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Sample records for minimal change disease

  1. Minimal change disease

    Science.gov (United States)

    ... get worse You develop new symptoms, including side effects from the medicines used to treat the disorder Alternative Names Minimal change nephrotic syndrome; Nil disease; Lipoid nephrosis; Idiopathic nephrotic syndrome of childhood Images ...

  2. Rituximab in Minimal Change Disease

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    Nima Madanchi

    2017-03-01

    Full Text Available Treatment with rituximab, a monoclonal antibody against the B-lymphocyte surface protein CD20, leads to the depletion of B cells. Recently, rituximab was reported to effectively prevent relapses of glucocorticoid-dependent or frequently relapsing minimal change disease (MCD. MCD is thought to be T-cell mediated; how rituximab controls MCD is not understood. In this review, we summarize key clinical studies demonstrating the efficacy of rituximab in idiopathic nephrotic syndrome, mainly MCD. We then discuss immunological features of this disease and potential mechanisms of action of rituximab in its treatment based on what is known about the therapeutic action of rituximab in other immune-mediated disorders. We believe that studies aimed at understanding the mechanisms of action of rituximab in MCD will provide a novel approach to resolve the elusive immune pathophysiology of MCD.

  3. Minimal change disease: a CD80 podocytopathy?

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    Ishimoto, Takuji; Shimada, Michiko; Araya, Carlos E; Huskey, Janna; Garin, Eduardo H; Johnson, Richard J

    2011-07-01

    Minimal change disease is the most common nephrotic syndrome in children. Although the etiology of minimal change disease remains to be elucidated, it has been postulated that it is the result of a circulating T-cell factor that causes podocyte cytoskeleton disorganization leading to increased glomerular capillary permeability and/or changes in glomerular basement membrane heparan sulfate glycosaminoglycans resulting in proteinuria. Minimal change disease has been associated with allergies and Hodgkin disease. Consistent with these associations, a role for interleukin-13 with minimal change disease has been proposed. Furthermore, studies evaluating podocytes also have evolved. Recently, increased expression of CD80 (also termed B7-1) on podocytes was identified as a mechanism for proteinuria. CD80 is inhibited by binding to CTLA-4, which is expressed on regulatory T cells. Recently, we showed that urinary CD80 is increased in minimal change disease patients and limited studies have suggested that it is not commonly present in the urine of patients with other glomerular diseases. Interleukin-13 or microbial products via Toll-like receptors could be factors that induce CD80 expression on podocytes. CTLA-4 appears to regulate CD80 expression in podocytes, and to be altered in minimal change disease patients. These findings lead us to suggest that proteinuria in minimal change disease is caused by persistent CD80 expression in podocytes, possibly initiated by stimulation of these cells by antigens or cytokines.

  4. Systemic mastocytosis associated with minimal change disease

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    Tony Amin

    2016-07-01

    Full Text Available Systemic Mastocytosis (SM has not previously been reported in association with minimal change disease (MCD. Mastocytosis is a rare myeloproliferative disease that is characterised by uncontrolled proliferation of aberrant mast cells. This can lead to a wide variety of symptoms and can present as either a cutaneous or a systemic disease. Systemic manifestations usually include bone marrow, intestine, liver and splenic infiltration of mast cells, with reports of renal manifestations being rare. This is a case report of a 70-year-old man who was known to have Systemic Mastocytosis and who presented with nephrotic range proteinuria. Renal biopsy diagnosed Minimal Change Disease with mast cell infiltration being an identified by C-kit staining. The patient was treated with steroids and is currently in remission of the proteinuria.

  5. Minimal-change disease secondary to etanercept.

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    Koya, Mariko; Pichler, Raimund; Jefferson, J Ashley

    2012-10-01

    Etanercept is a soluble tumor necrosis factor alpha (TNFα) receptor which is widely used in the treatment of rheumatoid arthritis, psoriasis and other autoimmune inflammatory disorders. It is known for its relative lack of nephrotoxicity; however, there are reports on the development of nephrotic syndrome associated with the treatment with TNFα antagonists. Here, we describe a patient with psoriasis who developed biopsy-proven minimal-change disease (MCD) shortly after initiating etanercept. Our case is unique in that the MCD resolved after discontinuation of this medication, notably without the use of corticosteroids, strongly suggesting a drug-related phenomenon.

  6. Clarithromycin-induced acute interstitial nephritis and minimal change disease

    OpenAIRE

    Russell, Wendy; Smith, William

    2009-01-01

    Drug associated acute interstitial nephritis and minimal change disease has been well documented but the simultaneous presentation of both is rare and has not been reported with clarithromycin. We describe a case of simultaneous acute tubulointerstitial nephritis and minimal change disease induced by clarithromycin. The patient had acute kidney injury, nephrotic syndrome, eosinophilic pneumonitis and a maculopapular skin rash. The role of steroid therapy in acute interstitial nephritis is con...

  7. Late de novo minimal change disease in a renal allograft

    OpenAIRE

    Madhan Krishan; Temple-Camp Cynric

    2009-01-01

    Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by...

  8. Clarithromycin-induced acute interstitial nephritis and minimal change disease.

    Science.gov (United States)

    Russell, Wendy; Smith, William

    2009-10-01

    Drug associated acute interstitial nephritis and minimal change disease has been well documented but the simultaneous presentation of both is rare and has not been reported with clarithromycin. We describe a case of simultaneous acute tubulointerstitial nephritis and minimal change disease induced by clarithromycin. The patient had acute kidney injury, nephrotic syndrome, eosinophilic pneumonitis and a maculopapular skin rash. The role of steroid therapy in acute interstitial nephritis is controversial but is accepted as beneficial in minimal change nephrotic syndrome. Steroid therapy in our patient resulted in complete clinical resolution.

  9. Late de novo minimal change disease in a renal allograft

    Directory of Open Access Journals (Sweden)

    Madhan Krishan

    2009-01-01

    Full Text Available Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function.

  10. Late de novo minimal change disease in a renal allograft.

    Science.gov (United States)

    Madhan, Krishan K; Temple-Camp, Cynric R E

    2009-03-01

    Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function.

  11. The Diagnosis of Minimal Change Disease in Diabetic Nephropathy

    OpenAIRE

    M. Barry Stokes

    2005-01-01

    Proteinuria is common in diabetic patients and usually reflects the presence of diabetic glomerulosclerosis. This paper reviews the differential diagnosis of proteinuria in diabetic patients and discusses the role of renal biopsy examination in identification and management of minimal change disease in this cohort. Identification of nondiabetic glomerular disease requires careful correlation of clinical history and renal biopsy findings and may have important implications for prognosis and th...

  12. A case of minimal change disease in a Fabry patient.

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    Zarate, Yuri A; Patterson, Larry; Yin, Hong; Hopkin, Robert J

    2010-03-01

    Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the GLA gene and deficiency in alpha-galactosidase A activity. Glycosphingolipids accumulation causes renal injury that manifests early during childhood as tubular dysfunction and later in adulthood as proteinuria and renal insufficiency. Nephrotic syndrome as the first evidence of Fabry-related kidney damage is rare. We report the case of a teenager with known Fabry disease and normal renal function who developed acute nephrotic syndrome. He was found to have typical glycosphingolipids accumulation with no other findings suggestive of alternative causes of nephrotic syndrome on kidney biopsy. After treatment with enzyme replacement therapy and oral steroids, he went into complete remission from nephrotic syndrome, a response that is atypical for Fabry disease patients who develop heavy proteinuria as a result of longstanding disease and chronic renal injury. The nephrotic syndrome in this patient appears to have developed secondary to minimal change disease. We recommend considering immunotherapy in addition to enzyme replacement therapy in those patients with confirmed Fabry disease and acute nephrotic syndrome with clinical and microscopic findings suggestive of minimal change disease.

  13. Lithium-induced minimal change disease and acute kidney injury

    OpenAIRE

    Parul Tandon; Natalie Wong; Zaltzman, Jeffrey S.

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremor...

  14. Minimal change disease versus IgA nephropathy.

    Science.gov (United States)

    Jabur, Wael Latif

    2009-01-01

    IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interes-tingly, the acute viral flare was without a concomitant relapse of proteinuria.

  15. Minimal change disease versus IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Jabur Wael

    2009-01-01

    Full Text Available IgA nephropathy is the most common type of the glomerulonephritis all over the world. However, its clinical presentation is variable, as is the underlying histopathological lesion. We report herein a case of an adult with steroid responsive minimal change disease and IgA mesangial deposits. During the first two weeks of therapy with prednisolone, the patient reported dramatic improvement in his clinical condition and remitted his disease. Unfortunately, at the end of the second month of prednisolone therapy, an acute flare of viral hepatitis was diagnosed. Interes-tingly, the acute viral flare was without a concomitant relapse of proteinuria.

  16. Proteinuria predicts relapse in adolescent and adult minimal change disease

    Directory of Open Access Journals (Sweden)

    Cristiane Bitencourt Dias

    2012-11-01

    Full Text Available OBJECTIVE: This study sought to outline the clinical and laboratory characteristics of minimal change disease in adolescents and adults and establish the clinical and laboratory characteristics of relapsing and non-relapsing patients. METHODS: We retrospectively evaluated patients with confirmed diagnoses of minimal change disease by renal biopsy from 1979 to 2009; the patients were aged >13 years and had minimum 1-year follow-ups. RESULTS: Sixty-three patients with a median age (at diagnosis of 34 (23-49 years were studied, including 23 males and 40 females. At diagnosis, eight (12.7% patients presented with microscopic hematuria, 17 (27% with hypertension and 17 (27% with acute kidney injury. After the initial treatment, 55 (87.3% patients showed complete remission, six (9.5% showed partial remission and two (3.1% were nonresponders. Disease relapse was observed in 34 (54% patients who were initial responders (n = 61. In a comparison between the relapsing patients (n = 34 and the non-relapsing patients (n = 27, only proteinuria at diagnosis showed any significant difference (8.8 (7.1-12.0 vs. 6.0 (3.6-7.3 g/day, respectively, p = 0.001. Proteinuria greater than 7 g/day at the initial screening was associated with relapsing disease. CONCLUSIONS: In conclusion, minimal change disease in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury. The relapsing pattern in our patients was associated with basal proteinuria over 7 g/day.

  17. Minimal-change renal disease and Graves’ disease: a case report and literature review

    OpenAIRE

    Hasnain, Wirasat; Stillman, Isaac E.; Bayliss, George P.

    2011-01-01

    Objective To describe a possible association between Graves' disease and nephrotic syndrome secondary to minimal change renal disease and to review the literature related to renal diseases in patients with Graves' disease. Methods The clinical, laboratory, and renal biopsy findings in a patient with Graves' disease and minimal change renal disease are discussed. In addition, the pertinent English-language literature published from 1966 to 2009, determined by means of a MEDLINE search, is revi...

  18. Minimal-change renal disease and Graves’ disease: a case report and literature review

    OpenAIRE

    Hasnain, Wirasat; Stillman, Isaac E.; Bayliss, George P.

    2011-01-01

    Objective: To describe a possible association between Graves' disease and nephrotic syndrome secondary to minimal change renal disease and to review the literature related to renal diseases in patients with Graves' disease. Methods: The clinical, laboratory, and renal biopsy findings in a patient with Graves' disease and minimal change renal disease are discussed. In addition, the pertinent English-language literature published from 1966 to 2009, determined by means of a MEDLINE search, is re...

  19. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    Science.gov (United States)

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  20. Rituximab in adult minimal change disease and focal segmental glomerulosclerosis.

    Science.gov (United States)

    Kronbichler, Andreas; Bruchfeld, Annette

    2014-01-01

    Treatment of nephrotic syndrome due to minimal change disease and focal segmental glomerulosclerosis remains a challenge since steroid dependence, steroid resistance and a relapsing disease course exhibits a high cumulative steroid dosage. The necessity of using alternative steroid-sparing immunosuppressive agents with potential toxic side effects also restricts their long-term use. Rituximab, a monoclonal antibody targeting CD20, has been increasingly used in the therapy of difficult-to-treat nephrotic syndrome. A clinical response has been shown for patients with steroid-dependent or frequently relapsing nephrotic syndrome, whereas the benefit seems to be limited in steroid-resistant patients, especially those with underlying focal segmental glomerulosclerosis. No potentially life-threatening adverse events have been observed in the treatment of adult minimal change disease and focal segmental glomerulosclerosis following rituximab administration. Since most reports are retrospective and evidence of efficacy is derived from small case series, more prospective trials in a controlled, randomized manner are highly desirable to delineate the use of rituximab or other B cell-depleting agents in steroid-dependent, frequently relapsing or steroid-resistant patients.

  1. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection.

    Science.gov (United States)

    Kwiatkowska, Ewa; Gołembiewska, Edyta; Ciechanowski, Kazimierz; Kędzierska, Karolina

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5-10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997)). In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010), Zachäus (2008), and Kirmizis et al. (2004)). In this paper, we present the case of minimal-change disease (MCD) as a result of Borrelia burgdorferi infection.

  2. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    Directory of Open Access Journals (Sweden)

    Ewa Kwiatkowska

    2012-01-01

    Full Text Available Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. (1997. In available literature, there were reports of human's glomerulonephritis associated with Borrelia burgdorferi infection. These cases refer to membranous and mesangial proliferative glomerulonephritis (Kirmizis and Chatzidimitriou (2010, Zachäus (2008, and Kirmizis et al. (2004. In this paper, we present the case of minimal-change disease (MCD as a result of Borrelia burgdorferi infection.

  3. Minimal change disease onset observed after bevacizumab administration.

    Science.gov (United States)

    Hanna, Ramy M; Lopez, Eduardo; Wilson, James; Barathan, Shrinath; Cohen, Arthur H

    2016-04-01

    This is a report of a patient with minimal change disease (MCD) onset after bevacizumab administration. A 72-year-old man with inoperable Grade 3 astrocytoma was treated with a combination of temozolomide and the vascular endothelial growth factor monoclonal antibody bevacizumab. After two biweekly treatments, he developed nephrotic syndrome. Despite cessation of bevacizumab, his renal function deteriorated and a renal biopsy disclosed MCD. Thereafter, he was started on high-dose oral prednisone and renal function immediately improved. Within weeks, the nephrotic syndrome resolved. Although rare, biologic agents can cause various glomerulopathies that can have important therapeutic implications. MCD should be considered in patients who develop nephrotic syndrome while exposed to antiangiogenic agents.

  4. Minimal change disease: A case report of an unusual relationship.

    Science.gov (United States)

    Edrees, Fahad; Black, Robert M; Leb, Laszlo; Rennke, Helmut

    2016-01-01

    Kidney injury associated with lymphoproliferative disorders is rare, and the exact pathogenetic mechanisms behind it are still poorly understood. Glomerular involvement presenting as a nephrotic syndrome has been reported, usually secondary to membranoproliferative glomerulonephritis. We report a case of a 63-year-old male who presented with bilateral leg swelling due to nephrotic syndrome and acute kidney injury. A kidney biopsy showed minimal change disease with light chain deposition; however, no circulating light chains were present. This prompted a bone marrow biopsy, which showed chronic lymphocytic leukemia (CLL) with deposition of the same kappa monoclonal light chains. Three cycles of rituximab and methylprednisolone resulted in remission of both CLL and nephrotic syndrome, without recurrence during a three-year follow-up.

  5. Minimal change disease: a variant of lupus nephritis.

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    Moysés-Neto, Miguel; Costa, Roberto S; Rodrigues, Fernanda F; Vieira Neto, Osvaldo M; Reis, Marlene A; Louzada Júnior, Paulo; Romão, Elen A; Dantas, Márcio

    2011-02-01

    Some patients with systemic lupus erythematosus (SLE) present with nephrotic syndrome due to minimal change disease (MCD). Histopathological diagnosis of patients with SLE and nephrotic-range proteinuria has shown that these patients present with diffuse proliferative glomerulonephritis and membranous glomerulonephritis, World Health Organization (WHO) classes IV and V, respectively, more frequently than the other classes. In the present study, we reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with SLE. A complete remission occurred after steroid treatment, which was followed by a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the patient went into complete remission again. The association of MCD and SLE may not be a coincidence, and MCD should be considered as an associated SLE nephropathy.

  6. Lithium-induced minimal change disease and acute kidney injury

    Directory of Open Access Journals (Sweden)

    Parul Tandon

    2015-01-01

    Full Text Available Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD and acute kidney injury (AKI. Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient′s symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome.

  7. Cell biology and genetics of minimal change disease.

    Science.gov (United States)

    Saleem, Moin A; Kobayashi, Yasuko

    2016-01-01

    Minimal change disease (MCD) is an important cause of nephrotic syndrome and is characterized by massive proteinuria and hypoalbuminemia, resulting in edema and hypercholesterolemia. The podocyte plays a key role in filtration and its disruption results in a dramatic loss of function leading to proteinuria. Immunologic disturbance has been suggested in the pathogenesis of MCD. Because of its clinical features, such as recurrent relapse/remission course, steroid response in most patients, and rare familial cases, a genetic defect has been thought to be less likely in MCD. Recent progress in whole-exome sequencing reveals pathogenic mutations in familial cases in steroid-sensitive nephrotic syndrome (SSNS) and sheds light on possible mechanisms and key molecules in podocytes in MCD. On the other hand, in the majority of cases, the existence of circulating permeability factors has been implicated along with T lymphocyte dysfunction. Observations of benefit with rituximab added B cell involvement to the disease. Animal models are unsatisfactory, and the humanized mouse may be a good model that well reflects MCD pathophysiology to investigate suggested "T cell dysfunction" directly related to podocytes in vivo. Several candidate circulating factors and their effects on podocytes have been proposed but are still not sufficient to explain whole mechanisms and clinical features in MCD. Another circulating factor disease is focal segmental glomerulosclerosis (FSGS), and it is not clear if this is a distinct entity, or on the same spectrum, implicating the same circulating factor(s). These patients are mostly steroid resistant and often have a rapid relapse after transplantation. In clinical practice, predicting relapse or disease activity and response to steroids is important and is an area where novel biomarkers can be developed based on our growing knowledge of podocyte signaling pathways. In this review, we discuss recent findings in genetics and podocyte biology in MCD.

  8. Cell biology and genetics of minimal change disease

    Science.gov (United States)

    Saleem, Moin A.; Kobayashi, Yasuko

    2016-01-01

    Minimal change disease (MCD) is an important cause of nephrotic syndrome and is characterized by massive proteinuria and hypoalbuminemia, resulting in edema and hypercholesterolemia. The podocyte plays a key role in filtration and its disruption results in a dramatic loss of function leading to proteinuria. Immunologic disturbance has been suggested in the pathogenesis of MCD. Because of its clinical features, such as recurrent relapse/remission course, steroid response in most patients, and rare familial cases, a genetic defect has been thought to be less likely in MCD. Recent progress in whole-exome sequencing reveals pathogenic mutations in familial cases in steroid-sensitive nephrotic syndrome (SSNS) and sheds light on possible mechanisms and key molecules in podocytes in MCD. On the other hand, in the majority of cases, the existence of circulating permeability factors has been implicated along with T lymphocyte dysfunction. Observations of benefit with rituximab added B cell involvement to the disease. Animal models are unsatisfactory, and the humanized mouse may be a good model that well reflects MCD pathophysiology to investigate suggested “T cell dysfunction” directly related to podocytes in vivo. Several candidate circulating factors and their effects on podocytes have been proposed but are still not sufficient to explain whole mechanisms and clinical features in MCD. Another circulating factor disease is focal segmental glomerulosclerosis (FSGS), and it is not clear if this is a distinct entity, or on the same spectrum, implicating the same circulating factor(s). These patients are mostly steroid resistant and often have a rapid relapse after transplantation. In clinical practice, predicting relapse or disease activity and response to steroids is important and is an area where novel biomarkers can be developed based on our growing knowledge of podocyte signaling pathways. In this review, we discuss recent findings in genetics and podocyte biology in

  9. Fulminant ulcerative colitis associated with steroid-resistant minimal change disease and psoriasis: A case report

    OpenAIRE

    Lok, Ka-Ho; Hung, Hiu-Gong; Yip, Wai-Man; Li, Kin-Kong; Li, Kam-Fu; Szeto, Ming-Leung

    2007-01-01

    A 43-year-old Chinese patient with a history of psoriasis developed fulminant ulcerative colitis after immunosuppressive therapy for steroid-resistant minimal change disease was stopped. Minimal change disease in association with inflammatory bowel disease is a rare condition. We here report a case showing an association between ulcerative colitis, minimal change disease, and psoriasis. The possible pathological link between 3 diseases is discussed.

  10. Fulminant ulcerative colitis associated with steroid-resistant minimal change disease and psoriasis: a case report.

    Science.gov (United States)

    Lok, Ka-Ho; Hung, Hiu-Gong; Yip, Wai-Man; Li, Kin-Kong; Li, Kam-Fu; Szeto, Ming-Leung

    2007-08-07

    A 43-year-old Chinese patient with a history of psoriasis developed fulminant ulcerative colitis after immunosuppressive therapy for steroid-resistant minimal change disease was stopped. Minimal change disease in association with inflammatory bowel disease is a rare condition. We here report a case showing an association between ulcerative colitis, minimal change disease, and psoriasis. The possible pathological link between 3 diseases is discussed.

  11. Fulminant ulcerative colitis associated with steroid-resistant minimal change disease and psoriasis: A case report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A 43-year-old Chinese patient with a history of psoriasis developed fulminant ulcerative colitis after immunosuppressive therapy for steroid-resistant minimal change disease was stopped. Minimal change disease in association with inflammatory bowel disease is a rare condition. We here report a case showing an association between ulcerative colitis, minimal change disease,and psoriasis. The possible pathological link between 3 diseases is discussed.

  12. Impairment of endothelial and subendothelial sites by a circulating plasma factor associated with minimal change disease

    NARCIS (Netherlands)

    Cheung, PK; Baller, JFW; Bakker, WW

    1996-01-01

    Background. The pathogenesis of albuminuria in minimal change disease (MCD) is unknown. A human plasma factor (denoted as 100KF) is able to induce minimal change-like glomerular alterations, i.e. loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase, following in v

  13. Impairment of endothelial and subendothelial sites by a circulating plasma factor associated with minimal change disease

    NARCIS (Netherlands)

    Cheung, PK; Baller, JFW; Bakker, WW

    1996-01-01

    Background. The pathogenesis of albuminuria in minimal change disease (MCD) is unknown. A human plasma factor (denoted as 100KF) is able to induce minimal change-like glomerular alterations, i.e. loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase, following in

  14. Impairment of endothelial and subendothelial sites by a circulating plasma factor associated with minimal change disease

    NARCIS (Netherlands)

    Cheung, PK; Baller, JFW; Bakker, WW

    1996-01-01

    Background. The pathogenesis of albuminuria in minimal change disease (MCD) is unknown. A human plasma factor (denoted as 100KF) is able to induce minimal change-like glomerular alterations, i.e. loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase, following in v

  15. Minimal change disease in graft versus host disease: a podocyte response to the graft?

    Science.gov (United States)

    Huskey, Janna; Rivard, Chris; Myint, Han; Lucia, Scott; Smith, Maxwell; Shimada, Michiko; Ishimoto, Takuji; Araya, Carlos; Garin, Eduardo H; Johnson, Richard J

    2013-12-01

    Nephrotic syndrome is a rare complication of hematopoietic cell transplantation. It has been suggested that nephrotic syndrome may represent a limited form of graft-versus-host disease although the pathological link between these two entities remains unclear. In this paper, we report a case of a 61-year-old female who underwent nonmyeloablative allogenic stem cell transplantation for T-cell prolymphocytic leukemia and subsequently developed biopsy proven minimal change disease shortly after cessation of her immunosuppression therapy. Urinary CD80 was markedly elevated during active disease and disappeared following corticosteroid-induced remission. We hypothesize that alloreactive donor T cells target the kidney and induce podocyte expression of CD80 that results in proteinuria from limited 'graft versus host' disease.

  16. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    OpenAIRE

    Ewa Kwiatkowska; Edyta Gołembiewska; Kazimierz Ciechanowski; Karolina Kędzierska

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. ...

  17. High prevalence of gastroesophageal reflux disease with minimal mucosal change in asthmatic patients.

    Science.gov (United States)

    Shimizu, Yasuo; Dobashi, Kunio; Kobayashi, Setsuo; Ohki, Ichiro; Tokushima, Masahiko; Kusano, Motoyasu; Kawamura, Osamu; Shimoyama, Yasuyuki; Utsugi, Mitsuyoshi; Mori, Masatomo

    2006-08-01

    It is known that the prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients is high. Although an endoscopic diagnosis of GERD based on the established Los Angeles (LA) classification requires the detection of erosive mucosal breaks, there are patients with GERD who have prominent erythema of the esophageal membrane without erosive mucosal breaks. Non-erosive mucosal change denotes the minimal change of the discoloring type of reflux esophagitis. This study was undertaken to determine the prevalence of GERD in asthmatic patients using the LA classification with the inclusion of minimal change, compared to the prevalence determined using the established LA classification without minimal change. The presence of GERD in asthmatic patients (n = 78), non-asthmatic disease control patients (n = 56), and healthy subjects (n = 150) was evaluated by endoscopic examination. The frequency of GERD in asthmatic patients based on the LA classification with minimal change was higher (54/78, 69.2%) than in asthmatic patients based on the LA classification without minimal change (37/78, 47.4%) (p disease control patients (17/56, 30.4%) and healthy subjects (27/150, 18.0%) based on the LA classification with minimum change. These data indicate that asthmatic patients have a high frequency of GERD. In addition, without the inclusion of minimum change to the diagnosis of GERD, the prevalence of GERD appears to be underestimated in asthmatic patients. Therefore, physicians should carefully observe asthmatic patients with minimal change on endoscopy.

  18. Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

    Science.gov (United States)

    Florens, N; Lemoine, S; Guebre-Egziabher, F; Valour, F; Kanitakis, J; Rabeyrin, M; Juillard, L

    2017-02-06

    There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

  19. Development of minimal-change glomerular disease and Hashimoto's thyroiditis during the treatment of sarcoidosis.

    Science.gov (United States)

    Ando, Fumiaki; Okado, Tomokazu; Sohara, Eisei; Rai, Tatemitsu; Uchida, Shinichi; Sasaki, Sei

    2013-11-01

    Minimal-change glomerular disease, sarcoidosis and autoimmune thyroid disease rarely occur in the same patient. We herein report a patient in which minimal-change glomerular disease and Hashimoto's thyroiditis developed during the treatment of sarcoidosis with steroids. A 66-year-old female was admitted to our hospital with symptoms of nephrotic syndrome. Nine months before admission, she was diagnosed as having ocular and pulmonary sarcoidosis, for which prednisolone at an initial dose of 40 mg/day was started. When the dose of prednisolone was tapered to 20 mg/day, she noticed swelling of the lower extremities. Examination confirmed the simultaneous occurrence of minimal-change glomerular disease and Hashimoto's thyroiditis, which were diagnosed based on kidney histology, ultrasonography of the thyroid gland and positive antithyroglobulin antibodies. We used intravenous methylprednisolone pulse therapy followed by 40 mg/day oral prednisolone. The patient achieved complete remission of nephrotic syndrome and steroids were tapered without relapse.

  20. Nephrotic syndrome of minimal change disease following exposure to mercury-containing skin-lightening cream.

    Science.gov (United States)

    Zhang, Lin; Liu, Fuyou; Peng, Youming; Sun, Lin; Chen, Chunguo

    2014-01-01

    A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.

  1. Minimal change disease with acute renal failure: a case against the nephrosarca hypothesis.

    Science.gov (United States)

    Cameron, Mary Ann; Peri, Usha; Rogers, Thomas E; Moe, Orson W

    2004-10-01

    An unusual but well-documented presentation of minimal change disease is nephrotic proteinuria and acute renal failure. One pathophysiological mechanism proposed to explain this syndrome is nephrosarca, or severe oedema of the kidney. We describe a patient with minimal change disease who presented with heavy proteinuria and acute renal failure but had no evidence of renal interstitial oedema on biopsy. Aggressive fluid removal did not reverse the acute renal failure. Renal function slowly returned concomitant with resolution of the nephrotic syndrome following corticosteroid therapy. The time profile of the clinical events is not compatible with the nephrosarca hypothesis and suggests an alternative pathophysiological model for the diminished glomerular filtration rate seen in some cases of minimal change disease.

