not form a major particle with discernible size, and both N-terminal and C- terminal domains were largely exposed. Rapidly progressive Alzheimer's disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-β42, with higher levels of distinctly structured amyloid-β42 particles composed of 30-100 monomers, and fewer particles composed of < 30 monomers. The link between rapid clinical decline and levels of amyloid-β42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer's disease phenotypes. These findings indicate that Alzheimer's disease exhibits a wide spectrum of amyloid-β42 structural states and imply the existence of prion-like conformational strains. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer's disease.

    PubMed

    Drummond, Eleanor; Nayak, Shruti; Faustin, Arline; Pires, Geoffrey; A Hickman, Richard; Askenazi, Manor; Cohen, Mark; Haldiman, Tracy; Kim, Chae; Han, Xiaoxia; Shao, Yongzhao; Safar, Jiri G; Ueberheide, Beatrix; Wisniewski, Thomas

    2017-03-04

    Rapidly progressive Alzheimer's disease (rpAD) is a particularly aggressive form of Alzheimer's disease, with a median survival time of 7-10 months after diagnosis. Why these patients have such a rapid progression of Alzheimer's disease is currently unknown. To further understand pathological differences between rpAD and typical sporadic Alzheimer's disease (sAD) we used localized proteomics to analyze the protein differences in amyloid plaques in rpAD and sAD. Label-free quantitative LC-MS/MS was performed on amyloid plaques microdissected from rpAD and sAD patients (n = 22 for each patient group) and protein expression differences were quantified. On average, 913 ± 30 (mean ± SEM) proteins were quantified in plaques from each patient and 279 of these proteins were consistently found in plaques from every patient. We found significant differences in protein composition between rpAD and sAD plaques. We found that rpAD plaques contained significantly higher levels of neuronal proteins (p = 0.0017) and significantly lower levels of astrocytic proteins (p = 1.08 × 10(-6)). Unexpectedly, cumulative protein differences in rpAD plaques did not suggest accelerated typical sAD. Plaques from patients with rpAD were particularly abundant in synaptic proteins, especially those involved in synaptic vesicle release, highlighting the potential importance of synaptic dysfunction in the accelerated development of plaque pathology in rpAD. Combined, our data provide new direct evidence that amyloid plaques do not all have the same protein composition and that the proteomic differences in plaques could provide important insight into the factors that contribute to plaque development. The cumulative protein differences in rpAD plaques suggest rpAD may be a novel subtype of Alzheimer's disease.

  18. Rapid progressive eosinophilic cardiomyopathy in a patient with Churg-Strauss syndrome (CSS).

    PubMed

    Rosenberg, M; Lorenz, H M; Gassler, N; Katus, H A; Frey, N

    2006-05-01

    Churg-Strauss syndrome (CSS) is a rare necrotizing, systemic vasculitis that is almost invariably associated with bronchial asthma. Although overall prognosis is good and treatment with corticosteroids alone or in combination with other immunosuppressive agents is typically successful, there are reports of patients that do not show signs of clinical improvement under the usual pharmacotherapy. Small clinical studies suggested that cardiac or gastrointestinal involvement is associated with an adverse prognosis. We here report the case of a 38 year old male patient with a history of bronchial asthma who was admitted to our hospital for further evaluation of progressive dyspnea. Blood eosinophilia, infiltrates of both lungs, signs of necrosis and eosinophil deposits on myocardial biopsy combined with a history of bronchial asthma established the diagnosis of CSS with cardiac involvement. We initiated an immunosuppressive therapy with prednisone and methotrexate. Upon tapering of the dosage of prednisone, we noticed worsening of symptoms and further deterioration of cardiac function. Despite the addition of cyclophosphamide and adjustment of heart failure medication, we were not able to stabilize the cardiac situation. Due to rapid progressive eosinophilic cardiomyopathy associated with CSS refractory to medical therapy, our patient was placed on the urgent heart transplantation waiting list and, in the meantime, has undergone successful cardiac transplantation.

  19. Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison's disease.

    PubMed

    Thompson, Michael D; Kalmar, Eileen; Bowden, Sasigarn A

    2015-05-28

    We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed. 2015 BMJ Publishing Group Ltd.

  20. Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison's disease

    PubMed Central

    Thompson, Michael D; Kalmar, Eileen; Bowden, Sasigarn A

    2015-01-01

    We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed. PMID:26021383

  1. Rapidly progressive stage IVB mycosis fungoides treated with low-dose total skin electron beam therapy.

    PubMed

    Chowdhary, Mudit; Kabbani, Ahmad A; Rimtepathip, Parin; Cole, David A; Cohen, David J

    2015-01-01

    Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell lymphoma. Normally, MF has an indolent course although patients can progress to an advanced disease state (stages IIB-IVB). Advanced-stage disease is typically aggressive, leaving patients with debilitating symptoms and a decreased quality of life. Moreover, advanced-stage MF often proves refractory to therapy and carries a very poor prognosis. Total skin electron beam (TSEB) therapy is a well-established and successful treatment for early stage MF; however, its efficacy dramatically decreases with advanced-stage disease. In fact, TSEB in advanced-stage MF is generally considered to be palliative. Current consensus guidelines recommend a dose of 30-36 Gy to be delivered in 8-10 weeks; however, limited studies exist to determine the ideal treatment in Stage IV MF. Herein, we describe a case of a 50-year-old male who developed rapidly progressive stage IVB (T3N3M1B0) MF and was treated with low-dose (24 Gy) TSEB over 8 weeks. The patient was not treated with any systemic therapy before starting TSEB due to the widespread nature and the speed of disease progression. Remarkably, our patient showed nearly complete (95%) response of his MF with no apparent side effects from radiation. Furthermore, he has remained in remission over 4 years, requiring only a small boost to a few "shadowed" areas. Our case illustrates the benefit of using TSEB in stage IV MF. Additionally, our experience shows that low-dose TSEB can occasionally be efficacious in stage IV disease.

  2. The associations of HLA and other genetic markers with glomerulonephritis.

    PubMed

    Rashid, H U; Papiha, S S; Agroyannis, B; Morley, A R; Ward, M K; Roberts, D F; Kerr, D N

    1983-01-01

    One hundred and seventy-nine patients with various forms of glomerulonephritis confirmed histologically were tested for HLA A and B antigens: Thirty-four with membranous glomerulonephritis were also typed for DR antigens. One hundred and forty-one of these patients were further tested for blood group, red cell enzyme, and plasma protein systems. The minimal-change and the mesangio-capillary glomerulonephritis showed a significant association with B8 and Bw44 antigens respectively, whereas the membranous nephritis in addition to B8 was also found to be associated with DR3 antigen. Previously described associations with Henoch-Schönlein and Berger's nephritis were not proved. A large group with nonspecific proliferative glomerulonephritis did not show any association with HLA. Among the other single-gene characters studied, a significant association was found with Bf (Factor B or C3 proactivator) and adenosine deaminase, both markers thought to be involved in the immune response. The close association of the markers located on chromosome 6 and glomerulonephritis indicates that there may be an immunological component in the aetiology of the disease. The significance of the various associations found is discussed.

  3. Heparanase Is Essential for the Development of Acute Experimental Glomerulonephritis.

    PubMed

    Garsen, Marjolein; Benner, Marilen; Dijkman, Henry B; van Kuppevelt, Toin H; Li, Jin-Ping; Rabelink, Ton J; Vlodavsky, Israel; Berden, Jo H M; Rops, Angelique L W M M; Elkin, Michael; van der Vlag, Johan

    2016-04-01

    Heparanase, a heparan sulfate (HS)--specific endoglucuronidase, mediates the onset of proteinuria and renal damage during experimental diabetic nephropathy. Glomerular heparanase expression is increased in most proteinuric diseases. Herein, we evaluated the role of heparanase in two models of experimental glomerulonephritis, being anti-glomerular basement membrane and lipopolysaccharide-induced glomerulonephritis, in wild-type and heparanase-deficient mice. Induction of experimental glomerulonephritis led to an increased heparanase expression in wild-type mice, which was associated with a decreased glomerular expression of a highly sulfated HS domain, and albuminuria. Albuminuria was reduced in the heparanase-deficient mice in both models of experimental glomerulonephritis, which was accompanied by a better renal function and less renal damage. Notably, glomerular HS expression was preserved in the heparanase-deficient mice. Glomerular leukocyte and macrophage influx was reduced in the heparanase-deficient mice, which was accompanied by a reduced expression of both types 1 and 2 helper T-cell cytokines. In vitro, tumor necrosis factor-α and lipopolysaccharide directly induced heparanase expression and increased transendothelial albumin passage. Our study shows that heparanase contributes to proteinuria and renal damage in experimental glomerulonephritis by decreasing glomerular HS expression, enhancing renal leukocyte and macrophage influx, and affecting the local cytokine milieu. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Membranoproliferative glomerulonephritis associated with autoimmune diseases.

    PubMed

    Zand, Ladan; Fervenza, Fernando C; Nasr, Samih H; Sethi, Sanjeev

    2014-04-01

    Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.

  5. Arterial hypertension in chronic glomerulonephritis. An analysis of 310 cases.

    PubMed

    Danielsen, H; Kornerup, H J; Olsen, S; Posborg, V

    1983-06-01

    310 cases of glomerulonephritis classified morphologically according to the criteria of the WHO were analyzed retrospectively in order to determine the frequency of arterial hypertension. The overall prevalence of arterial hypertension was 61%. Hypertension was most frequent and severe in membranoproliferative and sclerotic glomerulonephritis, but often mild and transient in extracapillary glomerulonephritis. Hypertension usually developed during the early stages of the disease when kidney function was well preserved and in only 16% was hypertension first seen during the uremic stage. No correlation was found between hypertension and the presence of the nephrotic syndrome. During dialysis, hypertension was present in 78%; in 90% of these patients hypertension was "controllable" and in 10% it was "uncontrollable".

  6. ANCA positivity in a patient with infective endocarditis-associated glomerulonephritis: a diagnostic dilemma.

    PubMed

    Ghosh, Gopal Chandra; Sharma, Brijesh; Katageri, Bhimarey; Bhardwaj, Minakshi

    2014-09-01

    Glomerulonephritis (GN) is an immunological phenomenon in bacterial endocarditis. These may be pauci-immune/vasculitic GN, post-infective GN, and sub-endothelial membranoproliferative glomerulonephritis. Each type of glomerulonephritis usually occurs in isolation. We report a case of infective endocarditis with dual existence of pauci-immune/vasculitic GN and post infective type of GN at the same time.

  7. Proteomics and glomerulonephritis: A complementary approach in renal pathology for the identification of chronic kidney disease related markers.

    PubMed

    L'Imperio, Vincenzo; Smith, Andrew; Chinello, Clizia; Pagni, Fabio; Magni, Fulvio

    2016-04-01

    Glomerulonephritis (GN) is one of the most common origins of chronic kidney disease and its careful evaluation is crucial for prognostic and therapeutic purposes, with the renal biopsy still playing a central role for the diagnosis. However, due to its invasiveness, it is not devoid of complications and many investigations have focused on identifying biomarkers for chronic kidney diseases using less-invasive and easy-to-collect samples, such as urine and blood. In this context, proteomics has played a crucial role in determining the molecular changes related to disease progression and early pathological glomerular modifications. Here, we report a review of selected literature for each GN, based on selected works published in the last 10 years, showing how these approaches have generated clinically relevant findings in the study of glomerulonephritis. We also describe several proteomic strategies, highlighting their technical advantages and limitations, future perspectives for proteomic applications in the study of GNs, and their possible application in routine practice.

  8. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis.

    PubMed Central

    Jennette, J. C.; Wilkman, A. S.; Falk, R. J.

    1989-01-01

    Anti-neutrophil cytoplasmic autoantibodies (ANCA) react with constituents of neutrophil primary granules and monocyte lysosomes. Indirect immunofluorescence microscopy using alcohol-fixed neutrophils demonstrates two ANCA types: one causing cytoplasmic staining (C-ANCA), and a second causing artifactual perinuclear staining (P-ANCA) that frequently has specificity for myeloperoxidase. Using indirect immunofluorescence microscopy (IIFM) and enzyme immunoassays (EIA), sera from over 300 patients with renal disease, with and without systemic vasculitis, were analyzed. Of 76 patients with pauci-immune glomerulonephritis with crescents or necrosis, 87% had ANCA by IIFM (38% of C-ANCA type, 49% of P-ANCA type), and 78% had ANCA by EIA. Of 55 patients with nonlupus immune complex-mediated glomerulonephritis, only 11% had ANCA by IIFM and 5% had ANCA by EIA. Of 24 patients with anti-GBM antibody-mediated glomerulonephritis, none had ANCA. Renal and extrarenal lesions were studied in 81 patients with ANCA-associated glomerulonephritis. These patients formed a pathologic continuum ranging from renal-limited to widespread systemic vascular injury, including patients with primary crescentic glomerulonephritis, Wegener's granulomatosis, and polyarteritis nodosa. In ANCA-positive patients the frequency of C-ANCA and P-ANCA correlated with disease distribution. P-ANCA was most frequent with renal-limited disease and C-ANCA was most frequent when there was lung and sinus involvement. It is proposed that ANCA are not only useful diagnostic markers, but may also be directly involved in a novel pathogenetic mechanism that is a frequent cause of crescentic glomerulonephritis and systemic necrotizing vasculitis. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2683800

  9. Significance of CD163-Positive Macrophages in Proliferative Glomerulonephritis.

    PubMed

    Li, Jun; Liu, Chang-Hua; Xu, Dao-Liang; Gao, Bo

    2015-11-01

    CD163, a marker of M2 macrophages, possesses anti-inflammatory properties. This study aims to investigate the clinicopathological significance of CD163-positive macrophages in proliferative glomerulonephritis. Renal tissue samples from patients with lupus nephritis (LN, n = 22), antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune necrotizing glomerulonephritis (PNGN, n = 10), type 1 membranoproliferative glomerulonephritis (n = 5), minimal change disease (n = 8) and normal control kidneys (n = 3) were included in this study. The expression of CD163, CD68, CD20 and CD3 in renal tissues was detected by immunohistochemistry or immunofluorescence. The level of urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined by enzyme-linked immunosorbent assay. CD163 was mainly expressed in active crescentic glomerulonephritis, proliferative glomerular lesions and areas of tubulointerstitial injury. Patients with LN-IV and PNGN had numerous CD163-positive cells in glomerular and acute tubulointerstitial lesions. CD163-positive cells in glomeruli positively correlated to proteinuria yet negatively correlated to estimated glomerular filtration rate. There was a positive correlation between the number of CD163 cells in acute tubulointerstitial lesions and NGAL levels, whereas a negative correlation between CD163 numbers and estimated glomerular filtration rate. The number of CD163-positive cells in crescentic glomerulonephritis was more than other groups. In LN, the number of CD163 cells in the tubulointerstitial and glomerular lesions had a positive correlation with activity index. Dual staining showed that CD163-positive cells also expressed CD68, although they did not show any staining for CD20 or CD3. CD163-positive macrophages were involved in the pathogenesis of proliferative glomerular lesions, active crescentic glomerulonephritis and acute tubular injury of patients with PNGN and active LN.

  10. Pathologic findings in mesangiopathic glomerulonephritis in Navajo Indians.

    PubMed

    Smith, S M; Hoy, W E; Pathak, D; Megill, D M; Tung, K S; Hughson, M D

    1989-02-01

    Immune complex-associated mesangiopathic glomerulonephritis was found in 64% of renal biopsies performed on Navajos over a 16-year period. It is characterized by mild mesangial expansion and predominant immunoglobulin (Ig) A and/or IgM deposits. Statistical analysis shows that glomerular deposits of IgG and C3, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and tubular atrophy are associated with renal insufficiency at the time of biopsy, and can be integrated into a pathologic index that has a high correlative value. Mesangiopathic glomerulonephritis is probably responsible for the high rates of non-diabetic end-stage renal disease seen in Navajo Indians.

  11. Rapidly progressive dementia due to bilateral internal carotid artery occlusion with infarction of the total length of the corpus callosum.

    PubMed

    Rabinstein, Alejandro A; Romano, Jose G; Forteza, Alejandro M; Koch, Sebastian

    2004-04-01

    The authors report a patient with rapidly progressive cognitive decline due to bilateral internal carotid artery occlusion (ICAO) resulting in multiple pathologically proven cerebral infarctions including the entire length of the corpus callosum. The gradual evolution of the deficits was suggestive of hemodynamic ischemia. Bilateral ICAO should be considered in the differential diagnosis of patients with rapidly cognitive decline. Although ICAO commonly spares the splenium, complete callosal infarction is possible in the presence of bilateral ICAO.

  12. S100A8/A9 (calprotectin) is critical for development of glomerulonephritis and promotes inflammatory leukocyte-renal cell interactions.

    PubMed

    Pepper, Ruth J; Wang, Hsu-Han; Rajakaruna, Gayathri K; Papakrivopoulou, Eugenia; Vogl, Thomas; Pusey, Charles D; Cook, H Terence; Salama, Alan D

    2015-05-01

    Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9(-/-)), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow-derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14(-/-) cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow-derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14(-/-) bone marrow-derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow-derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis.

  13. S100A8/A9 (Calprotectin) Is Critical for Development of Glomerulonephritis and Promotes Inflammatory Leukocyte–Renal Cell Interactions

    PubMed Central

    Pepper, Ruth J.; Wang, Hsu-Han; Rajakaruna, Gayathri K.; Papakrivopoulou, Eugenia; Vogl, Thomas; Pusey, Charles D.; Cook, H. Terence; Salama, Alan D.

    2015-01-01

    Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9−/−), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow–derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14−/− cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow–derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14−/− bone marrow–derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow–derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis. PMID:25759267

  14. Clinico-radiological diagnosis and grading of rapidly progressive osteoarthritis of the hip

    PubMed Central

    Zazgyva, Ancuţa; Gurzu, Simona; Gergely, István; Jung, Ioan; Roman, Ciprian O.; Pop, Tudor S.

    2017-01-01

    Abstract Due to the current lack of standard definitions for rapidly progressive osteoarthritis of the hip (RPOH) in the literature, this observational study aimed to describe new diagnostic criteria and a grading system for the disease. From a consecutive series of patients undergoing total hip replacement, 2 groups were selected: 1 with RPOH and 1 with primary hip osteoarthritis (POH), and their clinical, paraclinical, and demographic data were compared. The newly proposed clinico-radiological diagnostic criteria are based on characteristics of pain, joint mobility, and radiological assessment. The radiological grading system's inter- and intraobserver reliability was assessed through serial evaluations by 2 blinded reviewers. From the total 863 cases, 82 cases (9.5%) of RPOH were identified and compared with 107 cases of POH. Mean age and disease bilaterality were similar, with a predominance of female patients in the RPOH group (P = 0.03). There were significant differences between the 2 groups in disease onset and aggravation, and intraoperative blood loss. The grading system showed significant inter- and intraobserver agreement (weighted kappa 0.93, and 0.89). Our study presents distinctive, easily recognizable clinico-radiological characteristics of RPOH and confirmed the inter- and intraobserver reliability of the newly proposed grading system. PMID:28328832

  15. Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis.

    PubMed

    Xu, Y; Yang, C S; Li, Y J; Liu, X D; Wang, J N; Zhao, Q; Xiao, W G; Yang, P T

    2016-01-01

    Clinically amyopathic dermatomyositis (CADM) is a unique subset of dermatomyositis, showing a high incidence of lung involvements. The aim of this study is to identify risk factors, other than melanoma differentiation-associated protein (MDA)-5, for developing rapidly progressive-interstitial lung disease (RP-ILD) in patients with CADM. Forty CADM patients, in whom 11 patients developed RP-ILD, were enrolled. Clinical features and laboratory findings were compared between the patients with and without RP-ILD. We found that skin ulceration, CRP, serum ferritin, anti-MDA5 Ab, and lymphocytopenia were significantly associated with ILD. Multivariate logistic regression analysis indicated that anti-MDA5 Ab(+), elevated CRP, and decreased counts of lymphocyte were independent risk factors for RP-ILD, which can provide a precise predict for RP-ILD in CADM patients. When anti-MDA5 Ab(+) was removed from the multivariate regression model, using skin ulcerations, elevated serum ferritin and decreased counts of lymphocyte can also precisely predict RP-ILD. Except for MDA-5, more commonly available clinical characteristics, such as skin ulcerations, serum ferritin, and count of lymphocyte may also help to predict prognosis in CADM.

  16. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    NASA Astrophysics Data System (ADS)

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-09-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862) while for subacute ILD patients (disease duration 3–6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.

  17. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis.

    PubMed

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-09-12

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3-6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.

  18. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    PubMed Central

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-01-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862); while for subacute ILD patients (disease duration 3–6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM. PMID:27615411

  19. Opsonic antibody activity against Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

    PubMed Central

    Sjöström, K; Darveau, R; Page, R; Whitney, C; Engel, D

    1992-01-01

    Actinobacillus actinomycetemcomitans has been closely associated with early-onset, severe periodontitis, and such patients often have serum immunoglobulin G (IgG) antibodies reactive with antigens of this gram-negative pathogen. We examined the functionality and potential importance of these antibodies. The opsonic activity against A. actinomycetemcomitans of sera from 30 patients with rapidly progressive periodontitis (RPP) and from 28 periodontally normal subjects was tested by using polymorphonuclear leukocyte (PMN) chemiluminescence and bactericidal assays. Peak chemiluminescence values correlated strongly with killing observed in the PMN-dependent bactericidal assay (r = 0.88; P < 0.001). Neither the mean IgG titer nor the mean peak chemiluminescence differed significantly between the two groups. However, when the relationship between chemiluminescence and titer was examined, regression analysis showed that antibodies present in low-titer normal sera were significantly more effective at opsonizing A. actinomycetemcomitans than antibodies present in low-titer RPP patient sera (P = 0.04). Thus, periodontally normal individuals may be better able than RPP patients to clear A. actinomycetemcomitans in early stages of colonization, and anti-A. actinomycetemcomitans antibodies in RPP patients may be relatively ineffective in preventing infection by this organism. PMID:1398993

  20. Features of whey protein concentrate supplementation in children with rapidly progressive HIV infection.

    PubMed

    Moreno, Y F; Sgarbieri, V C; da Silva, M N; Toro, A A D C; Vilela, M M S

    2006-02-01

    HIV infection is associated with subnormal GSH levels. An increase in glutathione levels has been observed in HIV-infected adults under oral whey protein supplementation. We studied the features associated with a whey protein concentrate supplementation in children with rapidly progressive AIDS. A prospective double-blind clinical trial was carried out for 4 months with 18 vertically HIV-infected children (1.98-6.37 years), under antiretroviral therapy, who had received whey protein, maltodextrin (placebo) or none. Erythrocyte glutathione concentration, T lymphocyte counts (CD4+ and CD8+) and occurrence of associated co-infections were evaluated. Wilcoxon's and Fischer's Exact tests were used to assess differences between whey protein-supplemented and control (placebo and non-supplemented) groups. A significant median increase of 16.14 mg/dl (p = 0.018) in erythrocyte glutathione levels was observed in the whey protein-supplemented group; the TCD4/CD8 lymphocyte ratio showed a non significant increase and lower occurrence of associated co-infections was also observed. In conclusion, whey protein concentrate supplementation can stimulate glutathione synthesis and, possibly, decrease the occurrence of associated co-infections.

  1. Complete Genome Sequence of Mycobacterium tuberculosis Strain MtURU-001, Isolated from a Rapidly Progressing Outbreak in Uruguay

    PubMed Central

    Greif, Gonzalo; Iraola, Gregorio; Berná, Luisa; Coitinho, Cecilia; Rivas, Carlos M.; Naya, Hugo

    2014-01-01

    Despite efficient control programs, large clonal outbreaks of tuberculosis (TB) may arise in low-risk populations. Recently, an unusual TB outbreak was reported in Uruguay, reaching an elevated disease attack rate (53 to 69%). Here, we report the genome sequence of the Mycobacterium tuberculosis strain associated with this rapidly progressing outbreak, named MtURU-001. PMID:24459279

  2. Membranoproliferative glomerulonephritis presenting as arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis: a case report.

    PubMed

    Park, Chuiyoung; Choi, Seung Won; Kim, Misung; Park, Jongha; Lee, Jong Soo; Chung, Hyun Chul

    2014-10-22

    Hypocomplementemic urticarial vasculitis syndrome is a rare disorder characterized by chronic urticarial vasculitis, arthralgia, arthritis, and hypocomplementemia. Previously, only six patients with concomitant hypocomplementemic urticarial vasculitis syndrome, Jaccoud's arthropathy, and valvular heart disease have been reported. A 30-year-old Korean man presented with hypocomplementemic urticarial vasculitis syndrome. In addition to urticarial cutaneous lesions, he experienced polyarthralgia and arthritis that resulted in progressive deformity of the joints of both hands, cardiac valvulopathy with mitral, tricuspid, and aortic regurgitation, and intermittent neck swelling with laryngeal edema. He also developed nephritis with azotemia. His renal biopsy results revealed membranoproliferative glomerulonephritis, type I. He showed a partial response to a combination therapy of steroid, cyclophosphamide, and mycophenolate mofetil. We describe, to the best of our knowledge, the first case of glomerulonephritis presenting a arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis syndrome. A combination of corticosteroids, cyclophosphamide, and mycophenolate mofetil appear to be a safe and effective treatment for nephropathy, however are less effective for cutaneous vasculitis, cardiac valvulopathy, and arthropathy.

  3. Membranoproliferative glomerulonephritis presenting as arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis: a case report

    PubMed Central

    2014-01-01

    Introduction Hypocomplementemic urticarial vasculitis syndrome is a rare disorder characterized by chronic urticarial vasculitis, arthralgia, arthritis, and hypocomplementemia. Previously, only six patients with concomitant hypocomplementemic urticarial vasculitis syndrome, Jaccoud’s arthropathy, and valvular heart disease have been reported. Case presentation A 30-year-old Korean man presented with hypocomplementemic urticarial vasculitis syndrome. In addition to urticarial cutaneous lesions, he experienced polyarthralgia and arthritis that resulted in progressive deformity of the joints of both hands, cardiac valvulopathy with mitral, tricuspid, and aortic regurgitation, and intermittent neck swelling with laryngeal edema. He also developed nephritis with azotemia. His renal biopsy results revealed membranoproliferative glomerulonephritis, type I. He showed a partial response to a combination therapy of steroid, cyclophosphamide, and mycophenolate mofetil. Conclusions We describe, to the best of our knowledge, the first case of glomerulonephritis presenting a arthropathy and cardiac valvulopathy in hypocomplementemic urticarial vasculitis syndrome. A combination of corticosteroids, cyclophosphamide, and mycophenolate mofetil appear to be a safe and effective treatment for nephropathy, however are less effective for cutaneous vasculitis, cardiac valvulopathy, and arthropathy. PMID:25339233

  4. A case of multicentric Castleman's disease with membranoproliferative glomerulonephritis type 3-like lesion.

    PubMed

    Nagai, Kei; Usui, Joichi; Noguchi, Kazuyuki; Unai, Kei; Hiwatashi, Akira; Arakawa, Yoh; Togashi, Amane; Morito, Naoki; Saito, Chie; Yoh, Keigyou; Tsuruoka, Syuichi; Kojima, Hiroshi; Aita, Kumi; Nagata, Michio; Yamagata, Kunihiro

    2011-11-01

    Renal involvement is a significant complication of multicentric Castleman's disease (MCD) and various glomerular involvements have been reported. A 45-year-old Japanese man presented with persistent proteinuria, with lymphadenopathy and hypergammaglobulinemia. He had been diagnosed 4 years previously with MCD. As his renal impairment had progressed to renal failure, he underwent a renal biopsy. Histology revealed diffuse and global membranous lesions with large and heterogeneous epimembranous deposits. In addition, mesangial cell proliferation and focal extracapillary lesions were found. Under immunofluorescence, granular staining for anti-IgG, IgG1, IgG2 and IgA was strongly positive in the capillary loop, and weakly positive in the mesangium. As such, there was a diversity of histological features. Our perspective with regard to pathogenesis is that the formation of the immune-complex contributed to the membranoproliferative glomerulonephritis type 3-like lesion. This histological multiform with MCD is valuable for increasing our understanding of the mechanism for onset of immune-complex glomerular deposition and cellular proliferation of glomerulonephritis.

  5. [The x-ray diagnosis of a predisposition to nephrogenic pulmonary edema in glomerulonephritis patients].

    PubMed

    Kamenetskiĭ, M S; Pervak, M B; Tkachenko, G D; Vernikov, B L

    1995-01-01

    To develop criteria for determining predisposition to pulmonary edema in patients with glomerulonephritis, clinical, laboratory and X-ray examinations were made in 697 patients with glomerulonephritis at different stages of its development. X-ray examination included chest tele X-ray and its densitometric analysis. Twenty two patients underwent computerized tomography with histographic analysis. In 106 patients, X-ray findings were compared with the volume of circulating blood, cardiac and stroke indices. Changes in the lungs and pleural cavities were found in 22.7%, pulmonary edema was revealed in 15.7% of the patients. The prognostically unfavourable criteria for the development of pulmonary edema were found to be Stage II pulmonary venous hypertension with hypervolemia and peripheral edemas. The densitometrically detected increase in the density of the lower lungs in patients with Stage II venous hypertension suggests early manifestations of interstitial edema of the lung and the narrowing of the histogram angle limited by its ascending and descending lines is indicative of the fact that interstitial edema progresses to alveolar one.

  6. Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

    PubMed

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Chang, Anthony; Mohan, Chandra; Larin, Kirill V

    2016-08-01

    Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.

  7. Rapid progressive interstitial lung disease as initial manifestation of primary Sjögren’s syndrome: a case report

    PubMed Central

    Lin, Yihua; Yi, Qun; Cheng, Deyun

    2014-01-01

    Primary Sjögren’s syndrome is a chronic inflammatory disorder with many extraglandular organ systems involved, including the lungs. Diffuse interstitial lung disease is the most serious form of lung involvement. Parenchymal lung involvement in primary Sjögren’s syndrome is usually manifested by cough and/or slowly progressive dyspnea and most of the cases present as chronic course. We describe here a case of primary Sjögren’s syndrome who presented as rapid progressive interstitial lung disease. Improvement was obtained with treatment of corticosteroids and ventilatory support at early time. To the best of our knowledge, this is the first report documenting primary Sjögren’s syndrome initially presenting as rapid progressive interstitial lung disease and it enriches our understanding of the clinical manifestations of primary Sjögren’s syndrome. PMID:25664130

  8. Neurocognitive Features Distinguishing Primary Central Nervous System Lymphoma from Other Possible Causes of Rapidly Progressive Dementia

    PubMed Central

    Deutsch, Mariel B.; Mendez, Mario F.

    2015-01-01

    Objective Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). Background PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. Methods We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267–271). Results Median age was 66 (range 41–81); 70% were men. Time from symptom onset to evaluation was < 6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF ± 14-3-3 protein. Conclusions Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White-matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment. PMID:25812125

  9. Clinicopathological Correlations and Concomitant Pathologies in Rapidly Progressive Dementia: A Brain Bank Series.

    PubMed

    Grau-Rivera, Oriol; Gelpi, Ellen; Nos, Carlos; Gaig, Carles; Ferrer, Isidro; Saiz, Albert; Lladó, Albert; Molinuevo, José L; Graus, Francesc; Sánchez-Valle, Raquel

    2015-01-01

    Rapidly progressive dementia (RPD) is caused by a heterogeneous group of both neurodegenerative and non-neurodegenerative disorders. The presence of concomitant pathologies, mainly Alzheimer's disease (AD), may act as a confounding variable in the diagnostic process of this group of diseases. We aimed to describe clinicopathological features, including Alzheimer's co-pathology, and diagnostic accuracy in a postmortem series of RPD. Retrospective analysis of 160 brain donors with RPD (defined as 2 years of disease duration from the first symptom to death) registered at the Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, from 2001 to 2011. Prion diseases were the most frequent neuropathological diagnosis (67%), followed by non-prion neurodegenerative pathologies (17%), mostly AD and dementia with Lewy bodies, and non-neurodegenerative diseases (16%). We observed clinicopathological diagnostic agreement in 94% of the patients with prion RPD but only in 21% of those with non-prion RPD. Four patients with potentially treatable disorders were diagnosed, while still alive, as having Creutzfeldt-Jakob disease. Concomitant pathologies were detected in 117 (73%). Among all RPD cases, 51 presented moderate or frequent mature β-amyloid plaques (neuritic plaques), which are considered to be associated with positive amyloid biomarkers in vivo. Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers. © 2015 S. Karger AG, Basel.

  10. Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.

    PubMed

    Deutsch, Mariel B; Mendez, Mario F

    2015-03-01

    Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein. Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

  11. Injury markers but not amyloid markers are associated with rapid progression from mild cognitive impairment to dementia in Alzheimer's disease.

    PubMed

    van Rossum, Ineke A; Visser, Pieter Jelle; Knol, Dirk L; van der Flier, Wiesje M; Teunissen, Charlotte E; Barkhof, Frederik; Blankenstein, Marinus A; Scheltens, Philip

    2012-01-01

    Alzheimer's disease (AD) is a common cause of mild cognitive impairment (MCI). However, the time between the diagnosis of MCI and the diagnosis of dementia is highly variable. In this study we investigated which known risk factors and biomarkers of AD pathology were associated with rapid progression from MCI to dementia. Of the 203 subjects with MCI, 91 progressed to AD-type dementia and were considered to have MCI-AD at baseline. Subjects with MCI-AD were older, more frequently female and carrier of the APOE-ε4 allele, had lower scores on the Mini-Mental State Examination (MMSE), more medial temporal lobe atrophy (MTA) and lower levels of Aβ1-42 and increased levels of t-tau and p-tau in the cerebrospinal fluid (CSF) compared to subjects without AD-type dementia at follow up. Of the 91 subjects with MCI-AD, we had data available of CSF (n = 56), MTA (n = 76), and APOE-genotype (n = 63). Among the subjects with MCI-AD, MTA (hazard ratio (HR) 2.2, p = 0.004) and low MMSE score (HR 2.0 p = 0.007) were associated with rapid progression to dementia. High CSF t-tau (HR 1.7, p = 0.07) and p-tau (1.7, p = 0.08) tended to be associated with rapid progression to dementia. CSF Aβ1-42, APOE status, age, gender, and educational level were not associated with time to dementia. Our findings implicate a different role for biomarkers in diagnosis and prognosis of MCI-AD. While amyloid markers can be used to identify MCI-AD, injury markers may predict rapid progression to dementia.

  12. Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis

    PubMed Central

    Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie

    2016-01-01

    Abstract The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID:27258503

  13. Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis.

    PubMed

    Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie

    2016-05-01

    The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome.A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome.The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%).In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options.

  14. Serum immune responses predict rapid disease progression among children with Crohn's disease: immune responses predict disease progression.

    PubMed

    Dubinsky, Marla C; Lin, Ying-Chao; Dutridge, Debra; Picornell, Yoana; Landers, Carol J; Farrior, Sharmayne; Wrobel, Iwona; Quiros, Antonio; Vasiliauskas, Eric A; Grill, Bruce; Israel, David; Bahar, Ron; Christie, Dennis; Wahbeh, Ghassan; Silber, Gary; Dallazadeh, Saied; Shah, Praful; Thomas, Danny; Kelts, Drew; Hershberg, Robert M; Elson, Charles O; Targan, Stephan R; Taylor, Kent D; Rotter, Jerome I; Yang, Huiying

    2006-02-01

    Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.