  2. Validation of glomerular basement membrane thickness changes with aging in minimal change disease.

    Science.gov (United States)

    Sato, Shigeru; Sasaki, Yoshihiro; Adachi, Akiko; Ghazizadeh, Mohammad

    2010-01-01

    Measurement of the normal range of glomerular basement membrane (GBM) thickness by electron microscopy is required for the diagnosis of thin basement membrane disease or diabetic nephropathy; however, this measurement is influenced by aging. The aim of this study was to introduce a simple histogram plotting method for the validation of the results of the GBM thickness measurements by the accepted arithmetic mean ± SD method. We examined renal biopsy specimens obtained from 19 patients (10 males and 9 females) with minimal change disease, ranging in age from 3 to 70 years. Renal tissue samples obtained at autopsy from a male baby (3 months old) with no renal disease were also examined. For each case, GBM thicknesses at 10-15 evenly distributed points per glomerular loop were directly measured and the arithmetic mean ± SD was calculated. Subsequently, the arithmetic mean ± SD for each group of cases classified by age into 4 groups, i.e. babyhood (3 months old), childhood (3-11 years old), adulthood (12-57 years old), and old age (60-70 years old), was determined. On the other hand, a histogram of the frequency of GBM points measured against thickness was plotted to determine the distribution pattern and the range of measurements in each age group. The histogram plot showed 4 clearly divided modes for GBM thickness. Comparison of the results obtained by the 2 methods revealed a significant correlation indicating the feasibility of the histogram plotting method as a useful adjunct to validate GBM thickness measurements.

  3. Altered activity of plasma hemopexin in patients with minimal change disease in relapse

    NARCIS (Netherlands)

    Bakker, WW; van Dael, CML; Pierik, LJWM; van Wijk, JAE; Nauta, J; Borghuis, T; Kapojos, JJ

    2005-01-01

    Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n =18) or in remission (n =23) (after treatment with prednisolone) for presence or activity of

  4. Oxygen-dependent injury by a human plasma factor associated with minimal change disease

    NARCIS (Netherlands)

    Cheung, PK; Baller, JFW; Bakker, WW

    1998-01-01

    The mechanism by which a human plasma factor associated with proteinuria is able to cause experimental glomerular albumin leakage is unknown. This factor (called 100KF) is able to induce glomerular alterations in the rat kidney, similar to those seen in minimal change disease, including loss of glom

  5. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease.

    Science.gov (United States)

    Munyentwali, Helene; Bouachi, Khedidja; Audard, Vincent; Remy, Philippe; Lang, Philippe; Mojaat, Rachid; Deschênes, Georges; Ronco, Pierre M; Plaisier, Emmanuelle M; Dahan, Karine Y

    2013-03-01

    Development of steroid dependency in patients with nephrotic syndrome may require a long-term multi-drug therapy at risk of drug toxicity and renal failure. Rituximab treatment reduces the steroid dosage and the need for immunosuppressive therapy in pediatric patients. Here we retrospectively analyze the efficacy and safety of rituximab in adult patients with steroid-dependent minimal change disease. To do this, we analyzed the outcome of all adult patients treated with rituximab for steroid-dependent minimal change nephrotic syndrome over a mean follow-up of 29.5 months (range 5.1-82 months). Seventeen patients with steroid-dependent or frequently relapsing minimal change nephrotic syndrome, unresponsive to several immunosuppressive medications, were treated with rituximab. Eleven patients had no relapses after rituximab infusion (mean follow-up 26.7 months, range 5.1-82 months) and nine of them were able to come off all other immunosuppressive drugs and steroids during follow-up. Six patients relapsed at least once after a mean time of 11.9 months (mean follow-up 34.5 months, range 16.9-50.1 months), but their immunosuppressive drug treatment could be stopped or markedly reduced during this time. No adverse events were recorded. Thus, rituximab is efficient and safe in adult patients suffering from severe steroid-dependent minimal change disease. Prospective randomized trials are needed to confirm this study.

  6. Primary Sjögren's syndrome with minimal change disease--a case report.

    Science.gov (United States)

    Yang, Mei-Li; Kuo, Mei-Chuan; Ou, Tsan-Teng; Chen, Hung-Chun

    2011-05-01

    Glomerular involvement in patients with primary Sjögren's syndrome (pSS) has rarely been reported. Among them, membranoproliferative glomerulonephritis and membranous nephropathy are the more common types. We report a middle-aged female presenting concurrently with nephrotic syndrome and microscopic hematuria, and her pSS was diagnosed by positive anti-Ro (SSA)/anti-La (SSB) autoantibodies, dry mouth, severely diffuse impaired function of both bilateral parotid and submandibular glands, and a positive Schirmer test. Renal pathology revealed minimal change disease and thin basement membrane nephropathy. The patient's nephrotic syndrome resolved after treatment with corticosteroids. To our knowledge, this is the first report of minimal change disease in a patient with pSS.

  7. Renal manifestations of human brucellosis: First report of minimal change disease

    Directory of Open Access Journals (Sweden)

    Nikolaos Sabanis

    2016-01-01

    Full Text Available Human brucellosis is considered a great example of the complexity of clinical manifestations possibly affecting multiple organs or systems. Renal manifestations of human brucellosis have been documented in few case reports and one case series. Herein, we present a case of Nephrotic syndrome (NS due to minimal change disease in the course of acute brucellosis. A 53-year-old male farmer was admitted to our department with acute brucellosis and NS. Renal biopsy revealed minimal change disease. Combined treatment with prednisone (1 mg/kg, rifampicin (600 mg/day, and doxycycline (200 mg/day was initiated. Complete remission of NS was achieved at the end of the fourth week. One year later, the patient remained in complete remission of NS without any sign of relapse of brucellosis.

  8. Renal manifestations of human brucellosis: First report of minimal change disease.

    Science.gov (United States)

    Sabanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Tsotsiou, Eleni; Kalaitzoglou, Asterios; Kavlakoudis, Christos; Vasileiou, Sotirios

    2016-05-01

    Human brucellosis is considered a great example of the complexity of clinical manifestations possibly affecting multiple organs or systems. Renal manifestations of human brucellosis have been documented in few case reports and one case series. Herein, we present a case of Nephrotic syndrome (NS) due to minimal change disease in the course of acute brucellosis. A 53-year-old male farmer was admitted to our department with acute brucellosis and NS. Renal biopsy revealed minimal change disease. Combined treatment with prednisone (1 mg/kg), rifampicin (600 mg/day), and doxycycline (200 mg/day) was initiated. Complete remission of NS was achieved at the end of the fourth week. One year later, the patient remained in complete remission of NS without any sign of relapse of brucellosis.

  9. Malignant pleural mesothelioma with associated minimal change disease and acute renal failure.

    Science.gov (United States)

    Li, Jordan Y Z; Yong, Tuck Y; Kuss, Bryone J; Klebe, Sonja; Kotasek, Dusan; Barbara, Jeffrey A J

    2010-01-01

    Paraneoplastic manifestations in malignant pleural mesothelioma are rare. We report a case of malignant pleural mesothelioma associated with minimal change disease (MCD). A 58-year-old man with occupational exposure to asbestos presented with severe peripheral edema, heavy proteinuria, and acute renal failure shortly after the diagnosis of mesothelioma had been confirmed. The renal biopsy demonstrated MCD. The underlying pathogenesis of this association remains unknown.

  10. A Case of Nephrotic Syndrome With Minimal-Change Disease and Waldenstrom's Macroglobulinemia.

    Science.gov (United States)

    Grabe, Darren W; Li, Bo; Haqqie, Syed S

    2013-12-01

    Kidney disease is a rare complication of Waldenstrom's macroglobulinemia. We report a case of nephrotic syndrome and minimal change disease in a patient with biopsy proven Waldenstrom's macroglobulinemia. The patient presented with over 12 grams of proteinuria and was successfully treated with oral prednisone over the course of 4 weeks. Repeat serum protein electrophoresis as well as serum immunoelectrophoresis revealed no paraproteins, urine analysis was negative for protein or blood by dipstick and spot urine protein was 9 mg/dL with creatinine of 101 mg/dL at time of last office visit. This case illustrates the successful treatment with corticosteroids alone with prolonged complete remission.

  11. Minimal-change disease as a paraneoplastic syndrome in a patient with ovarian carcinoma.

    Science.gov (United States)

    González-Fontal, Guido R; Restrepo, Juan G; Henao-Martínez, Andrés F

    2011-12-01

    Minimal-change disease (MCD) is an exceptional paraneoplastic presentation. We are describing the case of an ovarian paraneoplastic nephrotic syndrome. The kidney biopsy was consistent with MCD. Steroids and immunosuppressive therapy were given with no change in the nephrotic-range proteinuria. A complete resolution of the nephrotic syndrome was soon observed with improvement of her clinical condition after five cycles of chemotherapy with paclitaxel and carboplatin and tumor-debulking surgery. Ovarian carcinoma paraneoplastic nephrotic syndrome secondary to MCD is an extremely rare event, which is important to recognize since it is responsive to the standard chemotherapy.

  12. IgM nephropathy: is it closer to minimal change disease or to focal segmental glomerulosclerosis?

    Science.gov (United States)

    Brugnano, R; Del Sordo, R; Covarelli, C; Gnappi, E; Pasquali, S

    2016-08-01

    Immunoglobulin (Ig)M nephropathy (IgMN), known since 1978, is a very controversial clinicopathological entity characterized by IgM diffuse deposits in the mesangium at immunofluorescence whereas light microscop identifies minimal glomerular lesion, hypercellularity and expansion of the mesangium or sclerotic focal, segmental lesion. Clinically, it is a nephrotic syndrome, especially in pediatric patients, or asymptomatic proteinuria and/or isolated hematuria. These characteristics narrowly define IgMN between minimal change disease and focal segmental glomerulosclerosis, so it is not often recognized as a separate pathology. Homogeneous epidemiologic, pathogenetic, clinical or histological data are not available. Recent research on the pathogenetic role of mesangial IgM has, however, renewed interest in IgMN and naturally the controversies.

  13. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    Science.gov (United States)

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome.

  14. Recurrent Acute Renal Failure in a Patient with Minimal Change Disease

    Directory of Open Access Journals (Sweden)

    Abdelrahman Mohammad

    2001-01-01

    Full Text Available We report on a 16-year old female patient with biopsy proved minimal change disease and steroid state. She was subsequentlygiven cyclosporin for varying periods of time with inadequate response. She developed four episodes of acute renal failure in the background of severe nephrotic state, 10 years after the onset of her illness. Three of these episodes could be reversed with albumin infusion and judicious use of diuretics while the fourth necessitated six sessions of ultrafiltration. In none of the episodes of ARF could we find any cause other than the nephrotic state itself.

  15. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy.

    Science.gov (United States)

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-06-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  16. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    OpenAIRE

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  17. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    OpenAIRE

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.

  18. Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy

    National Research Council Canada - National Science Library

    Janardan, Jyotsna; Ooi, Khai; Menahem, Solomon

    2014-01-01

    We report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses...

  19. Minimal changes in health status questionnaires: distinction between minimally detectable change and minimally important change

    Directory of Open Access Journals (Sweden)

    Knol Dirk L

    2006-08-01

    Full Text Available Abstract Changes in scores on health status questionnaires are difficult to interpret. Several methods to determine minimally important changes (MICs have been proposed which can broadly be divided in distribution-based and anchor-based methods. Comparisons of these methods have led to insight into essential differences between these approaches. Some authors have tried to come to a uniform measure for the MIC, such as 0.5 standard deviation and the value of one standard error of measurement (SEM. Others have emphasized the diversity of MIC values, depending on the type of anchor, the definition of minimal importance on the anchor, and characteristics of the disease under study. A closer look makes clear that some distribution-based methods have been merely focused on minimally detectable changes. For assessing minimally important changes, anchor-based methods are preferred, as they include a definition of what is minimally important. Acknowledging the distinction between minimally detectable and minimally important changes is useful, not only to avoid confusion among MIC methods, but also to gain information on two important benchmarks on the scale of a health status measurement instrument. Appreciating the distinction, it becomes possible to judge whether the minimally detectable change of a measurement instrument is sufficiently small to detect minimally important changes.

  20. Rifampicin-induced minimal change disease is improved after cessation of rifampicin without steroid therapy.

    Science.gov (United States)

    Park, Dong Hyuk; Lee, Sul A; Jeong, Hyeon Joo; Yoo, Tae-Hyun; Kang, Shin-Wook; Oh, Hyung Jung

    2015-03-01

    There are several reports to demonstrate that rifampicin, a major anti-tuberculosis agent, is associated with some adverse renal effects, with a few cases of rifampicin-induced minimal change disease (MCD). In the present case, a 68-year-old female presented with nausea, vomiting, foamy urine, general weakness and edema. She had been taking rifampicin for 4 weeks due to pleural tuberculosis. The patient had no proteinuria before the anti-tuberculosis agents were started, but urine tests upon admission showed heavy proteinuria with a 24-h urinary protein of 9.2 g/day, and serum creatinine, albumin, and total cholesterol levels were 1.36 mg/dL, 2.40 g/dL, and 283 mg/dL, respectively. MCD was diagnosed, and the patient achieved complete remission after cessation of rifampicin without undergoing steroid therapy.

  1. Minimal change disease: an unusual presentation of marginal zone MALT lymphoma.

    Science.gov (United States)

    Inayat, Faisal; Law, Jason K; Myers-Gurevitch, Patricia M; Seshan, Surya V; Perlman, Alan S

    2016-03-01

    Minimal change disease (MCD) in association with low-grade extra-nodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) (MALT lymphoma) is a rare clinicopathologic entity. We report a 68-year-old male who presented with nephrotic range proteinuria as the first manifestation of underlying MZL, confirmed with standard set of investigations. Being a steroid non-responder, he was treated with rituximab demonstrating a marked response with resolution of proteinuria. However, he relapsed after 3 months. Upon relapse, a combination of rituximab and bendamustine (R-Benda) was initiated achieving sustained resolution of proteinuria. No additional treatment was administered and the proteinuria has remained in remission for over a year.

  2. Minimal change disease associated with type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Moyses Neto, Miguel; Silva, Gyl Eanes Barros; Costa, Roberto S; Romão, Elen A; Vieira Neto, Osvaldo Merege; Dantas, Marcio

    2012-07-01

    A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

  3. A Unique Cause of Proteinuria in Pregnancy: Class II Lupus Nephritis with Concomitant Minimal Change Disease

    Science.gov (United States)

    Kunjal, Ryan; Adam-Eldien, Rabie; Makary, Raafat; Jo-Hoy, Francois; Heilig, Charles W.

    2016-01-01

    We report the case of a 22-year-old African American female who presented to another facility for routine follow-up in the 34th week of pregnancy with lower extremity swelling and nephrotic-range proteinuria. Although she was normotensive, it was initially thought that she had preeclampsia. She was monitored carefully and delivery was induced at 37 weeks of gestation. She was transferred to our hospital, where she was diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria. Renal biopsy revealed a surprising finding of minimal change disease (MCD) concomitant with class II lupus nephritis (LN). She was managed with pulses and then tapering doses of steroid therapy with dramatic resolution of the nephrotic syndrome. This case demonstrates not only the rare de novo occurrence of SLE in pregnancy, but the unique finding of MCD coexisting with class II LN. We propose that altered T cell activity may be the link between these seemingly distinct entities.

  4. Urinary fibrinogen and renal tubulointerstitial fibrinogen deposition: Discriminating between primary FSGS and minimal change disease.

    Science.gov (United States)

    Wang, Yu; Zheng, Chunxia; Xu, Feng; Liu, Zhihong

    2016-09-23

    Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are common types of primary glomerular disease; they share numerous clinical and pathological similarities but have different treatment regimens and prognoses. It is therefore necessary to distinguish between them and to explore the mechanism underlying their differences. Fibrinogen is reportedly involved in podocyte damage and in renal fibrosis in vitro and in animal models of kidney disease. We thus tested urinary fibrinogen, serum fibrinogen, and renal fibrinogen deposition levels in a cohort comprising 50 patients with FSGS and 40 patients with MCD. Our results suggested that urinary fibrinogen and renal interstitial fibrinogen deposition levels were significantly higher in the FSGS patients than in the MCD patients, while serum fibrinogen levels did not differ between the groups. Receiver operating characteristic (ROC) curve analysis showed an excellent diagnostic ability for urinary fibrinogen and a fair diagnostic ability for tubulointerstitial fibrinogen deposition in differentiating FSGS from MCD. Additionally, we found that urinary fibrinogen levels were positively correlated with the 24-h urine protein levels in patients with FSGS but not in patients with MCD. In conclusion, urinary fibrinogen and renal interstitial fibrinogen deposition is elevated in primary FSGS compared to MCD, which may be relevant to both diagnosis and pathogenesis.

  5. Predictors of Relapse in Adult-Onset Nephrotic Minimal Change Disease.

    Science.gov (United States)

    Lee, Hajeong; Yoo, Kyung Don; Oh, Yun Kyu; Kim, Dong Ki; Oh, Kook-Hwan; Joo, Kwon Wook; Kim, Yon Su; Ahn, Curie; Han, Jin Suk; Lim, Chun Soo

    2016-03-01

    Minimal change disease (MCD) is a well-known benign primary glomerulonephritis because of its distinct rare tendency to progress to end-stage renal disease. However, factors associated with relapse in adults are not well known. We aimed to identify predictors of relapse in adult-onset MCD patients.A retrospective cohort of 195 patients with adult-onset primary MCD with nephritic syndrome and disease onset between 1979 and 2013 was followed up for >12 months. The number of relapses was counted and predictors of relapse were analyzed.A total of 195 patients were included. Median age at diagnosis was 38 years (IQR, 23-53 years) and 113 (57.9%) were men. During 81 months (IQR, 44-153 months) of follow-up, 92% of patients achieved remission after initial treatment. However, only 60 (32.8%) did not experience a relapse and 11 patients failed to remit. Among the remaining 124 patients, 65 experienced a relapse once or twice and 59 experienced a relapse more than twice. Younger onset age, increased severity of nephrotic features such as lower serum albumin levels and higher cholesterol level were associated with relapse. Interestingly, the grade of mesangial proliferation was lower in patients who experienced a relapse. Initial combined treatment with corticosteroids (CS) and cyclophosphamide reduced the number of relapses. In addition, patients with shorter treatment duration tended to experience relapse more often. Multivariate analysis showed that younger onset age, combined mesangial proliferation, initial treatment regimen, and treatment duration were independent risk factors for relapse. Progression to end-stage renal disease was developed in only a patient.In conclusion, more than two-thirds of adult-onset nephrotic MCD patients experienced relapse, although their renal progression was rare. Younger onset age, CS without cyclophosphamide treatment, and shorter treatment duration were independent risk factors for relapse in adult-onset MCD patients.

  6. Cell biology and genetics of minimal change disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Moin A. Saleem

    2016-03-01

    Full Text Available Minimal change disease (MCD is an important cause of nephrotic syndrome and is characterized by massive proteinuria and hypoalbuminemia, resulting in edema and hypercholesterolemia. The podocyte plays a key role in filtration and its disruption results in a dramatic loss of function leading to proteinuria. Immunologic disturbance has been suggested in the pathogenesis of MCD. Because of its clinical features, such as recurrent relapse/remission course, steroid response in most patients, and rare familial cases, a genetic defect has been thought to be less likely in MCD. Recent progress in whole-exome sequencing reveals pathogenic mutations in familial cases in steroid-sensitive nephrotic syndrome (SSNS and sheds light on possible mechanisms and key molecules in podocytes in MCD. On the other hand, in the majority of cases, the existence of circulating permeability factors has been implicated along with T lymphocyte dysfunction. Observations of benefit with rituximab added B cell involvement to the disease. Animal models are unsatisfactory, and the humanized mouse may be a good model that well reflects MCD pathophysiology to investigate suggested “T cell dysfunction” directly related to podocytes in vivo. Several candidate circulating factors and their effects on podocytes have been proposed but are still not sufficient to explain whole mechanisms and clinical features in MCD. Another circulating factor disease is focal segmental glomerulosclerosis (FSGS, and it is not clear if this is a distinct entity, or on the same spectrum, implicating the same circulating factor(s. These patients are mostly steroid resistant and often have a rapid relapse after transplantation. In clinical practice, predicting relapse or disease activity and response to steroids is important and is an area where novel biomarkers can be developed based on our growing knowledge of podocyte signaling pathways. In this review, we discuss recent findings in genetics and

  7. Minimal Change Disease and IgA Deposition: Separate Entities or Common Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Brandon S. Oberweis

    2013-01-01

    Full Text Available Introduction. Minimal Change Disease (MCD is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  8. Minimal change disease and IgA deposition: separate entities or common pathophysiology?

    Science.gov (United States)

    Oberweis, Brandon S; Mattoo, Aditya; Wu, Ming; Goldfarb, David S

    2013-01-01

    Introduction. Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

  9. De novo minimal change disease after ABO-incompatible kidney transplantation.

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    Mochizuki, Yasushi; Iwata, Takahisa; Nishikido, Masaharu; Uramatsu, Tadashi; Sakai, Hideki; Taguchi, Takashi

    2012-07-01

    We report the clinical and pathological findings of a case of de novo minimal change disease (MCD) after ABO-incompatible living kidney transplantation. A 62-yr-old man with end-stage renal disease associated with type I diabetes received ABO-incompatible kidney transplantation from his 58-yr-old wife. Although allograft function was excellent immediately after surgery, massive proteinuria (35 g/d) appeared on post-transplantation day 5. After the allograft biopsy taken on post-transplantation day 6, he was treated with 12 cycles of plasma exchange, but the nephrotic-range proteinuria showed no remission. The biopsy specimen showed no significant pathological findings on light microscopy, but electron microscopy showed diffuse effacement of podocyte foot processes. Based on the diagnosis of de novo MCD, the patient received intravenous methylprednisolone pulse therapy, followed by high-dose steroid maintenance therapy. The steroid therapy induced complete remission of nephrotic syndrome and stable allograft function immediately, which was also maintained at one yr after the transplantation.

  10. [New insight in pathogenesis of podocyte disfunction in minimal change disease].

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    Liu, Shanshan; Chen, Jianghua

    2016-03-01

    Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like-4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over-expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD.

  11. Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease

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    Shendi, Ali M.; Salama, Alan D.; Khosravi, Maryam; Connolly, John O.; Trompeter, Richard

    2016-01-01

    Abstract Aim Treatment of frequently relapsing or steroid‐dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long‐term efficacy and safety are still limited. Methods We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid‐dependent, biopsy‐proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re‐treatment. Biochemical and clinical parameters were monitored over an extended follow‐up period of up to 43 months. Results Median steroid‐free survival after RTX was 25 months (range 4–34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 µ. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow‐up period. Conclusions Rituximab therapy is effective at maintaining prolonged steroid‐free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid‐dependent MCD. PMID:26860320

  12. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease.

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    Smeets, Bart; Stucker, Fabien; Wetzels, Jack; Brocheriou, Isabelle; Ronco, Pierre; Gröne, Hermann-Josef; D'Agati, Vivette; Fogo, Agnes B; van Kuppevelt, Toin H; Fischer, Hans-Peter; Boor, Peter; Floege, Jürgen; Ostendorf, Tammo; Moeller, Marcus J

    2014-12-01

    In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of idiopathic nephrotic syndrome with no immune complexes can improve the sensitivity to detect sclerotic lesions compared with standard methods. Ninety-five renal biopsies were stained for claudin-1 (PEC marker), CD44 (activated PECs), and LKIV69 (PEC matrix); 38 had been diagnosed as early primary FSGS and 57 as minimal change disease. PEC markers were detected on the tuft in 87% of the biopsies of patients diagnosed as primary FSGS. PEC markers were detected in FSGS lesions from the earliest stages of disease. In minimal change disease, no PEC activation was observed by immunohistology. However, in 25% of biopsies originally diagnosed as minimal change disease the presence of small lesions indicative of a sclerosing process were detected, which were undetectable on standard periodic acid-Schiff staining, even though only a single histologic section for each PEC marker was evaluated. Staining for LKIV69 detected lesions with the highest sensitivity. Two novel PEC markers A-kinase anchor protein 12 and annexin A3 exhibited similar sensitivity. In summary, detection of PECs on the glomerular tuft by immunostaining improves the differentiation between minimal change disease and primary FSGS and may serve to guide clinical decision making.

  13. Tacrolimus improves proteinuria remission in adults with cyclosporine A-resistant or -dependent minimal change disease.

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    Xu, Dechao; Gao, Xiang; Bian, Rongrong; Mei, Changlin; Xu, Chenggang

    2017-03-01

    Cyclosporin A (CsA) is considered as an effective treatment option for steroid-resistant or-dependent patients with adult-onset minimal change disease (MCD). However, CsA resistance or dependence is also observed in these patients. Tacrolimus (TAC) is a calcineurin inhibitor that is potent in cytokine suppression. The authors aim to evaluate the efficacy and safety of TAC therapy in CsA-resistant and-dependent adult-onset MCD patients. Patients with adult-onset MCD were enrolled in our department from 2008 to 2012. All patients were demonstrated to be resistant to or dependent on CsA therapy. Prednisone (0.5 mg/kg per day) combined with TAC (0.05-0.1 mg/kg per day) were prescribed to these patients for at least 6 months. The primary outcome was complete or partial remission of proteinuria. Secondary outcomes included time required for complete or partial remission, adverse events, number of relapses, and TAC dosages. A total of 11 MCD patients were enrolled in this observational study. The numbers of patients who presented with resistance to or dependence on CsA were 7 and 4, respectively. The total remission rate was 90.9% (10/11) with the complete remission rate 72.7% (8/11). Most remission patients achieved remission during the first 2 months of TAC therapy. Patients who presented with dependence on CsA had achieved complete remission with TAC therapy, while outcomes for CsA-resistant patients were four complete remissions, two partial remissions and one resistance. The adverse events were observed in this study included infection, diarrhoea, and worsened hypertension. Five patients who had remission experienced relapse. Tacrolimus improves proteinuria remission in adults with CsA-resistant or -dependent MCD. © 2016 Asian Pacific Society of Nephrology.

  14. Minimal change disease caused by exposure to mercury-containing skin lightening cream: a report of 4 cases.

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    Tang, Hon-Lok; Mak, Yuen-Fun; Chu, Kwok-Hong; Lee, William; Fung, Samuel Kaâ Shun; Chan, Thomas Yan-Keung; Tong, Kwok-Lung

    2013-04-01

    Mercury is a known cause of nephrotic syndrome and the underlying renal pathology in most of the reported cases was membranous nephropathy. We describe here 4 cases of minimal change disease following exposure to mercury-containing skin lightening cream for 2 - 6 months. The mercury content of the facial creams was very high (7,420 - 30,000 parts per million). All patients were female and presented with nephrotic syndrome and heavy proteinuria (8.35 - 20.69 g/d). The blood and urine mercury levels were 26 - 129 nmol/l and 316 - 2,521 nmol/d, respectively. Renal biopsy revealed minimal change disease (MCD) in all patients. The use of cosmetic cream was stopped and chelation therapy with D-penicillamine was given. Two patients were also given steroids. The time for blood mercury level to normalize was 1 - 7 months, whereas it took longer for urine mercury level to normalize (9 - 16 months). All patients had complete remission of proteinuria and the time to normalization of proteinuria was 1 - 9 months. Mercury-containing skin lightening cream is hazardous because skin absorption of mercury can cause minimal change disease. The public should be warned of the danger of using such products. In patients presenting with nephrotic syndrome, a detailed history should be taken, including the use of skin lightening cream. With regard to renal pathology, apart from membranous nephropathy, minimal change disease should be included as another pathological entity caused by mercury exposure or intoxication.

  15. An unexpected presentation: minimal change disease in an adult with treatment-naïve hepatitis C.

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    Stokes, Audrey L; Alhamad, Tarek; Abendroth, Catherine S; Farag, Hosam A; Verma, Navin

    2013-12-01

    Minimal change disease is the most common glomerular disease affecting children; its prevalence among adults, however, is eclipsed by other glomerular pathologies. Each of these diseases has a number of classic associations, such as membranoproliferative glomerulonephritis with hepatitis C. We report the case of a middle-aged African-American male who presented with the nephrotic syndrome and acute renal failure and was concomitantly diagnosed with a new hepatitis C infection. He also had a history of urethral strictures with potential reflux nephropathy, which--in combination with his African-American race--also made focal segmental glomerulosclerosis a diagnostic possibility. Full laboratory evaluation did not distinguish the cause of his massive proteinuria; subsequent renal biopsy ultimately revealed minimal change disease. A full course of high-dose steroids eventually reduced his proteinuria, after which his renal failure resolved as well without need for hemodialysis.

  16. A case of minimal change disease treated successfully with mycophenolate mofetil in a patient with systemic lupus erythematosus.

    Science.gov (United States)

    Hong, Young Hoon; Yun, Dae Young; Jung, Yong Wook; Oh, Myung Jin; Kim, Hyun Je; Lee, Choong Ki

    2011-12-01

    The World Health Organization classifies lupus nephritis as class I to V or VI. However, a few cases of minimal change glomerulopathy have been reported in association with systemic lupus erythematosus (SLE). Mycophenolate mofetil has been shown to be effective for treatment of minimal change disease and lupus nephritis. A 24-year-old woman diagnosed with SLE five years prior to presentation complained of a mild generalized edema. The urinalysis showed microscopic hematuria and proteinuria. The assessed amount of total proteinuria was 1,618 mg/24 hours. A renal biopsy demonstrated diffuse fusion of the foot processes of podocytes on electron microscopy. Mycophenolate mofetil was started in addition to the maintenance medications of prednisolone 10 mg/day and hydroxychloroquine 400 mg/day. After six months of treatment, the microscopic hematuria and proteinuria resolved, and the total urine protein decreased to 100 mg/24 hours.