  15. Serum Immune Responses Predict Rapid Disease Progression among Children with Crohn’s Disease: Immune Responses Predict Disease Progression

    PubMed Central

    Dubinsky, Marla C.; Lin, Ying-Chao; Dutridge, Debra; Picornell, Yoana; Landers, Carol J.; Farrior, Sharmayne; Wrobel, Iwona; Quiros, Antonio; Vasiliauskas, Eric A.; Grill, Bruce; Israel, David; Bahar, Ron; Christie, Dennis; Wahbeh, Ghassan; Silber, Gary; Dallazadeh, Saied; Shah, Praful; Thomas, Danny; Kelts, Drew; Hershberg, Robert M.; Elson, Charles O.; Targan, Stephan R.; Taylor, Kent D.; Rotter, Jerome I.; Yang, Huiying

    2007-01-01

    BACKGROUND AND AIM Crohn’s disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. METHODS Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. RESULTS Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5–80.4); p = 0.03). Pediatric CD patients positive for ≥1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). CONCLUSIONS The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients. PMID:16454844

  16. Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

    PubMed

    Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

    2016-12-01

    We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

  17. Rapid progressive course of later-onset Pompe disease in Chinese patients.

    PubMed

    Yang, Chih-Chao; Chien, Yin-Hsiu; Lee, Ni-Chung; Chiang, Shu-Chuan; Lin, Shuan-Pei; Kuo, Yung-Ting; Chen, Shun-Sheng; Jong, Yuh-Jyh; Hwu, Wuh-Liang

    2011-11-01

    Pompe disease presents with a wide variety of phenotypes ranging from a fatal disease in infancy (the infantile-onset form) to other milder later-onset forms. Currently, the clinical manifestations in Chinese patients with later-onset Pompe disease are still not well understood. Fifteen Chinese patients who were clinically diagnosed with Pompe disease at later than one year of age at the National Taiwan University Hospital from 1993 to 2009 were included in this study. Confirmatory diagnosis included both biochemical and molecular tests. Patient outcomes after recombinant human acid α-glucosidase (GAA) therapy were also evaluated by assessing the percentage of predicted forced vital capacity in the upright position, hours of daily ventilator use, and the functional status change using Walton Gardner Medwin Scale. The median age at symptom onset was 15 (12-35)years, and the median age at diagnosis was 21 (10-38)years. At the time of diagnosis or shortly after, 8 patients (53%) required mechanical ventilation. A quadriceps muscle biopsy from a 13-year-old boy already showed extensive glycogen storage and muscle fiber destruction. Mutation analysis revealed that the two dual mutations in the GAA gene c.[1935C>A; 1726G>A] (p.[D645E; G576S]) and c.[2238G>C; 1726G>A] (p.[W746C; G576S]) represented 66.5% of the mutated chromosomes. Using mutagenesis, we showed that the p.G576S pseudodeficiency mutation significantly decreased the residual enzyme activity of p.W746C. Most patients responded poorly to recombinant human GAA. Chinese patients with later-onset Pompe disease often showed onset of symptoms in their second decade of life with rapid disease progression, which is probably due to a specific pattern of GAA gene mutation. Therefore, early diagnosis and early treatment would be necessary to improve the prognosis of these patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Adjunctive effects of cyclosporine and macrolide in rapidly progressive cryptogenic organizing pneumonia with no prompt response to steroid.

    PubMed

    Lee, Jaehee; Cha, Seung Ick; Park, Tae In; Park, Jae Yong; Jung, Tae Hoon; Kim, Chang Ho

    2011-01-01

    Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. However, it can rapidly worsen and lead to respiratory failure that is refractory to corticosteroids. Adjunctive drugs have been used in refractory cases with various outcomes, but treatment experience is still lacking. We present a case of rapidly progressive COP accompanying air leak syndrome, which showed no prompt response to corticosteroids alone but gradual improvement with the addition of cyclosporine and macrolide. This case report supports the existing literature suggesting that an early therapeutic trial of this drug combination might be considered in COP patients whose condition worsens despite corticosteroid administration.

  19. Traumatic ventricular septal rupture associated with rapid progression of heart failure despite low Qp/Qs ratio: a case report.

    PubMed

    Murakawa, Kosuke; Yoshida, Susumu; Okada, Takayuki; Toyoshima, Chie; Yuyama, Reisuke; Minato, Naoki; Shiojima, Ichiro

    2016-04-12

    Ventricular septal rupture (VSR) secondary to blunt chest trauma is rare and associated with a diverse range of symptoms and clinical courses as well as disease severity. We present a case of traumatic VSR in which rapid progression of heart failure was observed in spite of relatively low pulmonary to systemic blood flow (Qp/Qs) ratio. A 40-year-old male was transported to the emergency department approximately 12 h after blunt chest trauma. VSR was diagnosed by echocardiography, and right heart catheterization revealed a Qp/Qs ratio of 1.52. Although medical treatment was initially attempted, subsequent rapid progression of heart failure necessitated emergent surgical repair of VSR. Because small, asymptomatic VSR often close spontaneously, surgical repair of traumatic VSR is indicated when the shunt rate is relatively large or heart failure is present. However, the present case highlights the need to consider emergent surgical repair of traumatic VSR, even when the shunt rate is relatively small.

  20. Anti-MDA-5 antibody-positive bullous dermatomyositis with palmar papules complicating rapidly progressive interstitial lung disease.

    PubMed

    Fujimoto, Noriki; Honda, Shinichiro; Wakabayashi, Makiko; Hamaguchi, Yasuhito; Fujimoto, Manabu; Tanaka, Toshihiro

    2016-07-01

    We present the first case of dermatomyositis showing both vesicle formation and palmar papules. The association of bullous formation and internal malignancy, and palmar papules and interstitial lung disease (ILD) is well known in dermatomyositis, respectively. This patient presented with vesicles; however, the immunoprecipitation assays detected anti-MDA-5 antibody and the patient complicated rapidly progressive ILD, but no malignancy. We propose that palmar papules might be regarded as more critical than blister formation.

  1. A case report of rapid progressive coarctation and severe middle aortic syndrome in an infant with Williams syndrome.

    PubMed

    Hall, E Kevin; Glatz, Jenifer; Kaplan, Paige; Kaplan, Bernard S; Hellinger, Jeffrey; Ernst, Linda; Gaynor, J William

    2009-01-01

    Williams syndrome is a genetic disorder caused by multiple contiguous gene deletions in chromosome 7. Presentation in early life is most often a result of luminal stenosis of right- and left-sided arterial vasculature. We report the case of a newborn infant who had a rapidly progressing diffuse form of arteriopathy that required two surgeries and one percutaneous balloon dilation within the first 2 months of her life.

  2. Rapidly-progressive catatonia responsive to zolpidem in a patient with ovarian teratoma-associated paraneoplastic encephalitis.

    PubMed

    Amorim, Edilberto; McDade, Eric M

    2016-08-01

    Psychiatric symptoms and catatonia are key components of the clinical presentation of paraneoplastic encephalitis; additionally symptoms can be long-lasting and often difficult to treat. We report a 73-year-old patient with rapidly progressive catatonia not responsive to immunotherapy, tumor resection, electroconvulsive therapy, or benzodiazepines who had significant improvement after zolpidem administration. This report suggests that zolpidem is an option in the treatment of patients with refractory catatonia and paraneoplastic encephalitis.

  3. Poststreptococcal glomerulonephritis in a patient with essential thrombocytosis.

    PubMed

    Ulusoy, Sukru; Ozkan, Gulsum; Sonmez, Mehmet; Mungan, Sevdegül; Köseoğlu, Rahman; Cansız, Muammer; Kaynar, Kübra

    2015-01-01

    In addition to being the main cause of glomerulonephritis in children, poststreptococcal glomerulonephritis (PSGN) has recently been shown in older patients, especially those with malignancy or diabetes mellitus. The pathogenesis of PSGN has been ascribed to activation of complement 3 (C3) of the alternative complement cascade which, along with immunoglobulin (Ig) G and IgM deposits, is observed in renal tissue. Our aim here is to discuss the probable causes of PSGN developing with isolated IgM deposition in a 52-year-old patient with essential thrombocytosis followed-up over the previous 3.5 years. These characteristics make our case the first to be reported in the literature.

  4. CD10 expression by melanoma cells is associated with aggressive behavior in vitro and predicts rapid metastatic progression in humans.

    PubMed

    Thomas-Pfaab, Marianne; Annereau, Jean-Philippe; Munsch, Coline; Guilbaud, Nicolas; Garrido, Ignacio; Paul, Carle; Brousset, Pierre; Lamant, Laurence; Meyer, Nicolas

    2013-02-01

    No biological or molecular marker of primary melanoma tumor cells has been shown to predict clinical outcome in melanoma. To determine whether CD10, CD133, nestin and CD20 may evaluate the prognosis of melanoma. The differential expression of these molecules was assessed in pairs of cell lines. We evaluated, by both immunohistochemical staining and RT-qPCR, their expression in a cohort of 32 patients (68 samples) with a history of metastatic melanoma, divided into two groups according to their clinical outcome profile. CD10 over expression in cancer cell lines was associated with more aggressive behavior in vitro. A CD10-positive staining was more frequent in patients in the "rapidly progressive" group than those in the "long survivor" group (23/35 versus 2/18, p<10(-4)). CD10 expression was associated with a lower median overall survival (1.15 year - IQR: [0.50-2.58] versus 4.27 - IQR: [1.66-6.33]; p=10(-4)). The Odds Ratio of displaying a "rapidly progressive" melanoma when tumor cells expressed CD10 was 15 (95% confidence interval: [3-78]). After adjusting for confounding factors, CD10 expression in melanoma tumor cells remained associated with an increased risk of death and more rapid disease progression (p=6×10(-4); HR=3.71). CD10 may predict clinical outcome in melanoma patients. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary hemorrhage in the course of pulmonary tuberculosis.

    PubMed

    Hsieh, Yao-Peng; Wen, Yao-Ko

    2012-01-01

    A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

  6. Primary glomerulonephritis: A review of important recent discoveries

    PubMed Central

    Floege, Jürgen

    2013-01-01

    The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect. PMID:26877924

  7. Membranous glomerulonephritis and Landry-Guillain-Barre syndrome.

    PubMed

    Murphy, B F; Gonzales, M F; Ebeling, P; Fairley, K F; Kincaid-Smith, P

    1986-10-01

    Two cases of idiopathic membranous glomerulonephritis associated with acute inflammatory demyelinating polyradiculoneuropathy (Landry-Guillian-Barre syndrome) are described. In both of the patients, the onset of the nephrotic syndrome coincided with the development of severe ascending sensorimotor neuropathy. Although this association has previously been reported in four other isolated cases, it is not generally recognized by nephrologists and may be of significance in the future understanding of the immunopathogenesis of both diseases.

  8. Plasmodium vivax malaria associated with acute post infectious glomerulonephritis.

    PubMed

    Kanodia, Kamal V; Vanikar, Aruna V; Kute, Vivek Balkrishna; Trivedi, Hargovind L

    2013-08-01

    Malaria remains a major health problem in many parts of the world leading to high morbidity and mortality related to renal dysfunction and relapsing nature of Plasmodium vivax malaria. Acute renal failure occurs commonly in Plasmodium falciparum malaria, although its rare occurrences have been reported in P. vivax malaria also. We reported a rare case of P. vivax malaria monoinfection associated with acute post infectious glomerulonephritis.

  9. Primary glomerulonephritis: A review of important recent discoveries.

    PubMed

    Floege, Jürgen

    2013-09-01

    The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect.

  10. Rapid Progression of Sporadic ALS in a Patient Carrying SOD1 p.Gly13Arg Mutation

    PubMed Central

    Kim, Myung-Jin; Bae, Jae-Han; Kim, Jeong-Min; Kim, Hye Ryoun; Yoon, Byung-Nam; Sung, Jung-Joon

    2016-01-01

    Amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease, is pathologically characterized by progressive loss of the upper and lower motor neurons. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for about 20% of familial ALS cases and a small percentage of sporadic ALS (SALS) cases, and have revealed a validated genotype-phenotype correlation. Herein, we report a p.Gly13Arg mutation in SOD1 exon 1 in a patient with SALS who presented with a rapidly progressive course, predominantly affecting the lower motor neurons. A 48-year-old man presented with progressive weakness and muscle atrophy of the left upper and lower limbs, followed by muscle fasciculation and cramping. The clinical features of the patient were clearly suggestive of ALS, and implied a sporadic form with rapid progression, predominantly affecting the lower motor neurons. Sequencing of the SOD1 gene by PCR revealed a missense mutation of G to C (c.37G>C) in exon 1, and amino acid substitution of glycine by arginine (p.Gly13Arg). This is the first case identifying the p.Gly13Arg mutation of SOD1 in the Korean population, and clinical assessments of this patient revealed a different phenotype compared with other cases. PMID:28035186

  11. Sustained remission of antineutrophil cytoplasmic antibody-mediated glomerulonephritis and nephrotic syndrome in mixed connective tissue disease.

    PubMed

    Konstantinov, Konstantin N; Harris, Alexis A; Barry, Marc; Murata, Glen H; Tzamaloukas, Antonios H

    2013-08-01

    A woman diagnosed with mixed connective tissue disease (MCTD) developed an anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) and nephrotic syndrome with normal serum creatinine. Percutaneous kidney biopsy showed pauci-immune glomerulonephritis with superimposed immune complex deposition. After treatment with cyclophophamide and prednisone, proteinuria decreased progressively to a level of 0.4 g/g creatinine, ANCA became undetectable, while serum creatinine remained normal seven years after the beginning of treatment. Sustained remission of nephrotic proteinuria with preserved renal function may follow treatment of ANCA-mediated disease developing in patients with MCTD.

  12. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, January--March 1994

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1994-06-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is required both, for the fundamental determination of kinetic parameters of coal devolatilization, and to refine existing devolatilization sub-models used in comprehensive coal combustion codes. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: the specific heat of coal/char during devolatilization, the heat of thermal decompose ion of the coal, the specific heat capacity of tars, and the heat of vaporization of tars. Progress reports are presented for the following tasks: heat of devoltalization of voltaile coal samples; specific heat and heat of fusion of tars; heat of vaporization of tars from rapid heating; and morphological characterization of coal/char samples as a function of extent of devoltalization.

  13. Human parvovirus B19-induced acute glomerulonephritis: a case report.

    PubMed

    Shimohata, Homare; Higuchi, Takashi; Ogawa, Yujiro; Fujita, Shogo; Nagai, Miho; Imaizumi, Masahiro; Maruyama, Hiroshi; Hirayama, Kouichi; Kobayashi, Masaki

    2013-01-01

    Human parvovirus B19 (HPV B19) infection is well known as a cause of erythema infectiosum in children. Acute glomerulonephritis due to HPVB19 infection is rarely observed in adults. Here, we present the case of a 45-year-old female who showed acute glomerulonephritis induced by HPVB19 infection with various autoantibodies. She had proteinuria (175 mg/g creatinine) and hematuria (20-29 erythrocytes per high-power field) in a urinalysis, and various autoantibodies such as antinuclear antibodies, proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA), antiglomerular basement membrane (GBM) antibodies, and anticardiolipin antibodies in a blood examination. A renal biopsy showed that endocapillary proliferative glomerulonephritis comprised of mononuclear cell infiltration. By using immunofluorescence microscopy, IgG, IgA, IgM, C3, C4, and C1q deposits were detected mainly in glomerular capillaries. Electron-dense deposits were detected in the subendothelial area and mesangial area by using electron microscopy. All symptoms and abnormal laboratory data were self-improved. Our patient's case may provide a clue to the etiology of ANCA-associated vasculitis or lupus nephritis.

  14. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

    PubMed

    Rabasco, Cristina; Cavero, Teresa; Román, Elena; Rojas-Rivera, Jorge; Olea, Teresa; Espinosa, Mario; Cabello, Virginia; Fernández-Juarez, Gema; González, Fayna; Ávila, Ana; Baltar, José María; Díaz, Montserrat; Alegre, Raquel; Elías, Sandra; Antón, Monserrat; Frutos, Miguel Angel; Pobes, Alfonso; Blasco, Miguel; Martín, Francisco; Bernis, Carmen; Macías, Manuel; Barroso, Sergio; de Lorenzo, Alberto; Ariceta, Gema; López-Mendoza, Manuel; Rivas, Begoña; López-Revuelta, Katia; Campistol, José María; Mendizábal, Santiago; de Córdoba, Santiago Rodríguez; Praga, Manuel

    2015-11-01

    C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

  15. Urinary neopterin: an immune activation marker in mesangial proliferative glomerulonephritis.

    PubMed

    Ueno, Kazuyuki; Shimizu, Masaki; Yokoyama, Tadafumi; Ishikawa, Sayaka; Tasaki, Yuko; Inoue, Natsumi; Sugimoto, Naotoshi; Ohta, Kazuhide; Yachie, Akihiro

    2015-04-01

    To clarify in vivo neopterin expression within the human kidney and its clinical role as a biomarker for immune complex-mediated mesangial proliferative glomerulonephritis (mesPGN) in children. We examined neopterin expression within the kidneys of 14 patients with mesPGN and five patients with minimal changes. We also measured the serum and urinary neopterin levels in fourteen patients with mesPGN and sixteen age-matched healthy controls and correlated the histological findings and clinical features. Neopterin expression was observed within the distal tubular epithelial cells. It was induced within the glomerular endothelial cells and infiltrated CD68-positive macrophages in the glomeruli and interstitial areas. Furthermore, urinary neopterin levels were significantly elevated and positively correlated with histopathological findings and the degree of proteinuria. These findings indicate that increased urinary neopterin may reflect macrophage activation and active inflammation within the kidney in immune complex-mediated glomerulonephritis. Neopterin may thus represent a useful biomarker of immune complex-mediated glomerulonephritis in the clinical setting.

  16. [Nephrotic syndrome presumable caused by an complex glomerulonephritis (author's transl)].

    PubMed

    Seelig, H P; Seelig, R; Fischer, K; Maurer, R; Safer, A; Schnitzlein, W

    1977-04-29

    The nephrotic syndrome presumably caused by an immune complex glomerulonephritis constitutes a major side effect attendant upon chronic administration of penicillamine. The possible induction of an immune-complex glomerulonephritis by penicillamine and its further development after stopping the drug was investigated in rats. --60 rats were fed perorally 2000 mg D-Penicillamine/kg BW/die resp. for a period of 8--44 days. Following unilateral nephrectomy the animals were observed for further 5 weeks. --Dependent to the time of penicillamine application there was an increasing deposition of IgG and C3 in a granular pattern along the glomerular basement membrane and within the mesangium. The IgG deposits initially were focal and segmental later on diffuse and global in distribution. 5 weeks after stopping the penicillamine the immune globulin deposits had disappeared completely or at least in part as did the mild focal glomerulonephritis and the moderate proteinuria which developed in some animals after a 44 day treatment with penicillamine. --The results confirm the hitherto presumed immune complex pathogenesis of the penicillamine induced nephropathy. The disappearance of the immunoglobulins deposited and of proteinuria stopping penicillamine alludes the good prognosis of this kind of nephropathy.

  17. Molecular Mapping of the Goodpasture's Epitope for Glomerulonephritis

    PubMed Central

    Bolton, W. Kline; Chen, Lanlin; Hellmark, Thomas; Fox, Jay; Wieslander, Jorgen

    2005-01-01

    Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of α3 type IV collagen (α3(IV)NC1) and non-nephritogenic α1(IV)NC1. CPs with aminoterminal α3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an α1(IV)NC1 CP with 69AA of α3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an α1(IV)NC1 with nine AA of α3(IV)NC1 (binding). GBM, S2 and D3 induced EAG. GBM immunized rats had intense IgG deposits but S2 and D3 rats had minimal deposits. A 13 mer rat peptide encompassing the aminoterminal site induced EAG sans antibody, while peptides not encompassing the region failed to induce GN. Asparagine at position 19 rather than isoleucine was essential for disease induction. These studies define critical limited AA sequences of α3(IV)NC1 associated with glomerulonephritis without antibody, and demonstrate that this region contains a T-cell epitope responsible for induction of glomerulonephritis. PMID:16555617

  18. The classification of glomerulonephritis in systemic lupus erythematosus revisited.

    PubMed

    Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio

    2004-02-01

    The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

  19. The classification of glomerulonephritis in systemic lupus erythematosus revisited.

    PubMed

    Weening, Jan J; D'Agati, Vivette D; Schwartz, Melvin M; Seshan, Surya V; Alpers, Charles E; Appel, Gerald B; Balow, James E; Bruijn, Jan A; Cook, Terence; Ferrario, Franco; Fogo, Agnes B; Ginzler, Ellen M; Hebert, Lee; Hill, Gary; Hill, Prue; Jennette, J Charles; Kong, Norella C; Lesavre, Philippe; Lockshin, Michael; Looi, Lai-Meng; Makino, Hirofumi; Moura, Luiz A; Nagata, Michio

    2004-02-01

    The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

  20. Rapidly progressing bilateral cataracts in a patient with beta thalassemia and pellagra.

    PubMed

    Athanasiadis, Ioannis; Konstantinidis, Aristeidis; Kyprianou, Ioannis; Robinson, Rosemary; Moschou, Vaia; Kouzi-Koliakos, Kokkona

    2007-09-01

    Soon after the diagnosis of pellagra in a 20-year-old patient with beta thalassemia, bilateral intumescent cataracts rapidly developed. We believe the patient's crystalline lenses were at an increased oxidative state due to iron overload from the thalassemia. Depletion of the lens epithelial cells of an important antioxidative agent (glutathione) as a result of niacin (vitamin B3) deficiency due to pellagra reduced the antioxidative capacity of the lenses. The oxidative damage led to rapid development of cataracts.

  1. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect

    Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  2. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study.

    PubMed

    Collins, Peter W; Lilley, Graeme; Bruynseels, Daniel; Laurent, David Burkett-St; Cannings-John, Rebecca; Precious, Elizabeth; Hamlyn, Vincent; Sanders, Julia; Alikhan, Raza; Rayment, Rachel; Rees, Alexandra; Kaye, Abigail; Hall, Judith E; Paranjothy, Shantini; Weeks, Andrew; Collis, Rachel E

    2014-09-11

    This prospective, observational study investigated the utility of Fibtem A5 and Clauss fibrinogen as predictors of progression of postpartum hemorrhage (PPH). A consecutive cohort of 356 women experiencing 1000 to 1500 mL PPH was recruited. Fibtem and fibrinogen were measured and subsequent transfusions, invasive procedures, and bleed volume recorded. Women progressing to 8 U blood products (red blood cells [RBCs] + fresh frozen plasma [FFP] + platelets) had a median (interquartile range) fibrinogen and Fibtem A5 of 2.1 (1.8-3.4) g/L and 12 (7-17) mm, respectively, compared with 3.9 (3.2-4.5) and 19 (17-23) for those not progressing. On multivariate analysis, Fibtem was an independent predictor for progression to bleeds >2500 mL (95% confidence interval [CI], 0.85 [0.77-0.95]). Receiver operating characteristic area under the curve (95% CI) for progression to RBC transfusion was 0.67 (0.60-0.74) for fibrinogen and 0.61 (0.54-0.68) for Fibtem, and progression to >2500 mL was 0.71 (0.61-0.81) and 0.75 (0.66-0.85) for fibrinogen and Fibtem, respectively. Fibtem A5 <10 mm was associated with more prolonged bleeds (median [95% CI], 127 [44-210] compared with 65 [59-71] minutes; P = .018) and longer stay in the high-dependency unit (23.5 [18.4-28.5] compared with 10.8 [9.7-11.8] hours). Fibtem is a rapidly available early biomarker for progression of PPH.

  3. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions.

    PubMed

    Hacker, Jill K

    2017-03-01

    Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735-743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. Copyright © 2017 American Society for Microbiology.

  4. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions

    PubMed Central

    2016-01-01

    ABSTRACT Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735–743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. PMID:28003421

  5. Developing Learning Progressions in Support of the New Science Standards: A RAPID Workshop Series

    ERIC Educational Resources Information Center

    Rogat, Aaron

    2011-01-01

    The hypothetical learning progressions presented here are the products of the deliberations of two working groups of science education researchers, each group also including a state science curriculum supervisor, organized by the Consortium for Policy Research in Education (CPRE), with support from the National Science Foundation. Their charge was…

  6. Quickly progressive amyotrophy of the thigh: An unusual cause of rapid chondrolysis of the knee.

    PubMed

    Ferrari, Maeva; Louati, Karine; Miquel, Anne; Behin, Anthony; Benveniste, Olivier; Sellam, Jérémie

    2015-05-01

    While rapidly destructive OA is more recognized in hip, we report the case of a 50-year-old woman who presented a rapid chondrolysis in the patellofemoral joint in a context of rapid loss of muscular strength. She had arthralgia, myalgia and proximal muscular deficit of the limbs. Creatine phospho kinase level was elevated and electromyogram exam showed a myogenic syndrome. Neither immune nor visceral disease was highlighted. As we suspected a polymyositis, we started corticosteroids and physiotherapy, then methotrexate and intravenous immunoglobulin. Concomitantly to the worsening of the muscular deficit and atrophy of hamstrings, she developed a persistent and disabling knee pain. Initial radiographs and magnetic resonance imaging (MRI) showed only a patellofemoral dysplasia and tiny cartilage damages. Because of aggravation of myalgia, we treated by mycophenolate mofetyl then rituximab. One year later, the knee remained painful and swollen. MRI showed signs of advanced osteoarthritis including an important loss of cartilage with an atrophy of hamstrings. Several articular corticosteroids injections were done. In the same time, the evolution of the muscular disease was unusual. Another histological analysis of muscle has highlighted a genetic myopathy due to mutation of calpain. Immunosuppressive treatments were stopped and a total joint replacement was performed. We show for the first time a case of rapid chondrolysis of patellofemoral joint related to a severe genetic myopathy.

  7. Case of adult T-cell leukemia/lymphoma with rapid progression of pulmonary areas of ground-glass attenuation and multiple nodules.

    PubMed

    Hanaka, Minako; Yatera, Kazuhiro; Itoh, Chiyo; Kawanami, Toshinori; Nakanishi, Tsukasa; Katsuragi, Takefumi; Shimajiri, Shohei; Ishimoto, Hiroshi; Tsukada, Junichi; Mukae, Hiroshi

    2013-03-01

    We report a case of adult T-cell leukemia/lymphoma (ATL) with rapidly progressive pulmonary areas of ground-glass attenuation (GGA) and nodules resulting from acute transformation of chronic ATL. A 48-year-old Japanese man was admitted for progressive dyspnea. Chest computed tomography showed rapidly progressive bilateral pulmonary areas of GGA and nodules. Flow cytometry of bronchoalveolar lavage fluid and immunohistochemical examination of lung biopsy specimens revealed invasion of ATL cells. Systemic chemotherapy improved the pulmonary findings. Rapidly expanding areas of GGA and nodules are a rare manifestation of pulmonary invasion of ATL that clinicians should nevertheless keep in mind.

  8. Rapid progression to pulmonary arterial hypertension crisis associated with mixed connective tissue disease in an 11-year-old girl.

    PubMed

    Okura, Yuka; Takezaki, Shunichiro; Yamazaki, Yasuhiro; Yamada, Masafumi; Kobayashi, Ichiro; Ariga, Tadashi

    2013-09-01

    Mixed connective tissue disease (MCTD) is rare in pediatric rheumatic diseases. Pulmonary arterial hypertension (PAH) associated with MCTD usually progresses gradually and is difficult to note at the asymptomatic phase. We report a 11-year-old girl with MCTD complicated with rapidly progressive PAH. Although PAH was not detected by echocardiogram or chest CT scan at the initial examination, it became clear in 1 year and suddenly came to cardiac arrest during an invasive procedure. She was successfully treated with extracorporeal assist and both vasodilative and immunosuppressive medication. A combination of echocardiogram and plasma BNP levels could be a useful marker for the follow-up of such cases. PAH could develop early in the course of pediatric MCTD and needs attention to unexpected acute exacerbation, especially under emotional stress.

  9. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

    PubMed Central

    Nogi, Shinichi; Sasaki, Noriko; Chinen, Naofumi; Honda, Kiri; Saito, Eiko; Wakabayashi, Takayuki; Yamada, Chiho; Suzuki, Yasuo

    2014-01-01

    Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis. PMID:25431723

  10. Successful Surgical Management of Retinopathy of Prematurity Showing Rapid Progression despite Extensive Retinal Photocoagulation

    PubMed Central

    Gadkari, Salil S; Kulkarni, Sucheta R; Kamdar, Rushita R; Deshpande, Madan

    2015-01-01

    The management of retinopathy of prematurity (ROP) can be challenging in preterm babies with a gestational age <30 weeks, those with very low birth weight and multiple risk factors (eg., oxygen therapy for respiratory distress, sepsis, neonatal jaundice). A premature infant presented with “hybrid” zone 1 disease in the right eye and aggressive posterior ROP in the left eye. Both eyes were adequately treated with laser photocoagulation; however, the eyes deteriorated and progressed to stage 4 ROP. Both eyes eventually underwent intravitreal bevacizumab followed by lens sparing vitrectomy with good anatomical and visual outcome. Anticipation of progression despite laser photocoagulation in certain clinical scenarios, frequent follow-up and timely surgical intervention is paramount. PMID:26180484

  11. Rapid In Vivo Validation of Tumor Suppressor Gene Function in Prostate Cancer Progression

    DTIC Science & Technology

    2016-07-01

    inactivate genes of interest within a genetically engineered mouse model of prostate cancer. Validation of our approach establishes a strong experimental...platform to systematically interrogate genes that are significantly mutated in human prostate cancer. Keywords CRISPR/Cas9, Genetically engineered ...gene loss on the progression and pathophysiology of prostate cancer without the need to create or breed new genetic alleles. We will accomplish this

  12. Rapidly Progressive Muscle Paralysis and Acute Respiratory Failure Following Endoscopic Botulinum Toxin Injection

    PubMed Central

    Khan, Ahmed; Shor, Julia; Forester, Gary P.

    2016-01-01

    Botulism toxin injection (BTI) is a well-known and relatively safe endoscopic treatment for achalasia. We report a case of a 90-year-old female diagnosed with achalasia who subsequently underwent BTI with symptomatic relief. The therapy was complicated by systemic botulism, however, leading to progressive muscle paralysis with diaphragmatic involvement requiring mechanical ventilation support. This is the first reported case of BTI for achalasia causing systemic botulism. PMID:27921065

  13. Heart transplantation in rapidly progressive end-stage heart failure associated with celiac disease

    PubMed Central

    Barrio, Juan P; Cura, Geraldine; Ramallo, German; Diez, Mirta; Vigliano, Carlos A; Katus, Hugo A; Mereles, Derliz

    2011-01-01

    Celiac disease is characterised by chronic immune-mediated malabsorption in genetically susceptible individuals induced by gluten proteins present in wheat, barley and rye. It occurs in adults and children at rates approaching 1% of the population. Cardiomyopathy associated with celiac disease is infrequent. The authors present here a first case of a severe progressive dilated cardiomyopathy that required heart transplantation in young woman with celiac disease. PMID:22696747

  14. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

    PubMed

    Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-03-01

    Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

  15. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba

    PubMed Central

    Kouri, Vivian; Khouri, Ricardo; Alemán‬, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B.; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-01-01

    Background Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Methods Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Findings Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. Interpretation CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba. PMID:26137563

  16. A child with spider bite and glomerulonephritis: a diagnostic challenge.

    PubMed

    Lung, J M; Mallory, S B

    2000-04-01

    A previously healthy 7-year-old white boy presented to St. Louis Children's Hospital with a 1-day history of headache, malaise, temperature of 38.7 degrees C, and a progressively erythematous, tender calf with central dusky purpura. On the morning of admission, his mother noticed a 2-mm crust on the patient's right calf with a 3-cm x 3-cm area of surrounding erythema. No history of recent trauma or bite was obtained. He had suffered two episodes of nonbloody, nonbilious emesis during the last day. In addition, over the previous 12 h, he presented brown urine without dysuria. His mother and brother had suffered from gastroenteritis over the previous week without bloody diarrhea. On initial physical examination, there was a 6-cm x 11-cm macular tender purpuric plaque with a central punctum on the right inner calf, which was warm and tender to the touch, with erythematous streaking towards the popliteal fossa (Fig. 1). The inguinal area was also erythematous with tender lymphadenopathy and induration, but without fluctuance. Laboratory studies included an elevated white blood cell count of 20, 800/microL with 6% bands, 86% segs, and 7% lymphocytes, hemoglobin of 12.5 g/dL, hematocrit of 35.1%, and platelets of 282,000/microL. The prothrombin time/activated partial tissue thromboplastin was 10. 4/28.0 s (normal PT, 9.3-12.3 s; normal PTT, 21.3-33.7 s) and fibrinogen was 558 mg/dL (normal, 192-379 mg/dL). Urinalysis showed 1+ protein, 8-10 white blood cells, too numerous to count red blood cells, and no hemoglobinuria. His electrolytes, blood urea nitrogen (BUN), and creatine were normal. The urine culture was negative. Blood culture after 24 h showed one out of two bottles of coagulase negative Staphylococcus epidermidis. The patient's physical examination was highly suggestive of a brown recluse spider bite with surrounding purpura. Over the next 2 days, the surrounding rim of erythema expanded. The skin within the plaque cleared and peeled at the periphery. The

  17. Be alert to tuberculosis-mediated glomerulonephritis: a retrospective study.

    PubMed

    Sun, L; Yuan, Q; Feng, J; Yao, L; Fan, Q; Ma, J; Wang, L

    2012-05-01

    Mycobacterium tuberculosis infection causing glomerulonephritis is a rare disorder. This retrospective study analyzed the clinical characteristics of patients diagnosed with tuberculosis-mediated glomerulonephritis (TB-GN) between 2002 and 2009, as well as the diagnostic tools used. These findings were then compared with those of patients with primary glomerulonephritis (P-GN). The records of all patients were reviewed. The diagnosis of TB-GN was based on renal hematuria and/or proteinuria and cure after antituberculosis therapy alone plus urine culture positive for M. tuberculosis, demonstration of typical tubercle granulomas on renal biopsy specimens, or the detection of M. tuberculosis DNA by polymerase chain reaction (PCR) on renal specimens. Forty-six patients with TB-GN and 49 patients with P-GN were included. Compared with patients in the P-GN group, most (76%) patients with TB-GN had a history of TB. Systemic symptoms were much more frequent in patients with TB-GN than local genitourinary symptoms. Serological testing showed a statistical difference between the two groups. Immunoglobulin A nephropathy was found in the majority (72%) of patients with TB-GN. M. tuberculosis DNA detection was positive in 39 (84.8%) patients, a much higher positive rate of diagnosis than that with urine culture for M. tuberculosis. The manifestation of TB-GN is atypical and nonspecific. It warrants a high index of suspicion when patients with renal hematuria and proteinuria fail to respond to standard treatments for P-GN. Clinicians should pay close attention to the medical history and results of special laboratory tests. M. tuberculosis DNA detection on renal biopsy specimens should be considered in order to confirm the diagnosis of TB-GN.

  18. Infantile immunoglobulin A nephropathy showing features of membranoproliferative glomerulonephritis.

    PubMed

    Kurosu, Akira; Oka, Noriko; Hamaguchi, Takeshi; Yoshikawa, Norishige; Joh, Kensuke

    2012-01-01

    Immunoglobulin A nephropathy (IgAN) showing predominant IgA and complement 3 (C3) deposition on the mesangium is an immune complex-mediated glomerulonephritis. This renal disease is the most common primary glomerular disease worldwide. However, infantile onset of IgAN is rare. In the present patient, urinary protein and occult blood were detected in a girl aged 1 year and 8 months on urinalysis at a nursery school. Despite being young, a kidney biopsy was performed for diagnosis and the correct choice of therapy. Glomerular mesangial cell proliferation and a double contour of the glomerular basement membrane (GBM) resembling a railroad track were noted on light microscopy. Therefore, the patient was diagnosed morphologically with membranoproliferative glomerulonephritis (MPGN), because mesangial hypercellularity and thickening of the GBM were identified. However, on immunofluorescent staining, the deposition of immune complexes mainly consisting of IgA, IgG, and C3 was noted in the mesangial region and glomerular capillary loops. On electron microscopy, electron-dense deposits were recognized in the subendothelial and paramesangial regions associated with mesangial cell interposition into the subendothelial space. Autoimmune diseases and infection-associated secondary glomerulonephritis were clinically excluded, because there were no relevant signs or symptoms. Steroid treatment was initiated and findings of urinalysis were normalized within 8 months. This patient was finally diagnosed with IgA nephropathy showing the features of MPGN. The present patient was the youngest among reported cases of IgA nephropathy, suggesting that early onset of IgAN is associated with an MPGN-like lesion. The present report provides information for pathogenesis of IgA nephropathy.

  19. [Activators and inhibitors of fibrinolysis in chronic glomerulonephritis and amyloidosis].

    PubMed

    Podorol'skaia, L V; Andreenko, G V; Poliantseva, L R; Bumblite, I D

    1996-01-01

    Functional activities of plasminogen activators (FPAA) and their inhibitors and plasminogen activators's (PA), antigen level were determined in 31 patients with chronic glomerulonephritis, 23 patients with amyloidosis and 15 healthy persons. High FPAA correlated with favourable prognosis of diseases, elevated PA antigen level and diminished alpha 1-antitrypsin, alpha 2-macroglobulin and antiactivator activities. There were decreased PA antigen level and increased inhibitor's activities in group with zero FPAA. Protein loaded functional probe demonstrated the presence of PA reserves in high FPAA patients and "pathological proteolysis" in zero FPAA patients. The last phenomenon was likely connected to nonspecific proteases differed from PA.