  17. The first description of severe anemia associated with acute kidney injury and adult minimal change disease: a case report

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    Qian Yimei

    2009-01-01

    Full Text Available Abstract Introduction Acute kidney injury in the setting of adult minimal change disease is associated with proteinuria, hypertension and hyperlipidemia but anemia is usually absent. Renal biopsies exhibit foot process effacement as well as tubular interstitial inflammation, acute tubular necrosis or intratubular obstruction. We recently managed a patient with unique clinical and pathological features of minimal change disease, who presented with severe anemia and acute kidney injury, an association not previously reported in the literature. Case presentation A 60-year-old Indian-American woman with a history of hypertension and diabetes mellitus for 10 years presented with progressive oliguria over 2 days. Laboratory data revealed severe hyperkalemia, azotemia, heavy proteinuria and progressively worsening anemia. Urine eosinophils were not seen. Emergent hemodialysis, erythropoietin and blood transfusion were initiated. Serologic tests for hepatitis B, hepatitis C, anti-nuclear antibodies, anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies were negative. Complement levels (C3, C4 and CH50 were normal. Renal biopsy unexpectedly displayed 100% foot process effacement. A 24-hour urine collection detected 6.38 g of protein. Proteinuria and anemia resolved during six weeks of steroid therapy. Renal function recovered completely. No signs of relapse were observed at 8-month follow-up. Conclusion Adult minimal change disease should be considered when a patient presents with proteinuria and severe acute kidney injury even when accompanied by severe anemia. This report adds to a growing body of literature suggesting that in addition to steroid therapy, prompt initiation of erythropoietin therapy may facilitate full recovery of renal function in acute kidney injury.

  18. A case of minimal change nephrotic syndrome with acute renal failure complicating Hashimotoâs disease.

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    Iwazu, Y; Nemoto, J; Okuda, K; Nakazawa, E; Hashimoto, A; Fujio, Y; Sakamoto, M; Ando, Y; Muto, S; Kusano, E

    2008-01-01

    A 63-year-old man was admitted to our hospital for evaluation of generalized edema. Coexistence of severe hypothyroidism and nephrotic syndrome was detected by laboratory examination. High titer of both antimicrosomal antibody and antithyroid peroxidase antibody indicated Hashimotoâs disease. Renal biopsy showed minimal change glomerular abnormality, but no findings of membranous nephropathy. A series of medical treatments, including steroid therapy, thyroid hormone and human albumin replacement therapy, were administered. However, acute renal failure accompanied by hypotension, was not sufficiently prevented. After 9 sessions of plasmapheresis therapy, the severe proteinuria and low serum albumin levels were improved. Even after resting hypotension was normalized, neither renal function nor thyroid function were fully recovered. After discharge, renal function gradually returned to normal, and the blood pressure developed into a hypertensive state concomitant with the normalization of thyroid function. This report is a rare case of autoimmune thyroid disease complicated with minimal change nephrotic syndrome. In most cases of nephritic syndrome, acute renal failure (ARF) has been reported to coexist with hypertension. Although pseudohypothyroidism is well-known in nephrotic pathophysiology, complications of actual hypothyroidism are uncommon. It is suggested that the development of hypotension and ARF could be enhanced not only by hypoproteinemia, but also by severe hypothyroidism.

  19. Relapse of minimal change disease following infection with the 2009 pandemic influenza (H1N1) virus.

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    Kim, Seo Rin; Lee, Soo Bong; Kim, Il Young; Lee, Dong Won; Rhee, Harin; Seong, Eun Young; Song, Sang Heon; Kwak, Ihm Soo

    2012-04-01

    We report a case of relapse of minimal change disease following infection with the influenza A (H1N1) virus responsible for the 2009 pandemic. A 22-year-old man who had been diagnosed with minimal change disease presented with systemic edema. He had achieved complete remission with an oral steroid (prednisolone 1 mg/kg/day) by the 17th day of administration. On the 27th day of prednisolone administration, he presented with a new onset of generalized edema after several days of productive coughing. His urine showed proteinuria (4+) with a protein/creatinine ratio (PCR) of 2852.1 mg/g. His nasal swab sample was positive for the 2009 pandemic influenza (H1N1) virus by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). He received oseltamivir (150 mg/day) for 5 days. A day after completing the oseltamivir therapy, his proteinuria returned to a normal range; urinalysis was negative for protein with PCR 79.2 mg/g. One month later, the patient remained normal with no proteinuria.

  20. Is there an association of hepatitis B virus infection with minimal change disease of nephrotic syndrome? A clinical observational report.

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    Zhou, Tian-Biao; Jiang, Zong-Pei

    2015-04-01

    The rate of hepatitis B virus (HBV) infection is high in the Chinese population, and the implications of HBV infection are widely recognized, and membranous nephropathy is the most common renal lesion to be associated with HBV infection. Minimal change disease (MCD) is one of the most important histopathological characteristics in patients with nephrotic syndrome. There is no any study to report that HBV infection is associated with the etiology of MCD. Herein, we report four MCD patients with HBV infection and speculate that there is an association of HBV infection with the pathological type of MCD. In this study, we also reported the treatment schedule for these four MCD patients, and found that the anti-virus alone and combination of anti-virus with immunosuppressive agent could obtain a benefit for MCD patients with HBV infection. However, a well-designed study should be performed to confirm this association.

  1. Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease.

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    Jun Tong

    Full Text Available To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS and minimal change disease (MCD.We isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis.Analysis of differential expressed genes (DEGs revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys.This report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases.

  2. Angiopoietin-Like-4, a Potential Target of Tacrolimus, Predicts Earlier Podocyte Injury in Minimal Change Disease.

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    Li, Jian-Si; Chen, Xiao; Peng, Lei; Wei, Shi-Yao; Zhao, Shi-Lei; Diao, Tian-Tian; He, Yi-Xin; Liu, Fang; Wei, Qiu-Ju; Zhang, Qing-Fang; Li, Bing

    2015-01-01

    Podocyte injury plays central roles in proteinuria and kidney dysfunction, therefore, identifying specific biomarker to evaluate earlier podocyte injury is highly desirable. Podocyte-secreted angiopoietin-like-4 (Angptl4) mediates proteinuria in different types of podocytopathy. In the present study, we established an experimental minimal change disease (MCD) rat model, induced by adriamycin (ADR) and resulted in definite podocyte injury, to identify the dynamic changes in Angptl4 expression. We also investigated the direct effects of tacrolimus on Angptl4 and podocyte repair. We determined that the glomerular Angptl4 expression was rapidly upregulated and reached a peak earlier than desmin, an injured podocyte marker, in the ADR rats. Furthermore, this upregulation occurred prior to heavy proteinuria and was accompanied by increased urinary Angptl4. We observed that the Angptl4 upregulation occurred only when podocyte was mainly damaged since we didn't observe little Angptl4 upregulation in MsPGN patients. In addition, we observed the glomerular Angptl4 mainly located in injured podocytes rather than normal podocytes. Moreover, we found that tacrolimus treatment significantly promoted podocyte repair and reduced glomerular and urinary Angptl4 expression at an earlier stage with a significant serum Angptl4 upregulation. And similar results were confirmed in MCD patients. In conclusion, this study represents the first investigation to demonstrate that Angptl4 can predict podocyte injury at earlier stages in MCD and the identification of earlier podocyte injury biomarkers could facilitate the prompt diagnosis and treatment of patients with podocytopathy, as well as determination of the prognosis and treatment efficacy in these diseases.

  3. Minimal Change Disease as a Secondary and Reversible Event of a Renal Transplant Case with Systemic Lupus Erythematosus.

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    Gkrouzman, Elena; Kirou, Kyriakos A; Seshan, Surya V; Chevalier, James M

    2015-01-01

    Secondary causes of minimal change disease (MCD) account for a minority of cases compared to its primary or idiopathic form and provide ground for consideration of common mechanisms of pathogenesis. In this paper we report a case of a 27-year-old Latina woman, a renal transplant recipient with systemic lupus erythematosus (SLE), who developed nephrotic range proteinuria 6 months after transplantation. The patient had recurrent acute renal failure and multiple biopsies were consistent with MCD. However, she lacked any other features of the typical nephrotic syndrome. An angiogram revealed a right external iliac vein stenosis in the region of renal vein anastomosis, which when restored resulted in normalization of creatinine and relief from proteinuria. We report a rare case of MCD developing secondary to iliac vein stenosis in a renal transplant recipient with SLE. Additionally we suggest that, in the event of biopsy-proven MCD presenting as an atypical nephrotic syndrome, alternative or secondary, potentially reversible, causes should be considered and explored.

  4. Minimal Change Disease as a Secondary and Reversible Event of a Renal Transplant Case with Systemic Lupus Erythematosus

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    Elena Gkrouzman

    2015-01-01

    Full Text Available Secondary causes of minimal change disease (MCD account for a minority of cases compared to its primary or idiopathic form and provide ground for consideration of common mechanisms of pathogenesis. In this paper we report a case of a 27-year-old Latina woman, a renal transplant recipient with systemic lupus erythematosus (SLE, who developed nephrotic range proteinuria 6 months after transplantation. The patient had recurrent acute renal failure and multiple biopsies were consistent with MCD. However, she lacked any other features of the typical nephrotic syndrome. An angiogram revealed a right external iliac vein stenosis in the region of renal vein anastomosis, which when restored resulted in normalization of creatinine and relief from proteinuria. We report a rare case of MCD developing secondary to iliac vein stenosis in a renal transplant recipient with SLE. Additionally we suggest that, in the event of biopsy-proven MCD presenting as an atypical nephrotic syndrome, alternative or secondary, potentially reversible, causes should be considered and explored.

  5. [Ultrastructure of glomerular podocyts in the incipient phase of minimal change nephrotic syndrome with thin basement membrane disease].

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    Ogawa, Ryo; Miyoshi, Ken-ichi; Nagao, Tomoaki; Jotoku, Masanori; Irita, Jun; Okura, Takafumi; Higaki, Jitsuo

    2012-01-01

    An 80-year-old woman was referred to the Division of Nephrology at Ehime University Hospital because of leg edema in December 2010. She had been treated with 300 mg of tocopherol for scleroderma since 2007 and treated with 9 mg of prednisolone (PSL) for autoimmune hearing loss since 2010. Due to the occurrence of mild hematuria (5-9/HPF), proteinuria (0.9 g/day) and an increased serum creatinine level (1.31 mg/dL), a renal biopsy was performed. Light microscopy (LM) showed minor abnormality in the glomeruli, and immunohistology showed the absence of deposits of immunoglobulins and complements. Electron microscopy (EM) showed a thin glomerular basement membrane with a limited level of podocyte abnormalities. Due to the findings of intimal thickening of interlobular arteries and subcapsular accumulation of global sclerosis on LM, she was diagnosed with nephrosclerosis and thin basement membrane disease. Four weeks later, her leg edema had increased considerably and urinary protein had increased to 12.4 g/day. The second biopsy showed similar findings in LM and IF as the first biopsy, but EM revealed diffuse foot process effacement. She was diagnosed with minimal change nephrotic syndrome (MCNS) and treated with methylprednisolone pulse therapy followed by 40 mg of oral PSL. Her urinary protein had completely disappeared 6 weeks later. Complete remission with PSL treatment indicates that urinary protein at first renal biopsy was due to MCNS. Our case exhibited podocyte features in the incipient phase of human MCNS.

  6. A patient with minimal change disease and acute focal tubulointerstitial nephritis due to traditional medicine: a case report and small literature review.

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    Lee, Keun-Hyeun; Jeong, Han-Sol; Rhee, Harin

    2014-01-01

    Gongjin-dan (GJD) is a traditional formula that is widely used in Korea and China, and it has been used from 1345 AD in China to improve the circulation between the kidneys and the heart and to prevent all diseases. However, its adverse effects have not yet been reported. We present a patient with minimal change disease and focal tubulointerstitial nephritis associated with GJD. A 72-year-old man visited the clinic for generalized edema 20 days after starting GJD. His serum albumin level was low and nephrotic-range proteinuria was detected. A kidney biopsy showed minimal change disease and acute tubulointerstitial nephritis. After stopping GJD, a spontaneous complete remission was achieved. We discuss the possible pathogenesis of GJD-induced minimal change disease and review the adverse effects of GJD's ingredients and traditional Chinese medicines that can induce proteinuria. We report a new adverse effect of GJD, which might induce increased IL-13 production and an allergic response, leading to minimal change disease and focal tubulointerstitial nephritis.

  7. Nephrotic syndrome; is rituximab the light at the end of the tunnel in the treatment of adult steroid-dependent minimal change disease and focal segmental glomerulosclerosis?

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    Kronbichler, Andreas; Mayer, Gert

    2014-01-01

    Implication for health policy/practice/research/medical education: Reports on patients with steroid-dependent nephrotic syndrome and underlying minimal change disease or focal segmental glomerulosclerosis have shown promising results. There is a strong need for more trials conducted in a prospective, controlled manner to clearly recommend rituximab therapy in this indication on a regular basis.

  8. Nephrotic syndrome due to minimal change disease secondary to spider bite: clinico-pathological case of a non-described complication of latrodectism.

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    Méndez, Gonzalo P; Enos, Daniel; Moreira, José Luis; Alvaredo, Fátima; Oddó, David

    2017-04-01

    The patient was an 18-year-old man who developed nephrotic syndrome after a 'wheat spider' bite (Latrodectus mactans). Due to this atypical manifestation of latrodectism, a renal biopsy was performed showing minimal change disease. The nephrotic syndrome subsided after 1 week without specific treatment. This self-limited evolution suggests that the mechanism of podocyte damage was temporary and potentially mediated by a secondary mechanism of hypersensitivity or direct effect of the α-latrotoxin. The patient did not show signs of relapse in subsequent checkup. This is the first reported case of nephrotic syndrome due to a minimal change lesion secondary to latrodectism.

  9. Nephrotic syndrome due to minimal change disease secondary to spider bite: clinico-pathological case of a non-described complication of latrodectism

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    Enos, Daniel; Moreira, José Luis; Alvaredo, Fátima; Oddó, David

    2017-01-01

    Abstract The patient was an 18-year-old man who developed nephrotic syndrome after a ‘wheat spider’ bite (Latrodectus mactans). Due to this atypical manifestation of latrodectism, a renal biopsy was performed showing minimal change disease. The nephrotic syndrome subsided after 1 week without specific treatment. This self-limited evolution suggests that the mechanism of podocyte damage was temporary and potentially mediated by a secondary mechanism of hypersensitivity or direct effect of the α-latrotoxin. The patient did not show signs of relapse in subsequent checkup. This is the first reported case of nephrotic syndrome due to a minimal change lesion secondary to latrodectism. PMID:28396739

  10. A Higher Frequency of CD4+CXCR5+ T Follicular Helper Cells in Adult Patients with Minimal Change Disease

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    Nan Zhang

    2014-01-01

    Full Text Available Background. T follicular helper (TFH cells are involved in the humoral immune responses. This study is aimed at examining the frequencies of different subsets of CD4+CXCR5+ TFH cells in adult patients with minimal change disease (MCD. Methods. A total of 27 patients and 14 healthy controls (HC were characterized for the levels of sera cytokines, inducible T-cell costimulator (ICOS, and programmed death 1 (PD-1 of positive TFH cells by flow cytometry. The level of sera IL-21 was examined; 24 h urinary protein and eGFR were calculated. The potential correlation between the frequency of different subsets of TFH cells and the values of clinical measures in MCD patients were analyzed. Results. The frequency of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, and CD4+CXCR5+PD-1+ TFH cells and the levels of sera IL-17A, IFN-γ, IL-2, IL-10, IL-4, and IL-21 were significantly higher in MCD patients (P<0.05 than that in the HC group. Furthermore, the percentages of circulating CD4+CXCR5+ TFH cells were negatively correlated with the values of eGFR (r=-0.4849, P<0.05 and the percentages of CD4+CXCR5+PD-1+ TFH cells were correlated positively with the levels of serum IL-21 (r=0.6137, P<0.05 and 24 h urinary protein (r=0.1410, P<0.05 in those patients. Also, the percentages of CD4+CXCR5+ICOS+ TFH cells were correlated positively with the levels of serum IL-21 (r=0.6201, P<0.05 and 24 h urinary protein (r=0.7519, P<0.05. Following standard therapies, the percentages of circulating CD4+CXCR5+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+ TFH cells and the levels of serum IL-21 were significantly reduced, but the levels of serum IL-4 and IL-10 were increased (P<0.05. Conclusions. A higher frequency of CD4+CXCR5+ TFH cells that existed in adult patients with MCD could be new target for intervention of MCD.

  11. Efficacy and safety of leflunomide in treatment of steroid-dependent and steroid-resistant adult onset minimal change disease.

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    Zhou, Junhua; Zhang, Yimiao; Liu, Gang; Li, Jun; Xu, Rong; Huang, Jing

    2013-08-01

    To observe the efficacy and safety of leflunomide combined with prednisone therapy (LEF therapy) in the treatment of patients with adult onset steroid-dependent and steroid-resistant minimal change disease (MCD). 16 MCD patients who had been treated with LEF therapy were retrospectively analyzed. 87.5% (14/16) of the patients were steroid-dependent and 12.5% (2/16) of the patients were steroid-resistant. The initial dose of LEF was 10 - 20 mg/day combined with prednisone 0.25 - 1.0 mg/kg/day, gradually tapering after 8 weeks. Clinical and laboratory data at baseline, 2nd, 4th, 8th, 12th, 24th, and 48th week were analyzed compared with initial course of prednisone monotherapy (PRED monotherapy) and cyclophosphamide combined with prednisone therapy (CTX therapy). All the 16 patients achieved different levels of remission in LEF therapy. 93.8% (15/16) of the patients, including the two steroid-resistant patients, achieved complete remission. During the treatment, 8 patients had adverse effects which could be well tolerated. Compared LEF therapy with PRED monotherapy (n = 16), the dose of prednisone to maintain remission was reduced (from median 22.5 mg/day to median 7.5 mg/day, p = 0.041); relapse rate during the follow-up decreased from 100% to 31.3% (p = 0.002); the median time before relapse increased from 20.3 weeks to 32.5 weeks. Compared LEF therapy with CTX therapy (n = 12), the dose of prednisone to maintain remission was reduced significantly (from median 22.5 mg/day to median 5.0 mg/day, p = 0.003); relapse rate during the follow-up decreased from 100% to 31.3% (p = 0.001); the median time before relapse increased from 11.7 weeks to 32.5 weeks. LEF therapy seems to be effective in steroid-resistant and steroiddependent MCD. This therapy may reduce the amount of prednisone to maintain remission and reduce the relapse rate compared with PRED monothrerapy and CTX therapy. LEF therapy was usually well tolerated.

  12. Bilateral Achilles Tendon Ruptures Associated With Ciprofloxacin Use in the Setting of Minimal Change Disease: Case Report and Review of the Literature.

    Science.gov (United States)

    Kawtharani, Firas; Masrouha, Karim Z; Afeiche, Nadim

    2016-01-01

    Fluoroquinolones are widely used antibiotics; however, numerous side effects have been reported in published studies, including a spectrum of tendinopathies, affecting numerous anatomic sites. Several risk factors have been identified, including advanced age (>60 years), corticosteroid use, renal failure or dialysis, female sex, and nonobesity. We present the case of an elderly male with minimal change disease treated with glucocorticoids and acute kidney injury, who sustained spontaneous nontraumatic bilateral Achilles tendon tears 4 days after initiating ciprofloxacin.

  13. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    Science.gov (United States)

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids.

  14. Responsiveness and minimal clinically important change

    DEFF Research Database (Denmark)

    Christiansen, David Høyrup; Frost, Poul; Falla, Deborah

    2015-01-01

    Study Design A prospective cohort study nested in a randomized controlled trial. Objectives To determine and compare responsiveness and minimal clinically important change of the modified Constant score (CS) and the Oxford Shoulder Score (OSS). Background The OSS and the CS are commonly used...... to assess shoulder outcomes. However, few studies have evaluated the measurement properties of the OSS and CS in terms of responsiveness and minimal clinically important change. Methods The study included 126 patients who reported having difficulty returning to usual activities 8 to 12 weeks after...... were observed for the CS and the OSS. Minimal clinically important change ROC values were 6 points for the OSS and 11 points for the CS, with upper 95% cutoff limits of 12 and 22 points, respectively. Conclusion The CS and the OSS were both suitable for assessing improvement after decompression surgery....

  15. Minimal Change and Bounded Incremental Parsing

    CERN Document Server

    Wiren, M

    1994-01-01

    Ideally, the time that an incremental algorithm uses to process a change should be a function of the size of the change rather than, say, the size of the entire current input. Based on a formalization of ``the set of things changed'' by an incremental modification, this paper investigates how and to what extent it is possible to give such a guarantee for a chart-based parsing framework and discusses the general utility of a minimality notion in incremental processing.

  16. [Minimally Invasive Treatment of Esophageal Benign Diseases].

    Science.gov (United States)

    Inoue, Haruhiro

    2016-07-01

    As a minimally invasive treatment of esophageal achalasia per-oral endoscopic myotomy( POEM) was developed in 2008. More than 1,100 cases of achalasia-related diseases received POEM. Success rate of the procedure was more than 95%(Eckerdt score improvement 3 points and more). No serious( Clavian-Dindo classification III b and more) complication was experienced. These results suggest that POEM becomes a standard minimally invasive treatment for achalasia-related diseases. As an off-shoot of POEM submucosal tumor removal through submucosal tunnel (per-oral endoscopic tumor resection:POET) was developed and safely performed. Best indication of POET is less than 5 cm esophageal leiomyoma. A novel endoscopic treatment of gastroesophageal reflux disease (GERD) was developed. Anti-reflux mucosectomy( ARMS) is nearly circumferential mucosal reduction of gastric cardia mucosa. ARMS is performed in 56 consecutive cases of refractory GERD. No major complications were encountered and excellent clinical results. Best indication of ARMS is a refractory GERD without long sliding hernia. Longest follow-up case is more than 10 years. Minimally invasive treatments for esophageal benign diseases are currently performed by therapeutic endoscopy.

  17. Clinicopathological features, diagnosis, and treatment of IgA nephropathy with minimal change disease related to exposure to mercury-containing cosmetics: a case report
.

    Science.gov (United States)

    Niu, Hong-Xin; Li, Shen-Heng; Li, Hong-Ying; Chen, Yi-Hua; Liu, Wei-Wei; Li, Pei-Lin; Long, Hai-Bo

    2017-04-01

    Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream. The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period. The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
.

  18. Glomerular Immune Deposits Are Predictive of Poor Long-Term Outcome in Patients with Adult Biopsy-Proven Minimal Change Disease: A Cohort Study in Korea.

    Directory of Open Access Journals (Sweden)

    Sung Woo Lee

    Full Text Available There has been little published information on risk factors for poor long-term outcome in adult biopsy-proven minimal change disease (MCD.Data from sixty-three adult, biopsy-proven primary MCD patients treated at a tertiary university hospital between 2003 and 2013 were analyzed. Baseline clinical and pathologic factors were assessed for the associations with composite outcome of creatinine doubling, end stage renal disease, or all-cause mortality.During a median (interquartile 5.0 (2.8-5.0 years, the composite outcome occurred in 11.1% (7/63 of patients. The rate of glomerular immune deposits was 23.8% (15/63. Patients with glomerular immune deposits showed a significantly lower urine protein creatinine ratio than those without deposits (P = 0.033. The rate of non-responders was significantly higher in patients with glomerular immune deposits than in those without deposits (P = 0.033. In patients with deposits, 26.7% (4/15 developed the composite outcome, while only 6.3% (3/48 developed the composite outcome among those without deposits (P = 0.049. In multivariate Cox proportional hazards regression analysis, the presence of glomerular immune deposits was the only factor associated with development of the composite outcome (hazard ratio: 2.310, 95% confidence interval: 1.031-98.579, P = 0.047.Glomerular immune deposits were associated with increased risk of a composite outcome in adult MCD patients. The higher rate of non-responders in patients with deposits might be related to the poor outcome. Future study is needed.

  19. Laparoscopic colonic resection in inflammatory bowel disease: minimal surgery, minimal access and minimal hospital stay.

    LENUS (Irish Health Repository)

    Boyle, E

    2008-11-01

    Laparoscopic surgery for inflammatory bowel disease (IBD) is technically demanding but can offer improved short-term outcomes. The introduction of minimally invasive surgery (MIS) as the default operative approach for IBD, however, may have inherent learning curve-associated disadvantages. We hypothesise that the establishment of MIS as the standard operative approach does not increase patient morbidity as assessed in the initial period of its introduction into a specialised unit, and that it confers earlier postoperative gastrointestinal recovery and reduced hospitalisation compared with conventional open resection.

  20. Post Hoc Analysis of Data from Two Clinical Trials Evaluating the Minimal Clinically Important Change in International Restless Legs Syndrome Sum Score in Patients with Restless Legs Syndrome (Willis-Ekbom Disease).

    Science.gov (United States)

    Ondo, William G; Grieger, Frank; Moran, Kimberly; Kohnen, Ralf; Roth, Thomas

    2016-01-01

    Determine the minimal clinically important change (MCIC), a measure determining the minimum change in scale score perceived as clinically beneficial, for the international restless legs syndrome (IRLS) and restless legs syndrome 6-item questionnaire (RLS-6) in patients with moderate to severe restless legs syndrome (RLS/Willis-Ekbom disease) treated with the rotigotine transdermal system. This post hoc analysis analyzed data from two 6-mo randomized, double-blind, placebo-controlled studies (SP790 [NCT00136045]; SP792 [NCT00135993]) individually and as a pooled analysis in rotigotine-treated patients, with baseline and end of maintenance IRLS and Clinical Global Impressions of change (CGI Item 2) scores available for analysis. An anchor-based approach and receiver operating characteristic (ROC) curves were used to determine the MCIC for the IRLS and RLS-6. We specifically compared "much improved vs minimally improved," "much improved/very much improved vs minimally improved or worse," and "minimally improved or better vs no change or worse" on the CGI-2 using the full analysis set (data as observed). The MCIC IRLS cut-off scores for SP790 and SP792 were similar. Using the pooled SP790+SP792 analysis, the MCIC total IRLS cut-off score (sensitivity, specificity) for "much improved vs minimally improved" was -9 (0.69, 0.66), for "much improved/very much improved vs minimally improved or worse" was -11 (0.81, 0.84), and for "minimally improved or better vs no change or worse" was -9 (0.79, 0.88). MCIC ROC cut-offs were also calculated for each RLS-6 item. In patients with RLS, the MCIC values derived in the current analysis provide a basis for defining meaningful clinical improvement based on changes in the IRLS and RLS-6 following treatment with rotigotine. © 2016 American Academy of Sleep Medicine.

  1. Cultural change and support of waste minimization

    Energy Technology Data Exchange (ETDEWEB)

    Boylan, M.S. [EG and G Idaho, Inc., Idaho Falls, ID (United States). Idaho National Engineering Lab.

    1991-12-31

    The process of bringing a subject like pollution prevention to top of mind awareness, where designed to prevent waste becomes part of business as usual, is called cultural change. With Department of Energy orders and management waste minimization commitment statements on file, the REAL work is just beginning at the Idaho National Engineering Laboratory (INEL); shaping the attitudes of 11,000+ employees. The difficulties of such a task are daunting. The 890 square mile INEL site and in-town support offices mean a huge diversity of employee jobs and waste streams; from cafeteria and auto maintenance wastes to high-level nuclear waste casks. INEL is pursuing a three component cultural change strategy: training, publicity, and public outreach. To meet the intent of DOE orders, all INEL employees are slated to receive pollution prevention orientation training. More technical training is given to targeted groups like purchasing and design engineering. To keep newly learned pollution prevention concepts top-of-mind, extensive site-wide publicity is being developed and conducted, culminating in the April Pollution Prevention Awareness Week coinciding with Earth Day 1992. Finally, news of INEL pollution prevention successes is shared with the public to increase their overall environmental awareness and their knowledge of INEL activities. An important added benefit is the sense of pride the program instills in INEL employees to have their successes displayed so publicly.

  2. Minimally invasive approaches for the treatment of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Marco Zoccali; Alessandro Fichera

    2012-01-01

    Despite significant improvements in medical management of inflammatory bowel disease,many of these patients still require surgery at some point in the course of their disease.Their young age and poor general conditions,worsened by the aggressive medical treatments,make minimally invasive approaches particularly enticing to this patient population.However,the typical inflammatory changes that characterize these diseases have hindered wide diffusion of laparoscopy in this setting,currently mostly pursued in high-volume referral centers,despite accumulating evidences in the literature supporting the benefits of minimally invasive surgery.The largest body of evidence currently available for terminal ileal Crohn's disease shows improved short term outcomes after laparoscopic surgery,with prolonged operative times.For Crohn's colitis,high quality evidence supporting laparoscopic surgery is lacking.Encouraging preliminary results have been obtained with the adoption of laparoscopic restorative total proctocolectomy for the treatment of ulcerative colitis.A consensus about patients' selection and the need for staging has not been reached yet.Despite the lack of conclusive evidence,a wave of enthusiasm is pushing towards less invasive strategies,to further minimize surgical trauma,with single incision laparoscopic surgery being the most realistic future development.

  3. Cerebral infarction in patient with minimal change nephrotic syndrome.

    Science.gov (United States)

    Babu, A; Boddana, P; Robson, S; Ludeman, L

    2013-01-01

    We report a case of 68-year-old Caucasian man who presented with cerebral infarcts secondary to arterial thrombosis associated with nephrotic syndrome. His initial presentation included edema of legs, left hemiparesis, and right-sided cerebellar signs. Investigations with computed tomography and magnetic resonance imaging of brain showed multiple cerebral infarcts in middle cerebral and posterior cerebral artery territory. Blood and urine investigations also showed impaired renal function, hypercholesterolemia, hypoalbuminaemia, and nephrotic range proteinuria. Renal biopsy showed minimal change disease. Cerebral infarcts were treated with antiplatelet agents and nephrotic syndrome was treated with high dose steroids. Patient responded well to the treatment and is all well till date.

  4. Minimally symptomatic hypocalcaemia unmasking celiac disease.

    Science.gov (United States)

    Lazaridis, A; Drosou, M E; Fontalis, A; Prousali, E; Hadwe, S E; Giouleme, O; Petidis, K

    2016-11-01

    Celiac disease is an autoimmune disease of the small intestine which occurs in genetically predisposed people of all ages. A large clinical spectrum of manifestations accompanies the onset of the disease with diarrhoea, flatulence and weight loss being the most common. However, findings like osteoporosis, iron deficiency, anaemia and hypocalcaemia could also insinuate the existence of the disease. We report the case of a 55-year-old man with numbness and tingling of the upper extremities due to hypocalcaemia that proved to be an uncommon case of celiac disease. A non-negligible number of adult patients with celiac disease can present with only minor and subclinical manifestations of the disease. As such, hypocalcaemia may be the sole manifestation of celiac disease. A high index of suspicion is needed for prompt diagnosis. © The Author(s) 2016.

  5. The effect of physical training on patients with rheumatoid arthritis: changes in disease activity, muscle strength and aerobic capacity. A clinically controlled minimized cross-over study

    DEFF Research Database (Denmark)

    Lyngberg, K; Danneskiold-Samsøe, B; Halskov, O

    1988-01-01

    cross-over study the effect of graduated progressive training has been evaluated in 18 RA-patients with moderately active disease. The training was performed twice weekly with aerobic conditioning and strength exercises progressing to strenuous exercises over an 8-week period. The design was a crossover...

  6. Minimalism

    CERN Document Server

    Obendorf, Hartmut

    2009-01-01

    The notion of Minimalism is proposed as a theoretical tool supporting a more differentiated understanding of reduction and thus forms a standpoint that allows definition of aspects of simplicity. This book traces the development of minimalism, defines the four types of minimalism in interaction design, and looks at how to apply it.

  7. The Evolving Role of Rituximab in Adult Minimal Change Glomerulopathy.

    Science.gov (United States)

    Brown, Landon C; Jobson, Meghan A; Payan Schober, Fernanda; Chang, Emily H; Falk, Ronald J; Nachman, Patrick H; Pendergraft, William F

    2017-01-01

    Minimal-change glomerulopathy is defined histologically by the presence of normal glomeruli on light microscopy and diffuse podocyte effacement on electron microscopy. Although effective in children, corticosteroid treatment in adults is more variable and time to response can be prolonged. Data to support rituximab use in adults with corticosteroid-dependent or resistant minimal-change glomerulopathy are limited. Here, we describe the clinical course of adults with corticosteroid-dependent or -resistant minimal-change glomerulopathy who received rituximab. Demographic and clinical data were collected and analyzed from all adult patients with native kidney, biopsy-proven, minimal-change glomerulopathy who were administered rituximab between 2009 and 2014 and cared for at the UNC Kidney Center. Ten patients with corticosteroid-resistant (n = 5) or corticosteroid-dependent (n = 5) idiopathic minimal-change glomerulopathy were treated with rituximab between 2009 and 2014. Rituximab treatment induced remission in all 10 patients with a median time to remission of 2 months. The median time from rituximab to corticosteroid discontinuation was 3.5 months. The median remission time was 29 months and follow-up time was 39.5 months. No serious adverse events attributable to rituximab were observed. Rituximab induced remission in all patients with corticosteroid-dependent or -resistant minimal-change glomerulopathy, and may hold great therapeutic potential with good efficacy and minimal toxicity. Mounting evidence implies that a well-conducted randomized controlled clinical trial using rituximab in adults with minimal-change glomerulopathy in both corticosteroid-resistant and corticosteroid-dependent patients is warranted. © 2017 S. Karger AG, Basel.

  8. Application of minimally invasive technique in surgical treatment of pancreatic diseases

    Directory of Open Access Journals (Sweden)

    ZHANG Yixi

    2015-05-01

    Full Text Available In recent years, with the rapid development of minimally invasive concept, from laparoscopic operation to three-dimension laparoscopic technique and to robotic surgical system, treatment modalities have changed a lot. Pancreatic diseases, including multiple lesions, have different prognoses. An appropriate surgical procedure should be selected while ensuring the radical treatment of disease, so as to minimize the injury to patients and the impairment of organ function. Minimally invasive technique is of great significance in the surgical treatment of pancreatic diseases.

  9. It is possible to classify non-erosive reflux disease (NERD) patients into endoscopically normal groups and minimal change groups by subjective symptoms and responsiveness to rabeprazole -- a report from a study with Japanese patients.

    Science.gov (United States)

    Kusano, Motoyasu; Shirai, Naohito; Yamaguchi, Kanako; Hongo, Michio; Chiba, Tsutomu; Kinoshita, Yoshikazu

    2008-12-01

    The hypothesis that non-erosive reflux disease (NERD) patients comprise various subgroups is gaining popularity. This study was conducted to investigate the possibility of categorizing NERD patients according to symptom types and response to acid-suppressive drug rabeprazole (RPZ) 10 mg/day. NERD patients were classified as grade N (endoscopically normal), M (minimal change), or erosive GERD, and answered a 51-item, yes-or-no questionnaire pre and post-treatment. Compared to erosive GERD, clear differences existed in pretreatment prevalence of symptoms and responsiveness to RPZ in grades N and M; the results suggested stomachaches (especially at night) were significant symptoms in grade N and dysmotility-like symptoms like bloated stomach were significant in grade M while gastroesophageal reflux symptoms were significant in erosive GERD. Clinical significance of classifying NERD was indicated from different symptoms and responsiveness to PPI.

  10. 食管微小病变对胃食管反流病的诊断意义及其临床特点%Diagnostic significance and clinical characteristics of esophageal minimal change in gastroesophageal reflux disease

    Institute of Scientific and Technical Information of China (English)

    陶丽媛; 吕宾; 范一宏; 张璐

    2015-01-01

    Objective To evaluate the diagnostic significance of esophageal minimal change in gastroesophageal reflux disease (GERD) and explore its clinical characteristics.Methods From May to September in 2013,patients with minimal esophageal mucosa changes including esophageal mucosa rough,white secretin adhesion,erythema,edema,increased brittleness,blurring of the Z line or zigzag looking and blurring of paliform blood vessel,or patients with Los Angeles classification (LA) which were identified by endoscopy were enrolled.The subjects received gastroesophageal reflux disease questionnaire (GcrdQ) investigation and the related history were collected.The total score of GerdQ over eight was set as the criteria for GERD diagnosis.The R × C chi-square test was performed for statistical analysis.Results A total of 417 valid questionnaires were completed.Of which,202 cases were in minimal change group,176 were in LA A group and 36 were in LA-B group.The diagnostic rate of GERD in minimal change group was 20.3% (41/202),which was lower than that of LA-A group (74.4%,131/176) and LA-B group (83.3 %,30/36),and the differences were statistically significant (x2 =129.144,P<0.01).The incidences of heartburn in minimal change group,LA A group and LA-B group were 25.7% (52/202),62.5% (110/176) and 86.1% (31/36),respectively.The incidences of reflux were 29.7% (60/202),67.6% (119/176) and 75.0% (27/36),respectively.The incidences of non cardiac chest pain were 5.4% (11/202),22.2% (39/176) and 22.2%(8/36),respectively.The incidences of heartburn,reflux and non cardiac chcst pain of minimal change group were all lower than those of LA A group and LA-B group,and the differences were statistically significant (x2 =75.775,64.120,24.016;all P<0.01).The leading cause of endoscopy examination in minimal change group was abdominal discomfort,which accounted for 49.0%(99/202).The leading causes of endoscopy examination in LA A group and LA-B group were esophageal

  11. [Minimally invasive cardiac surgery for aortic valve disease].

    Science.gov (United States)

    Fujimura, Y; Katoh, T; Hamano, K; Gohra, H; Tsuboi, H; Esato, K

    1998-12-01

    Recent surgical advances leading to good operative results have contributed to the trend to useminimally invasive approaches, even in cardiac surgery. Smaller incisions are clearly more cosmetically acceptable to patients. When using a minimally invasive approach, it is most important to maintain surgical quality without jeopardizing patients. A good operative visual field leads to good surgical results. In the parasternal approach, we use a retractor to harvest an internal thoracic artery in coronary artery bypass surgery. Retracting the sternum upward allows for a good surgical view and permits the use of an arch cannula rather than femoral cannulation. When reoperating for aortic valve repair, the j-sternotomy approach requires less adhesiolysis compared with the traditional full sternotomy. No special technique is necessary to perform aortic valve surgery using the j-sternotomy approach. However, meticulous attention must be paid to avoiding left ventricular air embolisms to prevent postoperative stroke or neurocognitive deficits, especially when utilizing a minimally invasive approach. Transesophageal echo is useful not only for monitoring cardiac function but also for monitoring the persence of air in the left ventricle and atrium. This paper compare as the degree of invasion of minimally invasive cardiac surgery and the traditional full sternotomy. No differences were found in the occurrence of systemic inflammatory response syndrome between patients undergoing minimally invasive cardiac surgery and the traditional technique. Therefore it is concluded that minimally invasive surgery for patients with aortic valve disease may become the standard approach in the near future.

  12. Minimally invasive surgical treatment of valvular heart disease.

    Science.gov (United States)

    Goldstone, Andrew B; Joseph Woo, Y

    2014-01-01

    Cardiac surgery is in the midst of a practice revolution. Traditionally, surgery for valvular heart disease consisted of valve replacement via conventional sternotomy using cardiopulmonary bypass. However, over the past 20 years, the increasing popularity of less-invasive procedures, accompanied by advancements in imaging, surgical instrumentation, and robotic technology, has motivated and enabled surgeons to develop and perform complex cardiac surgical procedures through small incisions, often eliminating the need for sternotomy or cardiopulmonary bypass. In addition to the benefits of improved cosmesis, minimally invasive mitral valve surgery was pioneered with the intent of reducing morbidity, postoperative pain, blood loss, hospital length of stay, and time to return to normal activity. This article reviews the current state-of-the-art of minimally invasive approaches to the surgical treatment of valvular heart disease.

  13. Entransy dissipation minimization for liquid-solid phase change processes

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The liquid-solid phase change process of a simple one-dimensional slab is studied in this paper.By taking entransy dissipation minimization as optimization objective,the optimal external reservoir temperature profiles are derived by using optimal control theory under the condition of a fixed freezing or melting time.The entransy dissipation corresponding to the optimal heat exchange strategies of minimum entransy dissipation is 8/9 of that corresponding to constant reservoir temperature operations,which is independent of all system parameters.The obtained results for entransy dissipation minimization are also compared with those obtained for the optimal heat exchange strategies of minimum entropy generation and constant reservoir temperature operations by numerical examples.The obtained results can provide some theoretical guidelines for the choice of optimal cooling or heating strategy in practical liquid-solid phase change processes.

  14. Minimal change-like glomerular alterations induced by a human plasma factor

    NARCIS (Netherlands)

    Cheung, PK; Klok, PA; Bakker, WW

    1996-01-01

    Circulating factors, including the plasma protease (100KF) described previously, have been suspected to play a role in the pathogenesis of minimal change disease (MCD) for several decades. This factor was able to induce MCD-like alterations in kidney tissue in vitro, i.e. impairment of glomerular po

  15. CHANGES IN RADIOGRAPHIC PARAMETERS AFTER MINIMALLY INVASIVE LUMBAR INTERBODY FUSION

    Directory of Open Access Journals (Sweden)

    Emiliano Vialle

    2015-12-01

    Full Text Available Objective : This study aims to evaluate changes in lumbosacral parameters after minimally invasive lumbar interbody fusion. The secondary aim was to evaluate whether interbody cage shape (crescent shaped or rectangular would influence the results. Method : Retrospective analysis of 70 patients who underwent one or two level lumbar interbody fusion through a minimally invasive posterolateral approach. This included midline preservation and unilateral facetectomy. Pre- and postoperative (three to six months postoperative radiographs were used for measuring lumbar lordosis (LL, segmental lordosis (SL at the level of interbody fusion, and sacral slope (SS. Further analyses divided the patients into Roussouly lumbar subgroups. Results : LL was significantly reduced after surgery (59o:39o, p=0.001 as well as the SS (33.8o:31.2o, p=0.05. SL did not change significantly (11.4:11.06, p=0.85. There were no significant differences when comparing patients who received crescent shaped cage (n=27 and rectangular cage (n=43. Hypolordotic patients (Roussouly types 1 and 2 had radiographic improvement in comparison to normolordotic and hyperlordotic groups (types 3 and 4. Conclusion : Minimally invasive lumbar interbody fusion caused reduction in lumbosacral parameters. Cage shape had no influence on the results.

  16. Sagittal sinus thrombosis in adult minimal change nephrotic syndrome.

    Science.gov (United States)

    Urch, C; Pusey, C D

    1996-02-01

    Nephrotic syndrome causes a hypercoagulable state, leading to both venous and arterial thrombosis. The mechanisms are as yet unclear, but numerous alterations in coagulant and anti-coagulant factors have been reported [Llach et al. 1985, Harris and Ismail 1994]. The most common clinical features in adults are renal vein thrombosis, femoral vein thrombosis and pulmonary embolism, although thrombosis in numerous other arterial and venous sites has been described [Cameron 1984, Llach et al. 1985]. Intracranial thrombosis is rare, although in adult nephrotic syndrome arterial thrombosis is well recognized [Fuh et al. 1991]. We report a patient with minimal change nephrotic syndrome who developed venous sinus thrombosis detected by magnetic resonance (MR) scanning.

  17. Craniocervical junction diseases treatment with a minimally invasive approach

    Directory of Open Access Journals (Sweden)

    Roberto Carlos Díaz

    2014-01-01

    Full Text Available Objective: To introduce a new minimally invasive surgical approach to anterior and lateral craniocervical junction diseases, preserving the midline posterior cervical spine stabilizing elements and reducing the inherent morbidity risk associated with traditional approaches. Methods: We describe a novel surgical technique in four cases of extra-medullary anterolateral compressive lesions located in the occipito-cervical junction, including infections and intra- and/or extradural tumor lesions. We used a paramedian trasmuscular approach through an anatomical muscle corridor using a micro MaXcess(r surgical expandable retractor, with the purpose of reducing morbidity and preserving the posterior muscle and ligamentous tension band. Results: This type of surgical approach provides adequate visualization and microsurgical resection of lesions and reduces muscle manipulation and devascularisation, preserving the tension of the ligament complex. There was minimal blood loss and a decrease in postoperative pain, with rapid start of rehabilitation and shorter hospitalization times. There were no intraoperative complications, and all patients recovered from their pre-operative symptoms. Conclusions: This novel surgical technique is feasible and adequate for the occipito-atlanto-axial complex, with better results than traditional procedures.

  18. Minimal Residual Disease Assessment in Lymphoma: Methods and Applications.

    Science.gov (United States)

    Herrera, Alex F; Armand, Philippe

    2017-09-21

    Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography and computed tomography scans, are imperfect. In other hematologic malignancies, particularly leukemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in many subtypes of lymphoma, the application of MRD assessment techniques, like flow cytometry or polymerase chain reaction-based methods, has been challenging because of the absence of readily detected circulating disease or canonic chromosomal translocations. Newer MRD detection methods that use next-generation sequencing have yielded promising results in a number of lymphoma subtypes, fueling the hope that MRD detection may soon be applicable in clinical practice for most patients with lymphoma. MRD assessment can provide real-time information about tumor burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics, allowing for many possible applications that could significantly affect the care of patients with lymphoma. Further validation of MRD assessment methods, including the incorporation of MRD assessment into clinical trials in patients with lymphoma, will be critical to determine how best to deploy MRD testing in routine practice and whether MRD assessment can ultimately bring us closer to the goal of personalized lymphoma care. In this review article, we describe the methods available for detecting MRD in patients with lymphoma and their relative advantages and disadvantages. We discuss preliminary results supporting the potential applications for MRD testing in the care of patients with lymphoma and strategies for including MRD assessment in lymphoma clinical trials.

  19. Minimally invasive surgery for inflammatory bowel disease: Current perspectives

    Institute of Scientific and Technical Information of China (English)

    Badri Shrestha

    2016-01-01

    The surgical management of complicated and recurrent inflammatory bowel disease(IBD),has remained a challenge.Minimally invasive surgery(MIS),in the form of laparoscopic resections,single port approach and robotic-assisted dissections in the management of IBD,have been examined in several prospective studies.All of them have shown advantages over open surgeryin terms of reduction of physical trauma of surgery,recovery time,better cosmetic outcomes and shorter hospitalization.However,it is important to appreciate that not all patients with IBD are suitable for MIS,so a combination of both open and MIS should be adopted to achieve optimum outcomes.A review on this subject performed by Neumann et al in this issue of World Journal of Gastrointestinal Pharmacology and Therapeutics have provided evidence in support of the contemporary practice of MIS in the management of IBD and the accompanying commentary further critically evaluates their application in clinical practice.

  20. Primary Sjögren’s syndrome with minimal change disease—A case report

    Directory of Open Access Journals (Sweden)

    Mei-Li Yang

    2011-05-01

    Full Text Available Glomerular involvement in patients with primary Sjögren’s syndrome (pSS has rarely been reported. Among them, membranoproliferative glomerulonephritis and membranous nephropathy are the more common types. We report a middle-aged female presenting concurrently with nephrotic syndrome and microscopic hematuria, and her pSS was diagnosed by positive anti-Ro (SSA/anti-La (SSB autoantibodies, dry mouth, severely diffuse impaired function of both bilateral parotid and submandibular glands, and a positive Schirmer test. Renal pathology revealed minimal change disease and thin basement membrane nephropathy. The patient’s nephrotic syndrome resolved after treatment with corticosteroids. To our knowledge, this is the first report of minimal change disease in a patient with pSS.

  1. Monitoring of minimal residual disease in leukemia, advantages and pitfalls.

    Science.gov (United States)

    Cazzaniga, Giovanni; Gaipa, Giuseppe; Rossi, Vincenzo; Biondi, Andrea

    2006-01-01

    The term 'minimal residual disease' (MRD) defines the level of disease detectable in patients in clinical remission during therapy, below the detection limit of conventional methods. Very sensitive methods can be used, able to identify one leukemic cell out of 10,000 normal lymphocytes. In vivo measurements of leukemia cytoreduction reflect the combined effect of clinical and biological variables, thus providing direct information on the effectiveness of treatment in each patient. Thus, these methods can potentially be used for tailoring treatment and personalize the cure. Although MRD studies are becoming an integral part of the modern management of patients with leukemia, several parameters are critical for the application and interpretation of MRD studies, including therapeutic context, timing of sampling, target genes and sensitivity of the polymerase chain reaction (PCR) assay, inter-laboratory standardization (particularly relevant in multicenter studies), selection of patients, retrospective or prospective nature of the study. Methodologies and pitfalls as well as results of clinical uses of MRD will be reviewed in this article by selecting significant examples of its clinical impact in the management of patients with leukemia.

  2. Minimal doses of hydroxyurea for sickle cell disease

    Directory of Open Access Journals (Sweden)

    C.S.P. Lima

    1997-08-01

    Full Text Available The use of hydroxyurea (HU can improve the clinical course of sickle cell disease. However, several features of HU treatment remain unclear, including the predictability of drug response and determination of adequate doses, considering positive responses and minimal side effects. In order to identify adequate doses of HU for treatment of sickle cell disease, 10 patients, 8 with sickle cell anemia and 2 with Sß thalassemia (8SS, 2Sß, were studied for a period of 6 to 19 months in an open label dose escalation trial (10 to 20 mg kg-1 day-1. Hemoglobin (Hb, fetal hemoglobin (Hb F and mean corpuscular volume (MCV values and reticulocyte, neutrophil and platelet counts were performed every two weeks during the increase of the HU dose and every 4 weeks when the maximum HU dose was established. Reduction in the number of vasoocclusive episodes was also considered in order to evaluate the efficiency of the treatment. The final Hb and Hb F concentrations, and MCV values were significantly higher than the initial values, while the final reticulocyte and neutrophil counts were significantly lower. There was an improvement in the concentration of Hb (range: 0.7-2.0 g/dl at 15 mg HU kg-1 day-1, but this concentration did not increase significantly when the HU dose was raised to 20 mg kg-1 day-1. The concentration of Hb F increased significantly (range: 1.0-18.1% when 15 mg HU was used, and continued to increase when the dose was raised to 20 mg kg-1 day-1. The final MCV values increased 11-28 fl (femtoliters. However, reticulocyte (range: 51-205 x 109/l and neutrophil counts (range: 9.5-1.3 x 109/l obtained at this dose were significantly lower than those obtained with 15 mg kg-1 day-1. All patients reported a decrease in frequency or severity of vasoocclusive episodes. These results suggest that a hydroxyurea dose of 15 mg kg-1 day-1 seems to be adequate for treatment of sickle cell disease in view of the minimal side effects observed and the improvement

  3. Minimal change disease caused by mercury-containing cosmetics: 7 cases report%七例化妆品汞中毒相关肾小球微小病变病报告

    Institute of Scientific and Technical Information of China (English)

    王艳艳; 谌贻璞; 王国勤; 董鸿瑞; 孙丽君; 王长江; 唐艳玲; 程虹

    2013-01-01

    目的 探讨化妆品汞中毒相关微小病变病(MCD)的临床病理表现及治疗方法.方法 回顾性分析首都医科大学附属北京安贞医院肾内科确诊的7例化妆品汞中毒相关MCD患者的临床及病理资料.结果 7例患者均为女性,平均年龄37.2岁,均曾间断使用美白祛斑化妆品.7例患者尿汞均明显升高,为正常值的2.2~ 59.1倍.其中2例患者化妆品的汞检测,汞浓度为国家规定化妆品汞限量的1000多倍.7例患者均表现为肾病综合征,肾组织病理检查符合MCD诊断.经停用含汞化妆品,并予糖皮质激素及驱汞治疗,7例患者肾病综合征均在应用激素后1~2个月完全缓解.结论 对非少年儿童及老年的MCD女性患者,要注意询问美白祛斑化妆品的应用史,检测尿和血汞浓度,以早期发现化妆品汞中毒相关MCD.%Objective To enhance the understanding of mercury poisoning related minimal change disease (MP-MCD).Methods A retrospective analysis about the clinical,laboratory and pathological manifestations,diagnosis,treatment and outcome of 7 patients with MP-MCD caused by skin-lightening cosmetics were conducted.Results All of the 7 patients were female with mean age 37.2 years.One patient had intermittently used skin-lightening cosmetics for 15 years and the other 6 patients continuously used the cosmetics for 2 ~ 6 months.Urine mercury levels of the 7 patients were significantly increased,reaching to 2.2 ~ 59.1 times of the normal value.The mercury content of 2 cosmetics used by patients was 1200 to 1560 times the mercury limit in cosmetics set by the government in 1987.Seven patients all presented as nephrotic syndrome,and all had MCD on renal biopsy.After the diagnosis of MP-MCD was confirmed,all the patients stopped using the mercurycontain cosmetics and accepted corticosteroid and chelation therapy.The nephrotic syndrome underwent complete remission after 1 ~ 2 months of therapy.Urine mercury levels in the 5 patients

  4. Optimal time-points for minimal residual disease monitoring change on the basis of the method used in patients with acute myeloid leukemia who underwent allogeneic stem cell transplantation: a comparison between multiparameter flow cytometry and Wilms' tumor 1 expression.

    Science.gov (United States)

    Rossi, Giovanni; Carella, Angelo Michele; Minervini, Maria Marta; di Nardo, Francesco; Waure, Chiara de; Greco, Michele Mario; Merla, Emanuela; Cillis, Giovanni Pio de; Di Renzo, Nicola; Melpignano, Angela; Capalbo, Silvana; Palumbo, Gaetano; Pisapia, Giovanni; Cascavilla, Nicola

    2015-02-01

    Minimal residual disease (MRD) of 30 adult AML patients was monitored by multiparameter flow cytometry (MFC) and WT1 expression before and after allogeneic stem cell transplantation (allo-SCT). Diagnostic performance of pre-transplant MRD measured by MFC was higher than that obtained by WT1 expression. Comparable results were displayed at day +30 post-transplant, while better values by WT1 compared to MFC were found at day +90. Positive MRD by MFC predicted a shorter disease free survival (DFS) before and 1 month after transplant (p=0.006 and p=0.005), while only high WT1 levels at 1 month from the transplant significantly impacted on DFS (p=0.010). Our results support the idea that MRD monitoring by MFC should be suggested before and 30 days after the transplant, while WT1 expression should be preferred after this procedure. The assessment of MRD at day +30 from allo-SCT is recommended as post transplant check-point for the predictive role displayed, independently of the method used.

  5. [Cerebral venous thrombosis in minimal change nephrotic syndrome].

    Science.gov (United States)

    Hirata, M; Kuroda, M; Koni, I

    1999-06-01

    A 46-year old man presented with an eight-day history of edema and was found to be nephrotic, with a plasma albumin level of 1.1 g/dl and urine protein excretion of 13.3 g/24 hrs. The level of plasma creatinine was normal at 1.0 mg/dl. A finding of renal biopsy was consistent with minimal change glomerulopathy. On the 6th hospital day, he suddenly developed a severe headache and was noted to have bilateral papilledema. Lumbar puncture revealed an opening pressure of 250 mm of water. Magnetic resonance venography showed an irregular flow in the superior sagittal sinus and right transverse sinus, a finding consistent with thrombus. The diagnosis of cerebral venous thrombosis was made, and the patient was given both Warfarin 2 mg/day and prednisolone 60 mg/day. A complete recovery from nephrotic syndrome was achieved within eight weeks. Nephrotic syndrome causes a hypercoagulable state, leading to both venous and arterial thrombosis. The most common clinical features are renal vein thrombosis, femoral vein thrombosis, and pulmonary embolism, however, cerebral venous sinus thrombosis is rare in patients with nephrotic syndrome. It is important to be aware of this complication, since prompt treatment with anticoagulation and control of nephrotic syndrome can lead to a successful outcome.

  6. Climate change and forest diseases

    Science.gov (United States)

    R.N. Sturrock; Susan Frankel; A. V. Brown; Paul Hennon; J. T. Kliejunas; K. J. Lewis; J. J. Worrall; A. J. Woods

    2011-01-01

    As climate changes, the effects of forest diseases on forest ecosystems will change. We review knowledge of relationships between climate variables and several forest diseases, as well as current evidence of how climate, host and pathogen interactions are responding or might respond to climate change. Many forests can be managed to both adapt to climate change and...

  7. Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Silva Sandra

    2007-10-01

    Full Text Available Abstract Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking. We report a case of a 53-year-old man who developed nephrotic syndrome 142 days after allogeneic stem cell transplantation for acute myeloid leukaemia. Onset of nephrotic syndrome occurred after reduction of immunosuppressants and was accompanied by manifestations of chronic graft-versus-host disease. Histological examination of the kidney was consistent with Minimal Change Disease. After treatment with prednisolone and mycophenolate mofetil he had complete remission of proteinuria and improvement of graft-versus-host disease. Eighteen months after transplantation the patient keeps haematological remission and normal renal function, without proteinuria. Since patients with chronic graft-versus-host disease might be considered at risk for development of nephrotic syndrome, careful monitoring of renal parameters, namely proteinuria, is advisable.

  8. Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review.