  20. Concomitant severe normocytic and normochromic anemia in poststreptococcal acute glomerulonephritis.

    PubMed

    Asano, Takeshi; Sudoh, Mariko; Watanabe, Makoto; Fujino, Osamu

    2009-10-01

    Although anemia frequently occurs in poststreptococcal acute glomerulonephritis (PSAGN), severe anemia is rare. We report severe normocytic, normochromic anemia (hematocrit, 19.8%) in PSAGN in a 6-year-old girl with edema, macrohematuria, and proteinuria for 1 month. The potential causes of severe anemia found in this case were: 1) longer duration of massive hematuria from onset of macrohemauria to treatment, 2) a level of erythropoietin much lower than that in cases of iron deficiency anemia, and 3) hemodilution. We speculate that these factors combined to cause an unusual case of severe anemia in PSAGN.

  1. Monoclonal gammopathy associated membranous glomerulonephritis: A rare entity.

    PubMed

    Gowda, K K; Joshi, K; Ramachandran, R; Nada, R

    2015-01-01

    A 40-year-old male presented with nephrotic syndrome. Light microscopic analysis of the renal biopsy showed thickening of the glomerular capillary wall. Immunofluorescence examination revealed granular deposition of monoclonal immunoglobulin (Ig) G3-kappa and complement C3 along the glomerular basement membrane. Electron microscopy showed subepithelial electron dense deposits, thus confirming membranous glomerulonephritis (MGN) with monoclonal gammopathy. MGN with monoclonal gammopathy is an extremely rare but distinctive entity. This patient was treated with a combination of bortezomib, thalidomide and dexamethasone and showed partial remission of his nephrotic state and dysproteinemia.

  2. Study of Proteins and Fibrinolysis in Patients with Glomerulonephritis

    PubMed Central

    Wardle, E. N.; Menon, I. S.; Rastogi, S. P.

    1970-01-01

    Plasma and urine fibrinolysis were studied in 36 patients with glomerulonephritis and proteinuria. In 40% of these plasma fibrinolytic activator activity was moderately reduced and fibrinolytic inhibitors were increased. Globulins with antiplasmin effect were raised, particularly in the earlier months. Both the serum cholesterol and the plasma fibrinogen were related to the level of serum albumin, and those patients with high fibrinogen levels were also those with poor plasma fibrinolytic activator and those showing a steady deterioration. Urinary fibrinolysis was greatly reduced in most patients and bore no relation to plasma fibrinolysis levels. Hence urokinase is not derived from circulating plasminogen activator. PMID:4246192

  3. An approach to the child with acute glomerulonephritis.

    PubMed

    Welch, Thomas R

    2012-01-01

    Acute glomerulonephritis (AGN) is a common condition in childhood. Many children with AGN can be managed in the primary care setting. The diagnosis is usually made on the basis of urinary findings, especially the presence of red blood cell casts. One of the most important initial investigations is determining the complement C3 level; hypocomplementemia is most characteristic of post streptococcal AGN, while normocomplementemia is most often seen with IgA nephropathy. Children whose AGN is accompanied by significant hypertension or renal insufficiency should be assessed by a specialist immediately. The presence of serious extrarenal signs or symptoms also merits urgent referral. Otherwise, serial followup in the primary care office is appropriate.

  4. Rapid progression to cardiac tamponade in Erdheim-Chester disease despite treatment with interferon alpha.

    PubMed

    Nakhleh, Afif; Slobodin, Gleb; Elias, Nizar; Bejar, Jacob; Odeh, Majed

    2016-07-01

    Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis with heterogeneous clinical manifestations. The most common presentation is bone pains typically involving the long bones. Approximately 75% of the patients develop extraskeletal involvement. Cardiac involvement is seen in up to 45% of the patients, and although, pericardial involvement is the most common cardiac pathology of this rare disease, cardiac tamponade due to ECD has been very rarely reported. We describe a case of a patient found to have ECD with multi-organ involvement and small pericardial effusion, which progressed to cardiac tamponade despite treatment with interferon alpha.

  5. Proliferative glomerulonephritis with monoclonal IgG deposits in a patient with autoimmune hemolytic anemia.

    PubMed

    Fujiwara, Takashi; Komatsuda, Atsushi; Ohtani, Hiroshi; Togashi, Masaru; Sawada, Ken-Ichi; Wakui, Hideki

    2013-06-01

    A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

  6. Rapidly progressive neurological deterioration in anti-AMPA receptor encephalitis with additional CRMP5 antibodies.

    PubMed

    Yang, Shuangshuang; Qin, Jie; Li, Jinghong; Gao, Yuan; Zhao, Lu; Wu, Jun; Song, Bo; Xu, Yuming; Sun, Shilei

    2016-11-01

    Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis positive for additional onconeural antibodies is rarely reported. Here we report the clinical features of a patient who developed limbic encephalitis with both glutamate receptor 2 (GluR2) and collapsin response mediator protein 5 (CRMP5) antibodies. Brain magnetic resonance imaging revealed multifocal encephalopathy. Chest computed tomography showed a highly suspicious malignant thymoma. He experienced rapid neurological deterioration during hospitalization. This report indicates that the clinical diversity of anti-AMPAR encephalitis and the presence of onconeural antibodies may lead to poor prognosis.

  7. [Current progress of fabricating tissue engineering scaffold using rapid prototyping techniques].

    PubMed

    Li, Xiang; Wang, Chengtao

    2008-08-01

    As one of the key factors for tissue engineering, scaffolds affect the spread and proliferation of seeded cells and the formation of new tissue. Although conventional methods can produce porous scaffolds with different porosities, they are lack controls the porous structures of the scaffolds. In recent years, rapid prototyping (RP) techniques have been developed and have successfully applied to fabricate TE scaffolds. RP techniques can provide accurate control over internal pore architectures and complex-shapes. As a result of these techniques, ideal tissue-engineered constructs could be prepared. This paper reviewed the advantages, potential and future directions of RP techniques in the design and fabrication of TE scaffolds.

  8. A case of rapid progression of postoperative hyperthermia: Dantrolene or not dilemma?

    PubMed Central

    Honardar, Marzieh R.; Rubio, Jesus; Bhananker, Sanjay M.

    2016-01-01

    Malignant hyperthermia (MH) is an extremely rare and life–threatening differential diagnosis of postoperative fever. We present an 8-month-old child scheduled for elective outpatient procedure who rapidly developed high fever, tachycardia, and respiratory acidosis shortly after transfer to the postanesthesia care unit. MH hotline expert recommended administering dantrolene, but there was no evidence of hypermetabolism or lactic acidosis. The patient remained clinically stable after admission to the pediatric intensive care unit and was discharged home the next day. The fever was likely due to viral infections as confirmed by a positive result of viral polymerase chain reaction for human metapneumovirus and rhinovirus/enterovirus. PMID:28149827

  9. The advanced lead-acid battery consortium—a worldwide cooperation brings rapid progress

    NASA Astrophysics Data System (ADS)

    Moseley, Patrick T.

    The development of valve regulated lead-acid (VRLA) batteries has, in recent years, been carried forward rapidly through the collaborative efforts of a worldwide consortium of battery manufacturers and related elements of industry; the Advanced Lead-Acid Battery Consortium (ALABC). This group has set aside its competitive instincts in order to achieve acceptable goals in respect of those parameters that are key factors controlling the marketability of electric vehicles (EVs): cost, cycle life, specific energy, specific power and rate of recharge. This paper provides an overview of the principal themes of the ALABC research and development programme.

  10. Cognard Type V intracranial dural arteriovenous fistula presenting in a pediatric patient with rapid, progressive myelopathy.

    PubMed

    Jermakowicz, Walter J; Weil, Alexander G; Vlasenko, Artyom; Bhatia, Sanjiv; Niazi, Toba N

    2017-08-01

    Cognard Type V dural arteriovenous fistulas (dAVFs) are a unique type of cranial vascular malformation characterized by congestion of the perimedullary venous system that may lead to devastating spinal cord pathology if left untreated. The authors present the first known case of a pediatric patient diagnosed with a Type V dAVF. A 14-year-old girl presented with a 3-week history of slowly progressive unilateral leg weakness that quickly progressed to bilateral leg paralysis, sphincter dysfunction, and complete sensory loss the day of her presentation. MRI revealed an extensive T2 signal change in the cervical spine and tortuous perimedullary veins along the entire length of the cord. An emergency cranial angiogram showed a Type V dAVF fed by the posterior meningeal artery with drainage into the perimedullary veins of the cervical spine. The fistula was not amenable to embolization because vascular access was difficult; therefore, the patient underwent urgent suboccipital craniotomy and ligation of the arterialized venous drainage from the fistula. The patient's clinical course immediately reversed; she had a complete recovery over the course of a year, and she remains asymptomatic at the 2-year follow-up. This report adds to a growing body of evidence that describes the diverse and unpredictable nature of Type V dAVFs and highlights the need to obtain a cranial angiogram in pediatric patients with unexplained myelopathy and cervical cord T2 signal change on MRI.

  11. Bronchiolitis obliterans organizing pneumonia: clinicopathologic review of a series of 45 Korean patients including rapidly progressive form.

    PubMed Central

    Chang, Joon; Han, Joungho; Kim, Dong Won; Lee, Inchul; Lee, Kyo Young; Jung, Soonhee; Han, Hye Seung; Chun, Bong Kwon; Cho, Seong Jin; Lee, Kibeom; Lim, Beom Jin; Shin, Dong Hwan

    2002-01-01

    Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological syndrome associated with a variety of disease entities. The aim of this study was to review cases with initial diagnosis of BOOP applying uniform histopathologic criteria, and analyze the clinical characteristics of proven cases of BOOP including rapidly progressive form. A total of 81 cases, initially diagnosed as BOOP and with available tissue sections, was collected. Thirty six cases (44.4%) were excluded from the study, more than two thirds of which were given a revised diagnosis of interstitial pneumonitis/fibrosis other than BOOP. Thirty one patients were classified as idiopathic BOOP, 8 patients as secondary BOOP, and 6 patients as rapidly progressive BOOP. Open lung biopsy specimen from all six cases with lethal outcome showed more severe interstitial inflammation and septal fibrosis and/or alveolar exudate with a varying degree than those with good prognosis. There was no difference by the sexes. The two most frequent presenting symptoms were cough and dyspnea. Bilateral multifocal consolidation was a common radiological finding. More than 70% cases of idiopathic BOOP experienced clinical improvements. The diagnosis of BOOP is usually suggested by clinicoradiologic findings, but needs to be confirmed histopathologically, preferably through surgical open or video-assisted thoracoscopic biopsy. PMID:11961300

  12. First Treatment of Relapsing Rapidly Progressive IgA Nephropathy With Eculizumab After Living Kidney Donation: A Case Report.

    PubMed

    Herzog, A L; Wanner, C; Amann, K; Lopau, K

    2017-09-01

    IgA nephropathy (IGAN) rarely can present as a crescent and progressive form leading to end-stage renal disease (ESRD) in a short period of time. Recurrence of IGAN after kidney transplantation is frequent, and complement components such as C3, C4d, and C5 seem to be involved. We present a case of a young male patient with ESRD caused by rapidly progressive IGAN and who demonstrated rapid recurrence of crescentic IGAN after kidney donation. In September 2014, a 28-year-old male patient was hospitalized due to IGAN with 60% of crescents. Cyclophosphamide, steroids, and plasmapheresis did not prevent ESRD. After 8 months of peritoneal dialysis, the patient received a blood group-compatible living donor kidney from his 57-year-old mother. Immunosuppression consisted of tacrolimus, mycophenolic acid, and steroids without induction therapy. Acute graft failure occurred 2 months later, and graft biopsy results revealed recurrence of crescentic IGAN. Cyclophosphamide was added to tacrolimus and steroid treatment, but graft function could not be restored despite viable kidney tissue in repeated biopsy specimens. Rescue therapy with 4 single doses of eculizumab was introduced while hemodialysis had already been initiated. After a cumulative dose of 1800 mg of eculizumab, kidney function did not recover. In this case, eculizumab was not effective in treating IGAN recurrence after transplantation. Therapy was started late when hemodialysis had already been initiated; an earlier start of therapy might be more effective. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Expansion of the classification of FTLD-TDP: distinct pathology associated with rapidly progressive frontotemporal degeneration.

    PubMed

    Lee, Edward B; Porta, Sílvia; Michael Baer, G; Xu, Yan; Suh, EunRan; Kwong, Linda K; Elman, Lauren; Grossman, Murray; Lee, Virginia M-Y; Irwin, David J; Van Deerlin, Vivianna M; Trojanowski, John Q

    2017-07-01

    Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) can typically be categorized into one of four distinct histopathologic patterns of TDP-43 pathology, types A to D. The strength of this histopathologic classification lies in the association between FTLD-TDP subtypes and various clinical and genetic features of disease. Seven cases of FTLD-TDP were identified here which were difficult to classify based on existing pathologic criteria. Distinct features common to these cases included TDP-43 aggregates over a wide neuroanatomic distribution comprised of granulofilamentous neuronal inclusions, abundant grains, and oligodendroglial inclusions. TDP-43 aggregates were phosphorylated and associated with loss of normal nuclear TDP-43 protein (nuclear clearance) but were negative for ubiquitin. Biochemical analysis confirmed the presence of insoluble and phosphorylated TDP-43 and also revealed a distinct pattern of TDP-43 C-terminal fragments relative to other FTLD-TDP subtypes. Finally, these cases were uniformly associated with a very rapid clinical course culminating in death within ~3 years of disease onset. We suggest that these cases may represent a unique clinicopathologic subtype of FTLD-TDP which we provisionally call "type E." The immature appearance of TDP-43 aggregates, widespread distribution, uniform biochemical profile and rapid clinical course highlights the clinical and pathologic variability within FTLD-TDP, and raises the possibility that type E neuropathology is the sequelae of a particularly virulent strain of TDP-43 proteinopathy.

  14. MM1+2C sporadic Creutzfeldt-Jakob disease presenting as rapidly progressive nonfluent aphasia.

    PubMed

    Allegri, Ricardo F; Bartoloni, Leonardo; Iturry, Mónica; Romero, Carlos; Begué, Christián; Sevlever, Gustavo; Taratuto, Ana Lía

    2014-01-01

    We report a 77-year-old man, presenting with progressive aphasia as an initial symptom, who developed severe dementia over the course of 20 months. Frontal cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of MM2C. Cerebellum showed focal coarse, patchy staining in different sections of the molecular layer, diffuse fine punctuate and coarse PrP immunopositive deposits in the granule cell layer, and focal synaptic immunostaining in the molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation has not yet been described in an MM1+2C subtype by histotyping.

  15. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

    PubMed

    Bonafede, Lucas; Ficicioglu, Can H; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Mills, Monte D; Forbes, Brian J; Davidson, Stefanie L; Binenbaum, Gil; Kaplan, Paige B; Nichols, Charles W; Verloo, Patrick; Leroy, Bart P; Maguire, Albert M; Aleman, Tomas S

    2015-12-01

    To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

  16. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    PubMed Central

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  17. Progress in the PRIDE technique for rapidly comparing protein three-dimensional structures

    PubMed Central

    Kirillova, Svetlana; Carugo, Oliviero

    2008-01-01

    Background Accurate and fast tools for comparing protein three-dimensional structures are necessary to scan and analyze large data sets. Findings The method described here is not only very fast but it is also reasonable precise, as it is shown by using the CATH database as a test set. Its rapidity depends on the fact that the protein structure is represented by vectors that monitors the distribution of the inter-residue distances within the protein core and the structure of which is optimized with the Freedman-Diaconis rule. Conclusion The similarity score is based on a χ2 test, the probability density function of which can be accurately estimated. PMID:18710497

  18. Rapidly progressive renal failure due to chronic lymphocytic leukemia - Response to chlorambucil

    PubMed Central

    Junglee, N. A.; Shrikanth, S.; Seale, J. R.

    2012-01-01

    Chronic lymphocytic leukemia tends to follow an indolent course and despite infiltration of leukemic cells in numerous organs, resultant target organ damage is uncommon. We present a case of an 83-year-old Caucasian lady who presented with rapidly worsening renal impairment over a several month period with a serum creatinine peak of 2.82 mg/dl. Despite numerous investigations an immediate cause was not apparent. A renal biopsy was therefore conducted which revealed dense infiltration of the interstitium with small lymphocytic lymphoma. Given her age and frailty she was treated with single alkylating agent chemotherapy (chlorambucil). This resulted in a marked decrease in lymphocyte count and resolution of renal impairment close to her previous baseline level. To our knowledge, this is the first case in the literature to demonstrate a marked resolution in renal impairment with chlorambucil alone. We also highlight the value of renal biopsy in identifying a rare cause of renal impairment. PMID:23087560

  19. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, July--September 1992

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1992-11-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is required both, for the fundamental determination of kinetic parameters of coal devolatilization, and to refine existing devolatilization sub-models used in comprehensive coal combustion codes. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: The specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars.

  20. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, April--June 1993

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1993-08-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is essential to the fundamental determination of kinetic parameters of coal devolatilization. These same properties are also needed to refine existing devolatilization sub-models utilized in large-scale modeling of coal combustion systems. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. The coal ranks to be investigated will include a high volatile A bituminous (PSOC 1451 D) and a low volatile bituminous (PSOC 1516D). An anthracite (PSOC 1468) will be used as a non-volatile coal reference. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: the specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars.

  1. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, October--December 1992

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1993-03-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is required both, for the fundamental determination of kinetic parameters of coal devolatilization, and to refine existing devolatilization sub-models used in comprehensive coal combustion codes. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: the specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars. Calibration of the heated grid calorimeter (Task 2) was completed this reporting period. Several refinements to the heated grid apparatus have been implemented which allow quantitative determination of sample heat capacity at high heating rates.

  2. Nephrotoxic nephritis and glomerulonephritis: animal model versus human disease.

    PubMed

    Muhammad, S

    2014-01-01

    Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is complex. Intricacy arises from factors such as autoimmunity, cancer and structural abnormalities within the kidney. Studies using animal models have highlighted crucial interaction between inflammatory cells and cells intrinsic to the kidney, both of which are fundamental to the pathogenesis of GN. This review aims to provide insight on a 'suitable' model for nephrotoxic nephritis and glomerulonephritis (NTN GN) and relate its experimental validity to humans. The BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic options for patients with GN and subsets thereof. Currently used immunosuppressive therapies for GN are not always uniformly effective and are frequently associated with serious side-effects. Corticosteroids are effective in several types of GN owing to their ability to inhibit the pro-inflammatory effects of cytokines known to promote glomerular inflammation. Differences between experimental and human GN complicate translation of experimental therapies into practice. More research is required to translate animal model research into a better comprehension of human GN disease. However, the complexity of GN research makes findings a challenge to replicate.

  3. IgM associated primary diffuse mesangial proliferative glomerulonephritis.

    PubMed Central

    Lawler, W; Williams, G; Tarpey, P; Mallick, N P

    1980-01-01

    Twenty-three cases of IgM associated primary diffuse mesangial proliferative glomerulonephritis are presented. In 18, IgM was the sole localising host immunoglobulin, and it was the predominant globulin in five; C3 was also present in 18. Light microscopy revealed variable diffuse and global mesangial proliferation in all cases, with additional focal global sclerosis in 16, focal segmental sclerosis in 15, and small capsular crescents in seven. Material for electron microscopy was available from 19 patients; in 13, occasional intramesangial electron dense deposits were identified, and in 18 there were irregular, rather ill defined areas of increased electron density in mesangial regions. Clinically, 14 patients presented with the nephrotic syndrome, and nine had asymptomatic proteinuria. During follow-up, only 10 patients showed no change in renal function or improved; the remainder showed increasing hypertension and/or renal function deterioration and four developed end stage renal failure. It is suggested that IgM associated mesangial proliferative glomerulonephritis should be considered as a distinct clinicoimmunopathological entity. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7002957

  4. Familial C4B Deficiency and Immune Complex Glomerulonephritis

    PubMed Central

    Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY

    2010-01-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617

  5. Familial C4B deficiency and immune complex glomerulonephritis.

    PubMed

    Soto, K; Wu, Y L; Ortiz, A; Aparício, S R; Yu, C Y

    2010-10-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease

    PubMed Central

    Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K.

    2016-01-01

    Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208

  7. Rapidly Progressive Renal Dysfunction in Two Elderly Patients with Renal Enlargement and Medullary Cystic Kidney Disease-like Acute Tubulointerstitial Injury

    PubMed Central

    Kawamoto, Shinya; Koda, Ryo; Yoshino, Atsunori; Takeda, Tetsuro; Ueda, Yoshihiko

    2016-01-01

    Medullary cystic kidney disease (MCKD) is a hereditary disease associated with bilateral medullary polycysts and interstitial fibrosis. MCKD is typically associated with slowly progressive renal dysfunction. We herein report two rare elderly cases with enlarged kidneys and rapidly progressive renal dysfunction without myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), PR3-ANCA, or anti-glomerular basement membrane (GBM) antibodies. Renal biopsies revealed extensive tubular dilatation and atrophy with interstitial fibrosis consistent with MCKD. Both patients began hemodialysis therapy a few months later. Our cases suggest a MCKD subgroup among elderly patients with an undefined genetic background, rapidly progressive renal dysfunction, and enlarged kidneys. PMID:27746439

  8. Nasopharyngeal carcinoma presenting with rapidly progressive severe visual disturbance: a case report

    PubMed Central

    2014-01-01

    Introduction Nasopharyngeal carcinoma is one of the most difficult tumors to diagnose correctly at the initial phase because of the occasional lack of nasal symptoms. The perineural spread of the trigeminal nerve is one of the most common and important routes in the intracranial paracavernous extension of nasopharyngeal carcinoma, but visual loss is very rare. Case presentation We report the case of a 54-year-old Japanese man with nasopharyngeal carcinoma, who presented with rapid and severe disturbance of left monocular visual acuity and eye movement with a 10-month history of ipsilateral otitis media and facial pain. Magnetic resonance imaging revealed a lesion in the left fossa of Rosenmüller, pterygopalatine fossa, sphenoid and ethmoid sinus, and the left cavernous sinus extending to the orbital apex through the superior orbital fissure. The histopathological diagnosis was nonkeratinizing undifferentiated nasopharyngeal carcinoma. Epstein–Barr virus was detected by in situ hybridization. Although focal radiotherapy induced remarkable tumor shrinkage and relieved ocular motor disturbance and facial pain, his visual acuity did not improve. Conclusion The awareness of cranial nerves in addition to intracranial and orbital apex involvement, as in this case, is important for appropriate diagnosis and treatment planning of nasopharyngeal carcinoma. PMID:25373786

  9. Final Progress Report: Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes Feasibility Study

    SciTech Connect

    Rawool-Sullivan, Mohini; Bounds, John Alan; Brumby, Steven P.; Prasad, Lakshman; Sullivan, John P.

    2012-04-30

    This is the final report of the project titled, 'Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes,' PMIS project number LA10-HUMANID-PD03. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). It summarizes work performed over the FY10 time period. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). Human analysts begin analyzing a spectrum based on features in the spectrum - lines and shapes that are present in a given spectrum. The proposed work was to carry out a feasibility study that will pick out all gamma ray peaks and other features such as Compton edges, bremsstrahlung, presence/absence of shielding and presence of neutrons and escape peaks. Ultimately success of this feasibility study will allow us to collectively explain identified features and form a realistic scenario that produced a given spectrum in the future. We wanted to develop and demonstrate machine learning algorithms that will qualitatively enhance the automated identification capabilities of portable radiological sensors that are currently being used in the field.

  10. Radiological and Pathological Correlation in Anti-MDA5 Antibody-positive Interstitial Lung Disease: Rapidly Progressive Perilobular Opacities and Diffuse Alveolar Damage.

    PubMed

    Chino, Haruka; Sekine, Akimasa; Baba, Tomohisa; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Itoh, Harumi; Sato, Shinji; Suzuki, Yasuo; Ogura, Takashi

    2016-01-01

    We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.

  11. Rapid mass spectrometric DNA diagnostics for assessing microbial community activity during bioremediation. 1997 annual progress report

    SciTech Connect

    Benner, W.H.; Hunter-Cevera, J.

    1997-01-01

    'The effort of the past year''s activities, which covers the first year of the project, was directed at developing DNA-based diagnostic procedures for implementation in high through-put analytical instrumentation. The diagnostic procedures under evaluation are designed to identify specific genes in soil microorganisms that code for pollutant-degrading enzymes. Current DNA-based diagnostic procedures, such as the ligase chain reaction (LCR) and the polymerase chain reaction (PCR), rely on gel electrophoresis as a way to score a diagnostic test. The authors are attempting to implement time-of-flight (TOF) mass spectrometry as a replacement for gel separations because of its speed advantage and potential for sample automation. The authors anticipate that if TOF techniques can be implemented in the procedures, then a very large number of microorganisms and soil samples can be screened for the presence of specific pollutant-degrading genes. The use of DNA-based procedures for the detection of biodegrading organisms or genes that code for pollutant-degrading enzymes constitutes a critical technology for following biochemical transformation and substantiating the impact of bioremediation. DNA-based technology has been demonstrated to be a sensitive technique for tracking micro-organism activity at the molecular level. These procedures can be tuned to identify groups of organisms, specific organisms, and activity at the molecular level. They are developing a P-monitoring strategy that relies on the combined use of DNA diagnostics with mass spectrometry as the detection scheme. The intent of this work is a two-fold evaluation of (1) the feasibility of replacing the use of gel separations for identifying polymerase chain reaction (PCR) products with a rapid and automatable form of electrospray mass spectrometry and (2) the use of matrix-assisted-laser-desorption-ionization mass spectrometry (MALDI-MS) as a tool to score oligonucleotide ligation assays (OLA).'

  12. Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease.

    PubMed

    Hayase, Tomomi; Shimizu, Jun; Goto, Tamako; Nozaki, Yasuyuki; Mori, Masato; Takahashi, Naoto; Namba, Eiji; Yamagata, Takanori; Momoi, Mariko Y

    2010-03-01

    We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.

  13. A challenging case of rapid progressive Kaposi sarcoma after renal transplantation: diagnostics by FDG PET/CT.

    PubMed

    Reuter, Stefan; Vrachimis, Alexis; Huss, Sebastian; Wardelmann, Eva; Weckesser, Mathias; Pavenstädt, Hermann

    2014-09-01

    De-novo malignancy is a serious posttransplant complication. While the incidence of Kaposi sarcoma (KS) is low, the time for its diagnosis is early after renal transplantation. Typically, it can be identified because of the classical skin lesion. We herein report an unusual case of rapid progressive KS without skin lesions in a 52-year-old patient leading to death within 8 months after kidney transplantation. This striking case illustrates the usefulness of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for demonstrating the cause of unexplained deterioration of patient's condition. Early identification of KS is critical because early (modification of) therapy can substantially improve patient's prognosis.

  14. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

    PubMed

    Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

    2015-01-12

    We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.

  15. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

    PubMed Central

    Hill, Rebecca M.; Kuijper, Sanne; Lindsey, Janet C.; Petrie, Kevin; Schwalbe, Ed C.; Barker, Karen; Boult, Jessica K.R.; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L.; Poon, Evon; Robinson, Simon P.; Ruddle, Ruth; Raynaud, Florence I.; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W.; Wharton, Stephen B.; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S.; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J.; Weiss, William A.; Chesler, Louis; Clifford, Steven C.

    2015-01-01

    Summary We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

  16. Whole Exome Sequencing of Rapid Autopsy Tumors and Xenograft Models Reveals Possible Driver Mutations Underlying Tumor Progression

    PubMed Central

    Xie, Tao; Musteanu, Monica; Lopez-Casas, Pedro P.; Shields, David J.; Olson, Peter; Rejto, Paul A.; Hidalgo, Manuel

    2015-01-01

    Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy due to its propensity to invade and rapidly metastasize and remains very difficult to manage clinically. One major hindrance towards a better understanding of PDAC is the lack of molecular data sets and models representative of end stage disease. Moreover, it remains unclear how molecularly similar patient-derived xenograft (PDX) models are to the primary tumor from which they were derived. To identify potential molecular drivers in metastatic pancreatic cancer progression, we obtained matched primary tumor, metastases and normal (peripheral blood) samples under a rapid autopsy program and performed whole exome sequencing (WES) on tumor as well as normal samples. PDX models were also generated, sequenced and compared to tumors. Across the matched data sets generated for three patients, there were on average approximately 160 single-nucleotide mutations in each sample. The majority of mutations in each patient were shared among the primary and metastatic samples and, importantly, were largely retained in the xenograft models. Based on the mutation prevalence in the primary and metastatic sites, we proposed possible clonal evolution patterns marked by functional mutations affecting cancer genes such as KRAS, TP53 and SMAD4 that may play an important role in tumor initiation, progression and metastasis. These results add to our understanding of pancreatic tumor biology, and demonstrate that PDX models derived from advanced or end-stage likely closely approximate the genetics of the disease in the clinic and thus represent a biologically and clinically relevant pre-clinical platform that may enable the development of effective targeted therapies for PDAC. PMID:26555578

  17. Chondrogenesis of embryonic limb bud cells in micromass culture progresses rapidly to hypertrophy and is modulated by hydrostatic pressure.

    PubMed

    Saha, Anurati; Rolfe, Rebecca; Carroll, Simon; Kelly, Daniel J; Murphy, Paula

    2017-04-01

    Chondrogenesis in vivo is precisely controlled in time and space. The entire limb skeleton forms from cells at the core of the early limb bud that condense and undergo chondrogenic differentiation. Whether they form stable cartilage at the articular surface of the joint or transient cartilage that progresses to hypertrophy as endochondral bone, replacing the cartilage template of the skeletal rudiment, is spatially controlled over several days in the embryo. Here, we follow the differentiation of cells taken from the early limb bud (embryonic day 11.5), grown in high-density micromass culture and show that a self-organising pattern of evenly spaced cartilage nodules occurs spontaneously in growth medium. Although chondrogenesis is enhanced by addition of BMP6 to the medium, the spatial pattern of nodule formation is disrupted. We show rapid progression of the entire nodule to hypertrophy in culture and therefore loss of the local signals required to direct formation of stable cartilage. Dynamic hydrostatic pressure, which we have previously predicted to be a feature of the forming embryonic joint region, had a stabilising effect on chondrogenesis, reducing expression of hypertrophic marker genes. This demonstrates the use of micromass culture as a relatively simple assay to compare the effect of both biophysical and molecular signals on spatial and temporal control of chondrogenesis that could be used to examine the response of different types of progenitor cell, both adult- and embryo-derived.

  18. Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report.

    PubMed

    Iida, Shin; Nakamura, Masataka; Asayama, Shinya; Kunieda, Takenobu; Kaneko, Satoshi; Osaka, Hitoshi; Kusaka, Hirofumi

    2017-02-28

    Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn error of metabolism inherited in autosomal recessive pattern and is associated with a wide spectrum of neurological abnormalities. We herein describe a 15-year-old boy with MTHFR deficiency who presented with a slowly progressive decline of school performance and a spastic gait. Rapidly deteriorating psychosis and repetitive seizures triggered by a febrile infection prompted neurological investigation. He had significantly elevated total plasma homocysteine and urinary homocystine levels, as well as a decreased plasma methionine level. Brain magnetic resonance imaging (MRI) revealed leukoencephalopathy. DNA gene sequencing showed c.446_447 del GC ins TT and c.137G > A, and c.665C > T heterozygous mutations in the MTHFR gene of the patient. Oral administration of betaine drastically improved his clinical symptoms within a few months. After 8 months of treatment, his total plasma homocysteine level moderately decreased; and the plasma methionine concentration became normalized. Furthermore, the white matter lesions on MRI had disappeared. This patient demonstrates the possibility that MTHFR deficiency should be considered in mentally retarded adolescents who display an abnormally elevated plasma level of homocysteine in association with progressive neurological dysfunction and leukoencephalopathy. Febrile infections may be an aggravating factor in patients with MTHFR deficiency.

  19. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, January--March 1993

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1993-07-01

    Knowledge of the thermodynamic and morphological properties of coal associated with rapid heating decomposition pathways is essential to progress in coal utilization technology. Specifically, knowledge of the heat of devolatilization, surface area and density of coal as a function of rank characteristics, temperature and extent of devolatilization in the context of rapid heating conditions is required both, for the fundamental determination of kinetic parameters of coal devolatilization, and to refine existing devolatilization sub-models used in comprehensive coal combustion codes. The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: the specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars. Morphological characterization of the parent coal samples has been completed by the University of Pittsburgh. Results are presented for true density, CO{sub 2} surface area, mercury porosimetry, and particle size and shape measurements using image analysis. The heat of thermal decomposition of PSOC 1451D (Task 5) will be calculated from the data reported here. The Task 10 effort, Morphological Characterization of Coal/Char Samples as a Function of Extent of Devolatilization, will continue at the University of Pittsburgh. Work will focus on measurement of the morphological characteristics of the char samples as a function of extent of reaction.

  20. Crescentic glomerulonephritis in a polar bear (Ursus maritimus).

    PubMed

    Baba, Hiroshi; Kudo, Tomoo; Makino, Yoshinori; Mochizuki, Yasumasa; Takagi, Takayo; Une, Yumi

    2013-11-01

    Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman's capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits.

  1. Crescentic Glomerulonephritis in a Polar Bear (Ursus maritimus)

    PubMed Central

    BABA, Hiroshi; KUDO, Tomoo; MAKINO, Yoshinori; MOCHIZUKI, Yasumasa; TAKAGI, Takayo; UNE, Yumi

    2013-01-01

    ABSTRACT Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been reported in dog and sheep. We report the pathological features of CrGN in a 17-year-old male polar bear that died due to renal failure. Histologically, the lesions were characterized by fibrocellular crescents, adhesion between Bowman’s capsule and the glomerular capillary tuft and an increase in the mesangial matrix in glomeruli. The proliferating cells in the crescent were partly immunopositive for cytokeratin and intensely positive for vimentin, WT-1 and α-smooth muscle actin, suggesting they originated from parietal epithelial cells. Ultrastructually, thickening of the glomerular basement membrane and loss of epithelial cell foot processes were observed with electron-dense deposits. PMID:23856758

  2. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-01-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  3. White-blue pyelocalyceal cyst with hydrotic glomerulonephritis.

    PubMed

    Chaurasia, Jai Kumar; Soni, Mayank; Ahmed, Murad; Naim, Mohammed

    2013-12-17

    A 5-month-old male infant presented with a 15 day history of distension of abdomen. On clinical examination, a soft lump was palpable in the left lumbar region. Radiological findings suggested an enlarged non-functional left kidney with ureteropelvic adhesive obstruction. The left renal mass was excised and submitted for histopathological examination. The excised renal mass was cystic with its wall partly white and partly blue. Gross and histopathological findings were diagnostic of a white-blue pyelocalyceal cyst with hydrotic glomerulonephritis. This entity needs to be differentiated from a large number of other cystic diseases of the kidney. Intrauterine screening and diagnosis may be significant for a possible early intrauterine uro-laparoscopic recanalisation of the pyeloureteral obstruction to save the affected kidney.

  4. Efficacy of school urinary screening for membranoproliferative glomerulonephritis type 1

    PubMed Central

    Kawasaki, Y; Suzuki, J; Nozawa, R; Suzuki, H

    2002-01-01

    Aims: In order to evaluate the efficacy of a school urinary screening programme, children with membranoproliferative glomerulonephritis (MPGN) type 1 were studied. Methods: A total of 52 patients who had been diagnosed with MPGN type 1 from 1970 to 1997 were studied; 35 were identified after 1974 on screening (group S), and 17 were identified by presenting symptoms (group N), mostly before 1989. Results: Mean blood pressure was 89 mm Hg in group S and 104 mm Hg in group N; urinary protein excretion was 0.9 g/day in group S and 3.0 g/day in group N. Histopathological evidence of chronic changes was found in six group S and 15 group N patients. No patients in group S had renal insufficiency, but five patients in group N required regular haemodialysis. Conclusions: Results suggest that early identification by school urinary screening may enable early management and so improve prognosis of MPGN. PMID:11806875

  5. Fibrillary glomerulonephritis with hepatitis C viral infection and hypocomplementemia.

    PubMed

    Ray, Susan; Rouse, Kelly; Appis, Andrew; Novak, Robert; Haller, Nairmeen Awad

    2008-01-01

    Fibrillary glomerulonephritis (FGN) is a relatively rare cause of renal disease, found in only 0.6-1.5% of native renal biopsies. The pathogenesis of FGN is not well described, and very few associations with disease processes other than hepatitis C virus (HCV) have been made. We describe a case that provides evidence in support of the FGN-HCV association, as well as introduces the association of FGN-HCV and hypocomplementemia. The case is a 53-year-old African-American female demonstrating a classical presentation of FGN complicated by a concomitant HCV infection. Treating an HCV infection with alpha-interferon has been shown to result in subsequent improvement in the nephrotic syndrome and renal function. However, this patient is unique in that she is complicated with hypocomplementemia, creating a complex treatment situation.