    Science.gov (United States)

    Silva, Sandra; Maximino, José; Henrique, Rui; Paiva, Ana; Baldaia, Jorge; Campilho, Fernando; Pimentel, Pedro; Loureiro, Alfredo

    2007-10-30

    Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking.We report a case of a 53-year-old man who developed nephrotic syndrome 142 days after allogeneic stem cell transplantation for acute myeloid leukaemia. Onset of nephrotic syndrome occurred after reduction of immunosuppressants and was accompanied by manifestations of chronic graft-versus-host disease. Histological examination of the kidney was consistent with Minimal Change Disease. After treatment with prednisolone and mycophenolate mofetil he had complete remission of proteinuria and improvement of graft-versus-host disease. Eighteen months after transplantation the patient keeps haematological remission and normal renal function, without proteinuria.Since patients with chronic graft-versus-host disease might be considered at risk for development of nephrotic syndrome, careful monitoring of renal parameters, namely proteinuria, is advisable.

  9. Concurrence of Bartter syndrome and minimal change nephrotic syndrome

    Institute of Scientific and Technical Information of China (English)

    SHEN Hui-jun; DAI Yu-wen; MAO Jian-hua; LIU Ai-min

    2009-01-01

    @@ Nephrotic syndrome(NS)is a common disease in children with a group of symptoms including heavy proteinuria(≥50 mg/kg per 24 hours),hypoalbuminaemia,hypercholesterolaemia and edema.Bartter syndrome(BS)is a clinically and genetically heterogenous kidney disease characterized by hypokalemia,hypochloremic metabolic alkalosis,obvious increase of rennin,angiotesin II,and normal blood pressure.

  10. Influence of low birth weight on minimal change nephrotic syndrome in children, including a meta-analysis

    NARCIS (Netherlands)

    N. Teeninga (Nynke); M.F. Schreuder (Michiel); A. Bökenkamp (Arend); H.A.D.V.D. Waal; J.A.E.V. Wijk

    2008-01-01

    textabstractBackground. Low birth weight (LBW) has been shown to lead to a low nephron endowment with subsequent glomerular hyperfiltration. Additional renal disease can therefore be expected to have a more severe course. Minimal change nephrotic syndrome (MCNS) is a common chronic illness in childh

  11. Long-term outcome after cyclophosphamide treatment in children with steroid-dependent and frequently relapsing minimal change nephrotic syndrome.

    NARCIS (Netherlands)

    Kyrieleis, H.A.; Levtchenko, E.N.; Wetzels, J.F.M.

    2007-01-01

    BACKGROUND: Seventy percent of children with minimal change nephrotic syndrome (MCNS) have a steroid-dependent or frequent relapsing course of the disease, and most are treated with cyclophosphamide. We describe the clinical course of children with biopsy-proven MCNS treated with cyclophosphamide fo

  12. Surgical and minimally invasive treatments for Peyronie's disease.

    Science.gov (United States)

    Kumar, Rajeev; Nehra, Ajay

    2009-11-01

    Peyronie's disease is a relatively common condition affecting men with estimates of current prevalent rates ranging from 1 to 4%. However, it has no clear management protocols, primarily due to a lack of high quality evidence in support of treatment options. This article aims to review the recent published literature on management strategies for Peyronie's disease. Intralesional interferon therapy has shown to result in significant improvement in Peyronie's disease plaques and curvature. Intralesional verapamil and extracorporeal shock wave therapy may help retard the progression of disease. Acellular, extracellular matrix-based grafts provide durable long-term satisfactory results in men requiring complex reconstruction. Further clinical trails are warranted to evaluate the role of oral systemic therapies for early Peyronie's disease. Injection therapy, primarily with interferon, seems to be the most promising treatment for early stage Peyronie's disease. For men with established plaques, surgery using either plication or grafts forms the mainstay. There is an increasing trend to use autologous graft material that is commercially available and avoids donor site complications from autologous tissue.

  13. Minimal clinically important difference in Parkinson's disease as assessed in pivotal trials of pramipexole extended release.

    Science.gov (United States)

    Hauser, Robert A; Gordon, Mark Forrest; Mizuno, Yoshikuni; Poewe, Werner; Barone, Paolo; Schapira, Anthony H; Rascol, Olivier; Debieuvre, Catherine; Fräßdorf, Mandy

    2014-01-01

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (pramipexole ER, pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  14. Segmentation of Arteries in Minimally Invasive Surgery Using Change Detection

    Science.gov (United States)

    Akbari, Hamed; Kosugi, Yukio; Kojima, Kazuyuki

    In laparoscopic surgery, the lack of tactile sensation and 3D visual feedback make it difficult to identify the position of a blood vessel intraoperatively. An unintentional partial tear or complete rupture of a blood vessel may result in a serious complication; moreover, if the surgeon cannot manage this situation, open surgery will be necessary. Differentiation of arteries from veins and other structures and the ability to independently detect them has a variety of applications in surgical procedures involving the head, neck, lung, heart, abdomen, and extremities. We have used the artery's pulsatile movement to detect and differentiate arteries from veins. The algorithm for change detection in this study uses edge detection for unsupervised image registration. Changed regions are identified by subtracting the systolic and diastolic images. As a post-processing step, region properties, including color average, area, major and minor axis lengths, perimeter, and solidity, are used as inputs of the LVQ (Learning Vector Quantization) network. The output results in two object classes: arteries and non-artery regions. After post-processing, arteries can be detected in the laparoscopic field. The registration method used here is evaluated in comparison with other linear and nonlinear elastic methods. The performance of this method is evaluated for the detection of arteries in several laparoscopic surgeries on an animal model and on eleven human patients. The performance evaluation criteria are based on false negative and false positive rates. This algorithm is able to detect artery regions, even in cases where the arteries are obscured by other tissues.

  15. Minimal change nephrotic syndrome associated with invasive thymoma: a case report with literature review.

    Science.gov (United States)

    Long, Quan; Wu, Ping; Jiang, Gengru; Zhu, Chun

    2014-04-01

    The present report describes a case of nephrotic syndrome (NS) with invasive thymoma. A male patient was hospitalized for severe edema with reduced urine output. He had a history of thymectomy and radiotherapy because of invasive thymoma 4 years before the development of NS. Renal biopsy displayed minimal change disease (MCD). Although imaging study showed probably recurrent sign of invasive thymoma, the patient still received steroid monotherapy for ~ 9 months and he got partial remission of NS at the 8th week. Therefore, we suggest that MCD should be taken into account as a pathological lesion type in old NS patients with thymoma. In spite of longer remission time, steroid monotherapy and combination therapy with immunosuppressant are effective for thymoma-associated MCD.

  16. Managing Obesity in Pregnancy: A Change in Focus from Harm Minimization to Prevention.

    Science.gov (United States)

    Grivell, Rosalie M; O'Brien, Cecelia M; Dodd, Jodie M

    2016-03-01

    Obesity represents a significant global health problem, contributing to the overall burden of disease worldwide and a 30% increase in cost of health care provision. Over 50% of women who enter pregnancy are classified as overweight or obese resulting in short and long term effects on maternal and child health outcomes.There is a substantial amount of literature focusing on interventions in the antenatal period have been associated with modest changes in weight gain during pregnancy. There has been little effect on clinical pregnancy and birth outcomes.The article discusses the evidence supporting the shift from harm minimization via antenatal intervention, to one of prevention by targeting the time prior to conception to optimize maternal weight. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Minimally Invasive Procedures - Direct and Video-Assisted Forms in the Treatment of Heart Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Josué Viana Neto, E-mail: jvcn@uol.com.br [Instituto do Coração do Nordeste (INCONE), Fortaleza, CE (Brazil); Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil); Melo, Emanuel Carvalho; Silva, Juliana Fernandes [Instituto do Coração do Nordeste (INCONE), Fortaleza, CE (Brazil); Rebouças, Leonardo Lemos; Corrêa, Larissa Chagas; Germano, Amanda de Queiroz [Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil); Machado, João José Aquino [Instituto do Coração do Nordeste (INCONE), Fortaleza, CE (Brazil)

    2014-03-15

    Minimally invasive cardiovascular procedures have been progressively used in heart surgery. To describe the techniques and immediate results of minimally invasive procedures in 5 years. Prospective and descriptive study in which 102 patients were submitted to minimally invasive procedures in direct and video-assisted forms. Clinical and surgical variables were evaluated as well as the in hospital follow-up of the patients. Fourteen patients were operated through the direct form and 88 through the video-assisted form. Between minimally invasive procedures in direct form, 13 had aortic valve disease. Between minimally invasive procedures in video-assisted forms, 43 had mitral valve disease, 41 atrial septal defect and four tumors. In relation to mitral valve disease, we replaced 26 and reconstructed 17 valves. Aortic clamp, extracorporeal and procedure times were, respectively, 91,6 ± 21,8, 112,7 ± 27,9 e 247,1 ± 20,3 minutes in minimally invasive procedures in direct form. Between minimally invasive procedures in video-assisted forms, 71,6 ± 29, 99,7 ± 32,6 e 226,1 ± 42,7 minutes. Considering intensive care and hospitalization times, these were 41,1 ± 14,7 hours and 4,6 ± 2 days in minimally invasive procedures in direct and 36,8 ± 16,3 hours and 4,3 ± 1,9 days in minimally invasive procedures in video-assisted forms procedures. Minimally invasive procedures were used in two forms - direct and video-assisted - with safety in the surgical treatment of video-assisted, atrial septal defect and tumors of the heart. These procedures seem to result in longer surgical variables. However, hospital recuperation was faster, independent of the access or pathology.

  18. Dissemination and clinical impact of minimal metastatic disease in gastrointestinal cancer

    NARCIS (Netherlands)

    Doekhie, Fania Shahanaaz

    2009-01-01

    In this thesis, we assess whether gastric and colorectal cancer (CRC) patients with minimal metastatic disease at the time of surgery who are at risk for disease recurrence, can be identified by detection of occult tumor cells (OTC) in lymph nodes or bone marrow or by analyzing the primary tumor for

  19. [Skin changes in rheumatic diseases].

    Science.gov (United States)

    Dobrić, Ivan

    2005-01-01

    The Intruduction includes those eflorescences that might be useful for diagnostics in rheumatology. Further in the text we have described four groups of rheumatic disorders. The first group: rheumatic diseases (lupus erythematosus, dermatomyositis, systemic scleroderma, the mixed connective tissue disease, allergic vasculitis, polyarteritis) which are the most common from the dermatological point of view. The second group: rheumatic diseases (Wegener's granulomatosis, rheumatoid arthritis, Sjögren, Reiter and Behçet syndrome and Kawasaki's disease) which are rarely of interest to our dermatologists. In this group there is also psoriatic arthritis, which is not rare in dermatology but its diagnostics and treatment belong to rheumatologists' field of expertise. The third group: infections (rheumatic fever, diseminated gonococcal infection, subacute bacterial endocarditis, Lyme disesease). The fourth group: metabolic disorders (gout). The diseases of the first group are described completely. In the second, third and fourth group of the diseases we have included only skin changes.

  20. Conformational Transitions and Glycation of Serum Albumin in Patients with Minimal-Change Glomerulopathy

    Science.gov (United States)

    Hong, Sae Yong; Lee, Eun Young; Yang, Jong Oh; Kim, Tae Yeong; Kim, Eun Hee; Cheong, Mi Young; Kim, Soo Hyun; Cheong, Chae Joon

    2004-01-01

    Background There has been a lack of study on the structural changes of serum albumin in patients with minimal change disease (MCD). To determine whether glycation and/or conformational transitions of albumin are involved in the pathogenesis of albuminuria, nine patients with MCD were enrolled in a prospective follow-up study for comparison of these parameters in serum albumin during the remission and relapse of nephrotic syndrome. Methods Circular dichroism measurements were made with purified albumin. Ellipticities at each wavelength were transformed to mean residue ellipticity. Monosaccharide composition was analyzed by high-pH anion-exchange chromatography with pulsed amperometric detection. Results There was no difference in the proportions of α-helix, β-conformation, and β-turn of albumin between the sera of control patients and those with nephrotic syndrome. However, the proportion of the random configuration was slightly higher in the plasma albumin of patients in relapse than in those in remission. The proportion of the random configuration was lower in the albumin of the serum than in the urine of patients with nephrotic syndrome, but there was no difference in the proportions of α-helix, β-conformation, and β-turn of albumin between their plasma and urine. Conclusion Our results suggest that conformational changes in albumin are involved in albuminuria in patients with MCD. PMID:15481604

  1. Thyroid nodules with minimal cystic changes have a low risk of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Na, Dong Gyu; Kim, Dae Sik; Kim, Soo Jin [Dept. of Radiology, Human Medical Imaging and Intervention Center, Seoul (Korea, Republic of); Kim, Ji Hoon [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    The goal of this study was to determine the risk of malignancy of thyroid nodules with minimal cystic changes. A total of consecutive 1,000 thyroid nodules (≥1 cm) with final diagnoses from two institutions were included in this study. The risk of malignancy of thyroid nodules was analyzed according to the internal content, which was categorized as purely solid, minimally cystic (cystic changes ≤10%), and partially cystic (cystic changes >10%). We also assessed the risk of malignancy of nodules with minimal cystic changes depending on echogenicity and presence of any suspicious ultrasonografic (US) features. The overall frequency of purely solid, minimally cystic, and partially cystic nodules was 730/1,000 (73%), 61/1,000 (6.1%), and 209/1,000 (20.9%), respectively, with risks of malignancy of 14.8% (108/730), 3.3% (2/61), and 3.3% (7/209), respectively. The risk of malignancy of nodules with minimal cystic changes was significantly lower than that of purely solid nodules (P=0.013). The risk of malignancy of nodules with minimal cystic changes was also lower than that of purely solid nodules in the group of hypoechoic nodules (P=0.063) and in the group of nodules with suspicious US features (P=0.028), but was not significantly different from that of partially cystic nodules regardless of echogenicity or the presence of suspicious US features (P≥0.652). Thyroid nodules with minimal cystic changes have a low risk of malignancy, similar to that of partially cystic nodules regardless of echogenicity or the presence of suspicious US features. The US lexicon could define solid nodules as nodules with purely solid internal content in order to enhance the accuracy of estimated risks of malignancy.

  2. Climate change and allergic disease.

    Science.gov (United States)

    Shea, Katherine M; Truckner, Robert T; Weber, Richard W; Peden, David B

    2008-09-01

    Climate change is potentially the largest global threat to human health ever encountered. The earth is warming, the warming is accelerating, and human actions are largely responsible. If current emissions and land use trends continue unchecked, the next generations will face more injury, disease, and death related to natural disasters and heat waves, higher rates of climate-related infections, and wide-spread malnutrition, as well as more allergic and air pollution-related morbidity and mortality. This review highlights links between global climate change and anticipated increases in prevalence and severity of asthma and related allergic disease mediated through worsening ambient air pollution and altered local and regional pollen production. The pattern of change will vary regionally depending on latitude, altitude, rainfall and storms, land-use patterns, urbanization, transportation, and energy production. The magnitude of climate change and related increases in allergic disease will be affected by how aggressively greenhouse gas mitigation strategies are pursued, but at best an average warming of 1 to 2 degrees C is certain this century. Thus, anticipation of a higher allergic disease burden will affect clinical practice as well as public health planning. A number of practical primary and secondary prevention strategies are suggested at the end of the review to assist in meeting this unprecedented public health challenge.

  3. Gross hepatomegaly due to ‘minimal change’ liver disease in a young female alcoholic

    OpenAIRE

    Majumdar, Sisir K.; Shaw, G K; Aps, E. J.; Thomson, Allan D.; O Gorman, P.; Bugler, J.

    1982-01-01

    The case of a grossly enlarged liver due to alcohol excess in a woman of 21 is reported. This case further demonstrates that a chronic alcoholic can have gross hepatomegaly with normal histology and normal liver function tests. The possible pathogenetic basis of ethanol-induced hepatomegaly (‘minimal change’ liver disease) is discussed.

  4. 77 FR 76050 - Public Workshop on Minimal Residual Disease; Public Workshop

    Science.gov (United States)

    2012-12-26

    ...The Food and Drug Administration (FDA), in cosponsorship with the American Society of Clinical Oncology, is announcing a public workshop that will provide a forum for discussion of extending the qualification of minimal residual disease (MRD) detection as a prognostic biomarker to an efficacy/response biomarker in evaluating new drugs for the treatment of acute myeloid leukemia (AML). Our......

  5. 77 FR 76051 - Public Workshop on Minimal Residual Disease; Public Workshop

    Science.gov (United States)

    2012-12-26

    ...The Food and Drug Administration (FDA), in cosponsorship with the American Society of Clinical Oncology, is announcing a public workshop that will provide a forum for discussion of extending the qualification of minimal residual disease (MRD) detection as a prognostic biomarker to that of an efficacy/response biomarker in evaluating new drugs for the treatment of chronic lymphocytic leukemia......

  6. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Denys, B.; van der Sluijs-Gelling, A. J.; Homburg, C.; van der Schoot, C. E.; de Haas, V.; Philippe, J.; Pieters, R.; van Dongen, J. J. M.; van der Velden, V. H. J.

    2013-01-01

    Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are ob

  7. Minimal residual disease diagnostics in acute lymphoblastic leukemia: Need for sensitive, fast, and standardized technologies

    NARCIS (Netherlands)

    J.J.M. van Dongen (Jacques); V.H.J. van der Velden (Vincent); M. Brüggemann (Monika); A. Orfao (Alberto)

    2015-01-01

    textabstractMonitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group

  8. [Modern minimal invasive combine surgical approach in varicose disease of lower limbs patients].

    Science.gov (United States)

    Berehovyĭ, O V; Hur'iev, A M; Kisel'ov, V O; Hrepachevs'kyĭ, V Ie; Sholokh, V M; Bon', D O

    2012-07-01

    The analysis of combine endovenous laser coagulations in 167 patients, treated from 2007 to 2011 with different types of chronic venous insufficiency of superficial veins of lower limbs varicous disease were analysed. The high efficiency of minimal invasive combine surgical treatment, using high energetic diode laser Dornier Medilas Fibertom with wave length of 940 nm was done.

  9. The treatment of relapse in adults with minimal change nephrotic syndrome: Myths and facts

    Directory of Open Access Journals (Sweden)

    Mazin M.T. Shigidi

    2011-01-01

    Full Text Available Few controlled trials have studied the treatment of relapse in adults with minimal change disease. Repeated courses of steroids, cyclophosphamide, cyclosporine and even mycophe-nolate mofetil (MMF, all seem to play a role. The aim of this study was to review and critically analyze the literature regarding the use of immunosuppressive therapy for the treatment of relapse in adults with minimal change nephrotic syndrome (MCNS. An intensive search was done for pub-lished trials in the general medical database. Retrieved studies were further sorted according to spe-cific inclusion and exclusion criteria. Selected trials were critically analyzed and evaluated using the Oxford Centre for Evidence-based Medicine Levels of Evidence, 2009 rating. Six studies were selected and systematically reviewed. One randomized controlled trial compared the use of cyclo-phosphamide versus cyclosporine (11 adults and showed that both drugs are effective in the treatment of frequent relapses [level 1b evidence (grade B]. Three trials (total of 20 patients tested the use of cyclosporine therapy and showed that cyclosporine, though effective in the treatment of relapse, is associated with an extremely high incidence of subsequent relapses following drug with-drawal. A long-term follow-up cross-sectional study of 95 patients, with 69 relapsers, supported the use of steroids in the treatment of occasional relapses [level 2c evidence (grade C]. One case series described the benefits of MMF [level 4 evidence (grade C]. Most of the the clinical trials studied were heterogeneous, underpowered by small adult populations, open-labelled, non-randomized, with poor statistical analysis, validity and utility. We conclude that there is poor evidence that successful treatment of the first relapse of adult MCNS can be achieved with a second course of steroids or cyclosporine. Also, there is weak evidence that frequent relapses can be treated using cyclophosphamide, cyclosporine or MMF

  10. Glomerular involution in children with frequently relapsing minimal change nephrotic syndrome: an unrecognized form of glomerulosclerosis?

    NARCIS (Netherlands)

    Dijkman, H.B.P.M.; Wetzels, J.F.M.; Gemmink, J.H.; Baede, J.; Levtchenko, E.N.; Steenbergen, E.

    2007-01-01

    Global glomerulosclerosis can be divided in the vascular (obsolescent) type and the glomerulopathic (solidified) type. In biopsies from children with recurrent nephrotic syndrome owing to minimal change nephropathy (MCN), we noticed small, globally sclerosed glomeruli that appeared to be distinct fr

  11. Minimally invasive surgery for inflammatory bowel disease: Review of current developments and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Philipp--Alexander Neumann; Emile Rijcken

    2016-01-01

    Patients with inflammatory bowel disease(IBD)com-prise a population of patients that have a high likelihood of both surgical treatment at a young age and repetitive operative interventions.Therefore surgical procedures need to aim at minimizing operative trauma with bestpostoperative recovery.Minimally invasive techniques have been one of the major advancements in surgery in the last decades and are nowadays almost routinely performed in colorectal resections irrespective of underlying disease.However due to special disease related characteristics such as bowel stenosis,interen-teric fistula,abscesses,malnutrition,repetitive sur-geries,or immunosuppressive medications,patients with IBD represent a special cohort with specific needs for surgery.This review summarizes current evidence of minimally invasive surgery for patients with Crohn’s disease or ulcerative colitis and gives an outlook on the future perspective of technical advances in this highly moving field with its latest developments in single port surgery,robotics and trans-anal techniques.

  12. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Hagemeister, F.B.; Cabanillas, F.; Velasquez, W.S.; Meistrich, M.L.; Liang, J.C.; McLaughlin, P.; Redman, J.R.; Romaguera, J.E.; Rodriguez, M.A.; Swan, F. Jr. (Univ. of Texas, M.D. Anderson Cancer Center, Houston (USA))

    1990-12-01

    Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease.

  13. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  14. New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

    Science.gov (United States)

    Rein, Lindsay Am; Sung, Anthony D; Rizzieri, David A

    2013-02-01

    Minimal residual disease (MRD) is a complex topic that has been studied extensively in hematologic malignancies given its clinical implications related to prognosis. However, methods to monitor and treat MRD, especially after stem cell transplantation, are not well defined and vary in different disease processes. Alternative transplant strategies, such as reduced-intensity conditioning, have altered the way we assess and address MRD after transplantation. Development of new diagnostic tools have allowed for higher sensitivity and specificity of testing. Both targeted chemotherapeutic agents and immunotherapies have been developed to treat MRD in hopes of improving patient outcomes. This article aims to address ways to define and manipulate MRD specifically after stem cell transplantation.

  15. Why is there resistance to change and how can it be minimized?

    Science.gov (United States)

    Somani, S M; Galle, B W; Roberts, A W

    1981-12-01

    The ability to implement change, as an administrative skill, is essential in effectively promoting progressive pharmacy practice. Often, pharmacy managers want to implement change but do not know how to approach the process without encountering much resistance from the staff. There are various sources of resistance that need to be recognized, including lack of trust, inaccurate or incomplete information, and potential loss. A pharmacy manager can take different approaches to minimize this resistance, depending on the organization and his or her management style. A pharmacy manager can use the techniques cited to turn the uncertainties of change into established gains and employee commitment.

  16. Minimal residual disease surveillance in chronic lymphocytic leukemia by fluorescence-activated cell sorting.

    Science.gov (United States)

    Ringelstein-Harlev, Shimrit; Fineman, Riva

    2014-10-01

    Achievement of complete response (CR) to therapy in chronic lymphocytic leukemia (CLL) has become a feasible goal, directly correlating with prolonged survival. It has been established that the classic definition of CR actually encompasses a variety of disease loads, and more sensitive multiparameter flow cytometry and polymerase chain reaction methods can detect the disease burden with a much higher sensitivity. Detection of malignant cells with a sensitivity of 1 tumor cell in 10,000 cells (10(-4)), using the abovementioned sophisticated techniques, is the current cutoff for minimal residual disease (MRD). Tumor burdens lower than 10(-4) are defined as MRD-negative. Several studies in CLL have determined the achievement of MRD negativity as an independent favorable prognostic factor, leading to prolonged disease-free and overall survival, regardless of the treatment protocol or the presence of other pre-existing prognostic indicators. Minimal residual disease evaluation using flow cytometry is a sensitive and applicable approach which is expected to become an integral part of future prospective trials in CLL designed to assess the role of MRD surveillance in treatment tailoring.

  17. Minimal Residual Disease Surveillance in Chronic Lymphocytic Leukemia by Fluorescence-Activated Cell Sorting

    Directory of Open Access Journals (Sweden)

    Shimrit Ringelstein-Harlev

    2014-10-01

    Full Text Available Achievement of complete response (CR to therapy in chronic lymphocytic leukemia (CLL has become a feasible goal, directly correlating with prolonged survival. It has been established that the classic definition of CR actually encompasses a variety of disease loads, and more sensitive multiparameter flow cytometry and polymerase chain reaction methods can detect the disease burden with a much higher sensitivity. Detection of malignant cells with a sensitivity of 1 tumor cell in 10,000 cells (10–4, using the abovementioned sophisticated techniques, is the current cutoff for minimal residual disease (MRD. Tumor burdens lower than 10–4 are defined as MRD-negative. Several studies in CLL have determined the achievement of MRD negativity as an independent favorable prognostic factor, leading to prolonged disease-free and overall survival, regardless of the treatment protocol or the presence of other pre-existing prognostic indicators. Minimal residual disease evaluation using flow cytometry is a sensitive and applicable approach which is expected to become an integral part of future prospective trials in CLL designed to assess the role of MRD surveillance in treatment tailoring.

  18. A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

    KAUST Repository

    Kannan, Venkateshan

    2017-03-29

    Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving the immune system and CNS that generates the principal subtypes of the disease observed in patients. The model captures several key features of MS, especially those that distinguish the chronic progressive phase from that of the relapse-remitting. In addition, a rare subtype of the disease, progressive relapsing MS naturally emerges from the model. The model posits the existence of two key thresholds, one in the immune system and the other in the CNS, that separate dynamically distinct behavior of the model. Exploring the two-dimensional space of these thresholds, we obtain multiple phases of disease evolution and these shows greater variation than the clinical classification of MS, thus capturing the heterogeneity that is manifested in patients.

  19. Bootstrap imputation with a disease probability model minimized bias from misclassification due to administrative database codes.

    Science.gov (United States)

    van Walraven, Carl

    2017-04-01

    Diagnostic codes used in administrative databases cause bias due to misclassification of patient disease status. It is unclear which methods minimize this bias. Serum creatinine measures were used to determine severe renal failure status in 50,074 hospitalized patients. The true prevalence of severe renal failure and its association with covariates were measured. These were compared to results for which renal failure status was determined using surrogate measures including the following: (1) diagnostic codes; (2) categorization of probability estimates of renal failure determined from a previously validated model; or (3) bootstrap methods imputation of disease status using model-derived probability estimates. Bias in estimates of severe renal failure prevalence and its association with covariates were minimal when bootstrap methods were used to impute renal failure status from model-based probability estimates. In contrast, biases were extensive when renal failure status was determined using codes or methods in which model-based condition probability was categorized. Bias due to misclassification from inaccurate diagnostic codes can be minimized using bootstrap methods to impute condition status using multivariable model-derived probability estimates. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Moving beyond resistance to restraint minimization: a case study of change management in aged care.

    Science.gov (United States)

    Johnson, Susan; Ostaszkiewicz, Joan; O'Connell, Beverly

    2009-01-01

    This case study describes a quality initiative to minimize restraint in an Australian residential aged care facility. The process of improving practice is examined with reference to the literature on implementation of research into practice and change management. The differences between planned and emergent approaches to change management are discussed. The concepts of resistance and attractors are explored in relation to our experiences of managing the change process in this initiative. The importance of the interpersonal interactions that were involved in facilitating the change process is highlighted. Recommendations are offered for dealing with change management processes in clinical environments, particularly the need to move beyond an individual mind-set to a systems-based approach for quality initiatives in residential aged care.

  1. Sensitivity to Change and Minimal Important Differences of the LupusQoL in Patients With Systemic Lupus Erythematosus

    Science.gov (United States)

    McElhone, Kathleen; Abbott, Janice; Sutton, Chris; Mullen, Montana; Lanyon, Peter; Rahman, Anisur; Yee, Chee‐Seng; Akil, Mohammed; Bruce, Ian N.; Ahmad, Yasmeen; Gordon, Caroline

    2016-01-01

    Objective As a health‐related quality of life (HRQOL) measure, the LupusQoL is a reliable and valid measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MIDs) for the 8 LupusQoL domains. Methods Patients experiencing a flare were recruited from 9 UK centers. At each of the 10 monthly visits, HRQOL (LupusQoL, Short Form 36 health survey [SF‐36]), global rating of change (GRC), and disease activity using the British Isles Lupus Assessment Group 2004 index were assessed. The responsiveness of the LupusQoL and the SF‐36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and additionally with changes in physician‐reported disease activity. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. Results A total of 101 patients were recruited. For all LupusQoL domains, mean HRQOL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF‐36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF‐36 was observed with a decrease in disease activity, but when disease activity worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from −2.4 to −8.7, and for improvement from 3.5 to 7.3; for the SF‐36, the same MID estimates were −2.0 to −11.1 and 2.8 to 10.9, respectively. Conclusion All LupusQoL domains are sensitive to change with patient‐reported deterioration or improvement in health status. For disease activity, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease‐specific domains, important to the patients, not captured by the SF‐36. PMID:26816223

  2. KDIGO指南解读:成人微小病变肾病和特发性局灶节段性肾小球硬化治疗%Management of minimal-change disease and idiopathic focal segmental glomerulosclerosis in adults:interpretation of KDIGO guideline

    Institute of Scientific and Technical Information of China (English)

    陈楠; 任红

    2012-01-01

    Minimal-change disease( MCD) and idiopathic focal segmental glomerulosclerosis (KSGS) are common reasons for nephrotic syndrome in adults. The KDIGO clinical practice guideline for glomerulonephritis published in June,2012 provided the newest recommendations on the treatment of primary and secondary glomerulonephritis. The doses and courses of glucocorticosteroid treatment in the first episode of MOD and FSGS,in relapsed patients,in corticosteroid dependent or corti-costeroid resistant patients were suggested. The recommendations for the choice of first-line immunosuppressive agents were given. Here we unscrambled the KDIGO guideline on the treatment of MCD and FSGS in adults regarding the characteristics of Chinese patients.%微小病变肾病(MCD)和特发性局灶节段性肾小球硬化(FSGS)是成人肾病综合征的常见病理类型.2012年6月发表的改善全球肾脏病预后组织(KDIGO)指南对多种原发及继发性肾小球肾炎的治疗给出了最新意见,对初发、复发、激素依赖和激素抵抗型MCD和FSGS患者的激素使用剂量、疗程及一线免疫抑制剂的选择等给予了建议.本文结合中国患者的特点对该指南关于MCD和FSGS治疗的建议做一解读.

  3. Clinical value of pre-transplant minimal residual disease in childhood lymphoblastic leukaemia: the results of the French minimal residual disease-guided protocol.

    Science.gov (United States)

    Gandemer, Virginie; Pochon, Cécile; Oger, Emmanuel; Dalle, Jean-Hugues H; Michel, Gérard; Schmitt, Claudine; de Berranger, Eva; Galambrun, Claire; Cavé, Hélène; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rorhlich, Pierre; Lutz, Patrick; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Bordigoni, Pierre

    2014-05-01

    Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non-ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T-cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high-risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD <10(-3) and the 27 with MRD ≥10(-3) . Multivariate analysis identified sex match and MRD as being significantly associated with 5-year survival. MRD ≥10(-3) compromised the 5-year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre-transplant MRD is still a major predictor of outcome for ALL. The MRD-guided strategy resulted in survival for 72·3% of patients with MRD<10(-3) and 40·4% of those with MRD ≥10(-3). © 2014 John Wiley & Sons Ltd.

  4. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    Science.gov (United States)

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML.

  5. 他克莫司联合小剂量激素治疗成人激素依赖或激素抵抗微小病变肾病的疗效%Efficacy of tacrolimus combined with small dose of hormone on adults with steroid-dependent or steroid-resistant minimal change disease

    Institute of Scientific and Technical Information of China (English)

    于锐; 田密; 刘大军; 李德天

    2012-01-01

    目的 观察不同疗程中他克莫司治疗成人激素依赖或激素抵抗微小病变肾病的疗效和复发率.方法 2007年5月至2010年2月我院收治经皮肾活检诊断微小病变肾病,经糖皮质激素规律治疗表现为激素依赖或激素抵抗的26例病例,随机分为短疗程组12例和长疗程组14例.短疗程组给予他克莫司联合口服泼尼松治疗6个月,长疗程组治疗18个月,前6个月治疗同短疗程组,此后单用小剂量他克莫司维持,观察两组的疗效及复发等情况.结果 短疗程组全部完成实验,治疗6个月后9例完全缓解,2例部分缓解,1例无效;治疗期间他克莫司的平均血药浓度保持在4~8 μg/L;治疗过程中及观察结束时,6例复发.长疗程组治疗18个月后,9例获得完全缓解,2例获得部分缓解,1例无效,2例因严重不良反应退出研究,长疗程组他克莫司的浓度在6个月内波动于5~8 μg/L,疗程结束时,2例复发.结论 他克莫司是有效的诱导缓解药物,小剂量他克莫司维持治疗可以有效降低复发率.%Objective To observe the efficacy and relapse-rate of tacrolimus on adults with steroid-dependent or steroid-resistant minimal change disease in different courses of treatment. Methods Twenty-six adult patients with steroid-dependent or steroid-resistant minimal change disease were divided into short-term( 12 cases )and long-term( 14 cases )groups randomly. The patients of short-term group and long-term group were treated with tacrolimus and predni-sone for 6 months and 18 months respectively, then the efficacy, relapses-rate of tacrolimus of the two groups was observed. Results All of the patients in the short-term group completed the study, 9 patients obtained complete remission after 6 months ;2 patients obtained partial remission;1 patient had no response. Average concentration of tacrolimus remained 4 ~ 8 jJtg/L in the period of treatment, and 6 cases recurred. 9 patients obtained complete remission

  6. Minimal important difference to infer changes in health-related quality of life-a systematic review.

    Science.gov (United States)

    Jayadevappa, Ravishankar; Cook, Ratna; Chhatre, Sumedha

    2017-07-01

    The objective of the study was to assess the usability of minimal important difference (MID) and minimal clinically important difference (MCID) for measuring meaningful changes in disease-specific and generic health-related quality-of-life (HRQoL) outcomes in patient-centered care. We adopted a two-step literature review process. First, we used PubMed and Google scholar to identify a broad range of search terms. Next, we searched OVID Medline, JSTOR, and PubMed for terms "MID," and "MCID." We excluded non-English language studies, articles older than 1995, those not related to generic- and disease-specific HRQoL measures, and protocols of future studies. Studies were grouped according to generic- and disease-specific measures. We assessed MID or MCID calculation methods, effect sizes, estimated values, and significance. Eighty articles satisfied the inclusion criteria. Our synthesis provides a comprehensive assessment of MID or MCID for 10 generic-specific and 80 disease-specific instruments. We observed a lack of consistency in the application of methods for computing MID or MCID for generic and disease-specific HRQoL measures. Only 43 (54%) studies used both anchor and distribution methods to elicit MID or MCID. Thirty-four articles estimated MID values only, whereas 47 articles estimated MCID. The anchor-based method yields conservative estimates of MID or MCID, compared to the distribution-based method. The distribution method does not take into account patient perspectives and should be accompanied by anchor method while computing MID. The MID should be interpreted with caution, and available estimates for a particular instrument must be used. This will help in integrating the MID estimates into the overall research or clinical plan for a specific context. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

    Science.gov (United States)

    Oran, Betül; Jorgensen, Jeff L.; Marin, David; Wang, Sa; Ahmed, Sairah; Alousi, Amin M.; Andersson, Borje S.; Bashir, Qaiser; Bassett, Roland; Lyons, Genevieve; Chen, Julianne; Rezvani, Katy; Popat, Uday; Kebriaei, Partow; Patel, Keyur; Rondon, Gabriela; Shpall, Elizabeth J.; Champlin, Richard E.

    2017-01-01

    Our aim was to improve outcome prediction after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia by combining cytogenetic and molecular data at diagnosis with minimal residual disease assessment by multicolor flow-cytometry at transplantation. Patients with acute myeloid leukemia in first complete remission in whom minimal residual disease was assessed at transplantation were included and categorized according to the European LeukemiaNet classification. The primary outcome was 1-year relapse incidence after transplantation. Of 152 patients eligible, 48 had minimal residual disease at the time of their transplant. Minimal residual disease-positive patients were older, required more therapy to achieve first remission, were more likely to have incomplete recovery of blood counts and had more adverse risk features by cytogenetics. Relapse incidence at 1 year was higher in patients with minimal residual disease (32.6% versus 14.4%, P=0.002). Leukemia-free survival (43.6% versus 64%, P=0.007) and overall survival (48.8% versus 66.9%, P=0.008) rates were also inferior in patients with minimal residual disease. In multivariable analysis, minimal residual disease status at transplantation independently predicted 1-year relapse incidence, identifying a subgroup of intermediate-risk patients, according to the European LeukemiaNet classification, with a particularly poor outcome. Assessment of minimal residual disease at transplantation in combination with cytogenetic and molecular findings provides powerful independent prognostic information in acute myeloid leukemia, lending support to the incorporation of minimal residual disease detection to refine risk stratification and develop a more individualized approach during hematopoietic stem cell transplantation. PMID:27540139

  8. Minimally Invasive Dentistry

    Science.gov (United States)

    ... to your desktop! more... What Is Minimally Invasive Dentistry? Article Chapters What Is Minimally Invasive Dentistry? Minimally ... techniques. Reviewed: January 2012 Related Articles: Minimally Invasive Dentistry Minimally Invasive Veneers Dramatically Change Smiles What Patients ...

  9. Disability Adjusted Life Years and minimal disease: application of a preference-based relevance criterion to rank enteric pathogens

    Directory of Open Access Journals (Sweden)

    Haagsma Juanita A

    2008-12-01

    Full Text Available Abstract Background Burden of disease estimates, which combine mortality and morbidity into a single measure, are used increasingly for priority setting in disease control, prevention and surveillance. However, because there is no clear exclusion criterion for highly prevalent minimal disease in burden of disease studies its application may be restricted. The aim of this study was to apply a newly developed relevance criterion based on preferences of a population panel, and to compare burden of disease estimates of five foodborne pathogens calculated with and without application of this criterion. Methods Preferences for twenty health states associated with foodborne disease were obtained from a population panel (n = 107 with the Visual Analogue Scale and the Time Trade-off (TTO technique. The TTO preferences were used to derive the relevance criterion: if at least 50% of a panel of judges is willing to trade-off time in order to be restored to full health the health state is regarded as relevant, i.e. TTO median is greater than 0. Subsequently, the burden of disease of each of the five foodborne pathogens was calculated both with and without the relevance criterion. Results The panel ranked the health states consistently. Of the twenty health states, three did not meet the preference-based relevance criterion. Application of the relevance criterion reduced the burden of disease estimate of all five foodborne pathogens. The reduction was especially significant for norovirus and rotavirus, decreasing with 94% and 78% respectively. Conclusion Individual preferences elicited with the TTO from a population panel can be used to empirically derive a relevance criterion for burden of disease estimates. Application of this preference-based relevance criterion results in considerable changes in ranking of foodborne pathogens.

  10. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma (TCR-gamma), or immunoglobulin heavy chain (IgH) genes of the malignant clone. Using primers located externally to the restriction site the competitor and the DNA from the malignant clone will be amplified...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  11. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    Science.gov (United States)

    Gajic-Veljanoski, O.; Pham, B.; Pechlivanoglou, P.; Krahn, M.; Higgins, Caroline; Bielecki, Joanna

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  12. Minimal Change Nephrotic Syndrome Which Was Most Likely Caused by Chronic Sinusitis.

    Science.gov (United States)

    Iwatani, Hirotsugu; Mori, Daisuke; Yamamoto, Satoko; Nakano, Chikako; Yamamoto, Ryohei; Masumura, Chisako; Shikina, Takashi; Imai, Takao; Inohara, Hidenori; Rakugi, Hiromi; Isaka, Yoshitaka

    2015-01-01

    A 33-year-old Japanese man was admitted with severe edema, and a renal biopsy confirmed minimal change nephrotic syndrome (MCNS). CT revealed his severe chronic sinusitis, and he first received antimicrobial therapy, which resulted in decreased proteinuria. The surgical operation for sinusitis resulted in the complete disappearance of proteinuria without corticosteroid or immunosuppressant therapy within one week. MCNS may be triggered by infection, but there are no previously reported cases of MCNS that is completely remitted by infection control alone. Therefore, we herein report the first case of MCNS that attained complete remission following therapy for chronic sinusitis alone, which suggests a strong etiology of chronic sinusitis for MCNS.

  13. Detection of highly and minimally leukotoxic Actinobacillus actinomycetemcomitans strains in patients with periodontal disease

    Directory of Open Access Journals (Sweden)

    Cortelli Sheila Cavalca

    2003-01-01

    Full Text Available This study examined the prevalence of highly and minimally leukotoxic Actinobacillus actinomycetemcomitans in patients with periodontal disease. Pooled subgingival plaque samples from 136 patients with some form of periodontal disease were examined. Subjects were between 14 and 76 years of age. Clinical examinations included periodontal pocket depth (PD, plaque index (PI and bleeding index (BI. The obtained plaque samples were examined for the presence of highly or minimally leukotoxic A. actinomycetemcomitans strains by the polymerase chain reaction (PCR. Chi-square and logistic regression were performed to evaluate the results. Forty-seven subjects were diagnosed with gingivitis, 70 with chronic periodontitis and 19 with aggressive periodontitis. According to chi-square there was no significant correlation detected between PD (chi2 = 0.73, PI (chi2 = 0.35, BI (chi2 = 0.09 and the presence of the highly leukotoxic A. actinomycetemcomitans. The highly leukotoxic A. actinomycetemcomitans strains were correlated with subjects that were 28 years of age and younger (chi2 = 7.41. There was a significant correlation between highly leukotoxic A. actinomycetemcomitans and aggressive periodontitis (chi2 = 22.06. This study of a Brazilian cohort confirms the strong association between highly leukotoxic A. actinomycetemcomitans strains and the presence of aggressive periodontitis.

  14. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy.

    Science.gov (United States)

    Santacruz, Rodrigo; Villamor, Neus; Aymerich, Marta; Martínez-Trillos, Alejandra; López, Cristina; Navarro, Alba; Rozman, María; Beà, Sílvia; Royo, Cristina; Cazorla, Maite; Colomer, Dolors; Giné, Eva; Pinyol, Magda; Puente, Xose S; López-Otín, Carlos; Campo, Elías; López-Guillermo, Armando; Delgado, Julio

    2014-05-01

    A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV, TP53, NOTCH1 and SF3B1 mutations. The median follow-up was 73 months (range, 2-202) from disease evaluation. The median treatment-free survival durations for patients achieving a complete response without or with minimal residual disease, a partial response and no response were 76, 40, 11 and 11 months, respectively (P<0.001). Multivariate analysis revealed that three variables had a significant impact on treatment-free survival: minimal residual disease (P<0.001), IGHV status (P<0.001) and β2-microglobulin levels (P=0.012). With regards to overall survival, factors predictive of an unfavorable outcome were minimal residual disease positivity (P=0.014), together with advanced age (P<0.001), unmutated IGHV status (P=0.001), TP53 mutations (P<0.001) and elevated levels of β2-microglobulin (P=0.003). In conclusion, for patients requiring front-line therapy, achievement of minimal residual disease negativity is associated with significantly prolonged treatment-free and overall survival irrespective of other prognostic markers or treatment administered.

  15. Minimal walking distance following exercise treatment in patients with arterial occlusive disease.

    Science.gov (United States)

    Rosetzsky, A; Struckmann, J; Mathiesen, F R

    1985-01-01

    79 patients with intermittent claudication were tested with peripheral blood pressure measurement and determination of minimal walking distance before and after a 3 months' period with scheduled walking exercises under supervision. No change in peripheral blood pressure was observed following the treatment whereas the minimum walking distance was increased with statistical significance. The gain was most pronounced in patients with an initial combination of high peripheral pressures and short walking distances. A graphic presentation allows for the estimation of the expected gain in individual patients with claudication.

  16. Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study

    Science.gov (United States)

    Cheminant, Morgane; Derrieux, Coralie; Touzart, Aurore; Schmit, Stéphanie; Grenier, Adrien; Trinquand, Amélie; Delfau-Larue, Marie-Hélène; Lhermitte, Ludovic; Thieblemont, Catherine; Ribrag, Vincent; Cheze, Stéphane; Sanhes, Laurence; Jardin, Fabrice; Lefrère, François; Delarue, Richard; Hoster, Eva; Dreyling, Martin; Asnafi, Vahid; Hermine, Olivier; Macintyre, Elizabeth

    2016-01-01

    Quantification of minimal residual disease may guide therapeutic strategies in mantle cell lymphoma. While multiparameter flow cytometry is used for diagnosis, the gold standard method for minimal residual disease analysis is real-time quantitative polymerase chain reaction (RQ-PCR). In this European Mantle Cell Lymphoma network (EU-MCL) pilot study, we compared flow cytometry with RQ-PCR for minimal residual disease detection. Of 113 patients with at least one minimal residual disease sample, RQ-PCR was applicable in 97 (86%). A total of 284 minimal residual disease samples from 61 patients were analyzed in parallel by flow cytometry and RQ-PCR. A single, 8-color, 10-antibody flow cytometry tube allowed specific minimal residual disease assessment in all patients, with a robust sensitivity of 0.01%. Using this cut-off level, the true-positive-rate of flow cytometry with respect to RQ-PCR was 80%, whereas the true-negative-rate was 92%. As expected, RQ-PCR frequently detected positivity below this 0.01% threshold, which is insufficiently sensitive for prognostic evaluation and would ideally be replaced with robust quantification down to a 0.001% (10-5) threshold. In 10 relapsing patients, the transition from negative to positive by RQ-PCR (median 22.5 months before relapse) nearly always preceded transition by flow cytometry (4.5 months), but transition to RQ-PCR positivity above 0.01% (5 months) was simultaneous. Pre-emptive rituximab treatment of 2 patients at minimal residual disease relapse allowed re-establishment of molecular and phenotypic complete remission. Flow cytometry minimal residual disease is a complementary approach to RQ-PCR and a promising tool in individual mantle cell lymphoma therapeutic management. PMID:26703963

  17. Flavor-changing Higgs decays in grand unification with minimal flavor violation

    Science.gov (United States)

    Baek, Seungwon; Tandean, Jusak

    2016-12-01

    We consider the flavor-changing decays of the Higgs boson in a grand unified theory framework which is based on the SU(5) gauge group and implements the principle of minimal flavor violation. This allows us to explore the possibility of connecting the tentative hint of the Higgs decay h→ μ τ recently reported in the CMS experiment to potential new physics in the quark sector. We look at different simple scenarios with minimal flavor violation in this context and how they are subject to various empirical restrictions. In one specific case, the relative strengths of the flavor-changing leptonic Higgs couplings are determined mainly by the known quark mixing parameters and masses, and a branching fraction B(h→ μ τ )˜ 1% is achievable without the couplings being incompatible with the relevant constraints. Upcoming data on the Higgs leptonic decays and searches for the μ → eγ decay with improved precision can offer further tests on this scenario.

  18. Alveolar dimensional changes relevant to implant placement after minimally traumatic tooth extraction with primary closure.

    Science.gov (United States)

    Carranza, Nelson; Bonta, Hernan; Gualtieri, Ariel F; Rojas, Mariana A; Galli, Federico G; Caride, Facundo

    2016-09-01

    The purpose of this study is to evaluate the dimensional changes that occur in the alveolar ridge after minimally traumatic tooth extraction by means of computed tomography (CT), with special focus on the portion of bone supporting the gingival zenith. Twenty subjects with indication for singlerooted tooth extraction and preserved alveolar walls were selected for this study. After a minimally traumatic extraction, two CT scans were performed; the first within 24 hours postextraction (TC1) and the second 6 months (TC2) later. A radiographic guide with a radiopaque marker was used to obtain references that enabled accurate measurements over time, in both vertical and horizontal directions. The bone crest immediately apical to the gingival zenith was identified and termed "osseous zenith". The displacement of the osseous zenith in horizontal and vertical direction was analyzed and correlated with several alveolar anatomical variables with the aim of identifying possible predictors for bone remodeling. Dimensional changes that occur in postextraction sockets within a 6month period showed significant vertical and horizontal displacement of the osseous zenith (p 3 mm) should be expected. The present study suggests that the width of the alveolar crest at its midlevel, rather than crestal width, may be correlated with the displacement of the osseous zenith. Sociedad Argentina de Investigación Odontológica.

  19. Flavor-Changing Higgs Decays in Grand Unification with Minimal Flavor Violation

    CERN Document Server

    Baek, Seungwon

    2016-01-01

    We consider the flavor-changing decays of the Higgs boson in a grand unified theory framework which is based on the SU(5) gauge group and implements the principle of minimal flavor violation. This allows us to explore the possibility of connecting the tentative hint of the Higgs decay $h\\to\\mu\\tau$ recently reported in the CMS experiment to potential new physics in the quark sector. We look at different simple scenarios with minimal flavor violation in this context and how they are subject to various empirical restrictions. In one specific case, the relative strengths of the flavor-changing leptonic Higgs couplings are determined by the known quark mixing parameters and masses alone, and a branching fraction ${\\cal B}(h\\to\\mu\\tau)\\sim1\\%$ is achievable without the couplings being incompatible with the relevant constraints. Upcoming data on the Higgs leptonic decays and searches for the $\\mu\\to e\\gamma$ decay with improved precision can offer further tests on this scenario.

  20. Minimally invasive treatment of the thoracic spine disease: completely percutaneous and hybrid approaches.

    Science.gov (United States)

    Tamburrelli, Francesco Ciro; Francesco Ciro, Tamburrelli; Scaramuzzo, Laura; Laura, Scaramuzzo; Genitiempo, Maurizio; Maurizio, Genitiempo; Proietti, Luca; Luca, Proietti

    2013-01-01

    The aim of the study was to evaluate the feasibility of a limited invasive approach for the treatment of upper thoracic spine disease. Seven patients with type-A thoracic fractures and three with tumors underwent long thoracic stabilization through a minimally invasive approach. Four patients underwent a completely percutaneous approach while the other three underwent a modified hybrid technique, a combination of percutaneous and open approach. The hybrid constructs were realized using a percutaneous approach to the spine distally to the spinal lesion and by open approach proximally. In two patients, the stabilization was extended proximally up to the cervical spine. Clinical and radiographic assessment was performed during the first year after the operation at 3, 6, and 12 months. No technically related complications were seen. The postoperative recovery was rapid even in the tumor patients with neurologic impairment. Blood loss was irrelevant. At one-year follow-up there was no loosening or breakage of the screws or failure of the implants. When technically feasible a completely percutaneous approach has to be taken in consideration; otherwise, a combined open-percutaneous approach could be planned to minimize the invasivity of a completely open approach to the thoracic spine.

  1. Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells.

    Science.gov (United States)

    Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M

    2016-08-01

    Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs.

  2. The minimal important difference for measures of urticaria disease activity: Updated findings.

    Science.gov (United States)

    Mathias, Susan D; Crosby, Ross D; Rosén, Karin E; Zazzali, James L

    2015-01-01

    The Urticaria Patient Daily Diary (UPDD) is a validated patient-reported outcome that captures key measures of urticaria disease activity. To update estimates of the minimal important difference (MID) for urticaria disease activity measures in the UPDD, including the weekly itch severity score, weekly number of hives score, weekly average size of largest hive score, and the composite measure of itch severity and number of hives over 7 days, or urticaria activity score 7 (UAS7). A total of 975 subjects with chronic idiopathic urticaria from three randomized, double-blind, placebo-controlled studies completed the UPDD and other patient-reported outcome assessments (the Dermatology Life Quality Index, Medical Outcomes Study Sleep Scale, the Chronic Urticaria Quality-of-Life Questionnaire, the EuroQoL-5 Dimension Questionnaire) multiple times. MIDs were estimated through a combination of distribution- and anchor-based methods. MID estimates ranged from 4.5 to 5.0 for the weekly itch severity score, 5.0 to 5.5 for weekly hives count score, 9.5 to 10.5 for the UAS7, and 4.0 to 4.5 for the weekly size of the largest hive score. This analysis provided confirmation of the previous MID estimates for the urticaria disease activity measures in the UPDD.

  3. DETECTION AND ITS CLINICAL VALUE OF MINIMAL RESIDUAL DISEASES IN ACUTE PROMYELOCYTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    姜国胜; 唐天华; 毕可红; 张玉昆; 任海全; 赵良玉; 郭桂月; 刘秀兰; 任青华; 姜枫勤; 刘传芳; 彭军; 田志刚

    2002-01-01

    Objective: To detect the minimal residual diseases (MRD) in acute promyelocytic leukemia (APL) after complete remission (CR) and to analyze its clinical value in prognosis. Methods: Reverse transcription Polymerase chain reaction (RT/PCR) was used to detect MRD of patients with APL. Results: MRD positive rate in patients with APL was 92.8% (39/42) before treatment and 56.7 (21/37) immediately after the ATRA or chemotherapy- induced CR. Furthermore, MRD positive rate wasrelated to the relapse in APL patients and could be considered as a marker to predict the relapse of patients with APL after CR. The MRD detection could also be applied to direct the consolidation therapy to prevent relapses. Conclusion: RT-PCR is valuable to monitor MRD and can be used as a marker to predict relapses.

  4. Minimal residual disease detection in mantle cell lymphoma: technical aspects and clinical relevance.

    Science.gov (United States)

    Pott, Christiane

    2011-07-01

    The prognostic impact of minimal residual disease (MRD) has been demonstrated for several hematologic malignancies. While in acute lymphoblastic leukemias MRD assessment by polymerase chain reaction (PCR)-based methods has been established as an important tool for clinical risk assessment and is part of clinical management, data demonstrating a prognostic value of MRD in mantle cell lymphoma (MCL) were sparse and results from randomized trials have been published only recently. In the present review technical aspects of different MRD detection methods are discussed, as well as the prognostic relevance of MRD in the context of clinical trials in patients with MCL. Furthermore, recommendations are given for workflow and useful implication of MRD in future clinical trials design.

  5. Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case.

    Science.gov (United States)

    Tsukamoto, Yoshitane; Otsuki, Taiichiro; Hao, Hiroyuki; Kuribayashi, Kozo; Nakano, Takashi; Kida, Aritoshi; Nakanishi, Takeshi; Funatsu, Eriko; Noguchi, Chihiro; Yoshihara, Shunya; Kaku, Koji; Hirota, Seiichi

    2015-12-01

    Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.

  6. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Maura Rosane Valério Ikoma

    2015-12-01

    Full Text Available ABSTRACT Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR gene assays are necessary in Brazil.

  7. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia

    Science.gov (United States)

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil. PMID:26670404

  8. Reliability and minimal detectable change of the weight-bearing lunge test: A systematic review.

    Science.gov (United States)

    Powden, Cameron J; Hoch, Johanna M; Hoch, Matthew C

    2015-08-01

    Ankle dorsiflexion range of motion (DROM) is often a point of emphasis during the rehabilitation of lower extremity pathologies. With the growing popularity of weight-bearing DROM assessments, several versions of the weight-bearing lunge (WBLT) test have been developed and numerous reliability studies have been conducted. The purpose of this systematic review was to critically appraise and synthesize the studies which examined the reliability and responsiveness of the WBLT to assess DROM. A systematic search of PubMed and EBSCO Host databases from inception to September 2014 was conducted to identify studies whose primary aim was assessing the reliability of the WBLT. The Quality Appraisal of Reliability Studies assessment tool was utilized to determine the quality of included studies. Relative reliability was examined through intraclass correlation coefficients (ICC) and responsiveness was evaluated through minimal detectable change (MDC). A total of 12 studies met the eligibility criteria and were included. Nine included studies assessed inter-clinician reliability and 12 included studies assessed intra-clinician reliability. There was strong evidence that inter-clinician reliability (ICC = 0.80-0.99) as well as intra-clinician reliability (ICC = 0.65-0.99) of the WBLT is good. Additionally, average MDC scores of 4.6° or 1.6 cm for inter-clinician and 4.7° or 1.9 cm for intra-clinician were found, indicating the minimal change in DROM needed to be outside the error of the WBLT. This systematic review determined that the WBLT, regardless of method, can be used clinically to assess DROM as it provides consistent results between one or more clinicians and demonstrates reasonable responsiveness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Change in condylar position in posterior bending osteotomy minimizing condylar torque in BSSRO for facial asymmetry.

    Science.gov (United States)

    Yang, Hoon Joo; Hwang, Soon Jung

    2014-06-01

    During the correction of an asymmetric mandible with sagittal split ramus osteotomy (SSRO), bony interference between the proximal and distal segments inevitably occurs. This results in positional change of the condyle. In order to avoid this, a posterior bending osteotomy (PBO) has been introduced. This is an additional vertical osteotomy posterior to the second molar after SSRO. To investigate the change in condylar position after SSRO with PBO, 22 patients with facial asymmetry were enrolled and divided into two groups based on the surgical method used to remove the bony interference after SSRO: PBO (n = 13) and the grinding method (n = 9). Each group was subdivided into large and small bony interference groups by estimating the volume of bony interference with simulation surgery. Condylar displacement was evaluated by three-dimensional superimposition and the amount of condylar displacement was calculated. The positional changes of the condyles were variable in each patient. When comparing patients with large bony interference in the PBO and grinding groups, the condyles were significantly inwardly rotated in the grinding group (p condylar torque. However, PBO would be beneficial in correcting large bony interferences while minimizing condylar torque.