  6. Fetal Renal Stem Cell Transplant in Nephrotic and Nonnephrotic Glomerulonephritis with Stage 2-4 Chronic Kidney Disease: Potential Effect on Proteinuria and Glomerular Filtration Rate.

    PubMed

    Tuganbekova, Saltanat; Gaipov, Abduzhappar; Turebekov, Zaiyrkhan; Saparbayev, Samat; Shaimardanova, Galiya; Popova, Nadezhda; Taubaldiyeva, Zhannat; Serebrennikova, Dina; Trimova, Rakhat

    2015-11-01

    Proteinuria is a major cause of glomerulosclerosis progression in glomerular diseases, and the development of end-stage renal disease is more rapid in nephrotic patients than in nonnephrotic ones. The renal parenchyma is less regenerable because it is a tissue consisting of renal cells. Thus, stem cells obtained from fetal kidney tissue might be effective for reducing proteinuria and delaying glomerulosclerosis in these patients. This report presents preliminary data from a prospective cohort study that included 17 patients with chronic glomerulonephritis in stage 2 to 4 chronic kidney disease who completed 3 visits during 1 year of follow-up. Fetal renal stem cells (multiple cells in suspension) were injected into the patient every 6 months. Patients were divided into 2 groups according to their nephrotic status, and 24-hour maximal proteinuria was recorded for at least 6 months (first group with proteinuria < 3.5 g/24 h, and second group with proteinuria > 3.5 g/24 h). During follow-up, group 1 was observed to have stable hemoglobin and total protein levels but significantly decreased albumin levels and glomerular filtration rates. In group 2, total protein with serum albumin significantly increased, and proteinuria and glomerular filtration rates significantly decreased. There was no significant difference in glomerular filtration rate decline between groups. Treatment with fetal renal stem cells significantly decreased proteinuria in nephrotic patients. However, this outcome also might have resulted from a reduction in glomerular filtration rate. Further studies with a larger number of patients and a control group would help to achieve better results that measure the efficacy of this treatment.

  7. Patterns of glomerulonephritis in Zimbabwe: survey of disease characterised by nephrotic proteinuria.

    PubMed

    Seggie, J; Davies, P G; Ninin, D; Henry, J

    1984-01-01

    Ninety-eight Zimbabweans with glomerulonephritis characterised by nephrotic proteinuria were studied. There was no evidence to implicate Schistosoma mansoni or S. haemotobium in the aetiology, although schistosomiasis was diagnosed in 54 patients in the series. Similarly, Plasmodium malariae proved unimportant as a cause of the nephrotic syndrome, only one patient showing focal segmental glomerulosclerosis which was associated with subclinical quartan malarial infection. Nevertheless, infections were shown to play a major role in the genesis of glomerulonephritis which was associated with beta-haemolytic streptococcal, hepatitis B and syphilitic infection in 45 patients in the series. The major patterns of disease in childhood proved to be membranous glomerulopathy associated with hepatitis B antigenaemia. In young adults post-streptococcal proliferative glomerulonephritis constituted the commonest disease pattern. In older adult patients a miscellany of primary and secondary glomerulonephritides was encountered but proliferative glomerulonephritis, which was both idiopathic and streptococcus-related, predominated.

  8. Targeting Spleen Tyrosine Kinase-Bruton's Tyrosine Kinase Axis for Immunologically Mediated Glomerulonephritis

    PubMed Central

    Chen, Jin-Shuen; Chang, Li-Chien; Huang, Shyh-Jer

    2014-01-01

    The importance of B-cell activation and immune complex-mediated Fc-receptor activation in the pathogenesis of immunologically mediated glomerulonephritis has long been recognized. The two nonreceptor tyrosine kinases, spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk), are primarily expressed by hematopoietic cells, and participate in B-cell-receptor- and Fc-receptor-mediated activation. Pharmacological inhibitors of Syk or Btk are undergoing preclinical development and clinical trials for several immune diseases; and Syk inhibitors have been shown to reduce disease activity in rheumatoid arthritis patients. However, the clinical therapeutic efficacies of these inhibitors in glomerulonephritis have not been evaluated. Herein, we review recent studies of Syk and Btk inhibitors in several experimental primary and secondary glomerulonephritis models. These inhibitors suppressed development of glomerular injury, and also ameliorated established kidney disease. Thus, targeting Syk and Btk signaling pathways is a potential therapeutic strategy for glomerulonephritis, and further evaluation is recommended. PMID:24795896

  9. Canadian Society of Nephrology Commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis: management of glomerulonephritis in adults.

    PubMed

    Cybulsky, Andrey V; Walsh, Michael; Knoll, Greg; Hladunewich, Michelle; Bargman, Joanne; Reich, Heather; Humar, Atul; Samuel, Susan; Bitzan, Martin; Zappitelli, Michael; Dart, Allison; Mammen, Cherry; Pinsk, Maury; Muirhead, Norman

    2014-03-01

    The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of adult nephrologists reviewed the guideline statements for management of glomerular disease in adults and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas for which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the choice of second-line agents, are discussed in more detail. Existing practice variation also is addressed. The relevance of treatment recommendations to the Canadian practitioner is discussed.

  10. Acute post-infection glomerulonephritis caused by new 'thongs'. A case report.

    PubMed

    O'Donnell, D; Markowitz, S

    1986-04-26

    Acute glomerulonephritis complicated secondary infection in a patient suffering from traumatic blisters caused by new footwear. This unlikely setting for acute glomerulonephritis was made more interesting by its occurrence in an adult in contrast with its more frequent recognition in a child. The age of the patient and the severity of the local symptoms masked the significance of the initial finding of haematuria until deteriorating renal function indicated the diagnosis of concomitant glomerular disease.

  11. Necrotizing ANCA-Positive Glomerulonephritis Secondary to Culture-Negative Endocarditis

    PubMed Central

    Van Haare Heijmeijer, Sophie; Wilmes, Dunja; Aydin, Selda; Clerckx, Caroline; Labriola, Laura

    2015-01-01

    Infective endocarditis (IE) and small-vessel vasculitis may have similar clinical features, including glomerulonephritis. Furthermore the association between IE and ANCA positivity is well documented, making differential diagnosis between IE- and ANCA-associated vasculitis particularly difficult, especially in case of culture-negative IE. We report on one patient with glomerulonephritis secondary to culture-negative IE caused by Bartonella henselae which illustrates this diagnostic difficulty. PMID:26819786

  12. Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis

    PubMed Central

    Stangou, M.; Bantis, C.; Skoularopoulou, M.; Korelidou, L.; Kouloukouriotou, D.; Scina, M.; Labropoulou, I. T.; Kouri, N. M.; Papagianni, A.; Efstratiadis, G.

    2016-01-01

    IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17–67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25–80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. PMID:27194829

  13. Polymorphisms in NADPH oxidase CYBA gene modify the risk of ESRD in patients with chronic glomerulonephritis.

    PubMed

    Zhou, Hui; Chen, Min; Zhu, Ying; Wang, Bing; Liu, Xiao-ning; Zuo, Zhi; Tang, Feng-Ying

    2016-01-01

    End-stage renal disease (ESRD) was defined as start of renal replacement therapy or death due to kidney disease. However, death due to acute kidney injury was not included. It typically occurs when chronic renal failure progresses to a point where the kidneys are permanently functioning at less than 10% of their capacity. Oxidative stress (OS) plays a crucial role in ESRD. Nicotinamide adenine dinucleotide phosphate (NADPH) is one of the most important enzymes during oxidative stress. Cytochrome b light chain (CYBA), encoded by a polymorphic gene, which is a critical component of the nicotinamide adenine dinucleotide (NADH)/NADPH oxidase system and plays an important role in electron transport and superoxide anion production, is located on chromosome band 16q24 and has six exons spanning almost 7.76 kb of genomic DNA. CYBA gene polymorphisms can influence the activity of NADPH oxidase. To evaluate the association between CYBA gene polymorphisms and ESRD, we genotyped five CYBA polymorphisms using TaqMan allelic discrimination assay on DNA samples from 306 healthy controls and 332 patients with ESRD. Our results suggested that rs1049255 polymorphism of CYBA modified the risk of ESRD (p  =  0.019; OR  =  0.625; 95%CI  =  0.424-0.921). GG genotype and G allele might be a protective factor against the risk of ESRD, especially in patients with chronic glomerulonephritis.

  14. Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy

    SciTech Connect

    Donadio, J.V. Jr.; Anderson, C.F.; Mitchell, J.C.; Holley, K.E.; Ilstrup, D.M.; Fuster, V.; Chesebro, J.H.

    1984-05-31

    Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of /sup 51/Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m/sup 2/ of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.

  15. The performance of matrices in daily clinical practice to predict rapid radiologic progression in patients with early RA.

    PubMed

    De Cock, D; Vanderschueren, G; Meyfroidt, S; Joly, J; Van der Elst, K; Westhovens, R; Verschueren, P

    2014-04-01

    To compare in daily clinical practice the reliability of matrices that forecast rapid radiologic progression (RRP) at year one, at year two, and over 2 years in patients with early rheumatoid arthritis (RA). Overall, 74 early RA patients with X-rays of hands and feet at baseline, year one, and year two were included. Initial DMARD combination therapy with steroids (ICTS) or DMARD monotherapy (IMT) was initiated according to patients' RA severity, based on rheumatologist opinion. The images were scored via the modified Sharp/van der Heijde (SvH) method. A total Sharp score progression of equal or higher than five per year was considered RRP. Six matrices were tested: ASPIRE CRP/ESR matrices, the BEST matrix, two SWEFOT matrices, and the ESPOIR matrix. Patients were placed in each of them yielding a RRP probability. The performance was tested by Area Under the Curve analysis reflecting the predictive value. Four patients developed RRP in year one, five in year two, and four over 2 years. With regard to face validity, the predicted probability did not correspond to the risk in reality: the one ICTS patient who developed RRP over 2 years was always found in the lowest RRP categories of all matrices. The ASPIRE CRP matrix yielded at least a moderate predicting value for the three time points. The other matrices showed moderate to no predicting value. The performance of all matrices was disappointing and it is impossible to fully rely on the existing matrices in daily clinical practice. © 2013 Published by Elsevier Inc.

  16. Antiproteinuric effect of pirfenidone in a rat model of anti-glomerular basement membrane glomerulonephritis.

    PubMed

    Takakura, Koji; Mizukami, Kazuhiko; Mitori, Hikaru; Noto, Takahisa; Tomura, Yuichi

    2014-08-15

    While pirfenidone has been established as an effective anti-fibrosis remedy, whether or not its antifibrotic effect contributes to a reduction of proteinuria remains unclear. We investigated the renoprotective properties of pirfenidone in an anti-glomerular basement membrane (GBM) glomerulonephritis model both prophylactically and therapeutically to determine its profile against proteinuria. In the prophylactic regimen, pirfenidone was treated immediately after anti-serum injection. We observed a significant reduction in the progression of proteinuria (P<0.05) and decline in renal function (P<0.01) and also noted histological improvement in renal injury. These effects appeared to be due to the maintained expression of nephrin and podocin on podocytes as well as the reduced expression of profibrotic factors like transforming growth factor-β (TGF-β). The expression of nephrin mRNA was strongly negatively correlated with the amount of urinary protein excretion (R=-0.84, P<0.001), implicating podocyte damage in the outcome of proteinuria (R(2)=0.70). These results suggest that preservation of podocytes with the pirfenidone treatment may have resulted in the decrease of proteinuria. In contrast, when the therapeutic regimen was initiated 2 weeks after nephritis induction, pirfenidone had little effect on the progression of proteinuria, although the decline of renal function and fibrosis were suppressed. Taken together, present findings suggested that pirfenidone prevented the progression of proteinuria only when administered prophylactically but was still able to ameliorate the decline of renal function independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen reduces proteinuria in anti-GBM nephritis via preservation of podocytes with markedly reduced efficacy when administered as a therapeutic regimen.

  17. Post-streptococcal glomerulonephritis leading to posterior reversible encephalopathy syndrome: a case report.

    PubMed

    Adikari, Madura; Priyangika, Dilani; Marasingha, Indika; Thamotheram, Sharmila; Premawansa, Gayani

    2014-09-13

    Posterior reversible encephalopathy syndrome is a clinical radiographic syndrome of heterogeneous etiologies. Developing hypertensive encephalopathy following post-streptococcal glomerulonephritis is a known but uncommon manifestation and developing posterior reversible encephalopathy syndrome in such a situation is very rare. We report a case with contrast-enhanced computed tomography and magnetic resonance imaging findings of posterior reversible encephalopathy syndrome in the background of acute post-streptococcal glomerulonephritis. A thirteen-year-old Sri Lankan boy presented with a focal fit by way of secondary generalization with duration of 10 minutes, and developed 2 similar fits subsequently following admission. He later developed severe hypertension with evidence of glomerulonephritis, which was diagnosed as acute post-streptococcal glomerulonephritis. A contrast-enhanced computed tomography imaging of brain done on day-3 revealed non-enhancing low-attenuating areas in fronto-parietal regions. A T2 weighted film of magnetic resonance imaging was done on day-10 of the admission and found to have linier sub-cortical hyper intensities in both parietal regions which were compatible with the radiological diagnosis of posterior reversible encephalopathy syndrome. Post-streptococcal glomerulonephritis is an important cause of acute nephritic syndrome especially in children. This case report illustrates a rare association of posterior reversible encephalopathy syndrome in a patient with post-streptococcal glomerulonephritis.

  18. CD11b is protective in complement-mediated immune complex glomerulonephritis.

    PubMed

    Alexander, Jessy J; Chaves, Lee D; Chang, Anthony; Jacob, Alexander; Ritchie, Maria; Quigg, Richard J

    2015-05-01

    In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH(-/-) mice chimeric for wild-type, CfH(-/-), CD11b(-/-), or FcRγ(-/-) bone marrow stem cells. Glomerulonephritis was worse in CD11b(-/-) chimeras compared with all others, whereas disease in FcRγ(-/-) and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b(-/-) chimeras had significantly more M1 macrophages and CD4(+) T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c(+) cells were similar in all experimental groups. CD11b(+) cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b(-/-) chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4(+) T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.

  19. Anti-glomerular basement membrane glomerulonephritis following nintedanib for idiopathic pulmonary fibrosis: a case report.

    PubMed

    Ismail, Ibrahim; Nigam, Sonu; Parnham, Alan; Srinivasa, Vinay

    2017-08-06

    We report a previously unrecognized and unreported case of a patient with anti-glomerular basement membrane glomerulonephritis following nintedanib, an orally active small molecule tyrosine kinase inhibitor. A 59-year-old Caucasian woman with a history of idiopathic pulmonary fibrosis presented with severe acute kidney injury (creatinine 285 umol/L) secondary to anti-glomerular basement membrane glomerulonephritis disease 4 months after commencement of nintedanib. She had hematuria with red blood cell casts, nephrotic range proteinuria (3.5g/24 hours) and significantly elevated anti-glomerular basement membrane glomerulonephritis titers at 860 chemiluminescent units. A kidney biopsy confirmed severe crescentic glomerulonephritis with linear immunoglobulin G deposition in glomerular basement membrane. Despite the commencement of treatment with plasma exchange and cyclophosphamide, she remained dialysis dependent. Nintedanib was discontinued. Onset of acute anti-glomerular basement membrane glomerulonephritis was found to be associated with recent nintedanib use suggesting that nintedanib may be a potential trigger for anti-glomerular basement membrane glomerulonephritis. This case highlights the importance of close monitoring of patients receiving new targeted therapies. Management of novel targeted agents in patients receiving dialysis is challenging because of the scarcity of specific data.

  20. Deletion of Nrf2 leads to rapid progression of steatohepatitis in mice fed atherogenic plus high-fat diet.

    PubMed

    Okada, Kosuke; Warabi, Eiji; Sugimoto, Hirokazu; Horie, Masaki; Gotoh, Naohiro; Tokushige, Katsutoshi; Hashimoto, Etsuko; Utsunomiya, Hirotoshi; Takahashi, Hiroshi; Ishii, Tetsuro; Yamamoto, Masayuki; Shoda, Junichi

    2013-05-01

    The transcription factor nuclear factor-E2-related factor-2 (Nrf2) inhibits lipid accumulation and oxidative stress in the liver by interfering with lipogenic pathways and inducing antioxidative stress genes. The involvement of Nrf2 in defense against the development of steatohepatitis was studied in an experimental model induced by an atherogenic plus high-fat (Ath + HF) diet. Wild-type (WT) and Nrf2-null mice were fed the diet. Their specimens were analyzed for pathology as well as for the expression levels of genes involved in fatty acid metabolism and those involved via the Nrf2 transcriptional pathway. In Nrf2-null mice fed the diet, steatohepatitis developed rapidly, leading to precirrhosis. The Ath + HF diet increased hepatic triglyceride levels and changed fatty acid composition in both mouse groups. However, oleic acid (C18:1 n-9) predominated in the livers of Nrf2-null mice. Correlating well with the pathology, the mRNA levels of the factors involved in fatty acid metabolism (Lxr, Srebp-1a, 1c, Acc-1, Fas, Scd-1, and Fatty acid transporting peptides 1, 3, 4), the inflammatory cytokine genes (Tnf-α and IL-1β), and the fibrogenesis-related genes (Tgf-β1 and α-Sma) were significantly increased in the livers of Nrf2-null mice fed the diet, compared with the levels of these factors in matched WT mice. Oxidative stress was significantly increased in the livers of Nrf2-null mice fed the diet. This change was closely associated with the decreased levels of antioxidative stress genes. Nrf2 deletion leads to the rapid onset and progression of steatohepatitis induced by an Ath + HF diet, through both up-regulation of co-regulators of fatty acid metabolism and down-regulation of oxidative metabolism regulators in the liver.

  1. Immune responses in rapidly progressive dementia: a comparative study of neuroinflammatory markers in Creutzfeldt-Jakob disease, Alzheimer's disease and multiple sclerosis.

    PubMed

    Stoeck, Katharina; Schmitz, Matthias; Ebert, Elisabeth; Schmidt, Christian; Zerr, Inga

    2014-10-15

    Immunological responses may contribute to disease progression and clinical heterogeneity in neurodegenerative dementia, for example, Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD). Recently, a rapidly progressive form of AD (rpAD) has been described. On neuropathological grounds classical AD and rpAD are not distinguishable at present. All those protein aggregopathies show a state of chronic inflammation with microglia activation and production of proinflammatory cytokines. In this context, it is hypothesized that the severity of the surrounding inflammation substantially contributes to disease progression and accelerated disease courses as seen in rpAD.

  2. [The interaction of atrial natriuretic peptide with other bioregulators of kidney function in chronic glomerulonephritis in children].

    PubMed

    Kucherenko, A G; Markov, Kh M; Zokirov, N Z; Naumova, V I

    1994-01-01

    A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.

  3. Rapid G0/1 transition and cell cycle progression in CD8(+) T cells compared to CD4(+) T cells following in vitro stimulation.

    PubMed

    Mishima, Takuya; Fukaya, Shotaro; Toda, Shoko; Ando, Yoshiaki; Matsunaga, Tsukasa; Inobe, Manabu

    2017-04-01

    T cell population consists of two major subsets, CD4(+) T cells and CD8(+) T cells, which can be distinguished by the expression of CD4 or CD8 molecules, respectively. Although they play quite different roles in an immune system, many of their basic cellular processes such as proliferation following stimulation are presumably common. In this study, we have carefully analyzed time course of G0/1 transition as well as cell cycle progression in the two subsets of quiescent T cell population following in vitro growth stimulation. We found that CD8(+) T cells promote G0/1 transition more rapidly and drive their cell cycle progression faster compared to CD4(+) T cells. In addition, expression of CD25 and effects of its blockade revealed that IL-2 is implicated in the rapid progression, but not the earlier G0/1 transition, of CD8(+) T cells.

  4. The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

    PubMed

    Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

    2013-11-04

    A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between

  5. Mycophenolate Mofetil (MMF) Efficacy in Glomerulonephritis (GN), a Retrospective Analysis.

    PubMed

    Huraib, Sameer O; Qureshi, Junaid I; Quadri, Khaja Hm; Al Flaiw, Ahmed; Al Ghamdi, Ghormullah; Jumani, Abdulqadir; Al Hejaili, Fayez; Raza, Hammad; Al Johani, Abdulaziz; Al-Katheri, Abdulmalik; Al-Khader, Abdullah A

    2005-01-01

    Mycophenolate Mofetil MMF has been widely used in post-transplant immunosuppression. Its role is emerging in GN. MMF demonstrated promising results compared with cyclosphosphamide in stage IV lupus nephritis, in a recently published trial. It has been found to have a wide safety profile, with mostly gastroinetestinal side effects, which can be avoided through titration. Its action is through inhibition of the enzyme IMDPH (ionosine monophosphate dehydrogenase), leading to purine antagonism and inhibition of lymphocytes. We were aiming to demonstrate the efficacy of MMF in our GN population. In this study, we reviewed 17 patients who received MMF (dose - 1 gm po bid) for the past year. They were only included if it was given for the management of resistant primary glomerulonephritis. Complete remission has been defined as proteinuria of less than 0.5 g/day and partial remission as a reduction of proteinuria 50% of starting MMF therapy; all 17 MMF therapy patients uniformly achieved good BP ((29%) achieved complete remission and this group consisted of 1 membranous GN, 2 lupus GN (type IV and membranous), one FSGS and one with MPGN. Four of 17 (23%) were non-responders to therapy. This group articles.aspx? id=41 to side effects. We conclude that the MMF appears to be an effective alternate treatment modality in resistant membranous GN, lupus nephritis (type IV and V) and possibly MPGN, and to a lesser extent in resistant FSGS. Further prospective data may demonstrate the efficacy of MMF in GN.

  6. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis

    PubMed Central

    Kain, Renate; Exner, Markus; Brandes, Ricarda; Ziebermayr, Reinhard; Cunningham, Dawn; Alderson, Carol A; Davidovits, Agnes; Raab, Ingrid; Jahn, Renate; Ashour, Oliver; Spitzauer, Susanne; Sunder-Plassmann, Gere; Fukuda, Minoru; Klemm, Per; Rees, Andrew J; Kerjaschki, Dontscho

    2009-01-01

    Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P41–49) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN. PMID:18836458

  7. Clinicopathological insights into lupus glomerulonephritis in Japanese and Asians.

    PubMed

    Yokoyama, Hitoshi; Okuyama, Hiroshi; Yamaya, Hideki

    2011-06-01

    Lupus nephritis comprises a spectrum of glomerular, vascular, and tubulointerstitial lesions, which has significant racial variation in severity and manifestations. The current classification (ISN/RPS 2003) has been improved successfully for the categorization of lupus glomerulonephritis (LGN). On the basis of this classification, 480 Japanese cases revealed the following distribution: class I 3%, class II 16%, class III 13%, class IV-S 11%, class IV-G 41%, class V 16%, and class VI 1%. Class IV-G with chronicity tended to have the worst renal outcome. Nephrotic syndrome was a more frequent complication in class IV-S (50%), class IV-G (72%), and class V (56%), with poor renal and actuarial outcomes. With regard to therapy, treatment options including glucocorticoids alone or combined with antimetabolites (azathioprine, mizoribine, mycophenolate mofetil), calcineurin inhibitors (cyclosporine A, tacrolimus), or alkylating agents (intravenous cyclophosphamide injection) improved the outcome of LGN; however, there is no high-grade clinical evidence from Japan. Further studies are needed to resolve the clinicopathological problems of LGN, especially IV-S, IV-G, and pure membranous lupus nephritis in Japanese patients.

  8. Increased intracellular levels of lysosomal beta-glucuronidase in peripheral blood PMNs from humans with rapidly progressive periodontitis.

    PubMed

    Pippin, D J; Cobb, C M; Feil, P

    1995-01-01

    Release of potent lysosomal enzymes by degranulation of polymorphonuclear leukocytes (PMNs) in host gingiva may contribute significantly to tissue destruction and the pathogenesis of periodontal disease. A pilot study established that peripheral blood PMNs from humans with rapidly progressive periodontitis (RPP) contained significantly increased amounts of intracellular lysosomal beta-glucuronidase as compared to healthy controls. This investigation gained insight into the question: are the increased levels of beta-glucuronidase in persons with RPP an a priori genetically determined PMN characteristic, or a reactive phenomenon induced by the periodontal disease process during granulopoiesis? Twelve healthy controls and twelve otherwise healthy individuals with RPP participated in a repeated measures design to T0 (initial, baseline), T1 (four weeks after disease control therapy), and T2 (two months later). At each visit clinical indices (GI, pocket depths, GCF flow, plaque index) were performed and peripheral blood obtained. PMNs were isolated and suspended as 5 x 10(6) cells in 2.0 ml of HBSS. PMN suspensions were tested for total intracellular beta-glucuronidase, degranulation induced by 1 x 10(-6)M and 5 x 10(-7) M FMLP challenges, and unchallenged for non-specific enzyme release. PMNs from individuals with RPP contained significantly higher absolute amounts of beta-glucuronidase and released greater absolute amounts at FMLP challenge at T0, T1, and T2 compared to controls. No relationship was found between any of the clinical indices and beta-glucuronidase levels and no pattern was discovered relating to the repeated measures over time. We conclude that RPP peripheral blood PMNs contain elevated levels of beta-glucuronidase that are not induced by the periodontal disease process.

  9. Granulomatosis with polyangiitis presenting with diffuse alveolar hemorrhage requiring extracorporeal membrane oxygenation with rapid multiorgan relapse

    PubMed Central

    Vanoli, Jennifer; Riva, Marta; Vergnano, Beatrice; D’Andrea, Gabriele; L’Imperio, Vincenzo; Pozzi, Maria Rosa; Grassi, Guido

    2017-01-01

    Abstract Rationale: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitis affecting small- and medium-sized blood vessels, mostly involving lung and kidney. Patient concerns: We report the case of a 33-year-old man that presented with acute respiratory distress syndrome caused by alveolar hemorrhage. Diagnoses: Aggressive GPA presenting with diffuse alveolar hemorrhage and multiorgan involvement. Inteventions: Immunosuppressive therapy, plasma exchange, extracorporeal membrane oxygenation (ECMO). Outcomes: Relapse occurred very early, despite immunosuppressive treatment, with a rare involvement of genital system (epididymitis) and rapidly progressive glomerulonephritis difficult to treat. Lessons: GPA is a challenging, multifaceted disease that can require aggressive supportive therapy and is associated with a high rate of relapse that may present with uncommon site of involvement. PMID:28353556

  10. [A clinico-morphologico-functional study of the kidneys in glomerulonephritis].

    PubMed

    Varshavskiĭ, V A; Sorokina, M N; Tomlina, N A; Kupriianova, L A

    1975-01-01

    The article deals with the results of a clinico-functional-morphological study of the kidneys in glomerulonephritis (50 observations) which was carried out with the use of the method of puncture biopsy of the kidneys. It was shown that clinical forms of glomerulonephritis, accompanied with hematuria, were characterized by the absence of fixation of immune complexes in the basal membrane of the glomeruli. According to the electron microscopy data, this corresponds to the dissappearance of deposits from the subendothelial parts of the basal membrane. The extramembranous glomerulonephritis, revealed with the help of electron microscopy technique, was characterized by the nephrotic syndrome. An increased tension of immunological processes in the glomeruli was accompanied by a more grave clinical course of glomerulonephritis, by impairment of not only glomerulous but tubular functions as well. A greater dicrease in the function of osmotic concentration of the urine in fibroplastic types of glomerulonephritis, as compared with non-firboplastic ones, was apparently connected not only with lesiones of tubules but rather with more expressed sclerotic changes in the interstitial tissue of the kidney.

  11. Anti–LAMP-2 Antibodies Are Not Prevalent in Patients With Antineutrophil Cytoplasmic Autoantibody Glomerulonephritis

    PubMed Central

    Brown, Michael C.; Smith, Rex Neal; Badhwar, Anshul K.; Parente, Oscar; Chung, Hyun chul; O’Dell, Donna; Bunch; McGregor, JulieAnne G.; Hogan, Susan L.; Hu, Yichun; Yang, Jia-Jin; Berg, Elisabeth A.; Niles, John; Jennette, J. Charles; Preston, Gloria A.; Falk, Ronald J.

    2012-01-01

    Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti–LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti–LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti–LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti–proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti–LAMP-2 titers, respectively. There was no correlation between anti–LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti–LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti–LAMP-2 antibodies and ANCA glomerulonephritis. PMID:22021709

  12. Circulating TGF-β1–Regulated miRNAs and the Risk of Rapid Progression to ESRD in Type 1 Diabetes

    PubMed Central

    Pezzolesi, Marcus G.; Satake, Eiichiro; McDonnell, Kevin P.; Major, Melissa; Smiles, Adam M.

    2015-01-01

    We investigated whether circulating TGF-β1–regulated miRNAs detectable in plasma are associated with the risk of rapid progression to end-stage renal disease (ESRD) in a cohort of proteinuric patients with type 1 diabetes (T1D) and normal eGFR. Plasma specimens obtained at entry to the study were examined in two prospective subgroups that were followed for 7–20 years (rapid progressors and nonprogressors), as well as a reference panel of normoalbuminuric T1D patients. Of the five miRNAs examined in this study, let-7c-5p and miR-29a-3p were significantly associated with protection against rapid progression and let-7b-5p and miR-21-5p were significantly associated with the increased risk of ESRD. In logistic analysis, controlling for HbA1c and other covariates, let-7c-5p and miR-29a-3p were associated with more than a 50% reduction in the risk of rapid progression (P ≤ 0.001), while let-7b-5p and miR-21-5p were associated with a >2.5-fold increase in the risk of ESRD (P ≤ 0.005). This study is the first prospective study to demonstrate that circulating TGF-β1–regulated miRNAs are deregulated early in T1D patients who are at risk for rapid progression to ESRD. PMID:25931475

  13. Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats.

    PubMed

    Higuchi, N; Maruyama, H; Kuroda, T; Kameda, S; Iino, N; Kawachi, H; Nishikawa, Y; Hanawa, H; Tahara, H; Miyazaki, J; Gejyo, F

    2003-08-01

    Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4+ T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.

  14. Maximal suppression of renin-angiotensin system in nonproliferative glomerulonephritis.

    PubMed

    Iodice, Carmela; Balletta, Mario M; Minutolo, Roberto; Giannattasio, Paolo; Tuccillo, Stefano; Bellizzi, Vincenzo; D'Amora, Maurizio; Rinaldi, Giorgio; Signoriello, Giuseppe; Conte, Giuseppe; De Nicola, Luca

    2003-06-01

    Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined. We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone. Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.

  15. ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

    PubMed Central

    Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.

    2016-01-01

    Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575

  16. Experimental immune complex-mediated glomerulonephritis in the nonhuman primate

    SciTech Connect

    Hebert, L.A.; Cosio, F.G.; Birmingham, D.J.; Mahan, J.D.; Sharma, H.M.; Smead, W.L.; Goel, R. )

    1991-01-01

    This study was undertaken to develop a model of immune complex (IC)-mediated glomerulonephritis (GN) in the nonhuman primate that could be used in subsequent studies to examine critically the role of the erythrocyte complement receptor (E-CR) in the pathogenesis of IC-mediated disease. Cynomolgus monkeys were chosen for study because they constitutively express E-CR levels that are either less than, equal to, or greater than that seen in normal man. After immunization with bovine gamma globulin (BGG), the GN induction protocol was begun in 10 cynomolgus by initiating daily i.v. administration of BGG in amounts sufficient to achieve or exceed antigen/antibody equivalence (assessed by the quantitative precipitin assay) for precipitating antibody present in the plasma volume. We found that within eight weeks of daily BGG administration of all the cynomolgus developed IC-mediated GN, irrespective of the initial E-CR level of the animals. However, the high E-CR cynomolgus tended to receive the higher BGG doses because of higher initial antibody levels to BGG. When the total number of glomerular deposits (determined by morphometric studies) per total BGG dose for each animal was plotted against the initial CR/E of that animal, there was a tendency for the animals with higher CR/E levels to have a lower number of glomerular deposits/BGG dose. Also, the total number of glomerular deposits correlated with the severity of the GN. During the early weeks of the GN induction protocol, the IC that formed in vivo (assessed by infusion of 125I-BGG) bound in large amounts to the circulating erythrocytes of the cynomolgus with medium or high E-CR levels. However, when tested after the onset of heavy proteinuria, which occurred between weeks 5 and 8 of daily BGG administration, the IC that formed in the circulation bound only poorly to circulating erythrocytes.

  17. Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus induced a remakable response of rapid progressive Uterine PEComa.

    PubMed

    Gao, Fang; Huang, Chengsuo; Zhang, Yiping; Sun, Ruirui; Zhang, Yujie; Wang, Huijun; Zhang, Shu

    2016-06-02

    Perivascular epithelioid cell tumor is a rare tumor. To date, there is no consensus of therapy to be recommended for unresectable disease. For a low incidence and a rarely curable disease, the finding of new therapy is essential. Here we report the first case of a patient with perivascular epithelioid cell tumor whose disease had a rapid progression after surgery and had a rapid remarkable response of combination therapy of a VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus. This result may have potential to deliver a new treatment option and inhibiting the mTOR pathway combined with inhibiting the VEGF pathways may be a useful strategy for malignant PEComas.

  18. Comparative Analysis of Outcomes of Kidney Transplantation in Patients With AA Amyloidosis and Chronic Glomerulonephritis.

    PubMed

    Sahutoglu, T; Atay, K; Caliskan, Y; Kara, E; Yazici, H; Turkmen, A

    2016-01-01

    Amyloid A (AA) amyloidosis is a multisystemic, progressive, and severe disease. Renal involvement is a prominent feature of the disease, and the outcome of patients on dialysis is poor. We aimed to analyze the outcomes of kidney transplantation in patients with AA amyloidosis in comparison with chronic glomerulonephritis (CGN). Charts of patients who underwent kidney transplantation between 1988 and 2012 were reviewed; 41 patients with AA amyloidosis were identified, and 41 age- and sex-matched control patients with chronic CGN were included. Baseline characteristics, immunosuppressive regimens, and transplantation-related outcomes were retrieved using a standardized form. The mean follow-up period was 70.9 ± 44.9 months. The 10-year patient survival was found to be significantly worse in the AA amyloidosis group (62.5%) compared to CGN group (100%) (P = .008). During the follow-up period, three of the 41 patients (9.7%) died of sepsis and one patient died of cardiac complications in the amyloidosis group, whereas there was no patients were lost in the CGN group. The first-year, fifth-year, and tenth-year mean graft survival rates, acute and chronic rejections, and mean creatinine levels at last visits were not significantly different between the groups. Proteinuria >1 g/d, cytomegalovirus and tuberculosis infections, and rhabdomyolysis were recorded at a significantly higher rate in patients with amyloidosis. As compared to patients with CGN, patients with AA amyloidosis had a lower patient survival; equal graft survival and rejection rates; and higher risks of developing proteinuria, cytomegalovirus and tuberculosis infections, and rhabdomyolysis. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Post-infectious glomerulonephritis with crescents in adults: a retrospective study

    PubMed Central

    Baikunje, Shashidhar; Vankalakunti, Mahesha; Nikith, A.; Srivatsa, A.; Alva, Suhan; Kamath, Janardhan

    2016-01-01

    Background Crescent formation generally reflects severe glomerular injury. There is sparse literature on post-infectious glomerulonephritis (PIGN) with crescents in adults. This retrospective study looked at nine such cases to see if there is a correlation between the severity of presentation, steroid treatment, histological severity and outcome. Methods Biopsy reports of all the adults who underwent kidney biopsy from February 2010 to June 2014 in a tertiary care hospital were screened and all the cases with the diagnosis of PIGN with crescents were selected. Clinical presentation, laboratory data, histology, treatment and outcome were analysed. Results Six patients had evidence of recent/current infection, but all except two were non-streptococcal. The mean creatinine was 360.67 μmol/L (range 70.72–770.85) and the mean estimated glomerular filtration rate (MDRD eGFR) was 30.28 mL/min/1.73 m2 (range 6.4–111.1) on presentation. All five patients who were treated with steroids had an excellent response. Among the four patients who did not receive steroids, two were left with significant renal impairment (mean MDRD eGFR 23.5 mL/min/1.73 m2) at a mean follow-up of 15.5 months (range 10–21). The mean percentage of glomeruli with crescents was 36.13% (range 11.76–100) and except in one, there was no tubular atrophy or interstitial fibrosis and none had glomerulosclerosis. None of the patients progressed to end-stage renal disease. Conclusion Non-streptococcal infections are more common precipitants. There was no correlation between histological and clinical severity. Patients treated with steroids had better renal outcomes. PMID:26985372

  20. CD11b is protective in complement-mediated immune complex glomerulonephritis

    PubMed Central

    Alexander, Jessy J; Chaves, Lee D; Chang, Anthony; Jacob, Alexander; Ritchie, Maria; Quigg, Richard J

    2015-01-01

    In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex–mediated glomerulonephritis in CfH−/− mice chimeric for wild-type, CfH−/−, CD11b−/−, or FcRγ−/− bone marrow stem cells. Glomerulonephritis was worse in CD11b−/− chimeras compared with all others, whereas disease in FcRγ−/− and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b−/− chimeras had significantly more M1 macrophages and CD4+ T cells. The renal dendritic cell populations originating from bone marrow–derived CD11c+ cells were similar in all experimental groups. CD11b+ cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b−/− chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex–mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4+ T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney. PMID:25565310

  1. Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix.