  10. Minimizing the total tardiness for the tool change scheduling problem on parallel machines

    Directory of Open Access Journals (Sweden)

    Antonio Costa

    2016-04-01

    Full Text Available This paper deals with the total tardiness minimization problem in a parallel machines manufacturing environment where tool change operations have to be scheduled along with jobs. The mentioned issue belongs to the family of scheduling problems under deterministic machine availability restrictions. A new model that considers the effects of the tool wear on the quality characteristics of the worked product is proposed. Since no mathematical programming-based approach has been developed by literature so far, two distinct mixed integer linear programming models, able to schedule jobs as well as tool change activities along the provided production horizon, have been devised. The former is an adaptation of a well-known model presented by the relevant literature for the single machine scheduling problem with tool changes. The latter has been specifically developed for the issue at hand. After a theoretical analysis aimed at revealing the differences between the proposed mathematical models in terms of computational complexity, an extensive experimental campaign has been fulfilled to assess performances of the proposed methods under the CPU time viewpoint. Obtained results have been statistically analyzed through a properly arranged ANOVA analysis.

  11. Minimizing errors in phase change correction measurements for gauge blocks using a spherical contact technique

    Science.gov (United States)

    Stoup, John R.; Faust, Bryon S.; Doiron, Theodore D.

    1998-09-01

    One of the most elusive measurement elements in gage block interferometry is the correction for the phase change on reflection. Techniques used to quantify this correction have improved over the year, but the measurement uncertainty has remained relatively constant because some error sources have proven historically difficult to reduce. The precision engineering division at the National Institute of Standards and Technology has recently developed a measurement technique that can quantify the phase change on reflection correction directly for individual gage blocks and eliminates some of the fundamental problems with historical measurement methods. Since only the top surface of the gage block is used in the measurement, wringing film inconsistencies are eliminated with this technique thereby drastically reducing the measurement uncertainty for the correction. However, block geometry and thermal issues still exist. This paper will describe the methods used to minimize the measurement uncertainty of the phase change on reflection evaluation using a spherical contact technique. The work focuses on gage block surface topography and drift eliminating algorithms for the data collection. The extrapolation of the data to an undeformed condition and the failure of these curves to follow theoretical estimates are also discussed. The wavelength dependence of the correction was directly measured for different gage block materials and manufacturers and the data will be presented.

  12. Minimal Clinically Important Difference in Parkinson’s Disease as Assessed in Pivotal Trials of Pramipexole Extended Release

    Directory of Open Access Journals (Sweden)

    Robert A. Hauser

    2014-01-01

    Full Text Available Background. The minimal clinically important difference (MCID is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson’s Disease Rating Scale (UPDRS scores in early Parkinson’s disease (EPD and for UPDRS scores and “OFF” time in advanced Parkinson’s disease (APD. Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR was −1.0 and −1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  13. [The detection of minimal residual disease in patients with chronic B-cell lymphatic leukemia using patient-specified polymerase chain reaction].

    Science.gov (United States)

    Sidorova, Iu V; Sorokina, T V; Biderman, B V; Nikulina, E E; Kisilichina, D G; Naumova, E V; Pochtar', M E; Lugovskaia, S A; Ivanova, V L; Kovaleva, L G; Ptushkin, V V; Nikitin, E A; Sudarikov, A B

    2011-12-01

    The new effective protocols of treatment of chronic B-cell lymphatic leukemia, including purine analogs and monoclonal antibodies, provide robust remissions under this disease. Accordingly, the requirements to remission quality assessment are changed too. In particular the assessment of minimal residual disease is obligatory. To assess minimal residual disease in terms of quantity in case of chronic B-cell lymphatic leukemia the technique of polymerase chain reaction was applied in real time with patient-specific primers from the area of V-D-J combinations of genes of heavy chain of immunoglobulin. The study included samples from 60 patients suffering of chronic B-cell lymphatic leukemia. In 15 of them (25%), it was impossible to apply neither the sequence analysis of genes of heavy chain of immunoglobulin nor the fitting of patient-specific primer. The results of quantitative determination of minimal residual disease were obtained in 45 patients (55 tests). The minimal residual disease was detected in 30 of 55 samples (54.5%) and was not detected in 25 of 55 samples (45.5%). At the same time, the quantitative determination of minimal residual disease was implemented in regard to the initial level of neoplastic cells. The method sensitivity qualified by serial dilutions, consisted 10(-5) or 1 neoplastic cell to 100 000 normal cells. The comparative analysis was applied to the results of determination of minimal residual disease using two methods -polymerase chain reaction in real time using patient-specified primers and four-color flow cytofluometry. The determination of minimal residual disease with both methods was implemented in 37 patients (45 tests). The results of both methods matched in 93.3% (42 tests out of 45) with maximal disparity of one degree. Then Spearman factor consisted 0.87 (p chronic B-cell lymphatic leukemia using the method of polymerase chain reaction in real time is rather sensitive and specific and correlates with the results received with

  14. Application of advanced cytometric and molecular technologies to minimal residual disease monitoring

    Science.gov (United States)

    Leary, James F.; He, Feng; Reece, Lisa M.

    2000-04-01

    Minimal residual disease monitoring presents a number of theoretical and practical challenges. Recently it has been possible to meet some of these challenges by combining a number of new advanced biotechnologies. To monitor the number of residual tumor cells requires complex cocktails of molecular probes that collectively provide sensitivities of detection on the order of one residual tumor cell per million total cells. Ultra-high-speed, multi parameter flow cytometry is capable of analyzing cells at rates in excess of 100,000 cells/sec. Residual tumor selection marker cocktails can be optimized by use of receiver operating characteristic analysis. New data minimizing techniques when combined with multi variate statistical or neural network classifications of tumor cells can more accurately predict residual tumor cell frequencies. The combination of these techniques can, under at least some circumstances, detect frequencies of tumor cells as low as one cell in a million with an accuracy of over 98 percent correct classification. Detection of mutations in tumor suppressor genes requires insolation of these rare tumor cells and single-cell DNA sequencing. Rare residual tumor cells can be isolated at single cell level by high-resolution single-cell cell sorting. Molecular characterization of tumor suppressor gene mutations can be accomplished using a combination of single- cell polymerase chain reaction amplification of specific gene sequences followed by TA cloning techniques and DNA sequencing. Mutations as small as a single base pair in a tumor suppressor gene of a single sorted tumor cell have been detected using these methods. Using new amplification procedures and DNA micro arrays it should be possible to extend the capabilities shown in this paper to screening of multiple DNA mutations in tumor suppressor and other genes on small numbers of sorted metastatic tumor cells.

  15. Climate change: potential impact on plant diseases.

    Science.gov (United States)

    Chakraborty, S; Tiedemann, A V; Teng, P S

    2000-06-01

    Global climate has changed since pre-industrial times. Atmospheric CO(2), a major greenhouse gas, has increased by nearly 30% and temperature has risen by 0.3 to 0.6 degrees C. The intergovernmental panel on climate change predicts that with the current emission scenario, global mean temperature would rise between 0.9 and 3.5 degrees C by the year 2100. There are, however, many uncertainties that influence these predictions. Despite the significance of weather on plant diseases, comprehensive analysis of how climate change will influence plant diseases that impact primary production in agricultural systems is presently unavailable. Evaluation of the limited literature in this area suggests that the most likely impact of climate change will be felt in three areas: in losses from plant diseases, in the efficacy of disease management strategies and in the geographical distribution of plant diseases. Climate change could have positive, negative or no impact on individual plant diseases. More research is needed to obtain base-line information on different disease systems. Most plant disease models use different climatic variables and operate at a different spatial and temporal scale than do the global climate models. Improvements in methodology are necessary to realistically assess disease impacts at a global scale.

  16. Preoperative localization and minimally invasive management of primary hyperparathyroidism concomitant with thyroid disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The coexistence of thyroid diseases with primary hyperparathyroidism (PHPT) can present a challenge in the clinical diagnosis and management for these patients. This study aims to determine the frequency of coexisting thyroid gland lesions in a consecutive series patients with PHPT, and to analyze the clinical features, diagnosis and treatment of these patients. Twenty-two cases of a total of 52 PHPT patients who had synchronous thyroid and parathyroid pathology were surgically managed in this study.Thirteen patients had ipsilateral thyroid nodules, and 9 patients had thyroid nodules in contralateral or bilateral side. Seven patients underwent direct parathyroidectomy and hemithyroidectomy via a mini-incision (about 3 cm), while other 15 procedures were converted to Kocher incision. Seventeen nodular goiter (32.7%), 2 thyroiditis (3.8%), 2 thyroid adenoma (3.8%) and 1 thyroid carcinoma (1.9%) coexisting with parathyroid adenoma were pathologically diagnosed. The sensitivity of preoperative ultrasonography (US) and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for parathyroid lesions was 63.6% and 85.7%; and the overall positive predictive values for MIBI and US were 100% and 95.5% respectively. A high incidence of thyroid diseases that coexisted with PHPT in literatures was briefly reviewed. Our study illustrated the need for clinical awareness of concomitant PHPT and thyroid disease. A combination of US, computed tomography (CT) and MIBI scintigraphy would be recommended for preoperative localization of enlarged parathyroid adenoma and for evaluation of thyroid lesions. Synchronous treatment of associated thyroid abnormalities is desirable, and open minimally invasive surgical approach with additional resection of isolated ipsilateral thyroid nodules is possible in some of these patients.

  17. Global Climate Change and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    EK Shuman

    2010-12-01

    Full Text Available Climate change is occurring as a result of warming of the earth’s atmosphere due to human activity generating excess amounts of greenhouse gases. Because of its potential impact on the hydrologic cycle and severe weather events, climate change is expected to have an enormous effect on human health, including on the burden and distribution of many infectious diseases. The infectious diseases that will be most affected by climate change include those that are spread by insect vectors and by contaminated water. The burden of adverse health effects due to these infectious diseases will fall primarily on developing countries, while it is the developed countries that are primarily responsible for climate change. It is up to governments and individuals to take the lead in halting climate change, and we must increase our understanding of the ecology of infectious diseases in order to protect vulnerable populations.

  18. Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes.

    Directory of Open Access Journals (Sweden)

    Ester Vilaprinyo

    2010-02-01

    Full Text Available Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

  19. 肾小球微小病变与局灶节段性肾小球硬化症足细胞中线粒体形态的定量研究%Stereological analysis on mitochondria in podocytes of minimal change disease and focal segmental glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    任雅丽

    2011-01-01

    目的 探索肾小球微小病变( MCD)与局灶节段性肾小球硬化症(rSGS)两种肾小球病中足细胞内线粒体的形态学差异.方法 选择5例MCD和5例FSGS病例,在透射电镜放大30 000倍的情况下,根据等距离曲线移动原则对每个病例拍照40张.根据Merz曲线和Gunderson测试系统选择线粒体和足细胞,测算并获得包括线粒体截面面积(A)、周长(C)、体积密度(VV)及面数密度(NA)等指标进行分析.结果 MCD和FSGS足细胞中线粒体相关参数的变异度及P值如下:A:0.47 vs 1.73,P=0.970;C:4.89 vs 24.71,P=0.590;VV:0.49 vs 1.74,P=0.946;NA:0.26 vs0.58,P=0.602.结论 FSGS和MCD足细胞中线粒体的A、C、VV和NA等参数无统计学差异(所有P >0.05),但FSGS中所有参数的变异度均比MCD中的更明显,仍需进一步进行体视学研究.%Objective To explore the difference of mitochondria in podocytes between minimal change disease(MCD) and focal segmental glomerulosclerosis(FSGS) by stereologic analysis.Methods We selected 5 cases of primary MCD and 5 cases of primary FSGS whose diagnosis were definite and had no any other complicated nephropathy.For each case,we took 40 photos under the magnification of 30 000 according to the rule of equidistant zigzag movement.Merz curve and Gunderson testing system were set to select mitochondria and podocytes and the associated parameters were obtained including profile area( A),circumference( C),volu me fraction( VV ),and numerical density per area( NA ) of mitochondria.Results The standard deviation value and P value of the parameters were as following in MCD vs FSGS:A(0.47vs 1.73,P =0.970),C(4.89 vs 24.71,P =0.590),VV(0.49 vs 1.74,P =0.946),and NA(0.26vs 0.58,P =0.602) Conclusion The parameters of A,C,VV,and NA did not demonstrate statistically significance( all P > 0.05),but all of them showed larger value of standard deviation in FSGS cases by comparison with that of MCD.

  20. Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy.

    Science.gov (United States)

    Chen, Hua-Jun; Zhu, Xi-Qi; Yang, Ming; Liu, Bin; Zhang, Yi; Wang, Yu; Teng, Gao-Jun

    2012-01-17

    Resting-state functional magnetic resonance imaging (fMRI) has facilitated the study of spontaneous brain activity by measuring low-frequency oscillations in blood-oxygen-level-dependent signals. Analyses of regional homogeneity (ReHo), which reflects the local synchrony of neural activity, have been used to reveal the mechanisms underlying the brain dysfunction in various neuropsychiatric diseases. However, it is not known whether the ReHo is altered in cirrhotic patients with minimal hepatic encephalopathy (MHE). We recruited 18 healthy controls and 18 patients with MHE. The ReHo was calculated to assess the strength of the local signal synchrony. Compared with the healthy controls, the patients with MHE had significantly decreased ReHo in the cuneus and adjacent precuneus, and left inferior parietal lobe, whereas the regions showing increased ReHo in patients with MHE included the left parahippocampal gyrus, right cerebellar vermis, and bilateral anterior cerebellar lobes. We found a positive correlation between the mean ReHo in the cuneus and adjacent precuneus and the score on the digit-symbol test in the patient group. In conclusion, the analysis of the regional homogeneity of resting-state brain activity may provide additional information with respect to a clinical definition of MHE.

  1. Why forefoot striking in minimal shoes might positively change the course of running injuries

    Directory of Open Access Journals (Sweden)

    Irene S. Davis

    2017-06-01

    Full Text Available It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of our body form. As our bodies have adapted to run, it seems unusual that up to 79% of modern day runners are injured annually. The etiology of these injuries is clearly multifactorial. However, 1 aspect of running that has significantly changed over the past 50 years is the footwear we use. Modern running shoes have become increasingly cushioned and supportive, and have changed the way we run. In particular, they have altered our footstrike pattern from a predominantly forefoot strike (FFS landing to a predominantly rearfoot strike (RFS landing. This change alters the way in which the body is loaded and may be contributing to the high rate of injuries runners experience while engaged in an activity for which they were adapted. In this paper, we will examine the benefits of barefoot running (typically an FFS pattern, and compare the lower extremity mechanics between FFS and RFS. The implications of these mechanical differences, in terms of injury, will be discussed. We will then provide evidence to support our contention that FFS provides an optimal mechanical environment for specific foot and ankle structures, such as the heel pad, the plantar fascia, and the Achilles tendon. The importance of footwear will then be addressed, highlighting its interaction with strike pattern on mechanics. This analysis will underscore why footwear matters when assessing mechanics. Finally, proper preparation and safe transition to an FFS pattern in minimal shoes will be emphasized. Through the discussion of the current literature, we will develop a justification for returning to running in the way for which we were adapted to reduce running-related injuries.

  2. Brain MRI changes in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

    1997-08-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

  3. Anthropogenic Climate Change and Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Hueiwang Anna Jeng

    2012-02-01

    Full Text Available Climate change is expected to have an impact on various aspects of health, including mucosal areas involved in allergic inflammatory disorders that include asthma, allergic rhinitis, allergic conjunctivitis and anaphylaxis. The evidence that links climate change to the exacerbation and the development of allergic disease is increasing and appears to be linked to changes in pollen seasons (duration, onset and intensity and changes in allergen content of plants and their pollen as it relates to increased sensitization, allergenicity and exacerbations of allergic airway disease. This has significant implications for air quality and for the global food supply.

  4. Flow cytometry quality requirements for monitoring of minimal disease in plasma cell myeloma.

    Science.gov (United States)

    Oldaker, Teri A; Wallace, Paul K; Barnett, David

    2016-01-01

    Current therapeutic approaches for plasma cell myeloma (PCM) attain an overall survival of more than 6 years for the majority of newly diagnosed patients. However, PFS and OS are the only accepted FDA clinical endpoints for demonstrating drug efficacy before they can be become frontline therapeutic options. There is, however, recognition that the increasing gap between drug development and approval for mainstream therapeutic use needs to be shortened. As such regulatory bodies such as the FDA are now considering whether biomarker response evaluation, as in measurement of minimal residual disease (MRD) as assessed by flow cytometry (FC), can provide an early, robust prediction of survival and therefore improve the drug approval process. Recently, FC MRD using a standardized eight-color antibody methodology has been shown to have a minimum sensitivity of 0.01% and an upper sensitivity of 0.001%. To ensure that all laboratories using this approach achieve the same levels of sensitivity it is crucially important to have standardized quality management procedures in place. This manuscript accompanies those published in this special issue and describes the minimum that is required for validating and quality monitoring of this highly specific test to ensure any laboratory, irrespective of location, will achieve the expected quality standards required. © 2015 International Clinical Cytometry Society.

  5. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies.

    Science.gov (United States)

    van Dongen, Jacques J M; van der Velden, Vincent H J; Brüggemann, Monika; Orfao, Alberto

    2015-06-25

    Monitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group assignment into different treatment arms, ranging from significant treatment reduction to mild or strong intensification. Also in relapsed ALL patients and patients undergoing stem cell transplantation, MRD diagnostics is guiding treatment decisions. This is also why the efficacy of innovative drugs, such as antibodies and small molecules, are currently being evaluated with MRD diagnostics within clinical trials. In fact, MRD measurements might well be used as a surrogate end point, thereby significantly shortening the follow-up. The MRD techniques need to be sensitive (≤10(-4)), broadly applicable, accurate, reliable, fast, and affordable. Thus far, flow cytometry and polymerase chain reaction (PCR) analysis of rearranged immunoglobulin and T-cell receptor genes (allele-specific oligonucleotide [ASO]-PCR) are claimed to meet these criteria, but classical flow cytometry does not reach a solid 10(-4), whereas classical ASO-PCR is time-consuming and labor intensive. Therefore, 2 high-throughput technologies are being explored, ie, high-throughput sequencing and next-generation (multidimensional) flow cytometry, both evaluating millions of sequences or cells, respectively. Each of them has specific advantages and disadvantages.

  6. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients.

    Science.gov (United States)

    Paiva, Bruno; Cedena, Maria-Teresa; Puig, Noemi; Arana, Paula; Vidriales, Maria-Belen; Cordon, Lourdes; Flores-Montero, Juan; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Martinez-Lopez, Joaquin; Ocio, Enrique M; Hernandez, Miguel T; Teruel, Ana-Isabel; Rosiñol, Laura; Echeveste, María-Asunción; Martinez, Rafael; Gironella, Mercedes; Oriol, Albert; Cabrera, Carmen; Martin, Jesus; Bargay, Joan; Encinas, Cristina; Gonzalez, Yolanda; Van Dongen, Jacques J M; Orfao, Alberto; Bladé, Joan; Mateos, Maria-Victoria; Lahuerta, Juan José; San Miguel, Jesús F

    2016-06-23

    The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first- to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P = .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P = .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249.

  7. TFDP3 confers chemoresistance in minimal residual disease within childhood T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Chu, Ming; Yin, Kailin; Dong, Yujun; Wang, Pingzhang; Xue, Yun; Zhou, Peng; Wang, Yuqi; Wang, Yuedan

    2017-01-01

    Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR). During the 4-week VXLD treatment, the level of TFDP3 increased 4-fold. High expression of TFDP3 was identified in the re-emerging lines (Jurkat/MRD) with increased chemoresistance, which is correlated with partially promoter demethylation of TFDP3. Downregulation of TFDP3 by RNA interference reversed chemoresistance in Jurkat/MRD accompanied by reinstated E2F1 activity that coincided with increased levels of p53, p73, and associated proapoptotic target genes. Importantly, TFDP3 silencing in vivo induced apparent benefit to overcome chemoresistance in combination with VXLD treatment. Collectively, TFDP3 confers chemoresistance in MRD within childhood T-ALL, indicating that TFDP3 is a potential gene therapy target for residual cancer. PMID:27902457

  8. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma

    Science.gov (United States)

    Lahuerta, Juan J.; Pepin, François; González, Marcos; Barrio, Santiago; Ayala, Rosa; Puig, Noemí; Montalban, María A.; Paiva, Bruno; Weng, Li; Jiménez, Cristina; Sopena, María; Moorhead, Martin; Cedena, Teresa; Rapado, Immaculada; Mateos, María Victoria; Rosiñol, Laura; Oriol, Albert; Blanchard, María J.; Martínez, Rafael; Bladé, Joan; San Miguel, Jesús; Faham, Malek; García-Sanz, Ramón

    2014-01-01

    We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (MM) patients using a sequencing-based platform in bone marrow samples from 133 MM patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD– by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD+. When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10−3 27 months, MRD 10−3 to 10−5 48 months, and MRD <10−5 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD+. In complete response patients, the TTP remained significantly longer for MRD– compared with MRD+ patients (131 vs 35 months; P = .0009). PMID:24646471

  9. Minimal Residual Disease Diagnostics and Chimerism in the Post-Transplant Period in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ulrike Bacher

    2011-01-01

    Full Text Available In acute myeloid leukemia (AML, the selection of poor-risk patients for allogeneic hematopoietic stem cell transplantation (HSCT is associated with rather high post-transplant relapse rates. As immunotherapeutic intervention is considered to be more effective before the cytomorphologic manifestation of relapse, post-transplant monitoring gains increasing attention in stem cell recipients with a previous diagnosis of AML. Different methods for detection of chimerism (e.g., microsatellite analysis or quantitative real-time PCR are available to quantify the ratio of donor and recipient cells in the post-transplant period. Various studies demonstrated the potential use of mixed chimerism kinetics to predict relapse of the AML. CD34+-specific chimerism is associated with a higher specificity of chimerism analysis. Nevertheless, a decrease of donor cells can have other causes as well. Therefore, efforts continue to introduce minimal residual disease (MRD monitoring based on molecular mutations in the post-transplant period. The NPM1 (nucleophosmin mutations can be monitored by sensitive quantitative real-time PCR in subsets of stem cell recipients with AML, but for approximately 20% of patients, suitable molecular mutations for post-transplant MRD monitoring are not available so far. This emphasizes the need for an expansion of the panel of MRD markers in the transplant setting.

  10. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL.

    Science.gov (United States)

    Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Burger, Jan; Ferrajoli, Alessandra; Jain, Nitin; Tambaro, Francesco Paolo; Estrov, Zeev; Jorgensen, Jeffrey; Challagundla, Pramoda; Faderl, Stefan H; Wierda, William G

    2014-06-12

    The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798.

  11. Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications

    Science.gov (United States)

    Del Principe, Maria Ilaria; Buccisano, Francesco; Maurillo, Luca; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; Consalvo, Maria Irno; Sarlo, Chiara; Conti, Consuelo; De Santis, Giovanna; De Bellis, Eleonora; Di Veroli, Ambra; Palomba, Patrizia; Attrotto, Cristina; Zizzari, Annagiulia; Paterno, Giovangiacinto; Voso, Maria Teresa; Del Poeta, Giovanni; Lo-Coco, Francesco; Arcese, William; Amadori, Sergio; Venditti, Adriano

    2016-01-01

    Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients’ risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help to identify patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry(MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management. PMID:27872732

  12. Effect of Minimal Disease in a Herd on Reproductive Parameters of Sows

    Directory of Open Access Journals (Sweden)

    Pavel Nevrkla

    2017-01-01

    Full Text Available The aim of this study was evaluation of reproductive performance in sows from herds with minimal disease. Total number of 40 sows were included in the observation and evaluated from the 1st to the 4th parity. The highest reproductive performance was recorded at the 3rd parity. Statistically significant difference (P < 0.05 was found between the 1st and the 3rd parity and highly statistically significant difference (P < 0.01 was recorded between the 2nd and the 3rd parity in number of live‑born piglets. Comparison of numbers of stillborn piglets showed statistically significant difference (P < 0.05 between the mean values of the 1st and the 4th parity. The results also showed highly statistically significant difference (P < 0.01 in number of reared piglets between the 3rd and the 4th parity. The conclusions of this study indicate that creation and maintenance of herds of sows with high health status lead to excellent results in the area of pig reproduction.

  13. Minimal Important Change in the Pelvic Floor Distress Inventory-20 among Women Opting for Conservative Prolapse Treatment

    NARCIS (Netherlands)

    Wiegersma, Marian; Panman, Chantal M C R; Berger, Marjolein Y; De Vet, Henrica C W; Kollen, Boudewijn J; Dekker, Janny H

    2016-01-01

    BACKGROUND: The Pelvic Floor Distress Inventory-20 is used to evaluate symptoms and treatment effects in women with pelvic floor disorders. To interpret changes in the scores of this inventory, information is needed on what patients and clinicians perceive as the minimal important (meaningful) chang

  14. Minimizing impacts of land use change on ecosystem services using multi-criteria heuristic analysis.

    Science.gov (United States)

    Keller, Arturo A; Fournier, Eric; Fox, Jessica

    2015-06-01

    Development of natural landscapes to support human activities impacts the capacity of the landscape to provide ecosystem services. Typically, several ecosystem services are impacted at a single development site and various footprint scenarios are possible, thus a multi-criteria analysis is needed. Restoration potential should also be considered for the area surrounding the permanent impact site. The primary objective of this research was to develop a heuristic approach to analyze multiple criteria (e.g. impacts to various ecosystem services) in a spatial configuration with many potential development sites. The approach was to: (1) quantify the magnitude of terrestrial ecosystem service (biodiversity, carbon sequestration, nutrient and sediment retention, and pollination) impacts associated with a suite of land use change scenarios using the InVEST model; (2) normalize results across categories of ecosystem services to allow cross-service comparison; (3) apply the multi-criteria heuristic algorithm to select sites with the least impact to ecosystem services, including a spatial criterion (separation between sites). As a case study, the multi-criteria impact minimization algorithm was applied to InVEST output to select 25 potential development sites out of 204 possible locations (selected by other criteria) within a 24,000 ha property. This study advanced a generally applicable spatial multi-criteria approach for 1) considering many land use footprint scenarios, 2) balancing impact decisions across a suite of ecosystem services, and 3) determining the restoration potential of ecosystem services after impacts.

  15. [A case of AKI-caused minimal change nephrotic syndrome with concomitant pleuritis].

    Science.gov (United States)

    Watanabe, Renya; Abe, Yasuhiro; Sasaki, Masaru; Hamauchi, Aki; Yasunaga, Tomoe; Kurata, Satoshi; Yasuno, Tetsuhiko; Ito, Kenji; Sasatomi, Yoshie; Hisano, Satoshi; Nakashima, Hitoshi

    2016-01-01

    A twenty-year-old man complaining of chest pain was diagnosed as nephrotic syndrome complicated with pleural effusion and ascites. Despite treatment with antibiotics, his fever and high inflammatory reaction persisted. After hospitalization, his urine volume decreased and renal function had deteriorated. As he was suffering from dyspnea, hemodialysis was performed together with chest drainage. His pleural effusion was exudative, and IVIG treatment was added to the antibiotic treatment. He was diagnosed as suspected developed minimal change nephrotic syndrome (MCNS) and administered prednisolone intravenously. His renal function ameliorated as a result of this treatment, enabling him to withdraw from hemodialysis. Inflammatory reaction gradually decreased and his general condition improved. The result of a renal biopsy examination carried out after the hemodialysis treatment confirmed MCNS, which suggested that MCNS had induced acute kidney injury (AKI) atypically in this case. Generally AKI is not induced by MCNS in youth, but it may occur under severe inflammatory conditions. Physicians should be aware that MCNS in young patients may lead to the development of AKI requiring hemodialysis treatment.

  16. Minimizing the regrets of long-term urban floodplain management decisions under deeply uncertain climate change

    Science.gov (United States)

    Hecht, J. S.; Kirshen, P. H.; Vogel, R. M.

    2016-12-01

    Making long-term floodplain management decisions under uncertain climate change is a major urban planning challenge of the 21stcentury. To support these efforts, we introduce a screening-level optimization model that identifies adaptation portfolios by minimizing the regrets associated with their flood-control and damage costs under different climate change trajectories that are deeply uncertain, i.e. have probabilities that cannot be specified plausibly. This mixed integer program explicitly considers the coupled damage-reduction impacts of different floodwall designs and property-scale investments (first-floor elevation, wet floodproofing of basements, permanent retreat and insurance), recommends implementation schedules, and assesses impacts to stakeholders residing in three types of homes. An application to a stylized municipality illuminates many nonlinear system dynamics stemming from large fixed capital costs, infrastructure design thresholds, and discharge-depth-damage relationships. If stakeholders tolerate mild damage, floodwalls that fully protect a community from large design events are less cost-effective than portfolios featuring both smaller floodwalls and property-scale measures. Potential losses of property tax revenue from permanent retreat motivate municipal property-tax initiatives for adaptation financing. Yet, insurance incentives for first-floor elevation may discourage locally financed floodwalls, in turn making lower-income residents more vulnerable to severe flooding. A budget constraint analysis underscores the benefits of flexible floodwall designs with low incremental expansion costs while near-optimal solutions demonstrate the scheduling flexibility of many property-scale measures. Finally, an equity analysis shows the importance of evaluating the overpayment and under-design regrets of recommended adaptation portfolios for each stakeholder and contrasts them to single-scenario model results.