    PubMed Central

    Okuda, S; Languino, L R; Ruoslahti, E; Border, W A

    1990-01-01

    Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological

  2. Implications of Antiphospholipid and Antineutrophilic Cytoplasmic Antibodies in the Context of Postinfectious Glomerulonephritis

    PubMed Central

    Leifer, Daniel

    2017-01-01

    While antineutrophil cytoplasmic antibody (ANCA) positivity has been documented in some patients with postinfectious glomerulonephritis (PIGN) and is associated with more severe disease, antiphospholipid antibodies (APA) are not known to be a common occurrence. We describe a child with severe acute kidney injury who was noted to have prolonged positivity of both ANCA and APA; a renal biopsy showed noncrescentic immune complex mediated glomerulonephritis with subepithelial deposits compatible with PIGN. He recovered without maintenance immunosuppressive therapy and at last follow-up had normal renal function. We discuss the cooccurrence and implications of ANCA and APA in children with PIGN. PMID:28255306

  3. [Goodpasture syndrome and (idiopathic) immune complex glomerulonephritis with pulmonary hemorrhage: 2 different syndromes?].

    PubMed

    Kuhn, M; Gartmann, J; Grob, P J; Widder, W; Hartmann, G

    1984-06-23

    While Goodpasture syndrome was previously defined purely clinically by the combination of pneumorrhagia and glomerulonephritis, today the following immunologic criteria must also be satisfied: evidence, provided by immunofluorescent investigation of the kidneys and lungs, of antibasement membrane antibodies in the serum and linear deposits of immunoglobulins, due to direct apposition of antibasement membrane antibodies. Cases where the lesions are caused by immune complexes should no longer be designated as Goodpasture syndrome. In the light of one of our own cases of immune complex glomerulonephritis with pneumorrhagia, the question is raised whether this subdivision by means of immunologic investigations is meaningful for the clinician.

  4. Kidney Transplantation Rates Across Glomerulonephritis Subtypes in the United States.

    PubMed

    OʼShaughnessy, Michelle M; Liu, Sai; Montez-Rath, Maria E; Lafayette, Richard A; Winkelmayer, Wolfgang C

    2017-10-01

    Whether kidney transplantation rates differ by glomerulonephritis (GN) subtype remains largely unknown. Using the US Renal Data System, we identified all adult patients with end-stage renal disease attributed to 1 of 6 GN subtypes who initiated dialysis in the US (1996-2013). Patients with diabetic nephropathy (DN) and autosomal-dominant polycystic kidney disease (ADPKD) served as "external" non-GN comparators. Using Cox proportional hazards regression, with death considered a competing risk, we estimated hazard ratios (HRs) (95% confidence intervals [CI]) for first kidney transplantation, controlling for year, demographics, comorbidities, socioeconomic factors, and Organ Procurement Organization. Among 718 480 patients studied, unadjusted and multivariable-adjusted transplant rates differed considerably across GN subtypes. Adjusted transplant rates were highest for patients with IgA nephropathy (IgAN) (referent) and lower for all other groups: focal segmental glomerulosclerosis (HR, 0.80; 95% CI, 0.77-0.82), membranous nephropathy (HR, 0.88; 95% CI, 0.83-0.93), membranoproliferative GN (HR, 0.84; 95% CI, 0.76-0.92), lupus nephritis (HR, 0.69; 95% CI, 0.66-0.71), vasculitis (HR, 0.66; 95% CI, 0.61-0.70), DN (HR, 0.50; 95% CI, 0.47-0.52), ADPKD (HR, 0.85; 95% CI, 0.82-0.88). Reduced kidney transplantation rates among comparator groups were driven more so by lower rates of waitlisting (HRs vs IgAN, ranged from 0.49 for DN to 0.92 for membranous nephropathy or ADPKD) than by lower rates of deceased donor kidney transplantation after waitlisting (rates were only significantly lower, vs IgAN, for those with secondary GN subtypes: lupus nephritis [HR,0.91; 95% CI, 0.86-0.97], vasculitis [HR, 0.85; 95% CI, 0.76-0.94), DN [HR, 0.73; 95% CI, 0.69-0.77]). Identifying underlying reasons for apparent disease-specific barriers to kidney transplantation might inform center-specific transplant candidate selection procedures, along with national organ allocation policies, leading

  5. The prognosis and pathogenesis of severe lupus glomerulonephritis.

    PubMed

    Schwartz, Melvin M; Korbet, Stephen M; Lewis, Edmund J

    2008-04-01

    The International Society of Nephrology/ Renal Pathology Society classification (ISN/RPS) of lupus glomerulonephritis (GN) divides diffuse GN (>/=50% involvement) into diffuse segmental (IV-S) and diffuse global GN (IV-G). This division tests whether the pathogenesis and clinical outcomes are the same as when similar patients are classified using the World Health Organization (WHO) classification into severe segmental (WHO III >/=50%) and diffuse global (WHO-IV) GN. Thirty-nine renal biopsies with WHO class IV and 44 with WHO III >/= 50% were reclassified using the ISN/RPS and were correlated with pathogenesis and outcome. There were 22 biopsies with ISN/RPS class IV-S. ISN/RPS class IV-G comprises two morphologically discrete classes of renal biopsies: 39 biopsies originally classified as WHO class IV (WHO-IV) and 22 that switched from WHO III >/=50% to ISN/RPS class IV-G (IV-Q). We will analyze IV-S, IV-Q and WHO-IV separately. WHO-IV had significantly more immune aggregate deposition than IV-S and IV-Q. WHO-IV had lower serum complements C3 (P = 0.05) and C4 (P = 0.05) than patients with IV-Q. Patients with WHO-IV had more remissions (56%) than IV-Q (23%) (P = 0.01), and stable renal function at the last follow-up was less frequent in patients with IV-Q (18%) than IV-S (50%, P = 0.05) and WHO-IV (62%, P = 0.001). Renal survival and renal survival without end-stage renal disease were different when the patients were diagnosed as WHO classes III >/=50% and IV, but the outcomes for ISN/RPS class IV-S and IV-G (WHO-IV plus IV-Q) were not different. WHO III >/=50% and WHO-IV lupus GN are not congruent with ISN/RPS IV-S and IV-G. The ISN/RPS minimizes pathological and outcome differences between classes IV-S and IV-G which results in the loss of informational content from the renal biopsies. ISN/RPS does not detect pathogenetic or clinical differences among patients with severe lupus GN.

  6. Granulomatosis with polyangiitis presenting with diffuse alveolar hemorrhage requiring extracorporeal membrane oxygenation with rapid multiorgan relapse: A case report.

    PubMed

    Vanoli, Jennifer; Riva, Marta; Vergnano, Beatrice; D'Andrea, Gabriele; L'Imperio, Vincenzo; Pozzi, Maria Rosa; Grassi, Guido

    2017-03-01

    Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitis affecting small- and medium-sized blood vessels, mostly involving lung and kidney. We report the case of a 33-year-old man that presented with acute respiratory distress syndrome caused by alveolar hemorrhage. Aggressive GPA presenting with diffuse alveolar hemorrhage and multiorgan involvement. Immunosuppressive therapy, plasma exchange, extracorporeal membrane oxygenation (ECMO). Relapse occurred very early, despite immunosuppressive treatment, with a rare involvement of genital system (epididymitis) and rapidly progressive glomerulonephritis difficult to treat. GPA is a challenging, multifaceted disease that can require aggressive supportive therapy and is associated with a high rate of relapse that may present with uncommon site of involvement.

  7. Association of Generalized Psoriasis and Mixed Glomerulonephritis in a 10-year-old Girl.

    PubMed

    Milošević, Danko; Husar, Karmela; Batinić, Danica; Ćorić, Marijana; Jović, Anamaria; Turudić, Daniel; Pelajić, Stipe; Dumić Čule, Ivo

    2017-07-01

    Generalized psoriasis and renal function disorder were previously described in sporadic adult cases, revealing a new entity - psoriatic nephropathy. So far there have been only two cases describing this association in children. We present and discuss a case of 10-year-old girl with the unique biopsy findings of double glomerulonephritis associated with the simultaneous onset of generalized psoriasis.

  8. [Prophylaxis and prognosis of preeclampsia in patients with chronic pyelonephritis and chronic glomerulonephritis].

    PubMed

    Zufarova, Sh A

    2010-01-01

    The investigations performed showed that pregnant women with chronic pyelonephritis (CP) and chronic glomerulonephritis (CG) have certain response to therapy done in accordance with level of kidney function activity. In the pregnant women with CP and CG and kidney functional reserve KFR > 10% and from 5 to 10% the treatment efficacy was higher and practically absent in pregnant women with KFR < 5%.

  9. [Efficiency of a complex preventive therapy including wobenzym in pregnant women with chronic pyelonephritis and glomerulonephritis].

    PubMed

    Zufarova, Sh A

    2010-01-01

    Pregnant women with pyelonephritis (PN) and glomerulonephritis (GN) were shown to have response to the therapy in accordance with level of kidney functional activity. The women with PN and GN have the treatment efficacy higher with Kidney Functional Reserve KFR > 10% and from 5 to 10% and practically absent in pregnant women with KFR < 5% (Kidney functional reserve).

  10. Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation.

    PubMed

    McGuire, Brendan M; Julian, Bruce A; Bynon, J Steve; Cook, William J; King, Steven J; Curtis, John J; Accortt, Neil A; Eckhoff, Devin E

    2006-05-16

    Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. To describe renal histologic characteristics and concomitant clinical features in HCV-infected patients with end-stage cirrhosis. Case series. Single-center liver transplant program in the United States. 30 patients who received liver transplants for HCV-induced cirrhosis. Kidney biopsy during liver engraftment. Clinical data and laboratory tests of renal function within 6 months before liver transplantation. Twenty-five patients had immune-complex glomerulonephritis: membranoproliferative glomerulonephritis type 1 (n = 12), IgA nephropathy (n = 7), and mesangial glomerulonephritis (n = 6). Of these patients, 10 had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For 5 others, the only renal abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. This small observational study did not include patients with nonviral cirrhosis and did not document post-transplantation outcomes. Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. Its potential to cause renal failure after liver transplantation may be underappreciated.

  11. HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases

    PubMed Central

    Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng

    2016-01-01

    Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989

  12. Systemic lupus erythematosus with membranous glomerulonephritis and transverse myelitis associated with anabolic steroid use.

    PubMed

    Radis, C D; Callis, K P

    1997-10-01

    This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.

  13. Bartonella Endocarditis and Pauci-Immune Glomerulonephritis: A Case Report and Review of the Literature.

    PubMed

    Raybould, Jillian E; Raybould, Alison L; Morales, Megan K; Zaheer, Misbah; Lipkowitz, Michael S; Timpone, Joseph G; Kumar, Princy N

    2016-09-01

    Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti-neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.

  14. Glomerular nitrite synthesis in in situ immune complex glomerulonephritis in the rat.

    PubMed Central

    Cook, H. T.; Sullivan, R.

    1991-01-01

    Nitrite (NO2-) is the major end product of nitric oxide (NO) production in cell culture. The authors have examined nitrite production by glomeruli in in situ immune complex glomerulonephritis in the rat. Glomerulonephritis was induced by unilateral renal perfusion of cationized human gamma G immunoglobulin (IgG) in preimmunized rats. NO2- was measured in culture supernatants of isolated glomeruli after 48 hours. NO2- was produced by nephritic glomeruli with a maximum 4 days after induction of glomerulonephritis (24.4 +/- 11.4 pmol/glomerulus/48 hours). Production was increased by lipopolysaccharide (LPS; 1 micrograms/ml) (54 +/- 4.9 pmol/glomerulus; P less than 0.001). NO2- production was inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine demonstrating synthesis through NO. Dexamethasone (10(-7) mol/l [molar]) reduced LPS-stimulated production by peritoneal macrophages and nephritic glomeruli (P less than 0.01). Macrophages isolated from nephritic glomeruli produced NO2- (4.9 +/- 0.6 nmols/10(5) cells). The production of NO by nephritic glomeruli has implications for mechanisms of glomerular injury and glomerular hemodynamics. The effect of dexamethasone may explain in part the ameliorative effect of steroids in glomerulonephritis. Images Figure 4 PMID:1951626

  15. A rare adult case of poststreptococcal acute glomerulonephritis with a retropharyngeal abscess.

    PubMed

    Takashima, Tsuyoshi; Hirata, Sae; Nonaka, Mai; Matsumoto, Keiichiro; Awanami, Yuki; Yamasaki, Masatora; Fukuda, Makoto; Miyazono, Motoaki; Ikeda, Yuji

    2017-05-01

    Retropharyngeal abscess is an infection involving the retropharyngeal space which is posterior to the pharynx and oesophagus, and it results as a complication of a primary infection elsewhere in the head and neck including the nasopharynx, paranasal sinuses, or middle ear, which drain lymph to the retropharyngeal lymph nodes. Their lymph nodes are prominent in children and atrophy with age. Therefore, retropharyngeal abscess is most frequently encountered in children, with 75% of cases occurring before the age of 5 years, and often in the first year of life. We experienced a rare adult case of poststreptococcal acute glomerulonephritis with a retropharyngeal abscess, and conservative therapy ameliorated them. According to past reports, only one child with a retropharyngeal abscess and poststreptococcal acute glomerulonephritis has been presented at a conference to date; this is the first adult case of poststreptococcal acute glomerulonephritis with a retropharyngeal abscess. Retropharyngeal abscess can be fatal including airway compression, so it is important to remember retropharyngeal abscess in a case of poststreptococcal acute glomerulonephritis with severe symptoms of neck.

  16. Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

    PubMed Central

    2011-01-01

    Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression. PMID:21831310

  17. Rapid CKD progression in a new mouse kidney remnant model: strain-dependent resistance is overcome by angiotensin II

    PubMed Central

    Leelahavanichkul, Asada; Yan, Qin; Hu, Xuzhen; Eisner, Christoph; Huang, Yuning; Chen, Richard; Mizel, Diane; Zhou, Hua; Wright, Elizabeth C.; Kopp, Jeffrey B.; Schnermann, Jürgen; Yuen, Peter S.T.; Star, Robert A.

    2011-01-01

    The remnant kidney model in C57BL6 mice does not develop progressive chronic kidney disease (CKD). In this study we modified the model to mimic features of human CKD and to define accelerants of disease progression using three strains of mice. Following the procedure there was a progressive increase in albuminuria, progressive loss in renal function, severe glomerulosclerosis and interstitial fibrosis, hypertension, cardiac fibrosis, and anemia by 4 weeks in CD-1 mice and by 12 weeks in 129S3 mice. In contrast, even after 16 weeks, the C57BL/6 mice with a remnant kidney had modestly increased albuminuria without increased blood pressure and without developing CKD or cardiac fibrosis. The baseline blood pressure, determined by radiotelemetry in conscious animals, correlated with CKD progression rates in each strain. Administering angiotensin II overcame the resistance of C57BL/6 mice to CKD following renal mass reduction displaying high blood pressure and albuminuria, severe glomerulosclerosis, and loss of renal function by 4 weeks. Decreasing blood pressure with olmesartan but not hydralazine in CD-1 mice with a remnant kidney reduced CKD progression and cardiac fibrosis. C57BL/6 mice with a remnant kidney and DOCA-salt hypertension developed modest CKD. Each strain had similar degrees of interstitial fibrosis in three different normotensive models of renal fibrosis. Thus reducing renal mass in CD-1 or 129S3 mice mimics many features of human CKD. Angiotensin II can convert the C57BL/6 strain from CKD-resistant to susceptible in this disease model. PMID:20736988

  18. Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters.

    PubMed

    Socías, M Eugenia; Sued, Omar; Laufer, Natalia; Lázaro, María E; Mingrone, Horacio; Pryluka, Daniel; Remondegui, Carlos; Figueroa, María I; Cesar, Carina; Gun, Ana; Turk, Gabriela; Bouzas, María B; Kavasery, Ravi; Krolewiecki, Alejandro; Pérez, Héctor; Salomón, Horacio; Cahn, Pedro

    2011-08-10

    Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.

  19. Interleukin-6 exacerbates glomerulonephritis in (NZB x NZW)F1 mice.

    PubMed Central

    Ryffel, B.; Car, B. D.; Gunn, H.; Roman, D.; Hiestand, P.; Mihatsch, M. J.

    1994-01-01

    The ability of interleukin-6 (IL-6) to modulate immune parameters and mesangial cell function suggests a role for this cytokine in the development of autoimmune glomerulonephritis. This hypothesis was tested in 6-month-old female (NZB x NZW)F1 mice that were administered recombinant human IL-6 (rhIL-6) (50 and 250 micrograms/kg s.c.) for 12 weeks, resulting in an accelerated and severe form of membranoproliferative glomerulonephritis associated with marked upregulation of mesangial major histocompatibility complex class II antigen and glomerular ICAM-1 expression. To distinguish direct effects of rhIL-6 on the renal mesangium from those mediated through the immune system, (NZB x NZW)F1 mice were immunosuppressed with cyclosporin. Immunosuppression by cyclosporin inhibited the development of glomerulonephritis, decreased class II antigen expression, and abrogated IL-6-mediated effects. Administration of neutralizing anti-IL-6 antibody had no effect on the spontaneous development of glomerulonephritis in (NZB x NZW)F1 mice. This finding, together with undetectable IL-6 serum levels, makes a pathogenetic role of endogenously produced IL-6 in this disease model unlikely. In contrast to (NZB x NZW)F1 mice, parental NZW or BALB/c mice given high doses of rhIL-6 (500 micrograms/kg) or recombinant murine IL-6 (100 micrograms/kg) daily for 4 weeks failed to develop morphological or biochemical evidence of glomerulonephritis. Induction of acute phase proteins, anemia, thrombocytosis, and induction of renal class II antigen confirmed the biological activity of IL-6 in these mice. In conclusion, while non-nephritogenic in normal mice, IL-6 accelerates the development of the genetically determined glomerulonephritis of (NZB x NZW)F1 mice through effects mediated by a modulated immune system. Since neutralizing IL-6 antibody treatment did not prevent the development of glomerulonephritis, it is unlikely that increased IL-6 production plays a role in the pathogenesis of lupus

  20. The effects of soluble recombinant complement receptor 1 on complement-mediated experimental glomerulonephritis.

    PubMed

    Couser, W G; Johnson, R J; Young, B A; Yeh, C G; Toth, C A; Rudolph, A R

    1995-05-01

    Complement is a major mediator of tissue injury in several types of glomerulonephritis. However, no therapeutic agents that inhibit complement activation are available for human use. sCR1 (TP10, BRL 55736) is a recombinant, soluble human complement receptor 1 (CR1) molecule lacking transmembrane and cytoplasmic domains that inhibits C3 and C5 convertase activity by preferentially binding C4b and C3b. To test the efficacy of sCR1 on complement-mediated glomerulonephritis, rats were pretreated with sCR1 (60 mg/kg per day) before and during the induction of three models of complement-dependent glomerulonephritis (concanavalin A and antithymocyte serum models of proliferative glomerulonephritis, passive Heyman nephritis). Daily sCR1 and complement hemolytic activity levels were measured, and renal histology and urine protein excretion were examined. Mean serum sCR1 levels of 100 to 200 micrograms/mL were maintained with a reduction in complement hemolytic activity to less than 15% in most animals. In the antithymocyte serum model, sCR1-treated animals had significant reductions in mesangiolysis, glomerular platelet and macrophage infiltrates, and proteinuria at 48 h. In the concanavalin A model, sCR1 significantly reduced glomerular C3 and fibrin deposits, platelet infiltrates, and proteinuria at 48 h. In passive Heymann nephritis, proteinuria was also significantly reduced (199 +/- 8.5 versus 125 +/- 16 mg/day, P < 0.002) at 5 days. It was concluded that sCR1 significantly reduces both morphologic and functional consequences of several different types of complement-mediated glomerulonephritis and deserves evaluation as a potential therapeutic agent in complement-mediated immune glomerular disease in humans.

  1. Rhodococcus fascians infection accelerates progression of tobacco BY-2 cells into mitosis through rapid changes in plant gene expression.

    PubMed

    Vandeputte, Olivier; Vereecke, Danny; Mol, Adeline; Lenjou, Marc; Van Bockstaele, Dirk; El Jaziri, Mondher; Baucher, Marie

    2007-01-01

    * To characterize plant cell cycle activation following Rhodococcus fascians infection, bacterial impact on cell cycle progression of tobacco BY-2 cells was investigated. * S-phase-synchronized BY-2 cells were cocultivated with R. fascians and cell cycle progression was monitored by measuring mitotic index, cell cycle gene expression and flow cytometry parameters. Cell cycle alteration was further investigated by cDNA-AFLP (amplified fragment length polymorphism). * It was shown that cell cycle progression of BY-2 cells was accelerated only upon infection with bacteria whose virulence gene expression was induced by a leafy gall extract. Thirty-eight BY-2 genes showed a differential expression within 6 h post-infection. Among these, seven were previously associated with specific plant cell cycle phases (in particular S and G2/M phases). Several genes also showed a differential expression during leafy gall formation. * R. fascians-infected BY-2 cells provide a simple model to identify plant genes related to leafy gall development. R. fascians can also be regarded as a useful biotic agent to alter cell cycle progression and, thereby, gain a better understanding of cell cycle regulation in plants.

  2. Cutaneous lymphocyte antigen expression loss and PD1 positivity in early cutaneous lesions of rapidly progressive mycosis fungoides

    PubMed Central

    Ogunrinade, Olakunle; Ahn, Christine S; Gergis, Usama; Yassin, Aminah H; Magro, Cynthia

    2014-01-01

    Key Clinical Message It's important to assess cases both clinically and pathologically for factors potentially predictive of an aggressive clinical course. We concluded that the relative immunosuppressive effects of PD1 may contribute to tumor progression while the lack of staining for cutaneous lymphocyte antigen may be an additional factor facilitating distant extracutaneous migration. PMID:25614814

  3. Baseline Circulating FGF21 Concentrations and Increase after Fenofibrate Treatment Predict More Rapid Glycemic Progression in Type 2 Diabetes: Results from the FIELD Study.

    PubMed

    Ong, Kwok-Leung; O'Connell, Rachel; Januszewski, Andrzej S; Jenkins, Alicia J; Xu, Aimin; Sullivan, David R; Barter, Philip J; Scott, Russell S; Taskinen, Marja-Riitta; Waldman, Boris; Colman, Peter G; Best, James D; Simes, John R; Rye, Kerry-Anne; Keech, Anthony C

    2017-07-01

    It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function. © 2017 American Association for Clinical Chemistry.

  4. Headache attack followed by rapid disease progression in pediatric moyamoya disease--how should we manage it?

    PubMed

    Vuignier, Sandra; Akioka, Naoki; Hamada, Hideo; Kashiwazaki, Daina; Kuroda, Satoshi

    2014-10-01

    A 4-year-old female was presented at our hospital with frequent right frontal headache attack. She was diagnosed with moyamoya disease and was conservatively followed up. One year later, the frequency of headache gradually decreased. However, follow-up MR imaging revealed that the disease stage markedly progressed in the right side and cerebral infarction occurred in the temporal lobe with atrophy of the right frontal lobe. She underwent direct and indirect revascularization on the right side. Aware of this case, we would like to emphasize that headache may be one subtype of ischemic attacks and require frequent MR follow-up to see the disease course. If there is any sign of disease progression, immediate surgical intervention should be indicated to avoid irreversible brain damage.

  5. Rapidly Progressive Interstitial Lung Disease Associated with Dermatomyositis Treated with Combination of Immunosuppressive Therapy, Direct Hemoperfusion with a Polymyxin B Immobilized Fiber Column and Intravenous Immunoglobulin.

    PubMed

    Takai, Motohisa; Katsurada, Naoko; Nakashita, Tamao; Misawa, Masafumi; Mochizuki, Takahiro; Kaneko, Norihiro; Motojima, Shinji; Aoshima, Masahiro

    2015-01-01

    Rapidly progressive interstitial lung disease (ILD) is associated with dermatomyositis (DM) and has a high mortality rate even with immunosuppressive agents. For such cases, there is no evidence on the combined effect of direct hemoperfusion with a Polymyxin B immobilized fiber column and intravenous immunoglobulin. We herein report a case of 61-year-old woman who presented with respiratory failure. She showed ILD associated with DM which did not improve with immunosuppressive agents, but was improved with the addition of both direct hemoperfusion with a Polymyxin B immobilized fiber column and intravenous immunoglobulin.

  6. It's not a tumor, it's a cataract! rapid myopic progression and diplopia secondary to the formation of an oil-drop cataract.

    PubMed

    Hodges, Jacob S; Marcus, Susannah; Page, Eva

    2013-03-01

    Oil-drop cataracts are detrimental to patients because of their capacity to cause rapid, and often unexplained, myopic progression with concomitant diplopia complaints. When not properly identified, they can lead to costly and unnecessary workups and referrals. Early diagnosis is important but unfortunately is often difficult because of the subtle nature in which these cataracts present, resulting in under-recognition by clinicians. This case report and discussion will focus on ways to assist the practitioner in diagnosing oil-drop cataracts to ensure appropriate management of the troublesome symptoms affected patients confront. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

  7. ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits.

    PubMed

    Haas, M; Jafri, J; Bartosh, S M; Karp, S L; Adler, S G; Meehan, S M

    2000-10-01

    Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were

  8. Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging

    PubMed Central

    Sawiak, Stephen J.; Perumal, Sunthara Rajan; Rudiger, Skye R.; Matthews, Loren; Mitchell, Nadia L.; McLaughlan, Clive J.; Bawden, C. Simon; Palmer, David N.; Kuchel, Timothy; Morton, A. Jennifer

    2015-01-01

    Variant late-infantile Batten disease is a neuronal ceroid lipofuscinosis caused by mutations in CLN6. It is a recessive genetic lysosomal storage disease characterised by progressive neurodegeneration. It starts insidiously and leads to blindness, epilepsy and dementia in affected children. Sheep that are homozygous for a natural mutation in CLN6 have an ovine form of Batten disease Here, we used in vivo magnetic resonance imaging to track brain changes in 4 unaffected carriers and 6 affected Batten disease sheep. We scanned each sheep 4 times, between 17 and 22 months of age. Cortical atrophy in all sheep was pronounced at the baseline scan in all affected Batten disease sheep. Significant atrophy was also present in other brain regions (caudate, putamen and amygdala). Atrophy continued measurably in all of these regions during the study. Longitudinal MRI in sheep was sensitive enough to measure significant volume changes over the relatively short study period, even in the cortex, where nearly 40% of volume was already lost at the start of the study. Thus longitudinal MRI could be used to study the dynamics of progression of neurodegenerative changes in sheep models of Batten disease, as well as to assess therapeutic efficacy. PMID:26161747

  9. Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?

    PubMed Central

    2013-01-01

    Background Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. Results In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2–12 months; age at death: 55–81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrPres) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrPres by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate negative control groups. Conclusions Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases. PMID:24252716

  10. [Fibronectin content in the urine of patients with chronic glomerulonephritis as a test for the efficiency of treatment].

    PubMed

    Mukhin, I V

    2001-04-01

    Renal fibronectin synthesis is impaired in patients with chronic glomerulonephritis. We measured urinary fibronectin for evaluating the efficiency of various methods of treatment. Traditional therapy of patients with the nephrotic syndrome at the stage of renal failure leads to decrease of fibronectinuria, which can be indicative of the progress of nephrosclerotic process in the renal parenchyma; monotherapy with wobenzyme during the azothemic stage of disease in patients with the urinary and nephrotic syndrome does not cause statistically significant changes in the level of urinary fibronectin, which can be regarded as inhibition of nephrosclerosis process. Hence, wobenzyme is the drug of choice, decreasing the velocity of nephrosclerotic processes, when pathogenetic therapy is largely limited or precluded. Combination of wobenzyme with pathogenetic drugs in patients with the nephrotic syndrome and intact renal function suppresses fibronectinuria due to mutual potentiation of the antiinflammatory effect. Decrease of fibronectin concentration in the urine after wobenzyme monotherapy in patients with the urinary syndrome without signs of chronic renal insufficiency confirms the antiinflammatory effect of the drug.

  11. Outcome analysis of aromatase inhibitor therapy to increase adult height in males with predicted short adult stature and/or rapid pubertal progress: a retrospective chart review.

    PubMed

    Shams, Kim; Cameo, Tamara; Fennoy, Ilene; Hassoun, Abeer A; Lerner, Shulamit E; Aranoff, Gaya S; Sopher, Aviva B; Yang, Christine; McMahon, Donald J; Oberfield, Sharon E

    2014-07-01

    Aromatase inhibitors (AIs) have been used off-label to increase adult height in short adolescent males. Studies have shown that AIs increase the predicted adult height (PAH) while delaying bone age (BA) maturation. We sought to determine whether AI therapy increases PAH in boys with short stature or rapid pubertal progression, and to evaluate any untoward effects. The charts of 27 boys with BA ≥ 13 and short stature [height ≥ 2 standard deviation (SD) below the mean or ≥ 2 SD below mid-parental target height (MPTH)] or rapid pubertal progress, treated with anastrozole were reviewed. Outcome measures included anthropomorphic, hormonal, and metabolic data. The AI therapy averaged 21 months (range 14-30 months) for all, with Rx group 1 receiving <18 months therapy (n=7) and Rx group 2 receiving 18-30 months therapy (n=20). Post-therapy, in Rx group 1 and all subjects, there was no significant change in the PAH, height SDS, or BA/chronological age (CA). In Rx group 2, there was a small, nonsignificant increase in PAH, no change in height SDS, and a small decrease in BA/CA. Post-therapy PAH was different from MPTH in all and in both Rx groups 1 and 2, p<0.02. Eight of them achieved near-final height, averaging 6.73 ± 1.40 cm less than MPTH and 1.91 ± 0.86 cm less than the pre-therapy PAH. Post-therapy, the initially decreased estradiol did not persist but mildly increased testosterone and decreased high-density lipoprotein were noted, as was an increase in hematocrit, and decrease in growth velocity. We suggest that although bone age progression may be slightly delayed with longer duration of therapy, an overall short-term AI therapy does not lead to a final height that is greater than the predicted pre-therapy height.

  12. Cervical (non-terminal) myelocystocele associated with rapidly progressive hydrocephalus and Chiari type II malformation--case report.

    PubMed

    Ochiai, Hidenobu; Kawano, Hirokazu; Miyaoka, Ryo; Nagano, Rie; Kohno, Keiichiro; Nishiguchi, Toshihiro; Shimao, Yoshiya

    2010-01-01

    An infant presented with a rare cervical (non-terminal) myelocystocele as a congenital skin-covered mass located in the midline of the posterior aspect of her neck. Magnetic resonance (MR) imaging and computed tomography showed a cystic mass filled with cerebrospinal fluid in the midline of the posterior aspect of the neck, with a fibrous streak extending from the bottom of the sac to the dorsal surface of the cervical cord. Brain MR imaging also showed a dilated ventricular system and Chiari type II malformation. The patient underwent plastic repair of the lesion, which was diagnosed as myelocystocele. After the surgery, the patient experienced respiratory distress. Ultrasound tomography from the anterior fontanel revealed deterioration of hydrocephalus, so a ventriculoperitoneal shunt was inserted, and the respiratory distress improved. The present case illustrates the possibility of rapidly worsening of hydrocephalus and Chari type II malformation after surgical repair of cervical (non-terminal) myelocystocele.

  13. Mantle cell lymphoma of blastoid variant with skin lesion and rapid progression: a case report and literature review.

    PubMed

    Cao, Qinghua; Li, Yang; Lin, Hanliang; Ke, Zunfu; Liu, Yongdong; Ye, Ziyin

    2013-12-01

    Mantle cell lymphoma (MCL) is a type of aggressive mature B-cell neoplasm. Skin involvement of MCL is extremely rare, with only 21 cases reported so far. We report a case of MCL with blastoid variant, presenting as skin lesion initially. A 53-year-old man presented with increasing petechiae and ecchymosis after slight hit. Biopsy of skin showed tumor cells densely infiltrated dermal and subcutis with blastoid cytological features and numerous mitotic figures. Immunohistochemistry study showed tumor cells were positive for CD20, CD79a, BCL2, CyclinD1, and MUM1 but lost CD5 expression. Fluorescence in situ hybridization (FISH) studies demonstrated t(11;14). Although received chemotherapy after the diagnosis established, the patient deteriorated rapidly and died 5 weeks after presenting with skin lesions.

  14. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes; Quarterly progress report, July--September 1993

    SciTech Connect

    Proscia, W M; Freihaut, J D

    1993-12-01

    The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. The coal ranks to be investigated will include a high volatile A bituminous (PSOC 1451D) and a low volatile bituminous (PSOC 1516D). An anthracite (PSOC 1468) will be used as a non-volatile coal reference. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars. Partial results on some of the tasks are given.

  15. Thermodynamic properties of pulverized coal during rapid heating devolatilization processes. Quarterly progress report, October--December 1993

    SciTech Connect

    Proscia, W.M.; Freihaut, J.D.

    1994-03-01

    The objective of this research is to obtain data on the thermodynamic properties and morphology of coal under conditions of rapid heating. Specifically, the total heat of devolatilization, external surface area, BET surface area and true density will be measured for representative coal samples. The coal ranks to be investigated will include a high volatile A bituminous (PSOC 1451D) and a low volatile bituminous (PSOC 1516D). An anthracite (PSOC 1468) will be used as a non-volatile coal reference. In addition, for one coal, the contribution of each of the following components to the overall heat of devolatilization will be measured: the specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars.

  16. Proliferative glomerulonephritis associated with monoclonal immune deposits: A case report and review of literature.

    PubMed

    Fatima, R; Jha, R; Gowrishankar, S; Narayen, G; Rao, B S

    2014-11-01

    Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly recognized entity caused by monoclonal deposition of IgG. PGNMID resembles immune complex glomerulonephritis (GN) on light and electron microscopy. The monotypic immunoglobulin deposits seen on immunofluorescence (IF) clinches the diagnosis. We report a case of proliferative GN associated MGRS and review the relevant literature. The patient had significant proteinuria and elevated serum creatinine. The renal biopsy showed proliferative GN with focal crescents and monoclonal immune deposits confirming a diagnosis of PGNMID. Serum work up showed no monoclonal proteins. Proliferative GN as a manifestation of a monoclonal gammopathy needs to be borne in mind especially in renal biopsies of older patients.

  17. Proliferative glomerulonephritis associated with monoclonal immune deposits: A case report and review of literature

    PubMed Central

    Fatima, R.; Jha, R.; Gowrishankar, S.; Narayen, G.; Rao, B. S.

    2014-01-01

    Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly recognized entity caused by monoclonal deposition of IgG. PGNMID resembles immune complex glomerulonephritis (GN) on light and electron microscopy. The monotypic immunoglobulin deposits seen on immunofluorescence (IF) clinches the diagnosis. We report a case of proliferative GN associated MGRS and review the relevant literature. The patient had significant proteinuria and elevated serum creatinine. The renal biopsy showed proliferative GN with focal crescents and monoclonal immune deposits confirming a diagnosis of PGNMID. Serum work up showed no monoclonal proteins. Proliferative GN as a manifestation of a monoclonal gammopathy needs to be borne in mind especially in renal biopsies of older patients. PMID:25484532

  18. [First case of primary IgA glomerulonephritis (Berger's disease) in Senegal].

    PubMed

    Diouf, B; Diao, M; Niang, A; Ka, E F; Moreira Diop, T

    1999-01-01

    Berger's disease or IgA glomerulonephritis is the most common glomerular nephropathy in Europe and represent a rare event in blacks. Here, we describe the case of a 43 years old black Senegalese whose disease was discovered while investigating a persistent proteinuria with high blood pressure and chronic renal failure, but without hematuria. We point out the uncommon feature of this clinical presentation and the importance of bad prognostic factors presented by this patient. We obtained a good outcome by means of converting enzyme inhibitors and corticosteroid therapies: regression of renal failure and normalization of blood pressure. The generalization of renal biopsy practice would lead to a better knowledge of the incidence of this disease among Senegalese people. Indeed, renal biopsy is the main tool to diagnose glomerulonephritis and subsequently adapt the therapy aimed at preventing the possible evolution to end stage renal disease.

  19. IgA glomerulonephritis. Mesangial IgA deposition without systemic signs (Berger's disease).

    PubMed

    Nagy, J; Brasch, H; Süle, T; Hámori, A; Deák, G; Ambrus, M

    1979-01-01

    Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.

  20. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  1. Acute Cardiac Tamponade in a 58-Year-Old Male with Poststreptococcal Glomerulonephritis

    PubMed Central

    Bottinor, Wendy; Fronk, Daniel; Sadruddin, Salima; Foster, Harriet; Patel, Nilang; Prinz, Andreas; Jovin, Ion S

    2016-01-01

    Pericarditis in conjunction with nephritis is an uncommon clinical scenario with a broad differential diagnosis. We present the case of a 58-year-old male who developed nephritis and pericardial effusion with tamponade physiology. In the following, we discuss the differential diagnosis for concomitant nephritis and pericarditis and discuss the work-up performed on our patient. We also review the epidemiology of postinfectious glomerulonephritis in adults and describe previous cases of Streptococcus pyogenes pericarditis in the literature. PMID:27826373

  2. Renal biopsy in patients with systemic lupus erythematosus: Not just lupus glomerulonephritis!

    PubMed

    Howell, David N

    2017-01-01

    Kidney biopsy is a mainstay in the diagnosis and management of renal disease in patients with systemic lupus erythematosus. Though biopsies from patients with lupus typically show various forms of immune complex glomerulonephritis, other pathologies are occasionally encountered, including unusual lupus-related nephropathies, other forms of autoimmune disease, and occasional renal disorders without any direct connection with lupus or autoimmunity. Electron microscopy is a powerful tool for detecting and classifying these unusual conditions, which frequently have important therapeutic and prognostic implications.

  3. Acute Cardiac Tamponade in a 58-Year-Old Male with Poststreptococcal Glomerulonephritis.

    PubMed

    Bottinor, Wendy; Fronk, Daniel; Sadruddin, Salima; Foster, Harriet; Patel, Nilang; Prinz, Andreas; Jovin, Ion S

    2016-09-01

    Pericarditis in conjunction with nephritis is an uncommon clinical scenario with a broad differential diagnosis. We present the case of a 58-year-old male who developed nephritis and pericardial effusion with tamponade physiology. In the following, we discuss the differential diagnosis for concomitant nephritis and pericarditis and discuss the work-up performed on our patient. We also review the epidemiology of postinfectious glomerulonephritis in adults and describe previous cases of Streptococcus pyogenes pericarditis in the literature.

  4. Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility

    PubMed Central

    Behmoaras, Jacques; Bhangal, Gurjeet; Smith, Jennifer; McDonald, Kylie; Mutch, Brenda; Lai, Ping Chin; Domin, Jan; Game, Laurence; Salama, Alan; Foxwell, Brian M; Pusey, Charles D; Cook, H Terence; Aitman, Timothy J

    2009-01-01

    Crescentic glomerulonephritis is an important cause of human kidney failure for which the underlying molecular basis is largely unknown. In previous studies, we mapped several susceptibility loci, Crgn1–Crgn7, for crescentic glomerulonephritis in the Wistar Kyoto (WKY) rat1. Here we show by combined congenic, linkage and microarray studies that the activator protein-1 (AP-1) transcription factor JunD is a major determinant of macrophage activity and is associated with glomerulonephritis susceptibility. Introgression of Crgn2 from the nonsusceptible Lewis strain onto the WKY background leads to significant reductions in crescent formation, macrophage infiltration, Fc receptor–mediated macrophage activation and cytokine production. Haplotype analysis restricted the Crgn2 linkage interval to a 430-kb interval containing Jund, which is markedly overexpressed in WKY macrophages and glomeruli. Jund knockdown in rat and human primary macrophages led to significantly reduced macrophage activity and cytokine secretion, indicating conservation of JunD function in macrophage activation in rats and humans and suggesting in vivo inhibition of Jund as a possible new therapeutic strategy for diseases characterized by inflammation and macrophage activation. PMID:18443593

  5. Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy.

    PubMed

    Horita, Yoshio; Tadokoro, Masato; Taura, Koichi; Suyama, Naofumi; Taguchi, Takashi; Miyazaki, Masanobu; Kohno, Shigeru

    2004-12-01

    We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.

  6. Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis.

    PubMed Central

    Schulze, M.; Pruchno, C. J.; Burns, M.; Baker, P. J.; Johnson, R. J.; Couser, W. G.

    1993-01-01

    In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation. Images Figure 1 Figure 2 Figure 3 PMID:7678717

  7. CCR6 Recruits Regulatory T Cells and Th17 Cells to the Kidney in Glomerulonephritis

    PubMed Central

    Turner, Jan-Eric; Paust, Hans-Joachim; Steinmetz, Oliver M.; Peters, Anett; Riedel, Jan-Hendrik; Erhardt, Annette; Wegscheid, Claudia; Velden, Joachim; Fehr, Susanne; Mittrücker, Hans-Willi; Tiegs, Gisa; Stahl, Rolf A.K.

    2010-01-01

    T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17–producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNγ-producing Th1 cells are CCR6−. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6−/− mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis. PMID:20299360

  8. Mycophenolate mofetil (MMF) treatment efficacy in children with primary and secondary glomerulonephritis

    PubMed Central

    Ostalska-Nowicka, Danuta; Malinska, Agnieszka; Silska, Magdalena; Perek, Bartlomiej; Zachwieja, Jacek

    2011-01-01

    Introduction The aim of our study was to analyse the efficacy and safety of mycophenolate mofetil (MMF) as part of the complex immunosuppressive therapy in children with different types of primary and secondary glomerulonephritis, who were not eligible for the standard treatment routine suggested by evidence-based guidelines. Material and methods The study group comprised 85 children with proteinuric glomerulopathies hospitalized between 2007 and 2010, who were non-responders to immunosuppressive therapy. The dose of MMF was established as 1 g/m2/24 h. Remission was defined as negative proteinuria in three consecutive urinalyses. Results The patients were divided into 4 groups: idiopathic nephrotic syndrome (n = 35), primary glomerulonephritis (n = 15), auto-antibody associated glomerulonephritis (n = 20) and lupus nephropathy (LN, n = 15). Ten patients from the first group (29%) and 5 patients each from the second and third group (34% and 25% respectively) did not respond to MMF therapy. On the other hand, all the children diagnosed with LN have reached clinical and biochemical remission. Conclusions Alternative rescue MMF therapy should always be taken into consideration in proteinuric patients who are non-responders to steroids, cyclosporine A and cyclophosphamide in whom the initial glomerular filtration rate is higher than 60 ml/min/1.73m2. It is recommended that MMF be administered as part of the standard treatment regimen in patients diagnosed with lupus nephropathy. In these groups of patients, the potent benefits of this therapy are higher than expected side-effects. PMID:22328889

  9. Mycophenolate mofetil (MMF) treatment efficacy in children with primary and secondary glomerulonephritis.

    PubMed

    Ostalska-Nowicka, Danuta; Malinska, Agnieszka; Silska, Magdalena; Perek, Bartlomiej; Zachwieja, Jacek; Nowicki, Michal

    2011-12-31

    The aim of our study was to analyse the efficacy and safety of mycophenolate mofetil (MMF) as part of the complex immunosuppressive therapy in children with different types of primary and secondary glomerulonephritis, who were not eligible for the standard treatment routine suggested by evidence-based guidelines. The study group comprised 85 children with proteinuric glomerulopathies hospitalized between 2007 and 2010, who were non-responders to immunosuppressive therapy. The dose of MMF was established as 1 g/m(2)/24 h. Remission was defined as negative proteinuria in three consecutive urinalyses. The patients were divided into 4 groups: idiopathic nephrotic syndrome (n = 35), primary glomerulonephritis (n = 15), auto-antibody associated glomerulonephritis (n = 20) and lupus nephropathy (LN, n = 15). Ten patients from the first group (29%) and 5 patients each from the second and third group (34% and 25% respectively) did not respond to MMF therapy. On the other hand, all the children diagnosed with LN have reached clinical and biochemical remission. Alternative rescue MMF therapy should always be taken into consideration in proteinuric patients who are non-responders to steroids, cyclosporine A and cyclophosphamide in whom the initial glomerular filtration rate is higher than 60 ml/min/1.73m(2). It is recommended that MMF be administered as part of the standard treatment regimen in patients diagnosed with lupus nephropathy. In these groups of patients, the potent benefits of this therapy are higher than expected side-effects.

  10. Correlation of disease activity in proliferative glomerulonephritis with glomerular spleen tyrosine kinase expression.

    PubMed

    McAdoo, Stephen P; Bhangal, Gurjeet; Page, Theresa; Cook, H Terence; Pusey, Charles D; Tam, Frederick W K

    2015-07-01

    Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.

  11. Dietary acid load and rapid progression to end-stage renal disease of diabetic nephropathy in Westernized South Asian people.

    PubMed

    van den Berg, Else; Hospers, Frédérique A P; Navis, Gerjan; Engberink, Marielle F; Brink, Elizabeth J; Geleijnse, Johanna M; van Baak, Marleen A; Gans, Rijk O B; Bakker, Stephan J L

    2011-01-01

    Diabetic nephropathy is now the most common cause of end-stage renal failure in many countries of the world. Despite increasing implementation of preventive treatment, the chance that an individual diabetic patient will reach end-stage renal failure has been increasing rather than decreasing during recent decades. Current dietary habits in The Netherlands and the rest of the Western world are slowly shifting from relatively alkalinizing (e.g., potatoes and vegetables) toward more acidifying (e.g., rice and meat). Moreover, immigrants who consumed traditional diets in their homelands, usually adapt to Western dietary habits. This phenomenon of diet acculturation could, for instance, be involved in the up to 40 times higher chance of development of end-stage renal failure in association with diabetes in South-Asian immigrants compared with whites, in Western countries. High ingestion of nonvolatile acids with food increases susceptibility for progression to end-stage renal failure. These high dietary acid loads lead to compensatory increases in renal acid excretion and ammoniagenesis. The price paid for maintenance of acid-base homeostasis is renal tubulointerstitial injury, with subsequent decline in renal function and induction of hypertension. The tendency for metabolic acidosis that results from the changing dietary habits could be corrected by a shift toward more alkalinizing food. We hypothesize that promoting such a shift can prevent the epidemic of end-stage renal failure in diabetes.

  12. Rapidly Progressive Hypertrophic Cardiomyopathy in an Infant with Noonan syndrome with multiple Lentigines. Palliative Treatment with a Rapamycin Analog

    PubMed Central

    Hahn, Andreas; Lauriol, Jessica; Thul, Josef; Behnke-Hall, Kachina; Logeswaran, Tushiha; Schänzer, Anne; Böğürcü, Nuray; Garvalov, Boyan K.; Zenker, Martin; Gelb, Bruce D.; von Gerlach, Susanne; Kandolf, Reinhard; Kontaridis, Maria I.; Schranz, Dietmar

    2015-01-01

    Noonan syndrome with multiple lentigines (NSML) frequently manifests with hypertrophic cardiomyopathy (HCM). Recently, it was demonstrated that mTOR inhibition reverses HCM in NSML mice. We report for the first time on the effects of treatment with a rapamycin analog in an infant with LS and a malignant form of HCM. In the boy, progressive HCM was diagnosed during the first week of life and diagnosis of NSML was established at age 20 weeks by showing a heterozygous Q510E mutation in the PTPN11 gene. Immunoblotting with antibodies against pERK, pAkt, and pS6RP in fibroblasts demonstrated reduced RAS/MAPK and enhanced Akt/mTOR pathway activities. Because of the patient’s critical condition, everolimus therapy was started at age 24 weeks and continued until heart transplantation at age 36 weeks. Prior to surgery, heart failure improved from NYHA stage IV to II and brain natriuretic peptide values decreased from 9600 to <1000 pg/ml, but no reversal of cardiac hypertrophy was observed. Examination of the explanted heart revealed severe hypertrophy and myofiber disarray with extensive perivascular fibrosis. These findings provide evidence that Akt/mTOR activity is enhanced in NSML with HCM and suggest that rapamycin treatment could be principally feasible for infantile NSML. But the preliminary experiences made in this single patient indicate that therapy should start early to prevent irreversible cardiac remodelling. PMID:25708222

  13. PTEN mediates the cross talk between breast and glial cells in brain metastases leading to rapid disease progression

    PubMed Central

    Hohensee, Ina; Chuang, Han-Ning; Grottke, Astrid; Werner, Stefan; Schulte, Alexander; Horn, Stefan; Lamszus, Katrin; Bartkowiak, Kai; Witzel, Isabell; Westphal, Manfred; Matschke, Jakob; Glatzel, Markus; Jücker, Manfred; Pukrop, Tobias; Pantel, Klaus; Wikman, Harriet

    2017-01-01

    Despite improvement of therapeutic treatments for breast cancer, the development of brain metastases has become a major limitation to life expectancy for many patients. Brain metastases show very commonly alterations in EGFR and HER2 driven pathways, of which PTEN is an important regulator. Here, we analyzed PTEN expression in 111 tissue samples of breast cancer brain metastases (BCBM). Loss of PTEN was found in a substantial proportion of BCBM samples (48.6%) and was significantly associated with triple-negative breast cancer (67.5%, p = 0.001) and a shorter survival time after surgical resection of brain metastases (p = 0.048). Overexpression of PTEN in brain-seeking MDA-MB-231 BR cells in vitro reduced activation of the AKT pathway, notably by suppression of Akt1 kinase activity. Furthermore, the migration of MDA-MB-231 BR cells in vitro was promoted by co-culturing with both astrocytes and microglial cells. Interestingly, when PTEN was overexpressed the migration was significantly inhibited. Moreover, in an ex vivo organotypic brain slice model, PTEN overexpression reduced invasion of tumor cells. This was accompanied by reduced astrocyte activation that was mediated by autocrine and paracrine activation of GM-CSF/ CSF2RA and AKT/ PTEN pathways. In conclusion, loss of PTEN is frequently detected in triple-negative BCBM patients and associated with poor prognosis. The findings of our functional studies suggest that PTEN loss promotes a feedback loop between tumor cells and glial cells, which might contribute to disease progression. PMID:28008153

  14. A three-decade analysis of 3,911 small intestinal neuroendocrine tumors: the rapid pace of no progress.

    PubMed

    Modlin, Irvin M; Champaneria, Manish C; Chan, Anthony K C; Kidd, Mark

    2007-07-01

    Small intestinal neuroendocrine tumors (SI-NETs) are the most common gastrointestinal neuroendocrine tumor, but their natural history and outcome remain poorly defined, which hinders both the prediction of disease progression and appropriate therapeutic options. We examined patterns, incidence, prognosis, and outcomes of these tumors over a 30-yr period. Data were extracted from the NCI's SEER registry (1973-2002). Incidence rates, distribution, and 5-yr survival rates were analyzed and adjusted (U.S. decennial census data). Of the 18,641 NETs, 3,911 (21.0%) were SI-NETs, of which 1,953 (49.6%) were ileal. Since 1973, both SI-NET and its ileal variant have increased annually by 3.8% and 2.1%, respectively. Ileal tumors, as a percentage of SI tumors, have increased from 52% to 63.6%. The age-adjusted incidence of ileal, small intestinal, and digestive system NETs has increased 225%, 460%, and 720% over 30 yr. Ileal tumors have specifically increased in prevalence in white (274%) and black (500%) men and women (213% and 286%, respectively); an overall increase of fourfold in blacks and 2.4-fold in whites. Although 83.3% of SI-NETs were staged, 83.7% were histologically ungraded. Five-year survival rates for SI-NETs were 62.6 +/- 1% (all stages), 73.8% (localized), 72% (regional), and 43.2% (distant). These have not significantly altered since 1973 (P= 0.11). SI-NETs have increased, particularly in men and in the black population, which may be due to in vivo changes, increased clinical and pathological awareness, or increased detection of tumors. SI-NETs are malignant, diagnosed late, and survival rates have remained unchanged over 30 yr.

  15. Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

    PubMed

    Birnbaum, Yochai; Mahaffey, Kenneth W; Criger, Douglas A; Gates, Kathy B; Barbash, Gabriel I; Barbagelata, Alejandro; Clemmensen, Peter; Sgarbossa, Elena B; Gibbons, Raymond J; Rahman, M Atiar; Califf, Robert M; Granger, Chistopher B; Wagner, Galen S

    2002-01-01

    We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion. Copyright 2002 S. Karger AG, Basel

  16. Female human pluripotent stem cells rapidly lose X chromosome inactivation marks and progress to a skewed methylation pattern during culture.

    PubMed

    Geens, M; Seriola, A; Barbé, L; Santalo, J; Veiga, A; Dée, K; Van Haute, L; Sermon, K; Spits, C

    2016-04-01

    Does a preferential X chromosome inactivation (XCI) pattern exist in female human pluripotent stem cells (hPSCs) and does the pattern change during long-term culture or upon differentiation? We identified two independent phenomena that lead to aberrant XCI patterns in female hPSC: a rapid loss of histone H3 lysine 27 trimethylation (H3K27me3) and long non-coding X-inactive specific transcript (XIST) expression during culture, often accompanied by erosion of XCI-specific methylation, and a frequent loss of random XCI in the cultures. Variable XCI patterns have been reported in female hPSC, not only between different hPSC lines, but also between sub-passages of the same cell line, however the reasons for this variability remain unknown. Moreover, while non-random XCI-linked DNA methylation patterns have been previously reported, their origin and extent have not been investigated. We investigated the XCI patterns in 23 human pluripotent stem cell (hPSC) lines, during long-term culture and after differentiation, by gene expression analysis, histone modification assessment and study of DNA methylation. The presence and location of H3K27me3 was studied by immunofluorescence, XIST expression by real-time PCR, and mono- or bi-allelic expression of X-linked genes was studied by sequencing of cDNA. XCI-specific DNA methylation was analysed using methylation-sensitive restriction and PCR, and more in depth by massive parallel bisulphite sequencing. All hPSC lines showed XCI, but we found a rapid loss of XCI marks during the early stages of in vitro culture. While this loss of XCI marks was accompanied in several cases by an extensive erosion of XCI-specific methylation, it did not result in X chromosome reactivation. Moreover, lines without strong erosion of methylation frequently displayed non-random DNA methylation, which occurred independently from the loss of XCI marks. This bias in X chromosome DNA methylation did not appear as a passenger event driven by clonal culture

  17. Rapidly progressing facial leishmaniasis: effective treatment with liposomal amphotericin B and a review of the management of Old World cutaneous leishmaniasis.

    PubMed

    Islam, Shamim

    2017-03-10

    Cutaneous leishmaniasis (CL), a common condition in many parts of the world, is being increasingly encountered in non-endemic countries secondary to immigration. The clinical manifestations and course can vary substantially, with appropriate management ranging from observation for self-healing lesions to urgent treatment to prevent damaging anatomical and cosmetic sequelae. While there are now several effective medications, optimal therapy is not well defined, and decision-making can be challenged by the location of lesions and various drug issues, including availability, mode of delivery and adverse effects. A 7-year-old Afghani boy who presented shortly after arriving in the United States with a rapidly progressing crusting and ulcerative facial rash caused by Leishmania tropica is described. The various drugs currently available for CL and experience of using liposomal amphotericin B specifically are reviewed.

  18. Effectiveness of initial treatment allocation based on expert opinion for prevention of rapid radiographic progression in daily practice of an early RA cohort.

    PubMed

    Durnez, Anne; Vanderschueren, Geert; Lateur, Luc; Westhovens, René; Verschueren, Patrick

    2011-04-01

    To evaluate expert treatment selection for early rheumatoid arthritis and to validate a prediction model for rapid radiographic progression (RRP) in daily practice. Patients received initial combination therapy with steroids (ICTS) or disease-modifying antirheumatic drug monotherapy (IMT) after informal evaluation of prognostic factors, followed by a tight control strategy. Changes in Sharp/van der Heijde score (total Sharp score (TSS)) of >5 units over 1 year (=RRP) were documented. The mean change in TSS and proportion with RRP were compared between groups. Based on the 28 swollen joint count, rheumatoid factor titre and C reactive protein/erythrocyte sedimentation rate, patients were placed in the ASPIRE prediction matrix, yielding a RRP risk. Numbers needed to treat (NNT) intensively to avoid one RRP after 1 year were calculated. The mean change in TSS after 1 year and the proportion with RRP was lower in the ICTS group (n=37) than in the IMT group (n=43). The mean calculated risk of RRP was higher in patients with radiographic progression. The mean NNT intensively to prevent RRP was lower in the ICTS group than in the IMT group. The positive predictive value of NNT for RRP prevention was 12.6%, but the negative predictive value reached 100%. ICTS seems more effective in preventing RRP than IMT. The predictive matrix model could be helpful in preventing overtreatment in practice.

  19. Rapid Progressive Seeding of a Community Acquired Pathogen in an Immune-Competent Host: End Organ Damage from Head to Bone

    PubMed Central

    Torres-Miranda, Daisy; Al-Saffar, Farah; Ibrahim, Saif; Diaz-Font, Stephanie

    2015-01-01

    Methicillin-sensitive Staphylococcus aureus (MSSA) meningitis is a rare disease when not related to neurosurgery: there are only few reported cases in the literature to date. We describe a case that highlights not only meningeal but also diffuse and rapidly progressive systemic involvement with multi-organ failure. A 64-year-old male presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Hospital course demonstrated MSSA bacteremia, of questionable source, that resulted in endocarditis affecting right and left heart in a patient with no history of intravenous drug use. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine, lungs and brain with consequent meningitis and stroke, even when treated empirically with vancomycin and then switched to nafcillin as indicated. Even though MSSA infections are well known, there are very few case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. Our case, also presented with an uncommon manifestation of persistent infection dissemination despite adequate antibiotic treatment. PMID:26294951

  20. A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity.

    PubMed

    Ahmed, Zeshan; Cooper, Jane; Murray, Tracey K; Garn, Katya; McNaughton, Emily; Clarke, Hannah; Parhizkar, Samira; Ward, Mark A; Cavallini, Annalisa; Jackson, Samuel; Bose, Suchira; Clavaguera, Florence; Tolnay, Markus; Lavenir, Isabelle; Goedert, Michel; Hutton, Michael L; O'Neill, Michael J

    2014-05-01

    Intracellular inclusions composed of hyperphosphorylated filamentous tau are a hallmark of Alzheimer's disease, progressive supranuclear palsy, Pick's disease and other sporadic neurodegenerative tauopathies. Recent in vitro and in vivo studies have shown that tau aggregates do not only seed further tau aggregation within neurons, but can also spread to neighbouring cells and functionally connected brain regions. This process is referred to as 'tau propagation' and may explain the stereotypic progression of tau pathology in the brains of Alzheimer's disease patients. Here, we describe a novel in vivo model of tau propagation using human P301S tau transgenic mice infused unilaterally with brain extract containing tau aggregates. Infusion-related neurofibrillary tangle pathology was first observed 2 weeks post-infusion and increased in a stereotypic, time-dependent manner. Contralateral and anterior/posterior spread of tau pathology was also evident in nuclei with strong synaptic connections (efferent and afferent) to the site of infusion, indicating that spread was dependent on synaptic connectivity rather than spatial proximity. This notion was further supported by infusion-related tau pathology in white matter tracts that interconnect these regions. The rapid and robust propagation of tau pathology in this model will be valuable for both basic research and the drug discovery process.

  1. Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy.

    PubMed

    Tonelli, A; Romaniello, R; Grasso, R; Cavallini, A; Righini, A; Bresolin, N; Borgatti, R; Bassi, M T

    2010-11-01

    Infantile neuroaxonal dystrophy, INAD, is a severe progressive psychomotor disorder with infantile onset and characterized by the presence of axonal spheroids throughout the central and peripheral nervous systems. A subset of INAD patients shows also brain iron accumulation which represents instead the distinctive feature of the idiopathic neurodegeneration with brain iron accumulation, NBIA. These diseases share the same causative gene, PLA2G6, encoding iPLA2-VIA, a calcium-independent phospholipase. Mutations that lead to a complete absence of protein are associated with a severe INAD profile, while compound heterozygous mutations with possibly a residual protein activity are instead associated with the less severe NBIA phenotype. Here we describe two INAD patients both with an unusually rapid disease progression and a peculiar neuroradiological presentation in one of them. Compound heterozygosity for a large intragenic deletion and a nonsense mutation was found in one of them while the other is carrying two novel splice-site mutations. Breakpoint-sequence analysis suggests a non-allelic-homologous-recombination (NAHR) event, probably underlying the rearrangement. These findings, while supporting the genotype-phenotype correlation already observed in INAD patients, provide the first sequence characterization of a genomic rearrangement in PLA2G6 gene, thus orienting the search for missing mutant alleles in PLA2G6 related diseases. © 2010 John Wiley & Sons A/S.

  2. Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

    PubMed

    Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

    2016-06-01

    Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.

  3. The Importance of Surgery as Part of Multimodal Therapy in Rapid Progressive Primary Extraosseous Ewing Sarcoma of the Cervical Intra- and Epidural Space

    PubMed Central

    Bostelmann, Richard; Leimert, Mario; Steiger, Hans Jakob; Gierga, Kristin; Petridis, Athanasios K.

    2016-01-01

    Primary extraosseous Ewing sarcomas (EESs) are an extremely rare pathological entity. Less than 32 cases have been reported in the literature. Here we report an uncommon case with very rapid progression in the cervical region with extra- and intradural involvement. We present a thorough review of the literature and discuss possible treatment modalities. The Medline database was searched using the search terms: Ewing sarcoma, extraosseus tumour, treatment, management, cervical spine. A previously healthy 29-year-old man complained of right-sided radiculopathy (C7). Magnetic resonance imaging showed an enhancing foraminal, sandglass shaped neurinoma-like lesion. Surgery revealed an intraand extra-dural lesion, which was histologically diagnosed as Ewing sarcoma. Despite gross total resection, there was a massive symptomatic tumor recurrence within 6 weeks. A second gross total resection was realized. The patient was treated according to the EURO E.W.I.N.G.-Protocol (VIDE) and recovered very well (progression-free interval during therapy). Several decompressive re-surgeries were realized with adjuvant radio-chemotherapy. At the last follow-up (17 months after initial surgery) the patient was in remission with a good quality of live. This case is to illustrate that despite extensive therapeutic efforts, the progression-free survival in case of primary EES may be very short. To maintain neurological function and good quality of live as long as possible, a multimodal strategy seems to be adequate. Like in the present case this implies several surgeries and adjuvant chemo-and radiotherapy. Whether this improves overall survival remains unclear. PMID:28176976

  4. Expression of Pisum sativum PsAO3 gene, which encodes an aldehyde oxidase utilizing abscisic aldehyde, is induced under progressively but not rapidly imposed drought stress.

    PubMed

    Zdunek-Zastocka, Edyta; Sobczak, Mirosław

    2013-10-01

    Aldehyde oxidase (AO; EC 1.2.3.1) catalyzes the final step of abscisic acid (ABA) biosynthesis, which is the oxidation of abscisic aldehyde (ABAld) to ABA. Gene expression analyses indicate that the stress-induced Pisum sativum PsAOγ isoform, which effectively uses ABAld as a substrate, is encoded by the PsAO3 gene. PsAO3 was heterologously expressed in Pichia pastoris and the recombinant PsAO3 protein revealed substrate preferences highly similar to the native PsAOγ protein present in the pea leaves and roots. Both proteins prefer indole-3-aldehyde and naphthaldehyde as substrates, although high activities against abscisic aldehyde and citral were also observed. The Km values of PsAO3 for naphthaldehyde and abscisic aldehyde (4.6 and 5.1 μM, respectively) were the lowest among the substrates tested. PsAO3 activity was almost completely inhibited by potassium cyanide, diphenyleneiodonium, and methanol. Rapidly imposed drought stress did not increase the level of PsAO3 mRNA or activity of any AO isoform, although an enhanced ABA accumulation and induction of PsNCED2 and -3 (9-cis-epoxycarotenoid dioxygenase; EC 1.13.11.51) expression, both in the pea roots and leaves, was observed. During a progressively induced drought, the level of PsAO3 transcript and PsAOγ activity increased significantly in the roots and leaves, whereas ABA accumulation occurred only in the leaves where it was accompanied by induction of the PsNCED3 expression. Therefore, we suppose that next to NCED, also AO (mainly PsAOγ) might be involved in regulation of the drought-induced ABA synthesis. However, while the "constitutive activity" of PsAOγ is sufficient for the fast generation of ABA under rapid drought stress, the enhanced PsAOγ activity is required for the progressive and long-term ABA accumulation in the leaves under progressive drought stress. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study.

    PubMed

    Kamara, David A; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D; Smith, Colette J

    2014-03-25

    No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with

  6. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

    PubMed Central

    2014-01-01

    Background No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years’ follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. Results 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years’ follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years’ follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions Our results suggest using three years’ follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable

  7. T cells, adhesion molecules and modulation of apoptosis in visceral leishmaniasis glomerulonephritis

    PubMed Central

    2010-01-01

    Background Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-α, IL-1α were searched and quantified. Results We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the

  8. The effect of Helicobacter pylori eradication on proteinuria in patients with primary glomerulonephritis

    PubMed Central

    Ayli, Deniz; Gonul, Ipek; Yuksel, Osman; Ozturk, Ramazan; Yildiz, Ayla; Yenigun, Ezgi; Piskinpasa, Serhan; Turgut, Didem; Koc, Eyup; Odabas, Ali Riza

    2013-01-01

    Introduction Glomerulonephritis is still the primary cause among the diseases causing end stage renal disease. Helicobacter pylori (HP), also having a local proinflammatory effect on gastric mucosa, can trigger a local and systemic inflammatory response, and consequently have a role in the development of extragastrointestinal defects. Material and methods The study was composed of patients diagnosed with primary glomerulonephritis who had dyspeptic complaints throughout the diagnosis. Patients who received endoscopic biopsy upon the determination of pathologic findings in their upper gastrointestinal endoscopy were HP positive in their biopsy material. A triple eradication therapy was initiated for HP. Results The study included 14 female and 19 male patients, 33 in total, whose biopsy material was determined to be HP positive. Before the eradication for HP, we found serum albumin to be 34.0 (19.0–51.0) g/l, serum total protein 58.6 ±12.9 g/l, serum creatinine 0.9 (0.5–1.2) and proteinuria 3069 (652–12392) mg/day in 24-hour urine. After the eradication, however, serum albumin was found to be 40 (20–52) g/l, serum total protein 62.3 ±11.1 g/l, serum creatinine 1.02 (0.6–1.29) mg/dl and proteinuria was 2850 (172–15181) mg/day in 24-hour urine. A comparison of the results showed that a statistically significant difference is established between the serum albumin, total protein and creatinine values (p = 0.001, p = 0.001 and p = 0.021, respectively), but not between proteinuria values in 24-hour urine (p = 0.990). Conclusions Patients with primary glomerulonephritis, HP eradication treatment has an effect on serum albumin levels. PMID:26322088

  9. Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice

    PubMed Central

    Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J

    2013-01-01

    Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh−/−) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19+ B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness. PMID:23347386

  10. Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice.

    PubMed

    Jacob, Alexander; Chaves, Lee; Eadon, Michael T; Chang, Anthony; Quigg, Richard J; Alexander, Jessy J

    2013-07-01

    Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh(-/-)) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19(+) B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.

  11. Glomerular common gamma chain confers B- and T-cell-independent protection against glomerulonephritis.

    PubMed

    Luque, Yosu; Cathelin, Dominique; Vandermeersch, Sophie; Xu, Xiaoli; Sohier, Julie; Placier, Sandrine; Xu-Dubois, Yi-Chun; Louis, Kevin; Hertig, Alexandre; Bories, Jean-Christophe; Vasseur, Florence; Campagne, Fabien; Di Santo, James P; Vosshenrich, Christian; Rondeau, Eric; Mesnard, Laurent

    2017-01-19

    Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells. The Rag2(-/-)Il2rg(-/-) or Rag2(-/-)Il2rb(-/-) mice harbor an additional deletion of either the common gamma chain (γC) or the interleukin-2 receptor β subunit (IL-2Rβ), respectively, impairing IL-15 signaling in particular. As expected, all these strains developed severe anti-GBM-GN. Additionally, bone marrow replenishment experiments allowed us to deduce a protective role for the glomerular-expressed γC during anti-GBM-GN. Given that IL-15 has been found highly expressed in nephritic kidneys despite the absence of lymphocytes, we then studied this cytokine in vitro on primary cultured podocytes from immune-deficient mice (Rag2(-/-)Il2rg(-/-) and Rag2(-/-)Il2rb(-/-)) compared to controls. IL-15 induced downstream activation of JAK1/3 and SYK in primary cultured podocytes. IL-15-dependent JAK/SYK induction was impaired in the absence of γC or IL-2Rβ. We found γC largely induced on podocytes during human glomerulonephritis. Thus, renal lesions are indeed modulated by intrinsic glomerular cells through the γC/IL-2Rβ receptor response, to date classically described only in immune cells.

  12. Ruptured Sinus of Valsalva with Infective Endocarditis Complicated with Post-Infectious Acute Glomerulonephritis: A Rare Case Presentation

    PubMed Central

    Daga, Mradul Kumar

    2016-01-01

    Ruptured Sinus of Valsalva (RSOV) is a rarely seen disease condition. RSOV can have varied presentations from being asymptomatic with just a cardiac murmur to profound hypotension. There has been simultaneous occurrence of RSOV with Infective Endocarditis (IE) in literature. Glomerulonephritis has also been reported in approximately 20% patients with IE. Large amount of proteinuria or decline in kidney functions is rarely encountered and mostly this finding has been incidental on routine evaluation. The co-existence of all the three conditions in a single patient is rare. This case was diagnosed to have RSOV with IE and was also diagnosed with post-infectious glomerulonephritis on renal biopsy. Patient was advised corrective cardiac surgery, but due to financial constraints, patient could not be operated and he died. Here, we report for the first time an unusual presence of both RSOV and sub-aortic membrane with IE complicated by glomerulonephritis. PMID:27891383

  13. Association of parvovirus B19 infection with acute glomerulonephritis in healthy adults: case report and review of the literature.

    PubMed

    Mori, Y; Yamashita, H; Umeda, Y; Uchiyama-Tanaka, Y; Nose, A; Kishimoto, N; Kijima, Y; Nagata, T; Mori, M; Matsubara, H; Yoshida, H; Iwasaka, T

    2002-01-01

    An otherwise healthy 20-year-old woman presented with an erythematous rash on her face as well as arthralgia and anemia. She also had systemic edema, proteinuria and hypertension. Laboratory data on admission showed hypocomplementemia, human parvovirus B 19 (HPV) DNA and both immunoglobulin (Ig) M and IgG antibodies to HPV in her serum. Renal biopsy specimens showed features of endocapillary glomerulonephritis under light microscopy. Electron microscopy showed massive subendothelial electron-dense deposits. No cause was probable other than immune complex-mediated glomerulonephritis associated with HPV infection. In a review of this and similar cases reported in the literature, several characteristic features come to light: female dominance, onset in the second or third decade of life, hypocomplementemia, histologic renal endocapillary and/or mesangioproliferative glomerulonephritis with subendothelial deposits and spontaneous recovery.

  14. [Application of guidelines in clinical practice: a multicenter analysis of the treatment of membranous glomerulonephritis in Piedmont, Italy].

    PubMed

    Rollino, Cristiana; Coppo, Rosanna; Giacchino, Franca; Savoldi, Silvana; Manganaro, Marco; Amore, Alessandro; Colla, Loredana; Ferro, Michela; Demicheli, Giovanni; Berutti, Silvia; Burdese, Manuel; Paternoster, Giuseppe; Cravero, Raffaella; Benozzi, Luisa; Vagelli, Giuseppe; Messuerotti, Alessandra; Licata, Carolina; Bainotti, Serena; Patti, Rosaria Rita; Quaglia, Marco; Costantini, Luigia; Stratta, Piero; Segoloni, Giuseppe

    2010-01-01

    The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

  15. Biology of the mesangial cell in glomerulonephritis--role of cytokines.

    PubMed

    Ooi, B S; Cohen, D J; Veis, J H

    1996-12-01

    The mesangial cell occupies a central position in the genesis of the pertubations occurring during the pathogenesis of glomerulonephritis. In vitro studies have shown that this cell is a metabolically active cell producing a variety of cytokines which act as autocoids; such cytokines are also liberated by the monocytes/macrophages which infiltrate the glomerulus in nephritis. This review summarizes the evidence for the participation of these cytokines in animal models of nephritis and in human renal disease, focusing on the roles of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, colony-stimulating factor-beta, tumor necrosis factor, interleukin-1, and interleukin-6.

  16. Tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis on immunosuppressive therapy.

    PubMed

    Al-Brahim, Nabeel; Zaki, Ashraf H; El-Merhi, Khaled; Ahmad, Mahmoud S

    2013-07-01

    Kaposi sarcoma is a malignant vascular neoplasm uncommonly seen in immunosuppressed patients. Herein we report an unusual case of tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis treated with prednisolone and cyclosporine. The patient presented after 10 months of starting the treatment with a tonsillar mass. Histological examination was typical of monomorphic spindle cell proliferation with slit-like vascular channels. The tumor cells expressed CD34, D2-40 and positive nuclear stain for HHV-8. Kaposi sarcoma is associated with immunosuppression and rarely occurs in the tonsil. Clinicians should be aware of this rare presentation of Kaposi sarcoma.

  17. Membranous glomerulonephritis and cellular crescents induced by levamisole-adulterated cocaine abuse: a case report

    PubMed Central

    Moll-Guillen, Jose-Luis; Espí-Reig, Jordi; Blanes-Julia, Marino; García-Martínez, Ana-María; Pujol-Marco, Conrad; Hernández-Jaras, Julio

    2015-01-01

    Levamisole is illicitly employed as a cocaine adulterant. The consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated syndromes. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole. Likewise, patients with ANCA-associated vasculitis (AAV) and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. Here, we report an unusual case of a patient in which kidney biopsy showed membranous glomerulonephritis with cellular crescents associated with levamisole-contaminated cocaine use. PMID:26605317

  18. Progeria with post-streptococcal glomerulonephritis: a rare case report with differential diagnosis.

    PubMed

    Sebastian, Alphy A; Ahsan, Auswaf K

    2013-02-01

    Hutchinson-Gilford progeria syndrome is a rare autosomal dominant disorder associated with skin fragility. It is characterized by craniofacial disproportion, delayed dentition, micrognathia, and plucked bird appearance. The genetic defect is mainly de nova mutation in the lamin A gene. This report describes a 16-year-old patient with classical features of progeria along with post-streptococcal glomerulonephritis. The symptoms of hepatomegaly were also present in the patient. The differential diagnoses of this lesion are also discussed in detail in this literature.

  19. Glomerulonephritis associated with simultaneous canine adenovirus-1 and Dirofilaria immitis infection in a dog.

    PubMed

    Sánchez-Cordón, P J; Salguero, F J; Núnez, A; Gómez-Villamandos, J C; Carrasco, L

    2002-06-01

    This article describes a case of glomerulonephritis and immunocomplex (IgM, IgG and C3c) deposition in the mesangium and basement membranes of a 2-year-old dog with canine viral hepatitis and dirofilariasis. The deposits observed in the mesangium were in the vicinity of cells with viral replication. However, no clear relationship was found between viral replication and the deposition of immunocomplexes in the glomerular capillary basement membranes, which may be the reason why these deposits have only been tentatively related to the concomitant infestation by Dirofilaria immitis.

  20. Polyarthritis and membranoproliferative glomerulonephritis as paraneoplastic manifestation of Hodgkin's lymphoma: A case report and literature review.

    PubMed

    Erlij, Daniel; Calderón, Beatriz; Rivera, Angela; Mella, Cristián; Valladares, Ximena; Roessler, Emilio; Rivera, María Teresa; Méndez, Gonzalo

    2016-01-01

    Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.

  1. Hydralazine-induced pauci-immune glomerulonephritis: intriguing case series with misleading diagnoses

    PubMed Central

    Babar, Faizan; Posner, Jeffery N.; Obah, Eugene A.

    2016-01-01

    Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects. PMID:27124161

  2. Hydralazine-induced pauci-immune glomerulonephritis: intriguing case series with misleading diagnoses.

    PubMed

    Babar, Faizan; Posner, Jeffery N; Obah, Eugene A

    2016-01-01

    Hydralazine has been used since the 1950s for the management of hypertension. Evidence for hydralazine-associated vasculitis dates to pre-ANCA (antineutrophil cytoplasmic antibodies) era. This abstract describes two cases of ANCA-positive pauci-immune glomerulonephritis (GN) in challenging scenarios where diagnosis was misconstrued. A comprehensive literature review was done to understand the pathogenesis of drug-induced pauci-immune GN. We have described key diagnostic features that are helpful in distinguishing idiopathic ANCA vasculitis from drug-induced vasculitis. Additionally, we have also described different treatments meant to provide therapy options with the least side effects.

  3. Modification by Drugs of Urinary Fibrin Fibrinogen Degradation Products in Glomerulonephritis

    PubMed Central

    Clarkson, A. R.; MacDonald, Mary K.; Cash, John D.; Robson, James S.

    1972-01-01

    Treatment with indomethacin, aspirin, or prednisone has been shown to reduce urinary fibrin/fibrinogen degradation products (F.D.P.) in approximately two-thirds of patients with proliferative glomerulonephritis. This reduction which is dose-dependent for prednisone but not for indomethacin or aspirin in the range of doses used occurs within two to three days of beginning treatment and is thought to result from decreased intraglomerular fibrin deposition rather than alteration of glomerular permeability to F.D.P. In patients who responded in this manner treatment was associated with reductions in the degree of proteinuria and maintenance or improvement in renal function. PMID:5046478

  4. Synchrotron radiation (SR) diffraction enhanced imaging (DEI) of chronic glomerulonephritis (CGN) mode.

    PubMed

    Chen-Chen, Xia; Yadav, Arun Kumar; Kai, Zhang; Yi-Feng, Peng; Qing-Xi, Yuan; Pei-Ping, Zhu; Li-Jin, Feng; Xu-Dong, Xu; A-Shan, Wu; Guang-Yu, Tang

    2016-01-01

    The aim of this study is to investigate microstructural changes in chronic glomerulonephritis (CGN) rabbit model under diffraction enhanced imaging (DEI) technology of synchrotron radiation (SR). The chronic glomerulonephritis (CGN) models were obtained within two months after 5 New Zealand white rabbits were treated with doxorubicin hydrochloride. Blood exams, urine tests and kidney histological studies were carried out after the 5 rabbits were humanely sacrificed by hyperanesthesia. The kidney tissues were fixed in 4% formalin for one week before DEI experiment, with another 5 normal rabbits used as the control group. The experiment was performed at Beijing Synchrotron Radiation Facility (BSRF) with a 4W1A beam line (beam energy was 14keV). On routine scanning process, the rocking curve was detected, and slope position on the curve was selected to make a 360° spatial CT scan; DEI reconstruction software was used to generate a 3-dimensional image, from which the difference in grey value between the chronic glomerulonephritis (CGN) group and the control group was measured and analyzed using MATLAB and SPSS. Without radio-contrast, DEI provided clear visibility of the microstructures including artery, vein, straight collecting ducts, papillary tubules, glomeruli in both the chronic glomerulonephritis (CGN) group and the control group, with a spatial resolution as low as 10μm. MATLAB grey value extraction and SPSS analysis showed that cortex of CGN group (91 to 112) lost more gray value compared to the control group (121 to 141), T tests P <  0.05. Equivalant cortical ROI (data points 450×80) quantitative analysis showed that gross grey value of CGN group (ranking from 55 to 160) was smaller than the control group (ranking from 75 to 175). DEI images correlated well with pathologic images. Morphological changes in the microstructure of contstartabstractCGN kidney was revealed, due to the advantage of phase-contrast imaging (PCI) mechanism, and the diagnostic

  5. Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center experience.

    PubMed

    Rampelli, S K; Rajesh, N G; Srinivas, B H; Harichandra Kumar, K T; Swaminathan, R P; Priyamvada, P S

    2016-01-01

    There is limited data on the etiology, clinical and histopathological spectrum and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population. This prospective study was done to evaluate the etiology, clinicohistological patterns and predictors of outcome of CrGN in South Indian population. All the patients received standard protocol based immunosuppression in addition to supportive care. Immune-complex glomerulonephritis (ICGN) was the most common etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n = 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7; 17.5%). The patients with PauciGN were significantly older compared to those with ICGN (44.5 ± 15 years vs. 31.8 ± 11 years; P = 0.01). The patients with PauciGN presented with significantly higher serum creatinine (9.7 ± 4.4 vs. 6.6 ± 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the end of 3 months follow-up, only two patients went into complete remission (5.4%). Majority of the patients had end-stage renal failure (48.6%) and were dialysis dependent and seven patients (18.9%) expired. There was no signifi difference in the renal survival (10.9 ± 1.9 vs. 9.6 ± 3.3 months) or patient survival (17.5 ± 2.1 vs. 17.3 ± 4.3 months). The parameters associated with adverse outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04-0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022).

  6. [Rapid and slow progression of the infection by the type 1 human immunodeficiency virus in a population of seropositive subjects in Madrid].

    PubMed

    Soriano, V; Martín, R; del Romero, J; Castilla, J; Bru, F; Bravo, R; Gutiérrez, M; Martínez, P; Valencia, E; García, S; Mas, A; Moreno, V; Laguna, F; Rodríguez, C; Sabín, M L; González-Lahoz, J

    1996-12-07

    The rate of progression to AIDS in HIV-1 infected subjects is variable, and circumstances associated with more rapid or slow development of severe immunodeficiency might be grouped in three categories; environmental cofactors, host features, and particular virulence of the virus itself. Currently, it is not yet clear the the relative impact of each one. A cross-sectional study was done in a cohort of 1,783 IV-1 infected persons from three centers located in Madrid, mainly devoted to attend persons at risks for HIV infection. Long-term nonprogressors (LTNP) were defined as those with more than 8 years of confirmed HIV seropositivity, and CD4+ T-cell count above 500 x 10(6)/I in the absence of antiretroviral therapy or symptoms suggesting immunodeficiency. Rapid progressors (RP) were those with less than 5 years from seroconversion and repeatedly current CD4+ T-cell count below 200 x 10(6)/I. An analysis of different epidemiological, immunological and virological features was performed comparing LTNP and RP. Among 1,783 HIV (+) subjects studied, 100 (5.6%) fulfilled criteria for LTNP and 12 (0.7%) for RP. Among LTNP, stabilized CD4 slope was seen in 16 (33%) out of 48 after more than 8 years of infection. Variables statistically associated with LTNP were: past history of intravenous drug addiction (80% of them), male gender (79% of them), high alcohol intake (48% of them), HIV-1 non-syncitium inducing viral phenotype, and very low or undetectable HIV-1 plasma viremia. In contrast, variables associated with RP were: infection by sexual contact (75% of cases), female gender (50% of them), syncitium-inducing viral plenotype, and high titers of plasma viremia. The CD4/CD8 ratio below 1 was seen in all RP and in 88% of LTNP. However, a preferent depletion of CD4+ cell occurred in the first group, instead of an enhancement of the CD8 T-cell count in LTNP. The prevalence of serological markers for hepatotropic viruses and other potential infectious cofactors was not higher

  7. Using SAR and GPS for Hazard Management and Response: Progress and Examples from the Advanced Rapid Imaging and Analysis (ARIA) Project

    NASA Astrophysics Data System (ADS)

    Owen, S. E.; Simons, M.; Hua, H.; Yun, S. H.; Agram, P. S.; Milillo, P.; Sacco, G. F.; Webb, F.; Rosen, P. A.; Lundgren, P.; Milillo, G.; Manipon, G. J. M.; Moore, A. W.; Liu, Z.; Polet, J.; Cruz, J.

    2014-12-01

    ARIA is a joint JPL/Caltech project to automate synthetic aperture radar (SAR) and GPS imaging capabilities for scientific understanding, hazard response, and societal benefit. We have built a prototype SAR and GPS data system that forms the foundation for hazard monitoring and response capability, as well as providing imaging capabilities important for science studies. Together, InSAR and GPS have the ability to capture surface deformation in high spatial and temporal resolution. For earthquakes, this deformation provides information that is complementary to seismic data on location, geometry and magnitude of earthquakes. Accurate location information is critical for understanding the regions affected by damaging shaking. Regular surface deformation measurements from SAR and GPS are useful for monitoring changes related to many processes that are important for hazard and resource management such as volcanic deformation, groundwater withdrawal, and landsliding. Observations of SAR coherence change have a demonstrated use for damage assessment for hazards such as earthquakes, tsunamis, hurricanes, and volcanic eruptions. These damage assessment maps can be made from imagery taken day or night and are not affected by clouds, making them valuable complements to optical imagery. The coherence change caused by the damage from hazards (building collapse, flooding, ash fall) is also detectable with intelligent algorithms, allowing for rapid generation of damage assessment maps over large areas at fine resolution, down to the spatial scale of single family homes. We will present the progress and results we have made on automating the analysis of SAR data for hazard monitoring and response using data from the Italian Space Agency's (ASI) COSMO-SkyMed constellation of X-band SAR satellites. Since the beginning of our project with ASI, our team has imaged deformation and coherence change caused by many natural hazard events around the world. We will present progress on our

  8. Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data

    PubMed Central

    Granger, Benjamin; Combe, Bernard; Le Loet, Xavier; Saraux, Alain; Guillemin, Francis; Fautrel, Bruno

    2016-01-01

    Introduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX). Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year. Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)—or anti-citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP. Conclusions Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance. PMID:27252898

  9. Executive Center Makes Rapid Progress.

    ERIC Educational Resources Information Center

    Dumarsq, Carolyn C.; Scott, Charles A.

    1987-01-01

    In a pilot test, superintendents participated in self-assessment activities in the American Association of School Administrator's Executive Development Center program. Activity stages centered on professional attitudes and skills, personal health, and fitness. Data provided a profile for professional development. Participants felt activities were…

  10. Rapid Steroid Hormone Actions Initiated at the Cell Surface and the Receptors that Mediate Them with an Emphasis on Recent Progress in Fish Models

    PubMed Central

    Thomas, Peter

    2011-01-01

    In addition to the classic genomic mechanism of steroid action mediated by activation of intracellular nuclear receptors, there is now extensive evidence that steroids also activate receptors on the cell surface to initiate rapid intracellular signaling and biological responses that are often nongenomic. Recent progress in our understanding of rapid, cell surface-initiated actions of estrogens, progestins, androgens and corticosteroids and the identities of the membrane receptors that act as their intermediaries is briefly reviewed with a special emphasis on studies in teleost fish. Two recently discovered novel proteins with seven-transmembrane domains, G protein-coupled receptor 30 (GPR30), and membrane progestin receptors (mPRs) have the ligand binding and signaling characteristics of estrogen and progestin membrane receptors, respectively, but their functional significance is disputed by some researchers. GPR30 is expressed on the cell surface of fish oocytes and mediates estrogen inhibition of oocyte maturation. mPRα is also expressed on the oocyte cell surface and is the intermediary in progestin induction of oocyte maturation in fish. Recent results suggest there is cross-talk between these two hormonal pathways and that there is reciprocal down-regulation of GPR30 and mPRα expression by estrogens and progestins at different phases of oocyte development to regulate the onset of oocyte maturation. There is also evidence in fish that mPRs are involved in progestin induction of sperm hypermotility and anti-apoptotic actions in ovarian follicle cells. Nonclassical androgen and corticosteroid actions have also been described in fish models but the membrane receptors mediating these actions have not been identified. PMID:22154643

  11. Successful polymyxin B hemoperfusion treatment associated with serial reduction of serum anti-CADM-140/MDA5 antibody levels in rapidly progressive interstitial lung disease with amyopathic dermatomyositis.

    PubMed

    Teruya, Aoi; Kawamura, Kodai; Ichikado, Kazuya; Sato, Shinji; Yasuda, Yuko; Yoshioka, Masakazu

    2013-12-01

    Clinically amyopathic dermatomyositis (CADM), a subtype of dermatomyositis with subtle or no muscle involvement, is occasionally accompanied by fatal, rapidly progressive interstitial lung disease (RP-ILD) that is resistant to aggressive immunosuppressive therapy. The presence of anti-CADM-140/MDA5 antibodies is diagnostic for patients with dermatomyositis (particularly CADM) and is known to be strongly associated with the pathogenesis, disease activity, and mortality of RP-ILD. Polymyxin-B direct hemoperfusion (PMX-DHP), originally developed for the removal of endotoxin, has been demonstrated to be effective for treating various types of acute respiratory failure. We describe a patient with amyopathic dermatomyositis who developed RP-ILD characterized by elevated anti-CADM-140/MDA5 autoantibodies, was resistant to combined steroid and immunosuppressant therapy, and was treated successfully with PMX-DHP. To our knowledge, this is the first case to indicate a serial reduction of anti-CADM-140/MDA5 autoantibodies, associated with clinical improvement, following PMX-DHP. Early intervention using PMX-DHP may improve the prognosis of RP-ILD accompanied by CADM.

  12. Deep Learning Representation from Electroencephalography of Early-Stage Creutzfeldt-Jakob Disease and Features for Differentiation from Rapidly Progressive Dementia.

    PubMed

    Morabito, Francesco Carlo; Campolo, Maurizio; Mammone, Nadia; Versaci, Mario; Franceschetti, Silvana; Tagliavini, Fabrizio; Sofia, Vito; Fatuzzo, Daniela; Gambardella, Antonio; Labate, Angelo; Mumoli, Laura; Tripodi, Giovanbattista Gaspare; Gasparini, Sara; Cianci, Vittoria; Sueri, Chiara; Ferlazzo, Edoardo; Aguglia, Umberto

    2017-03-01

    A novel technique of quantitative EEG for differentiating patients with early-stage Creutzfeldt-Jakob disease (CJD) from other forms of rapidly progressive dementia (RPD) is proposed. The discrimination is based on the extraction of suitable features from the time-frequency representation of the EEG signals through continuous wavelet transform (CWT). An average measure of complexity of the EEG signal obtained by permutation entropy (PE) is also included. The dimensionality of the feature space is reduced through a multilayer processing system based on the recently emerged deep learning (DL) concept. The DL processor includes a stacked auto-encoder, trained by unsupervised learning techniques, and a classifier whose parameters are determined in a supervised way by associating the known category labels to the reduced vector of high-level features generated by the previous processing blocks. The supervised learning step is carried out by using either support vector machines (SVM) or multilayer neural networks (MLP-NN). A subset of EEG from patients suffering from Alzheimer's Disease (AD) and healthy controls (HC) is considered for differentiating CJD patients. When fine-tuning the parameters of the global processing system by a supervised learning procedure, the proposed system is able to achieve an average accuracy of 89%, an average sensitivity of 92%, and an average specificity of 89% in differentiating CJD from RPD. Similar results are obtained for CJD versus AD and CJD versus HC.

  13. Vanillic Acid Ameliorates Cationic Bovine Serum Albumin Induced Immune Complex Glomerulonephritis in BALB/c Mice.

    PubMed

    Motiram Kakalij, Rahul; Tejaswini, G; Patil, Madhoosudan A; Dinesh Kumar, B; Diwan, Prakash V

    2016-06-01

    Preclinical Research Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally-induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune-complex glomerulonephritis in female BALB/c mice. Pre-immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF-α levels. Co-administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171-179, 2016.   © 2016 Wiley Periodicals, Inc.

  14. The role of Th1 and Th17 cells in glomerulonephritis.

    PubMed

    Azadegan-Dehkordi, Fatemeh; Bagheri, Nader; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud

    2015-04-01

    T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis.

  15. Lymphocyte surface markers in acute rheumatic fever and post-streptococcal acute glomerulonephritis.

    PubMed Central

    Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H

    1977-01-01

    Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301

  16. Granulomatosis with Polyangiitis Presenting as Pauci-Immune Crescentic Glomerulonephritis in Pregnancy

    PubMed Central

    Kunjal, Ryan; Makary, Raafat; Poenariu, Andreea

    2016-01-01

    Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management. PMID:27293925

  17. Diffuse alveolar haemorrhage in ANCA-negative pauci-immune crescentic glomerulonephritis.

    PubMed

    Sandhu, Gagangeet; Casares, Pablo; Farias, Antony; Ranade, Aditi; Jones, James

    2010-10-01

    Pulmonary renal syndrome (PRS) is a combination of diffuse pulmonary haemorrhage and glomerulonephritis (GN). Though an established form of presentation in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated GN and vasculitis, diffuse pulmonary haemorrhage is extremely unusual in those with ANCA-negative GN. We present here a case of a 76-year-old Hispanic female with stage IV chronic kidney disease (serum creatinine of 2 mg/dL), who presented with diffuse alveolar haemorrhage and nephritic syndrome. Less than 1 week prior to the full-blown PRS, she was treated for an apparent pneumonia as was evidenced by a right lower lobe infiltrate on her chest X-ray. Retrospectively, this was likely a focal pulmonary haemorrhage. ANCA were persistently negative, and the remainder of her immunologic workup was normal. Renal biopsy was diagnostic of crescentic pauci-immune GN. The patient required a ventilator and haemodialysis support (serum creatinine 6 mg/dL), and was successfully treated with methylprednisolone, cyclophosphamide and a total of six cycles of plasmapheresis. Once her oliguria resolved, the creatinine plateaued at 2.7 mg/dL. Our case illustrates that diffuse alveolar haemorrhage can be a distinct clinical feature even in patients with ANCA-negative pauci-immune crescentic glomerulonephritis.

  18. Role of the plasma contact system in the pathogenesis of experimental anti-GBM glomerulonephritis.

    PubMed Central

    Villaro, J; Sánchez Ibarrola, A; Purroy, A

    1988-01-01

    To study the participation of the Hageman factor-related contact system of plasma in the pathogenesis of glomerulonephritis (GN), an anti-BM GN was induced in a group of 10 normal Brown Norway rats and another of seven Brown Norway BN/Mai Pfd f rats. The latter strain is characterized by a congenital deficiency of plasma prekallikrein and of high-molecular weight kininogen, with lengthening of the activated partial thromboplastin time. In the deficient group, one animal developed crescents in less than 25% of glomeruli, five in 25-50% and one in 50-75%. In the group of normal rats, extracapillary proliferation was of greater severity: one animal showed crescents in less than 25% of glomeruli, two in 50-75% and five in more than 75% of glomeruli. Although in both groups intense glomerular fibrin deposition was documented, the intensity of these deposits was less severe in the deficient animals. These data suggest, in the first place, that functional integrity of the contact system is not a necessary requirement for glomerular fibrinogenesis, other mechanisms being implicated in this phenomenon. On the other hand, this functional deficit has exerted a protective effect on crescent formation, which suggests that the contact system can play a role as a mediator of injury in glomerulonephritis, perhaps through the release of contact system-dependent mediators of inflammation. PMID:3396222

  19. C3 glomerulonephritis and autoimmune disease: more than a fortuitous association?

    PubMed

    Alexander, Mariam P; Fervenza, Fernando C; De Vriese, An S; Smith, Richard J H; Nasr, Samih H; Cornell, Lynn D; Herrera Hernandez, Loren P; Zhang, Yuzhou; Sethi, Sanjeev

    2016-04-01

    C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent.

  20. An immune-complex glomerulonephritis of Chinook salmon, Oncorhynchus tshawytscha (Walbaum).

    PubMed

    Lumsden, J S; Russell, S; Huber, P; Wybourne, B A; Ostland, V E; Minamikawa, M; Ferguson, H W

    2008-12-01

    Chinook salmon from New Zealand were shown to have a generalized membranous glomerulonephritis that was most severe in large fish. Marked thickening of the glomerular basement membrane was the most consistent lesion, with the presence of an electron-dense deposit beneath the capillary endothelium.Severely affected glomeruli also had expansion of the mesangium and loss of capillaries,synechiae of the visceral and parietal epithelium and mild fibrosis of Bowmans capsule. Chinook salmon from British Columbia, Canada with bacterial kidney disease caused by Renibacterium salmoninarum had similar histological lesions. They also had thickened glomerular basement membranes that were recognized by rabbit antiserum to rainbow trout immunoglobulin. This was true only when frozen sections of kidney were used and not formalin-fixed tissue. An attempt to experimentally produce a glomerulopathy in rainbow trout by repeated immunization with killed R. salmoninarum was not successful. Case records from the Fish Pathology Laboratory at the University of Guelph over a 10-year period revealed that a range of species were diagnosed with glomerulopathies similar to those seen in Chinook salmon. The majority of these cases were determined to have chronic inflammatory disease. This report has identified the presence of immunoglobulin within thickened basement membranes of Chinook salmon with glomerulonephritis and supports the existence of type III hypersensitivity in fish.

  1. [Follow-up of two patients with mesangial IgA glomerulonephritis exposed to cadmium and organic solvents].

    PubMed

    Fernández, J; Colomé, Jaime Fernández; Sanz-Gallén, P; Sanz-Gallén, Pere; Nogué, S; Xarau, Santiago Nogué

    2010-01-01

    For several years we carried out a follow-up of two patients with IgA mesangial glomerulonephritis with antecedents of exposure to toxic substances (cadmium and organic solvents). The first case involved a 47 year old male who was diagnosed with mesangial IgA glomerulonephritis eight years ago; he had been working for twelve years as a solderer. He had used metal bars containing 25% cadmium as part of the soldering material. Very high levels of cadmium were detected in his blood and urine. The second case involved a 50 year male who was exposed to a wide number of organic dissolvents for 23 years. Three years ago he was diagnosed with a proliferative diffuse mesangial glomerulonephritis with IgA deposits; in spite of that, the patient continued working until one year ago, when was found to have a chronic stage 3 renal disease secondary to IgA nephropathy. Patients diagnosed with mesangial IgA glomerulonephritis should be kept apart from exposure to nephrotoxic substances.

  2. Membranoproliferative glomerulonephritis

    MedlinePlus

    ... glomeruli. The glomeruli of the kidney help filter wastes and fluids from the blood to form urine. ... the glomerular basement membrane. This membrane helps filter wastes and extra fluids from the blood. Damage to ...

  3. Post-streptococcal acute glomerulonephritis complicated by gouty arthritis: a case report.

    PubMed

    Kuniyoshi, Yasutaka; Kamura, Azusa; Yasuda, Sumie; Tashiro, Makoto

    2015-06-17

    Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients.

  4. Treatment-resistant recurrent membranoproliferative glomerulonephritis in renal allograft responding to rituximab: case report.

    PubMed

    Farooqui, M; Alsaad, K; Aloudah, N; Alhamdan, H

    2015-04-01

    We report a case of idiopathic membranoproliferative glomerulonephritis (MPGN) recurring 2 years after a living-unrelated kidney transplantation. The disease was refractory to intravenous immunoglobulin and plasmapheresis. Treatment with 2 doses of rituximab resulted in remission of the disease. The disease relapsed 18 months later after an episode of cytomegalovirus pneumonitis. After treatment of the pneumonitis, a lung biopsy was performed owing to persistent chest symptoms, which revealed bronchiolitis obliterans with organizing pneumonia. Bone marrow examination and culture revealed presence of acid-fast bacilli, and culture grew Mycobacterium tuberculosis. A repeated course of rituximab was withheld because of infection with tuberculosis, the patient's chest symptoms, and rare reports of noninfectious lung disease after the use of rituximab. The patient continues to have proteinuria with impaired kidney function. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Posterior reversible encephalopathy syndrome in a patient with hepatitis B induced type 1 membranoproliferative glomerulonephritis.

    PubMed

    Sathyanarayanan, Vishwanath; Razak, Abdul; Narayan, Girish; Prabhu, Mukhyaprana; Ramachandran, Balasubramanian; Ranjini, Kudva; Vidya, Monappa; Joshi, Kusum

    2010-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare complication of nephrotic syndrome and corticosteroid therapy. Here, we discuss an 18 year old man with type 1 membranoproliferative glomerulonephritis (MPGN) secondary to hepatitis B infection who developed posterior leukoencephalopathy while on therapy with lamivudine and prednisone. He developed seizures and vision loss. He also had hypertension, but no sudden elevation was recorded at any time. Magnetic resonance imaging revealed patchy areas of altered signal intensity involving cortical gray and subcortical white matter in the bilateral frontoparietal regions, occipital cortices, temporal cortices and cerebellar hemispheres, and hyperintensity on T2W and FLAIR sequences. Tapering of prednisone and controlling hypertension resulted in clinical improvement within a few days, and in a month MRI was normal. Diagnosing PRES requires a high index of suspicion when treating similarly susceptible patients. PRES as a complication during the treatment of MPGN secondary to hepatitis B has, to our knowledge, never been reported previously in the literature.

  6. The dissociation of arterial hypertension and lupus glomerulonephritis in systemic lupus erythematosus.

    PubMed

    Petrin, J; Rozman, B; Dolenc, P; Logar, D; Bozic, B; Vizjak, A; Ferluga, D; Jezersek, P

    1993-06-01

    In spite of several articles questioning the general opinion that arterial hypertension in patients with systemic lupus erythematosus (SLE) is only the consequence of lupus glomerulonephritis (LGN), this still remains the usual pathophysiologic explanation. The purpose of this study was to explore the correlations between hypertension and LGN and to assess the importance of hypertension control for the prognosis of patients. A retrospective analysis of 173 patients with SLE over a period of 14 years was performed. For most of the patients, data were available from regular follow-up visits over an average of 6 years. Our results show a dissociation of hypertension and LGN and an association of hypertension and renal dysfunction. Severe hypertensive renal vascular lesions correlated well with a decrease of renal function. Successful treatment of hypertension is therefore essential in order to prevent deterioration of renal function in patients with LGN.

  7. Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN

    PubMed Central

    Salvadori, Maurizio; Rosso, Giuseppina

    2016-01-01

    This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies. PMID:27458560

  8. Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis.

    PubMed

    Hohenstein, Bernd; Daniel, Christoph; Johnson, Richard J; Amann, Kerstin U; Hugo, Christian P M

    2013-01-01

    Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibα antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse.

  9. [Effect of Astragali and Angelica particle on proteinuria in Chinese patients with primary glomerulonephritis].

    PubMed

    Shen, Peicheng; Yang, Xuejun; He, Liqun

    2016-06-01

    To investigate the effect of the traditional Chinese herbs Astragali and Angelicae Sinensis (A & As) particle [contains Huangqi (Radix Astragali Mongolica), Danggui (Radix Angelicae Sinensis), Huzhanggeng (Rhizoma Polygoni Cuspidati) and Danshen (Radix Salviae Miltiorrhizae)] on proteinuria in glomerulonephritis patients with stage 2 chronic kidney disease. A prospective, multi-center, and randomized controlled clinical trial was performed for 24 weeks. From March 2011 to April 2012, 158 patients from nine hospitals in China participated. They were randomized into the A & As group (79 cases, A & As particle 15.2 g/day) and losartan group (79 cases, losartan 50 mg/day). At each follow-up visit, clinical data including blood pressure, urinalysis, 24-h-urinary protein excretion, serum albumin and serum creatinine were collected. All 158 patients completed the follow-up. Proteinuria in the losartan group exhibited a biphasic time-dependent decline with a significant steady reduction from baseline to week 12 (P = 0.0014), and a platform level during the remaining 12-week follow-up (P > 0.05). In contrast, there was a continual significant decrease of proteinuria in the A & As group (P < 0.001). When compared with the losartan results, proteinuria in the A & As group from week 16 to week 24 was significantly reduced (P < 0.001). Stable eGFRs and blood pressure were also observed in both groups. Medication side effects were minimal and non-fatal. For Chinese glomerulonephritis patients with stage 2 chronic kidney disease, therapy with A & As particles may provide effective anti-proteinuria treatment.

  10. Matrix metalloproteinase-12 (MMP-12) deficiency attenuates experimental crescentic anti-GBM glomerulonephritis.

    PubMed

    Abraham, Abu P; Ma, Frank Y; Mulley, William R; Nikolic-Paterson, David J; Tesch, Greg H

    2016-11-08

    MMP-12 (macrophage elastase) is an enzyme that can cleave various extracellular matrix proteins and is required for macrophage infiltration and pulmonary fibrosis in experimental emphysema. We have shown previously that MMP-12 is highly up-regulated in experimental anti-glomerular basement membrane (GBM) disease. The aim of this study was to determine whether MMP-12 is required for glomerular macrophage infiltration and crescent formation in anti-GBM glomerulonephritis. Accelerated anti-GBM disease was induced in groups of MMP-12 gene deficient mice (MMP-12-/-) and wild type C57BL/6 J (WT) controls, which were killed 12 days after injection of anti-GBM serum. WT and MMP-12-/- mice developed glomerular damage and glomerular tuft adhesions to Bowman's capsule. Both groups developed severe proteinuria. WT mice also developed significant loss of renal function and crescents in 22% of glomeruli, which were associated with macrophage infiltration and Bowman's capsule rupture. In contrast, MMP-12-/- mice were partially protected from renal function decline, crescent formation and Bowman's capsule rupture. This was associated with reduced macrophage infiltration in both glomeruli and the interstitium, and with reduced expression of CCL2, TNF-α and iNOS mRNA in MMP12-/- kidneys. In addition, KIM-1 mRNA levels were reduced in MMP-12-/- mice indicating less tubular damage. These data demonstrate that endogenous MMP-12 facilitates macrophage accumulation and activation in anti-GBM glomerulonephritis which is required for glomerular crescent formation, Bowman's capsule rupture, tubular damage and renal function decline. This article is protected by copyright. All rights reserved.

  11. Anti–Melanoma Differentiation–Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis

    PubMed Central

    MOGHADAM-KIA, SIAMAK; ODDIS, CHESTER V.; SATO, SHINJI; KUWANA, MASATAKA; AGGARWAL, ROHIT

    2016-01-01

    Objective Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti–melanoma differentiation–associated gene 5 (anti–MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti–MDA-5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM. Methods CADM patients were identified in the University of Pittsburgh Myositis Center Database and matched 1:1 (sex and age) to classic DM controls. Anti–MDA-5 was measured by serum enzyme-linked immunosorbent assay. Kaplan-Meier, log rank, and chi-square tests were used for analysis. Results We identified 61 CADM patients (62% women, mean age 48.2 years) and 61 classic DM controls (64% women, mean age 44.8 years). The frequencies of anti–MDA-5-positivity, ILD, and RPILD were similar in the 2 cohorts (MDA-5 positive: CADM 13.1% [8 of 61] and DM 13.1% [8 of 61], ILD positive: CADM 31.1% [19 of 61] and DM 26.2% [16 of 61], and RPILD positive: CADM 8.2% [5 of 61] and DM 5% [3 of 61]; P=1, 0.55, and 0.46, respectively). Anti–MDA-5-positivity was significantly associated with ILD, since 50% of MDA-5–positive subjects (8 of 16) had ILD versus 25.5% of MDA-5–negative subjects (27 of 106; P=0.04). Anti–MDA-5 was strongly associated with RPILD (P < 0.001). Anti–MDA-5–positive patients with ILD had worse baseline pulmonary function testing variables compared to anti–MDA-5–negative patients. Anti–MDA-5-positivity was significantly associated with poor survival (P=0.007). Conclusion Anti–MDA-5 antibody is significantly associated with ILD, RPILD, worse pulmonary outcome, and survival in US classic DM and CADM patients. PMID:26414240

  12. Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis.

    PubMed

    Moghadam-Kia, Siamak; Oddis, Chester V; Sato, Shinji; Kuwana, Masataka; Aggarwal, Rohit

    2016-05-01

    Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti-melanoma differentiation-associated gene 5 (anti-MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti-MDA-5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM. CADM patients were identified in the University of Pittsburgh Myositis Center Database and matched 1:1 (sex and age) to classic DM controls. Anti-MDA-5 was measured by serum enzyme-linked immunosorbent assay. Kaplan-Meier, log rank, and chi-square tests were used for analysis. We identified 61 CADM patients (62% women, mean age 48.2 years) and 61 classic DM controls (64% women, mean age 44.8 years). The frequencies of anti-MDA-5 positivity, ILD, and RPILD were similar in the 2 cohorts (MDA-5 positive: CADM 13.1% [8 of 61] and DM 13.1% [8 of 61], ILD positive: CADM 31.1% [19 of 61] and DM 26.2% [16 of 61], and RPILD positive: CADM 8.2% [5 of 61] and DM 5% [3 of 61]; P = 1, 0.55, and 0.46, respectively). Anti-MDA-5 positivity was significantly associated with ILD, since 50% of MDA-5-positive subjects (8 of 16) had ILD versus 25.5% of MDA-5-negative subjects (27 of 106; P = 0.04). Anti-MDA-5 was strongly associated with RPILD (P < 0.001). Anti-MDA-5-positive patients with ILD had worse baseline pulmonary function testing variables compared to anti-MDA-5-negative patients. Anti-MDA-5 positivity was significantly associated with poor survival (P = 0.007). Anti-MDA-5 antibody is significantly associated with ILD, RPILD, worse pulmonary outcome, and survival in US classic DM and CADM patients. © 2016, American College of Rheumatology.

  13. Independent or synergistic relationship of proteinuria and glomerular filtration rate on patient and renal survival in patients with glomerulonephritis?

    PubMed

    Haider, Dominik G; Masghati, Salome; Goliasch, Georg; Fuhrmann, Valentin; Soleiman, Afschin; Wolzt, Michael; Baierl, Andreas; Druml, Wilfred; Hörl, Walter H

    2014-12-01

    Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN). In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Full data sets were available from 1,892 subjects. Classes of CKD on the basis of estimated GFR (eGFR) and of proteinuria grouped as <1, 1-3.5, and >3.5 g/24 h were tested for their association with all-cause mortality and ESRD. During a median follow-up of 130 months [interquartile range (IQR) 90; 178] 478 patients (25.3 %) died. Median eGFR was 49 ml/min/1.73 m(2) (IQR 24; 81) and proteinuria 3.8 g/24 h (IQR 1.7; 8.0). Adjusted multivariate Cox regression indicated that renal survival but not overall survival is related to proteinuria >3.5 g/24 h [as opposed to <1 g/24 h; hazard ratio (HR) 1.91] and shows progression to ESRD. However, subgroup analyses revealed that this risk with proteinuria >3.5 g/24 h exists only in patients with immunoglobulin (Ig)A GN (HR 4.93), miscellaneous GN (HR 1.74), and CKD stage 5 (HR 2.50). Additionally, proteinuria is a risk factor for renal survival in males more than in females with GN and proteinuria >3.5 g/24 h (HR 1.91). Proteinuria is a strong risk factor for renal survival particularly in patients with proteinuria >3.5 g/24 but not for all types of GN, nor for all CKD stages. Proteinuria is not a risk factor for overall survival in patients with GN.

  14. [Extramembranous glomerulonephritis of acquired syphilis in a patient recently infected by the hepatitis B virus. Demonstration of the treponemal antigen in the kidney by indirect immunofluorescence].

    PubMed

    Schillinger, F; Montagnac, R; Goclowski, C; Dine, G; Alessandri, E; Hopfner, C; Birembaut, P

    1983-01-22

    A 38 years old male homosexual with active secondary syphilis presented with pure nephrotic syndrome while HBs and HBe tests were positive without clinical hepatitis. He had circulating immune complexes, IgG--IgM cryoglobulinemia and high IgA, IgM and IgE levels; the C3 and C4 complement constituents were normal. Examination of renal biopsy sections under light, fluorescent and electronic microscopy showed stage I membranous glomerulonephritis the syphilitic origin of which was confirmed by indirect immunofluorescence and by rapid cure under penicillin treatment. This case calls for the following comments: (1) glomerular deposits are extramembranous rather than subendothelial in syphilitic nephrosis, a disease now classified among circulating immune complexes diseases; (2) in the kidney, the treponema antigen can be demonstrated by indirect immunofluorescence and the anti-treponema antibody, by elution; (3) the outcome of the nephrotic syndrome is always favourable, either spontaneously or after penicillin treatment; (4) syphilis and HBs antigens are frequently associated, particularly in homosexual patients; one should be looked for when the other is discovered.

  15. A rapid assay for circulating anti-glomerular basement membrane antibodies in Goodpasture syndrome.

    PubMed

    Saxena, R; Isaksson, B; Bygren, P; Wieslander, J

    1989-03-10

    A rapid ELISA for the detection of circulating anti-glomerular basement membrane antibodies in Goodpasture syndrome is described. The specificity of the test was shown to be highly dependent on the antigens used. Using the purified Goodpasture antigen it was possible to shorten the incubation times to 10 min in a routine assay using alkaline phosphatase-labeled second antibodies and the total assay was complete in 30 min. 200 reference sera, 500 sera from patients with various types of glomerulonephritis and 32 sera from patients with Goodpasture syndrome were analyzed by this rapid assay. The assay was able to discriminate between Goodpasture syndrome and other forms of glomerulonephritis. Using enzyme amplification it was possible to further shorten the incubation times to 1 min and the total time of the assay to 6 min.

  16. An unusual case of IgA-dominant postinfectious glomerulonephritis: a case report and review of the literature.

    PubMed

    Wagrowska-Danilewicz, M; Danilewicz, M; Fisiak, I; Piskorska, J

    2016-06-01

    We report a case of IgA-dominant postinfectious glomerulonephritis in a 49-year-old man presenting with acute kidney injury, nephrotic range proteinuria and hematuria. He suffered from ischemic heart disease, cardiac insufficiency, mitral regurgitation, tricuspid insufficiency, septal aneurysm and hypertension. Renal biopsy revealed segmental and focal endocapillary and mesangial hypercellularity, and thickening of the glomerular capillary wall. Immunofluorescence showed co-dominant strong coarse granular immunostaining of IgA, IgG and C3 mainly along the glomerular capillary wall. On electron microscopy some large subepithelial hump-shaped deposits were present. In summary, this case demonstrates the presence of a broad spectrum of glomerular histological findings in postinfectious glomerulonephritis.

  17. Autoimmunity to the alpha 3 chain of type IV collagen in glomerulonephritis is triggered by ‘autoantigen complementarity’

    PubMed Central

    Reynolds, John; Preston, Gloria A.; Pressler, Barrak M.; Hewins, Peter; Brown, Michael; Roth, Aleeza; Alderman, Elizabeth; Bunch, Donna; Jennette, J. Charles; Cook, H. Terence; Falk, Ronald J.; Pusey, Charles D.

    2015-01-01

    ‘Autoantigen complementarity’ is a theory proposing that the initiator of an autoimmune response is not necessarily the autoantigen or its molecular mimic, but may instead be a peptide that is ‘antisense/complementary’ to the autoantigen. We investigated whether such complementary proteins play a role in the immunopathogenesis of autoimmune glomerulonephritis. Experimental autoimmune glomerulonephritis, a model of anti-glomerular basement membrane (GBM) disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the α3 chain of type IV collagen. In this study, WKY rats were immunized with a complementary α3 peptide (c-α3-Gly) comprised of amino acids that ‘complement’ the well characterized epitope on α3(IV)NC1, pCol(24–38). Within 8 weeks post-immunization, these animals developed cresentic glomerulonephritis, similar to pCol(24–38)-immunized rats, while animals immunized with scrambled peptide were normal. Anti-idiotypic antibodies to epitopes from c-α3-Gly-immunized animals were shown to be specific for α3 protein, binding in a region containing sense pCol(24–38) sequence. Interestingly, anticomplementary α3 antibodies were identified in sera from patients with anti-GBM disease, suggesting a role for ‘autoantigen complementarity’ in immunopathogenesis of the human disease. This work supports the idea that autoimmune glomerulonephritis can be initiated through an immune response against a peptide that is anti-sense or complementary to the autoantigen. The implications of this discovery may be far reaching, and other autoimmune diseases could be due to responses to these once unsuspected ‘complementary’ antigens. PMID:25841937

  18. Statin attenuates experimental anti-glomerular basement membrane glomerulonephritis together with the augmentation of alternatively activated macrophages.

    PubMed

    Fujita, Emiko; Shimizu, Akira; Masuda, Yukinari; Kuwahara, Naomi; Arai, Takashi; Nagasaka, Shinya; Aki, Kaoru; Mii, Akiko; Natori, Yasuhiro; Iino, Yasuhiko; Katayama, Yasuo; Fukuda, Yuh

    2010-09-01

    Macrophages are heterogeneous and include classically activated M1 and alternatively activated M2 macrophages, characterized by pro- and anti-inflammatory functions, respectively. Macrophages that express heme oxygenase-1 also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects of statin in experimental anti-glomerular basement membrane glomerulonephritis and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti-glomerular basement membrane glomerulonephritis and treated with atorvastatin (20 mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7, together with increased mRNA levels of the M1 macrophage-associated cytokines, interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. In contrast, statin reduced the level of proteinuria, reduced infiltration of macrophages in glomeruli with suppression of monocyte chemotactic protein-1 expression, and inhibited the formation of necrotizing and crescentic lesions. The number of glomerular ED3-positive macrophages decreased with down-regulation of M1 macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2 macrophages with up-regulation of the M2 macrophage-associated chemokines and cytokines, chemokine (C-C motif) Iigand-17 and interleukin-10. Statin also increased the glomerular interleukin-10-expressing heme oxygenase-1-positive macrophages. Statin inhibited macrophage development, and suppressed ED3-positive macrophages, but augmented ED2-positive macrophages in M2-associated cytokine environment in vitro. We conclude that the anti-inflammatory effects of statin in glomerulonephritis are mediated through inhibition of macrophage infiltration as well as augmentation of anti-inflammatory macrophages.

  19. Interagency partnering for weed prevention--progress on development of a National Early Detection and Rapid Response System for Invasive Plants in the United States

    USGS Publications Warehouse

    Westbrooks, R.; Westbrooks, R.

    2011-01-01

    Over the past 50 years, experience has shown that interagency groups provide an effective forum for addressing various invasive species issues and challenges on multiple land units. However, more importantly, they can also provide a coordinated framework for early detection, reporting, identification and vouchering, rapid assessment, and rapid response to new and emerging invasive plants in the United States. Interagency collaboration maximizes the use of available expertise, resources, and authority for promoting early detection and rapid response (EDRR) as the preferred management option for addressing new and emerging invasive plants. Currently, an interagency effort is underway to develop a National EDRR System for Invasive Plants in the United States. The proposed system will include structural and informational elements. Structural elements of the system include a network of interagency partner groups to facilitate early detection and rapid response to new invasive plants, including the Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW), State Invasive Species Councils, State Early Detection and Rapid Response Coordinating Committees, State Volunteer Detection and Reporting Networks, Invasive Plant Task Forces, and Cooperative Weed Management Areas. Informational elements and products being developed include Regional Invasive Plant Atlases, and EDRR Guidelines for EDRR Volunteer Network Training, Rapid Assessment and Rapid Response, and Criteria for Selection of EDRR Species. System science and technical support elements which are provided by cooperating state and federal scientists, include EDRR guidelines, training curriculum for EDRR volunteers and agency field personnel, plant identification and vouchering, rapid assessments, as well as predictive modeling and ecological range studies for invasive plant species.

  20. Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis

    PubMed Central

    1983-01-01

    The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral

  1. Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-gamma.

    PubMed

    Kitching, A Richard; Turner, Amanda L; Semple, Timothy; Li, Ming; Edgtton, Kristy L; Wilson, Gabrielle R; Timoshanko, Jennifer R; Hudson, Billy G; Holdsworth, Stephen R

    2004-07-01

    IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers. At 13 wk, WT mice developed EAG with linear mouse anti-GBM antibody deposition, histologic injury, proteinuria, and mild tubulointerstitial disease. Compared with WT mice, IL-12p40-/- mice had decreased histologic injury and trends to decreased leukocyte infiltrates. In contrast, 40% (4 of 10) of IFN-gamma-/- mice developed significant crescent formation and focal or diffuse interstitial infiltrates (WT, 0 of 8). Compared with WT and/or IL-12p40-/- mice, IFN-gamma-/- mice developed increased injury: histologic injury, total glomerular cell numbers, leukocytes in glomeruli, and renal expression of P-selectin and intercellular adhesion molecule 1. All groups developed similar serum anti-alpha3-alpha5(IV)NC1 antibodies and glomerular Ig deposition, but IFN-gamma-/- mice had decreased anti-alpha3-alpha5(IV)NC1 IgG2a. Therefore, IFN-gamma-/- mice developed increased cellular reactants despite a potentially less damaging antibody response. Dermal delayed-type hypersensitivity was increased in alpha3-alpha5(IV)NC1 immunized IFN-gamma-/- mice and was suppressed by recombinant murine IFN-gamma. CD4+ cells from draining nodes of immunized IFN-gamma-/- mice showed increased proportions of proliferating CD4+ cells but similar numbers of apoptotic cells. These studies demonstrate that in renal organ-specific autoimmunity, IL-12 is pathogenetic but IFN-gamma is protective. They lend weight to the hypothesis that depending on the context/severity of the nephritogenic immune response

  2. Lack of Endothelial Nitric Oxide Synthase Aggravates Murine Accelerated Anti-Glomerular Basement Membrane Glomerulonephritis

    PubMed Central

    Heeringa, Peter; van Goor, Harry; Itoh-Lindstrom, Yoshie; Maeda, Nobuyo; Falk, Ronald J.; Assmann, Karel J. M.; Kallenberg, Cees G. M.; Jennette, J. Charles

    2000-01-01

    Nitric oxide (NO) radicals generated by endothelial nitric oxide synthase (eNOS) are involved in the regulation of vascular tone. In addition, NO radicals derived from eNOS inhibit platelet aggregation and leukocyte adhesion to the endothelium and, thus, may have anti-inflammatory effects. To study the role of eNOS in renal inflammation, the development of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was examined in mice lacking a functional gene for eNOS and compared with wild-type (WT) C57BL/B6j mice. WT C57BL/6j mice (n = 12) and eNOS knockout (−/−) mice (n = 12) were immunized intraperitoneally with sheep IgG (0.2 mg in complete Freund’s adjuvant). At day 6.5 after immunization, mice received a single i.v. injection of sheep anti-mouse GBM (1 mg in 200 μl PBS). Mice were sacrificed at day 1 and 10 after induction of the disease. All WT mice survived until day 10, whereas 1 eNOS−/− mouse died and 2 more became moribund, requiring sacrifice. At day 10, eNOS−/− mice had higher levels of blood urea nitrogen than WT mice (P < 0.02), although proteinuria was comparable. Immunofluorescence microscopy documented similar IgG deposition in both WT and eNOS−/− mice, but eNOS−/− mice had more extensive glomerular staining for fibrin at day 10 (P < 0.007). At day 10, light microscopy demonstrated that eNOS−/− mice had more severe glomerular thrombosis (P < 0.003) and influx of neutrophils (P < 0.006), but similar degrees of overall glomerular endocapillary hypercellularity and crescent formation. In conclusion, accelerated anti-GBM glomerulonephritis is severely aggravated in eNOS−/− mice, especially with respect to glomerular capillary thrombosis and neutrophil infiltration. These results indicate that NO radicals generated by eNOS play a protective role during renal inflammation. PMID:10702405

  3. Clinical spectrum and outcome of crescentic glomerulonephritis in children in developing countries.

    PubMed

    Dewan, Deepak; Gulati, Sanjeev; Sharma, Raj K; Prasad, Narayan; Jain, Manoj; Gupta, Amit; Kumar, Alok

    2008-03-01

    Crescentic glomerulonephritis (CsGN) is an uncommon entity in children. This prospective study was conducted to evaluate the aetiology, clinical spectrum and outcome in children with crescentic glomerulonephritis. The single-centre prospective study comprised of 22 children with biopsy proven CsGN who had been referred to our institute over the period January 2000 to December 2005. These patients were subjected to detailed clinical and biochemical examinations. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide with or without plasmapheresis. All patients received supportive care, including control of hypertension and oedema and supportive management of renal insufficiency. During this 5-year period, CsGN accounted for 5.1% of all biopsies done in children. The mean age was 12.27 years (range 4 years to 18 years). There were eight girls and 14 boys. The mean duration of symptoms prior to referral was 2.47 months (range 5 days to 21 months). Aetiology was immune complex in 19 cases, anti-glomerular basement membrane (anti-GBM) antibody disease in two cases and pauci-immune (Wegener's granulomatosis) in one case. The percentage of crescents ranged from 50% to 100% (mean 70.6%). Twenty-one out of 22 (95.5%) children in our series had hypertension at presentation that required treatment with antihypertensive medications. The serum creatinine level at presentation ranged from 1.5 mg/dl to 11.4 mg/dl (mean 5.5 mg/dl). Of the 22 children, two were lost to follow-up, while the mean follow-up period of the rest of the 20 children was 8.13 months (range 1 month to 43 months). At the last follow-up of the 22 children, ten had stage 5 chronic kidney disease (CKD) and three had stage 4 CKD, while seven children had a calculated glomerular filtration rate (GFR) of >60 ml/min per 1.73 m(2) body

  4. ELECTRON MICROSCOPIC STUDIES OF HUMAN GLOMERULONEPHRITIS WITH FERRITIN-CONJUGATED ANTIBODY

    PubMed Central

    Andres, Giuseppe A.; Accinni, Lidia; Hsu, Konrad C.; Zabriskie, John B.; Seegal, Beatrice C.

    1966-01-01

    1. Kidney biopsies from 4 cases of severe acute glomerulonephritis were obtained 11 to 25 days after the onset of clinical manifestations of the disease. These tissues were treated with ferritin-conjugated antibodies to 7S γ-globulin, β1C, and Type 12 streptococcal products. Adjacent pieces of the biopsied material were treated with control ferritin-labeled antisera or with ferritin alone. As further controls, normal renal tissue and renal tissue from patients with other kidney diseases were treated with the same antisera. The 3 antisera to 7S γ-globulin, β1C and Type 12 streptococcus were specifically bound in electron-opaque foreign material in the following renal areas: (a) the lumen of glomerular capillaries; (b) medullary arteriolar walls (2 cases); (c) pinocytic vacuoles and absorption droplets of endothelial or mesangial cells; (d) canals between proliferating mesangial or endothelial cells which connect the capillary lumen with the deep mesangial region or with the endothelial side of the basement membrane; (e) basement membrane proper; (f) subendothelial and certain subepithelial deposits; and (g) Bowman's space. 2. None of the 3 ferritin-conjugated antisera listed above were bound to the nuclei of glomerular cells or to portions of the cytoplasm other than those specified. 3. Ferritin-conjugated antisera to pneumococcus Type II and vaccinia virus and ferritin alone were not bound to any structures in the glomerular tissue. 4. None of the ferritin-conjugated antisera bound to normal renal tissue or to kidney tissue from other renal disease. 5. The data obtained are compatible with the following working hypothesis: Antigen-antibody aggregates of Type 12 streptococcal products, γ-globulin, and complement are present in the circulating blood of patients with severe acute glomerulonephritis. Large amounts of the complexes are caught in the filtering system of the glomeruli. The inflammatory reactions seen in the glomerular structures result from the

  5. Expression of alternatively spliced fibronectin variants during remodeling in proliferative glomerulonephritis.

    PubMed Central

    Barnes, J. L.; Torres, E. S.; Mitchell, R. J.; Peters, J. H.

    1995-01-01

    Fibronectin (Fn) plays an important role in tissue remodeling during embryogenesis, wound repair, and vascular disease, and is thought to regulate cellular processes such as cell adhesion, migration, proliferation, and differentiation through specialized domains within the molecule. In addition, Fn can be alternatively spliced at three regions: extradomains EIIIA, EIIIB, and a variable segment V, potentially giving rise to functionally distinct variants of the molecule. We have previously shown a sequential expression of cellular Fn first by platelets, followed by macrophages, then mesangial cells in habu snake venom-induced proliferative glomerulonephritis (Am J Pathol 145: 585-597, 1994). These studies examined the cellular sources and glomerular localization of Fn in general but did not distinguish between the various alternatively spliced isoforms. In this study, we examine by in situ hybridization and immunohistochemistry the temporal expression and cellular sources of EIIIA, EIIIB, and V in a model of proliferation glomerulonephritis that has cell migration, proliferation, and extracellular matrix synthesis as features of tissue remodeling. Macrophages were the first cells to express Fn mRNA showing an EIIIA+, EIIIB-, and V95+ pattern beginning at 8 hours after habu snake venom injection. Migrating mesangial cells at the margins of early lesions (8 and 24 hours) did not overexpress mRNA encoding these Fn variants, but immunofluorescence microscopy revealed V95 and EIIIA protein at the margins of lesions. EIIIB was absent in lesions at this time. At 48 hours and peaking at 72 hours after habu snake venom injection, mesangial cells in central aspects of glomerular lesions expressed abundant mRNA and protein for V95 and EIIIA. EIIIB mRNA and protein was slight in the mesangium at these times. Parietal epithelial cells, particularly adjacent to glomerular lesions, also expressed abundant mRNA and protein for all three variants throughout the course of the disease

  6. Bullous Pemphigoid Associated with the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin in a Patient with Liver Cirrhosis Complicated with Rapidly Progressive Hepatocellular Carcinoma.

    PubMed

    Harada, Masaru; Yoneda, Akitoshi; Haruyama, Sanehito; Yabuki, Kei; Honma, Yuichi; Hiura, Masaaki; Shibata, Michihiko; Matsuoka, Hidehiko; Uchiwa, Yasuhiro

    2017-09-15

    A 78-year-old man presented with cutaneous blisters of the limbs and abdominal distension. He had been treated for various diseases, including liver cirrhosis. He had begun receiving sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, for diabetes mellitus three years before the hospitalization. A skin biopsy demonstrated bullous pemphigoid. Ultrasonography (US) revealed multiple liver tumors, although he had been receiving regular US studies. We stopped sitagliptin and started insulin and corticosteroids. However, his renal dysfunction progressed, and he died 14 days after the hospitalization. We should therefore be careful of various complications, including bullous pemphigoid and progression of tumors, when using DPP-4 inhibitors.

  7. The Small Tellurium Compound AS101 Ameliorates Rat Crescentic Glomerulonephritis: Association with Inhibition of Macrophage Caspase-1 Activity via Very Late Antigen-4 Inactivation

    PubMed Central

    Hachmo, Yafit; Kalechman, Yona; Skornick, Itai; Gafter, Uzi; Caspi, Rachel R.; Sredni, Benjamin

    2017-01-01

    Crescentic glomerulonephritis (CGN) is the most aggressive form of GN and, if untreated, patients can progress to end-stage renal failure within weeks of presentation. The α4β1 integrin very late antigen-4 (VLA-4) is an adhesion molecule of fundamental importance to the recruitment of leukocytes in inflammation. We addressed the role of VLA-4 in mediating progressive renal injury in a rat model of CGN using a small tellurium compound. AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate]. This compound has been previously shown to uniquely inhibit VLA-4 activity by redox inactivation of adjacent thiols in the exofacial domain of VLA-4. The study shows that administration of AS101 either before or after glomerular basement membrane anti-serum injection ameliorates crescent formation or preserves renal function. This was associated with profound inhibition of critical inflammatory mediators, accompanied by decreased glomerular infiltration of macrophages. Mechanistic studies demonstrated vla-4 inactivation on glomerular macrophages both in vitro and in vivo as well as inhibition of caspase-1 activity. Importantly, this cysteine protease activity modification was dependent on VLA-4 inactivation and was associated with the anti-inflammatory activity of AS101. We propose that inactivation of macrophage VLA-4 by AS101 in vivo results in a decrease of inflammatory cytokines and chemokines produced in the glomeruli of diseased rats, resulting in decreased further macrophage recruitment and decreased extracellular matrix expansion. Thus, AS101, which is currently in clinical trials for other indications, might be beneficial for treatment of CGN. PMID:28326083

  8. Modeling rapidly rotating stars

    NASA Astrophysics Data System (ADS)

    Rieutord, M.

    2006-06-01

    We review the quest of modeling rapidly rotating stars during the past 40 years and detail the challenges to be taken up by models facing new data from interferometry, seismology, spectroscopy... We then present the progress of the ESTER project aimed at giving a physically self-consistent model for the structure and evolution of rapidly rotating stars.

  9. Severe and rapidly progressing cognitive phenotype in a SCA17-family with only marginally expanded CAG/CAA repeats in the TATA-box binding protein gene: A case report

    PubMed Central

    2012-01-01

    Background The autosomal dominant spinocerebellar ataxias (SCAs) confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington’s disease. Case presentation We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype. Conclusions The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based. PMID:22889412

  10. Effects of pegylated interferon alpha-2a on hepatitis-C-virus-associated glomerulonephritis.

    PubMed

    Sugiura, Tokio; Yamada, Takuji; Kimpara, Yuri; Fujita, Naoya; Goto, Kenji; Koyama, Norihisa

    2009-01-01

    Hepatitis C virus (HCV) infection leads to chronic liver disease, but it has also been associated with extrahepatic manifestations. Membranoproliferative glomerulonephritis (MPGN) is the most common renal disease associated with HCV. Although renal disease related to HCV in adults has been well studied, it has not been well studied in children because it is rare. A recent study found that antiviral therapy was effective for adult patients with HCV-associated MPGN. We report a 9-year-old girl with HCV-associated MPGN. Her HCV genotype was 1b, and her virus load was high. The first renal biopsy showed mesangial proliferation and partial double contours of the basement membrane on light microscopy and immunofluorescence staining with immunoglobulin (Ig) M, IgG, and C3. The patient was successfully treated with pegylated interferon (IFN) alpha-2a monotherapy. The antiviral therapy was generally well tolerated. After antiviral therapy, a sustained virological response-defined as negative HCV ribonucleic acid (RNA) at least 24 weeks after antiviral treatment-was achieved, the proteinuria disappeared, and the second renal biopsy showed improvement.

  11. Volatile Organic Metabolites Identify Patients with Mesangial Proliferative Glomerulonephritis, IgA Nephropathy and Normal Controls

    PubMed Central

    Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou

    2015-01-01

    Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction–chromatography– mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool. PMID:26443483

  12. [A case of combination therapy with MMF and steroids for idiopathic membranoproliferative glomerulonephritis].

    PubMed

    Mori, Yutaro; Ihara, Katsuhito; Yamaguchi, Wakaba; Fujii, Tetsuro; Toda, Takayuki; Nagata, Michio; Matsui, Noriaki

    2013-01-01

    A 26-year-old man diagnosed with nephrotic syndrome was administered steroid monotherapy. Urinary protein excretion was 2-3 g/day despite the therapy. Percutaneous renal biopsy revealed Type I idiopathic membranoproliferative glomerulonephritis (IMPGN). Although intravenous steroid therapy at the dose of 1,000 mg/day for 3 days was administered, proteinuria persisted at the level of 1 g/day. Renal dysfunction (cystatin C, 1.33 mg/L) was evident. Strong inflammation was suggested by occult blood (3+) and urinary (red blood cells: 30-50/high power field) sediment. We considered steroid monotherapy to be ineffective, and initiated combina-tion therapy with mycophenolate mofetil (MMF) and steroids. Consequently, urinary protein excretion moderately decreased to 0.34 g/day without adverse events or worsening of the renal function. The steroid quantity could be reduced without relapse. Subsequently, we were able to reduce the dose of MMF gradually, then terminated the medication. IMPGN is a rare disease with a poor renal prognosis. Recently, MMF therapies for IMPGN have been attempted, but there are few cases in Japan. Our case suggests that combination therapy with MMF and steroids is effective and safe for treating IMPGN.

  13. [Urokinase as a blood and urine plasminogen activator in chronic glomerulonephritis and amyloidosis].

    PubMed

    Andreenko, G V; Poliantseva, L R; Podorol'skaia, L V; Bumblite, I D

    1999-01-01

    To estimate the individual role of the plasminogen activators (PA) urokinase (u-PA) and tissue (t-PA) in the development of two renal diseases (the nephrotic forms of chronic glomerulonephritis (CGN) and amyloidosis, the baseline plasma and urine levels of u-PA and t-PA antigens, their functional activity (FPAA), and changes in these parameters were determined after protein loading test (0.7 g/kg). In healthy individuals and patients with amyloidosis, the baseline FPAA changes from 0 to the maximum were caused only by the alterations of u-PA levels, in those with CGN, they were induced by the changes in the content of u-PA and t-AP antigens. The functional loading test revealed PA reserves solely in patients having a high baseline FPAA for both nephropathies: u-PA in amyloidosis and t-PA in CGN. In all the patients, the urine levels of u-PA antigens were 20-40 times more than those of t-PA antigens and 5-6 times less than those plasma u-PA. The findings suggest that urokinase may be regarded as the major plasminogen activator involved in CGN and amyloidosis.

  14. A Case of Thyroid Storm Associated with Cardiomyopathy and Poststreptococcal Glomerulonephritis.

    PubMed

    Underland, Lisa J; Villeda, Gerson A Vallencia; Pal, Abhijeet; Lam, Leslie

    2016-01-01

    Thyroid storm has a high mortality rate and is often associated with a precipitating factor such as intercurrent illness or infection. It is rare in pediatric patients. Cardiac disease in hyperthyroidism mostly manifests itself as tachycardia but more serious cardiac findings have also been described. A 5-year-old male with recent strep throat infection presented with dilated cardiomyopathy, hematuria, and symptoms and lab findings consistent with severe hyperthyroidism. He was diagnosed with thyroid storm secondary to concurrent Graves' disease and poststreptococcal glomerulonephritis (PSGN). After starting the treatment with methimazole and a beta-blocker, his cardiac disease gradually improved and the PSGN resolved over time. There are no specific pediatric criteria for thyroid storm. Adult criteria can be difficult to apply to pediatric cases. Criteria for diagnosis of thyroid storm are less clear for pediatric patients. Dilated cardiomyopathy is a rare cardiac manifestation of hyperthyroidism. PSGN is due to glomerular immune complexes and can complicate group A strep infection. Providers should be aware of cardiac disease as a complication of hyperthyroidism. PSGN should not mechanistically be related to hyperthyroidism but can precipitate the signs of thyroid storm such as hypertension. This association has not been previously reported in the literature.

  15. C3 Glomerulopathy and post-infectious glomerulonephritis define a disease spectrum.

    PubMed

    Al-Ghaithi, Badria; Chanchlani, Rahul; Riedl, Magdalena; Thorner, Paul; Licht, Christoph

    2016-11-01

    Post-infectious glomerulonephritis (PIGN) usually follows a benign course, but few children have an atypical, severe presentation, and these exceptional cases have been linked to the dysregulation of the complement alternative pathway (CAP). There is a considerable overlap in the histopathological features of PIGN and C3 glomerulopathy (C3G), which is also associated with CAP dysregulation but has a poorer outcome. We hypothesized that PIGN and C3G define a disease spectrum, and that in the past there may be some children with C3G who were misclassified with PIGN before C3G was described as a separate disease entity. Children with PIGN (n = 33) diagnosed between 1985 and 2010 who underwent a renal biopsy due to their unusual course were reviewed and of them, 8 were reclassified into C3G based on the current classification criteria. Outcome was based on the degree of proteinuria, C3 level, and renal function at follow-up. Sixteen (72.7%) children with typical PIGN recovered completely as compared to only 2 (25%) with C3G. Of note, children with "typical" PIGN had a more severe disease course at onset; however, the outcome at last follow up was favorable. Our results support the hypothesis that PIGN and C3G form a disease spectrum and have different long-term clinical implications and management strategies.

  16. [Analysis of the treatment with traditional Chinese medicine in chronic glomerulonephritis based on histopathologic type].

    PubMed

    Hu, Z Y; Chen, Y P; Zha, P

    1992-08-01

    The histopathologic type of 189 cases of chronic glomerulonephritis (GN) were confirmed by renal biopsies, they were subdivided into 3 groups. 77 patients of Western medicine (WM) group was treated by conventional WM (prednison or CTX), and after treatment the total effective rate was 55.8%. The TCM-WM group was treated by the same WM plus treatment according to Syndrome Differentiation with Chinese medicinal herbs, and the total effective rate was 86% in 50 patients. The TCM group was treated by Chinese medicinal herbs, and the total effective rate was 67.3% in 62 cases. There was very significant difference (P < 0.01) between the WM and the TCM-WM group. Among the patients of TCM-WM and TCM groups, 67% of 112 cases were manifested as Dampness-Heat Syndrome, so it suggested that one of the important method for GN treatment is clearing away Dampness-Heat. The effects of TCM-WM group is much better than the WM group in treating mesangio-proliferative GN and membranous GN. It was difficult for WM in treating IgA nephropathy, membrano-proliferative GN and focal glomerulosclerosis, but Chinese medicinal herbs were effective with replenishing Qi and strengthening the Spleen, clearing away Dampness-Heat, promoting blood circulation and relieving Stasis, etc.

  17. Efficacy and safety of rituximab treatment in children with primary glomerulonephritis.

    PubMed

    Zachwieja, Jacek; Silska, Magdalena; Ostalska-Nowicka, Danuta; Soltysiak, Jolanta; Lipkowska, Katarzyna; Blumczynski, Andrzej; Musielak, Anna

    2012-01-01

    The aim of our study was to analyze the efficacy and safety of rituximab, a chimeric monoclonal antibody against CD20 lymphocytes, as a nonstandard immunosuppressive therapy in children with different types of primary glomerulonephritis who were not eligible for routine treatment. The study group was composed of 16 children with proteinuric glomerulopathies, not responding to standard immunosuppressive therapy. The indications included steroid-resistant nephrotic syndrome (n=14) and steroid-dependent nephrotic syndrome (n=2). The dose of rituximab was established as 375 mg/m2 of body surface area, administered by intravenous infusion once weekly for 1 to 4 weeks, depending on the CD19 lymphocyte count. We evaluated proteinuria and plasma concentration of CD19 lymphocytes at intervals of 1, 3 and 6 months, after which patients received a single repeat dose. Remission, defined as proteinuria less than 150 mg per 24 hours, was observed in 7 of the 16 children. There were no statistically significant differences in leukocyte counts between single and multiple rituximab doses. We also did not observe any clinical or biochemical side effects. In conclusion, we postulate that alternative rituximab therapy should be taken into consideration in nephrotic patients not responding to standard therapy.

  18. Combined optical coherence tomography and optical coherence elastography for glomerulonephritis classification

    NASA Astrophysics Data System (ADS)

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Mohammadzai, Qais; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Chang, Anthony; Mohan, Chandra; Larin, Kirill V.

    2016-03-01

    Acute Glomerulonephritis caused by anti-glomerular basement membrane disease has a high mortality due to delayed diagnosis. Thus, an accurate and early diagnosis is critical for preserving renal function. Currently, blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution. Optical coherence tomography (OCT) is a noninvasive imaging technique that provides superior spatial resolution (micron scale) as compared to ultrasound and CT. Pathological changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signal, such as optical attenuation and speckle variance. Moreover, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, we utilized OCT to detect the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, classification accuracy using only optical metrics was clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improved from 76% to 95%. These results show that OCT combined with OCE can be potentially useful for nephritis detection.

  19. Membranoproliferative glomerulonephritis with isolated C3 deposits: case report and literature review.

    PubMed

    Darouich, Sihem; Goucha, Rym; Jaafoura, Mohamed Habib; Zekri, Semy; Kheder, Adel; Ben Maiz, Hédi

    2011-02-01

    Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.

  20. [Dense deposit nephropathy: a peculiar variant of glomerulonephritis or a distinct disease entity (author's transl)].

    PubMed

    Rossmann, P; Matousovic, K; Bucek, J

    1975-01-01

    In four renal biopsies of two patients with chronic glomerulonephritis (GN), the so-called dense deposit nephropathy (NDD) was diagnosed by means of light, electron, and immunofluorescence microscopy. In routine paraffin sections the picture approached that of the membrano-proliferative GN. In semithin sections (toluidine blue, periodic acid-Ag-methenamine) and especially in the ultrastructure there appeared extensive confluent deposits of a very dense substance, infiltrating the lamina densa of glomerular capillaries, basal membranes of both Bowman's capsules and tubules, and arteriolar walls. In this localization, a non-diffuse "psdudolinear" deposition of beta1c was detected, whereas antisera to main Ig-fractions and fibrin(ogen) were not fixed. In a biopsy performed six years later, a concentration of dense depositis towards the mesangial area and a partial regeneration of basal membranes were observed. In a part of dense deposits there appeared vacuolization, primarily in tubular and arteriolar basal membranes. In glomeruli, focal IgM deposits were apparent at an advanced stage. NDD apparently is a sequel of a particular metabolic (immune?) process, afflicting solely the renal membranous system and distinctly dns known at present. The noncharacteristic clinical presentation resembles chronic. GN, is very protracted, lengthy, and relatively benigh, with a chance of functional and possible even morphological remission.

  1. Oligosaccharide composition is similar in drusen and dense deposits in membranoproliferative glomerulonephritis type II.

    PubMed

    D'souza, Yvonne B; Jones, Carolyn J P; Short, Colin D; Roberts, Ian S D; Bonshek, Richard E

    2009-04-01

    Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.

  2. Amelioration of immune complex-mediated glomerulonephritis by synthetic protease inhibitors.

    PubMed

    Jennette, J C; Tidwell, R R; Geratz, J D; Bing, D H; Falk, R J

    1987-06-01

    Proteases are involved in the pathogenesis of inflammatory diseases by participating in the activation of mediator systems and by producing proteolytic tissue injury. Homeostatic control of inflammation is accomplished in part by physiologic protease inhibitors. The authors investigated the effectiveness of a number of synthetic protease inhibitors in ameliorating the glomerular injury induced by immune complex-mediated glomerulonephritis in mice. Two amidine-type protease inhibitors, bis (5-amidino-2-benzimidazolyl)methane and 1,2-bis (5-amidino-2-benzimidazolyl)ethane, had the greatest effects. They caused a marked reduction in glomerular necrosis (P less than 0.001) but did not affect the amount or site of immune complex localization or leukocyte influx. The inhibition constants of the protease inhibitors against nine purified physiologic proteases were determined. These results were discussed in relation to the effectiveness of the protease inhibitors in reducing glomerular injury. This investigation indicates that the administration of synthetic prot