  17. Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes.

    Science.gov (United States)

    Shah, Amy S; Dolan, Lawrence M; Dabelea, Dana; Stafford, Jeanette M; D'Agostino, Ralph B; Mayer-Davis, Elizabeth J; Marcovina, Santica; Imperatore, Giuseppina; Wadwa, R Paul; Daniels, Stephen R; Reynolds, Kristi; Hamman, Richard F; Bowlby, Deborah A; Maahs, David M

    2015-06-01

    Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D. We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c). We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz. Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Class II-associated invariant chain peptide as predictive immune marker in minimal residual disease in acute myeloid leukemia

    NARCIS (Netherlands)

    M.M. van Luijn (Marvin M.); W. van den Ancker (Willemijn); S.M. van Ham (Marieke); A.A. van de Loosdrecht (Arjan)

    2014-01-01

    textabstractThe majority of patients with acute myeloid leukemia (AML) reach complete remission after high-dose chemotherapy. Still, half of these patients experience a relapse due to presence of minimal residual disease (MRD). Here we discuss the poor prognostic role of class II-associated

  19. Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL

    NARCIS (Netherlands)

    Willemse, MJ; Seriu, T; Hettinger, K; d'Aniello, E; Hop, WCJ; Panzer-Grumayer, ER; Biondi, A; Schrappe, M; Kamps, WA; Masera, G; Gadner, H; Riehm, H; Bartram, CR; van Dongen, JJM

    2002-01-01

    We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of o

  20. Class II-associated invariant chain peptide as predictive immune marker in minimal residual disease in acute myeloid leukemia

    NARCIS (Netherlands)

    M.M. van Luijn (Marvin M.); W. van den Ancker (Willemijn); S.M. van Ham (Marieke); A.A. van de Loosdrecht (Arjan)

    2014-01-01

    textabstractThe majority of patients with acute myeloid leukemia (AML) reach complete remission after high-dose chemotherapy. Still, half of these patients experience a relapse due to presence of minimal residual disease (MRD). Here we discuss the poor prognostic role of class II-associated invarian

  1. Class II-associated invariant chain peptide as predictive immune marker in minimal residual disease in acute myeloid leukemia

    OpenAIRE

    van Luijn, Marvin M.; van den Ancker, Willemijn; van Ham, S Marieke; Arjan A. van de Loosdrecht

    2014-01-01

    The majority of patients with acute myeloid leukemia (AML) reach complete remission after high-dose chemotherapy. Still, half of these patients experience a relapse due to presence of minimal residual disease (MRD). Here we discuss the poor prognostic role of class II-associated invariant chain peptide (CLIP) expression on residual leukemic cells.

  2. [Multiple myeloma: Maintenance therapy after autologous hematopoietic stem cell transplantation, depending on minimal residual disease].

    Science.gov (United States)

    Solovyev, M V; Mendeleeva, L P; Pokrovskaya, O S; Nareyko, M V; Firsova, M V; Galtseva, I V; Davydova, Yu O; Kapranov, N M; Kuzmina, L A; Gemdzhian, E G; Savchenko, V G

    2017-01-01

    To determine the efficiency of maintenance therapy with bortezomib in patients with multiple myeloma (MM) who have achieved complete remission (CR) after autologous hematopoietic stem cell (auto-HSCT), depending on the presence of minimal residual disease (MRD). In January 2014 to February 2016, fifty-two MM patients (19 men and 33 women) aged 24 to 66 years (median 54 years), who had achieved CR after auto-HSCT, were randomized to perform maintenance therapy with bortezomib during a year. On day 100 after auto-HSCT, all the patients underwent immunophenotyping of bone marrow plasma cells by 6-color flow cytometry to detect MRD. Relapse-free survival (RFS) was chosen as a criterion for evaluating the efficiency of maintenance therapy. After auto-HSCT, MRD-negative patients had a statistically significantly higher 2-year RFS rate than MRD-positive patients: 52.9% (95% confidence interval (CI), 35.5 to 70.5%) versus 37.2% (95% CI, 25.4 to 49.3%) (p=0.05). The presence of MRD statistically significantly increased the risk of relapse (odds ratio 1.7; 95% CI, 1.2 to 3.4; p=0.05). Two-year cumulative risk of relapse (using the Kaplan-Meier) after auto-HSCT did not statistically significantly differ in MRD-negative patients receiving (n=15) and not receiving (n=10) maintenance therapy with bortezomib (p=0.58). After completion of maintenance treatment, 42% of the MRD-positive patients achieved a negative status. In the MRD-positive patients who had received maintenance therapy, the average time to recurrence was 5 months longer than that in the naïve patients: 17.3 versus 12.3 months. The MRD status determined in MM patients who have achieved CR after auto-HSCT is an important factor for deciding on the use of maintenance therapy.

  3. AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR LYMPHOMA: AN EVALUATION OF GRAFTS SOURCE AND MINIMAL RESIDUAL DISEASE

    Institute of Scientific and Technical Information of China (English)

    HOU Shu-ling; ZHANG Qiao-hua; HAN Wei-e; GUI Wei; WANG Yu-luan

    2005-01-01

    Objective: To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) for aggressive lymphoma and to study the problem of minimal residual disease (MRD). Methods: 14 lymphoma patients who had lymphoma with high risk factors, relapsed lymphoma or refractory lymphoma received autologous bone marrow transplantation (ABMT). 14 lymphoma patients who were similar to ABMT group received autologous peripheral blood stem cells transplantation (APBSCT). Regimen of CBV (cyclophos phamide 50~60 mg/kg/d×2 d, carmustine 15 mg/kg/d×1 d,etoposide 45~60 mg/kg/d×1 d) was received by all the patients as conditioning regimen in the transplant pretreatment followed by ABMT or APBSCT. Autologous peripheral blood stem cell (APBSC) was mobilized by CTX 2g~3g/m2/d×2 d iv and G-CSF 5 μg/kg/d for five to seven days. MRD was continually supervised by PCR in bone marrow before and after transplantation. Cellular immunocyte function, such as natural killer cell (NK), CD3, CD4, CD8 and sIL-2R was tested before and twenty days after transplantation. Results: In ABMT group, the median time for hematopoietic recovery of absolute neutrophilia counts ≥0.5×109/L and platelet counts ≥20×109/L was +18 days and +20 days respectively. In contrast, the APBSCT group was both at 12 days. Patients who have undergone ABMT all got complete remission (CR), while 81.8% patients in APBSCT group got CR. The 3-year disease free survival (DFS) in APBSCT and ABMT group was 75% and 72.7% respectively (P>0.05). The mean days of immunity recovering in APBSCT was ±20 days. After transplantation, MRD in 11 patients were positive, in whom 6 patients died. Conclusion: Aggressive lymphoma patients' hemapoiesis recovered more rapidly in APBSCT group than that in ABMT group, but 3-year DFS had no statistical difference. Patients positive for IgH/TCR-γ by

  4. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  5. The response of Mediterranean thermohaline circulation to climate change: a minimal model

    Directory of Open Access Journals (Sweden)

    P. Th. Meijer

    2009-11-01

    Full Text Available Physics-based understanding of the effects of paleoclimate and paleogeography on the thermohaline circulation of the Mediterranean Sea requires an ocean model capable of long integrations and involving a minimum of assumptions about the atmospheric forcing. Here we examine the sensitivity of the deep circulation in the eastern Mediterranean basin to changes in atmospheric forcing, considered a key factor in the deposition of organic-rich sediments (sapropels. To this extent we explore the setup of an ocean general circulation model (MOMA with realistic (present-day bathymetry and highly idealized forcing. The model proves able to qualitatively capture some important features of the large-scale overturning circulation, in particular for the eastern basin. The response to (i a reduction in the imposed meridional temperature gradient, or (ii a reduction in net evaporation, proves to be non-linear and, under certain conditions, of transient nature. Consistent with previous model studies, but now based on a minimum of assumptions, we find that a reduction in net evaporation (such as due to an increase in freshwater input may halt the deep overturning circulation. The ability to perform long model integrations allows us to add the insight that, in order to have the conditions favourable for sapropel formation persist, we must also assume that the vertical mixing of water properties was reduced. The "minimal" model here presented opens the way to experiments in which one truly follows the basin circulation into, or out of, the period of sapropel formation and where forcing conditions are continously adjusted to the precession cycle.

  6. The response of Mediterranean thermohaline circulation to climate change: a minimal model

    Directory of Open Access Journals (Sweden)

    P. Th. Meijer

    2009-06-01

    Full Text Available Physics-based understanding of the effects of paleoclimate and paleogeography on the thermohaline circulation of the Mediterranean Sea requires an ocean model capable of long integrations and involving a minimum of assumptions about the atmospheric forcing. Here we examine the sensitivity of the deep circulation in the eastern Mediterranean basin to changes in atmospheric forcing, considered a key factor in the deposition of organic-rich sediments (sapropels. To this extent we explore the setup of an ocean general circulation model (MOMA with realistic (present-day bathymetry and highly idealized forcing. The model proves able to qualitatively capture some important features of the large-scale overturning circulation, in particular for the eastern basin. The response to (i a reduction in the imposed meridional temperature gradient, or (ii a reduction in net evaporation, proves to be non-linear and, under certain conditions, of transient nature. Consistent with previous model studies, but now based on a minimum of assumptions, we find that a reduction in net evaporation (such as due to an increase in freshwater input may halt the deep overturning circulation. The ability to perform long model integrations allows us to add the insight that, in order to have the conditions favourable for sapropel formation persist, we must also assume that the vertical mixing of water properties was reduced. The "minimal" model here presented opens the way to experiments in which one truly follows the basin circulation into, or out of, the period of sapropel formation and where forcing conditions are continuously adjusted to the precession cycle.

  7. DD genotype of ACE gene in boys: may it be a risk factor for minimal change nephrotic syndrome?

    Science.gov (United States)

    Alasehirli, Belgin; Balat, Ayşe; Büyükçelik, Mithat

    2012-01-01

    It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.

  8. Bcl-2 GENE REARRANGEMENT DETERMINED BY PCR AS A MEAN TO DETECT MINIMAL RESIDUAL DISEASE IN MALIGNANT LYMPHOMAS

    Institute of Scientific and Technical Information of China (English)

    XIANG Zhi-fu; LU Yu-ying; LAI Yong-rong; CHEN Yan; LI Hui-yu; ZOU Ping

    1999-01-01

    Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase chain reaction (PCR) to detect bcl-2 gene rearrangement and using serial dilution method to define the sensitivity of PCR. Results: In 9 different malignant lymphoma cell lines, Su-DHL-4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was 1:105. In 16 patients with follicular lymphoma, the peripheral blood and bone marrow were PCR positive in 4 cases both at initial diagnosis and after complete remission. Conclusion:Detection of bcl-2 gene rearrangement by PCR provides a sensitive and specific assay of minimal residual disease.It is helpful to improve staging of disease, prognosis and evaluation of the treatment results.

  9. Evaluation of minimal disseminated disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients.

    Science.gov (United States)

    Dolmans, M M; Iwahara, Y; Donnez, J; Soares, M; Vaerman, J L; Amorim, C A; Poirel, H

    2016-10-01

    What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? Minimal disseminated disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented

  10. Minimally invasive unilateral pedicle screw fixation and lumbar interbody fusion for the treatment of lumbar degenerative disease.

    Science.gov (United States)

    Lin, Bin; Xu, Yang; He, Yong; Zhang, Bi; Lin, Qiuyan; He, Mingchang

    2013-08-01

    Minimally invasive unilateral pedicle screw fixation for the treatment of degenerative lumbar diseases has won the support of many surgeons. However, few data are available regarding clinical research on unilateral pedicle screw fixation associated with minimally invasive techniques for the treatment of lumbar spinal diseases. The purpose of this study was to evaluate clinical outcomes in a selected series of patients with lumbar degenerative diseases treated with minimally invasive unilateral vs classic bilateral pedicle screw fixation and lumbar interbody fusion. Patients in the unilateral group (n=43) underwent minimally invasive unilateral pedicle screw fixation with the Quadrant system (Medtronic, Memphis, Tennessee). The bilateral group (n=42) underwent bilateral instrumentation via the classic approach. Visual analog scale pain scores, Oswestry Disability Index scores, fusion rate, operative time, blood loss, and complications were analyzed. Mean operative time was 75 minutes in the unilateral group and 95 minutes in the bilateral group. Mean blood loss was 220 mL in the unilateral group and 450 mL in the bilateral group. Mean postoperative visual analog scale pain score was 3.10±0.16 in the unilateral group and 3.30±1.10 in the bilateral group. Mean postoperative Oswestry Disability Index score was 15.67±2.3 in the unilateral group and 14.93±2.6 in the bilateral group. Successful fusion was achieved in 92.34% of patients in the unilateral group and 93.56% of patients in the bilateral group. Minimally invasive unilateral pedicle screw fixation is an effective and reliable option for the surgical treatment of lumbar degenerative disease. It causes less blood loss, requires less operative time, and has a fusion rate comparable with that of conventional bilateral fixation. Copyright 2013, SLACK Incorporated.

  11. Rituximab in minimal change nephropathy and focal segmental glomerulosclerosis: report of four cases and review of the literature.

    NARCIS (Netherlands)

    Peters, H.P.E.; Kar, NC van de; Wetzels, J.F.M.

    2008-01-01

    Minimal change nephropathy (MCNS) and focal segmental glomerulosclerosis (FSGS) are the main causes of the idiopathic nephrotic syndrome. MCNS usually responds to steroids and the long-term prognosis is generally good. However, some patients require prolonged treatment with immunosuppressive agents.

  12. Responsiveness and Minimal Clinically Important Change of the Pain Disability Index in Patients With Chronic Back Pain

    NARCIS (Netherlands)

    Soer, Remko; Reneman, Michiel F.; Vroomen, Patrick C. A. J.; Stegeman, Patrick; Coppes, Maarten H.

    2012-01-01

    Study Design. Prospective cohort study. Objective. The objective of this study was to test the responsiveness and minimal clinically important change (MCIC) of the Pain Disability Index (PDI) in patients with chronic back pain (CBP). Summary of Background Data. Treatment of patients with CBP is prim

  13. Minimal Important Change in the Pelvic Floor Distress Inventory-20 among Women Opting for Conservative Prolapse Treatment

    NARCIS (Netherlands)

    Wiegersma, Marian; Panman, Chantal M. C. R.; Berger, Marjolein Y.; De Vet, Henrica C. W.; Kollen, Boudewijn J.; Dekker, Janny H.

    BACKGROUND: The Pelvic Floor Distress Inventory-20 is used to evaluate symptoms and treatment effects in women with pelvic floor disorders. To interpret changes in the scores of this inventory, information is needed about what patients and clinicians perceive as the minimal important (meaningful)

  14. Developing neonatal minimally invasive surgery: Innovation, techniques, and helping an industry to change.

    Science.gov (United States)

    Rothenberg, Steven S

    2015-02-01

    The field of minimally invasive surgery (MIS) in neonates and infants is a relatively new field, evolving over the last 20years. This has required the development of not only new techniques but new instruments. The process has resulted in a unique partnership between pediatric minimally invasive surgeons and industry, as both groups have struggled to find the right mix of need, technical viability, and economic sustainability. The results have spawned a new generation of MIS instrumentation that not only enables the neonatal MIS surgeon but also leads the way in the field of mini-laparoscopy in children and adults.

  15. Impact of climate change on waterborne diseases

    OpenAIRE

    Enzo Funari; Maura Manganelli; Luciana Sinisi

    2012-01-01

    Change in climate and water cycle will challenge water availability but it will also increase the exposure to unsafe water. Floods, droughts, heavy storms, changes in rain pattern, increase of temperature and sea level, they all show an increasing trend worldwide and will affect biological, physical and chemical components of water through different paths thus enhancing the risk of waterborne diseases. This paper is intended, through reviewing the available literature, to highlight environmen...

  16. Climate change impacts on coffee rust disease

    Science.gov (United States)

    Alfonsi, W. M. V.; Koga-Vicente, A.; Pinto, H. S.; Alfonsi, E. L., Sr.; Coltri, P. P.; Zullo, J., Jr.; Patricio, F. R.; Avila, A. M. H. D.; Gonçalves, R. R. D. V.

    2016-12-01

    Changes in climate conditions and in extreme weather events may affect the food security due to impacts in agricultural production. Despite several researches have been assessed the impacts of extremes in yield crops in climate change scenarios, there is the need to consider the effects in pests and diseases which increase losses in the sector. Coffee Arabica is an important commodity in world and plays a key role in Brazilian agricultural exports. Although the coffee crop has a world highlight, its yield is affected by several factors abiotic or biotic. The weather as well pests and diseases directly influence the development and coffee crop yield. These problems may cause serious damage with significant economic impacts. The coffee rust, caused by the fungus Hemileia vastarix,is among the diseases of greatest impact for the crop. The disease emerged in Brazil in the 70s and is widely spread in all producing regions of coffee in Brazil, and in the world. Regions with favorable weather conditions for the pathogen may exhibit losses ranging from 30% to 50% of the total grain production. The evaluation of extreme weather events of coffee rust disease in futures scenarios was carried out using the climatic data from CMIP5 models, data field of coffee rust disease incidence and, incubation period simulation data for Brazilian municipalities. Two Regional Climate Models were selected, Eta-HadGEM2-ES and Eta-MIROC5, and the Representative Concentration Pathways 8.5 w/m2 was adopted. The outcomes pointed out that in these scenarios the period of incubation tends to decrease affecting the coffee rust disease incidence, which tends to increase. Nevertheless, the changing in average trends tends to benefit the reproduction of the pathogen. Once the temperature threshold for the disease reaches the adverse conditions it may be unfavorable for the incidence.

  17. Quantification of the Mutant CALR Allelic Burden by Digital PCR: Application to Minimal Residual Disease Evaluation after Bone Marrow Transplantation.

    Science.gov (United States)

    Mansier, Olivier; Migeon, Marina; Saint-Lézer, Arnaud; James, Chloé; Verger, Emmanuelle; Robin, Marie; Socié, Gérard; Bidet, Audrey; Mahon, François-Xavier; Cassinat, Bruno; Lippert, Eric

    2016-01-01

    With the recent discovery of CALR mutations, >80% of patients with myeloproliferative neoplasms carry a phenotype-driving mutation. For JAK2 V617F, the most frequent mutation in myeloproliferative neoplasms, accurate determination of mutational loads is of interest at diagnosis, for phenotypic and prognostic purposes, and during follow-up for minimal residual disease assessment. We developed a digital PCR technique that allowed the accurate determination of CALR allelic burdens for the main mutations (types 1 and 2). Compared with the commonly used fluorescent PCR product analysis, digital PCR is more precise, reproducible, and accurate. Furthermore, this method reached a very high sensitivity. We detected at least 0.025% CALR mutants. It can thus be used for patient characterization at diagnosis and for minimal residual disease monitoring. When applied to patients with primary myelofibrosis who underwent hematopoietic stem cell transplant, the digital PCR detected low levels of minimal residual disease. After negativation of the mutational load in all patients, the disease reappeared at a low level in one patient, preceding hematologic relapse. In conclusion, digital PCR adapted to type 1 and 2 CALR mutations is an inexpensive, highly precise, and sensitive technique suitable for evaluation of myeloproliferative neoplasm patients during follow-up.

  18. Climate change and plant disease management.

    Science.gov (United States)

    Coakley, S M; Scherm, H; Chakraborty, S

    1999-09-01

    ▪ Abstract  Research on impacts of climate change on plant diseases has been limited, with most work concentrating on the effects of a single atmospheric constituent or meteorological variable on the host, pathogen, or the interaction of the two under controlled conditions. Results indicate that climate change could alter stages and rates of development of the pathogen, modify host resistance, and result in changes in the physiology of host-pathogen interactions. The most likely consequences are shifts in the geographical distribution of host and pathogen and altered crop losses, caused in part by changes in the efficacy of control strategies. Recent developments in experimental and modeling techniques offer considerable promise for developing an improved capability for climate change impact assessment and mitigation. Compared with major technological, environmental, and socioeconomic changes affecting agricultural production during the next century, climate change may be less important; it will, however, add another layer of complexity and uncertainty onto a system that is already exceedingly difficult to manage on a sustainable basis. Intensified research on climate change-related issues could result in improved understanding and management of plant diseases in the face of current and future climate extremes.

  19. Global climate change and infectious diseases

    Energy Technology Data Exchange (ETDEWEB)

    Shope, R. (Yale Univ. School of Medicine, New Haven, CT (United States))

    1991-12-01

    The effects of global climate change on infectious diseases are hypothetical until more is known about the degree of change in temperature and humidity that will occur. Diseases most likely to increase in their distribution and severity have three-factor (agent, vector, and human being) and four-factor (plus vertebrate reservoir host) ecology. Aedes aegypti and Aedes albopictus mosquitoes may move northward and have more rapid metamorphosis with global warming. These mosquitoes transmit dengue virus, and Aedes aegypti transmits yellow fever virus. The faster metamorphosis and a shorter extrinsic incubation of dengue and yellow fever viruses could lead to epidemics in North America. Vibrio cholera is harbored persistently in the estuaries of the U.S. Gulf Coast. Over the past 200 years, cholera has become pandemic seven times with spread from Asia to Europe, Africa, and North America. Global warming may lead to changes in water ecology that could enhance similar spread of cholera in North America. Some other infectious diseases such as LaCrosse encephalitis and Lyme disease are caused by agents closely dependent on the integrity of their environment. These diseases may become less prominent with global warming because of anticipated modification of their habitats. Ecological studies will help as to understand more fully the possible consequences of global warming. New and more effective methods for control of vectors will be needed. 12 refs., 1 tab.

  20. Could (Disseminated and Residual Minimal Disease be a useful prognostic marker in non-Hodgkin paediatric Lymphomas?

    Directory of Open Access Journals (Sweden)

    Lara Mussolin

    2014-06-01

    Full Text Available Minimal Disseminated Disease (MDD represents the small number of tumour cells in the patients' bone marrow at the time of diagnosis, whereas Minimal Residual Disease (MRD represents the small number of tumour cells remaining in the bone marrow during treatment. Generally, MDD and MRD are measured by polymerase chain reaction, a highly sensitive technique. For a long time, bone marrow involvement has been considered an uncommon event in solid tumours. However, in recent years, several studies demonstrated that MDD and MRD could be powerful tools in paediatric non-Hodgkin lymphoma for stratifying patients in different prognostic groups. Risk stratification in future clinical trials on non-Hodgkin lymphoma based on these newly identified risk categories should be useful to improve therapies in order to increase survival for high-risk patients and decrease toxicity for low-risk patients.http://dx.doi.org/10.7175/cmi.v8i2.902 

  1. The Changing Pattern of Nontuberculous Mycobacterial Disease

    Directory of Open Access Journals (Sweden)

    Joseph O Falkinham

    2003-01-01

    Full Text Available Nontuberculous mycobacteria are human opportunistic pathogens whose source of infection is the environment. These include both slow-growing (eg, Mycobacterium kansasii and Mycobacterium avium and rapid-growing (eg, Mycobacterium abscessus and Mycobacterium fortuitum species. Transmission is through ingestion or inhalation of water, particulate matter or aerosols, or through trauma. The historic presentation of pulmonary disease in older individuals with predisposing lung conditions and in children has been changing. Pulmonary disease in elderly individuals who lack the classic predisposing lung conditions is increasing. Pulmonary disease and hypersensitivity pneumonitis have been linked with occupational or home exposures to nontuberculous mycobacteria. There has been a shift from Mycobacterium scrofulaceum to M avium in children with cervical lymphadenitis. Further, individuals who are immunosuppressed due to therapy or HIV-infection are at a greatly increased risk for nontuberculous mycobacterial infection. The changing pattern of nontuberculous mycobacterial disease is due in part to the ability of these pathogens to survive and proliferate in habitats that they share with humans, such as drinking water. The advent of an aging population and an increase in the proportion of immunosuppressed individuals suggest that the prevalence of nontuberculous mycobacterial disease will increase.

  2. Octocoral diseases in a changing ocean

    Science.gov (United States)

    Weil, Ernesto; Rogers, Caroline S.; Croquer, Aldo

    2017-01-01

    Octocorals (Cnidaria, Octocorallia) constitute a geographically widely distributed and common group of marine invertebrates commonly referred to as “soft-corals,” “sea fans,” “horny corals,” “sea feathers,” and “sea plumes.” They are found from shallow coastal habitats to mesophotic and abyssal depths. Octocorals are important members of most Atlantic-Caribbean, Indo-Pacific, and Mediterranean coastal and mesophotic reef communities; however, information about their susceptibility to diseases, predation, and competition, and their relationship with changing environmental conditions is limited. At least 19 diseases have been observed in at least 42 common octocoral species throughout their range. Twelve of these have been reported in the wider Caribbean (CA), one in Brazil (BR), two in the Mediterranean (ME), one in the Eastern Pacific (EP), and three in the western Pacific (WP). Pathogenic and/or environmental causes have been identified for eight diseases, including viruses, terrestrial fungi, protozoans, bacteria and cyanobacteria, filamentous algae, parasitic copepods, and high temperature. Only a few of the suspected pathogens have been tested with Koch’s postulates. At least eight disease outbreaks have led to extensive octocoral mortalities in the CA, ME, BR, and EP with detrimental ecological consequences. The fungal disease Aspergillosis has produced the highest mortalities in the CA and the EP. Other fungi, protozoans, and the bacterium Vibrio coralliilyticus were identified as potential causes of the death of millions of colonies in two Mediterranean disease outbreaks. Bacterial and fungal agents seemed to be responsible for the mass mortalities in Brazil and the WP. Most outbreaks in all regions were linked to high thermal anomalies associated with climate change, which seems to be the major driver. Other biological stressors such as predation and/or competition produce injuries that may contribute to the spread of infections and

  3. Changing Spectrum of Celiac Disease in India

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    Kaushal Kishor Prasad

    2010-12-01

    Full Text Available Objective:Celiac disease is an important cause of chronic diarrhea, failure to thrive, and anemia in children. Mode of presentation of celiac disease has changed in last few years. Study was conducted to determine the mode of clinical presentation of a large group of patients with celiac disease and whether there has been a change in the presentation with the time. Methods:A prospective study was conducted on 134 children diagnosed to be having celiac disease in the Pediatric Gastroenterology, PGIMER, Chandigarh, from July 1st 2006 to December 31st 2007. Their detailed clinical profile was recorded on a pretested proforma and all patients underwent hemogram, liver function tests, IgA Anti tTG, and upper GI endoscopy. Findings:Major symptoms at presentation were diarrhea (54.5%, failure to thrive (52.2%, abdominal distension (41%, anemia (40%, pain abdomen (19.4%, vomiting (15.7% and constipation (2.2% of cases. 60.4% of patients had short stature. Anemia was microcytic hypochromic in 79.1% of patients, and dimorphic in 20.9%. Serum transaminases were raised in 38.8 % of cases. The mean serum anti tTG level was 164.24U/ml (Range 0-749 U/ml and levels correlated with the severity of small intestinal damage on biopsy. 15 patients were negative for the serology but 8 out of them had IgA deficiency and all had histopathology suggestive of celiac disease. Conclusion:Classical presentation of celiac disease is less commonly encountered these days probably related to the more widespread use of serologic testing and early recognition of atypical manifestations of celiac disease.

  4. [Possible changes in energy-minimizer mechanisms of locomotion due to chronic low back pain - a literature review].

    Science.gov (United States)

    de Carvalho, Alberito Rodrigo; Andrade, Alexandro; Peyré-Tartaruga, Leonardo Alexandre

    2015-01-01

    One goal of the locomotion is to move the body in the space at the most economical way possible. However, little is known about the mechanical and energetic aspects of locomotion that are affected by low back pain. And in case of occurring some damage, little is known about how the mechanical and energetic characteristics of the locomotion are manifested in functional activities, especially with respect to the energy-minimizer mechanisms during locomotion. This study aimed: a) to describe the main energy-minimizer mechanisms of locomotion; b) to check if there are signs of damage on the mechanical and energetic characteristics of the locomotion due to chronic low back pain (CLBP) which may endanger the energy-minimizer mechanisms. This study is characterized as a narrative literature review. The main theory that explains the minimization of energy expenditure during the locomotion is the inverted pendulum mechanism, by which the energy-minimizer mechanism converts kinetic energy into potential energy of the center of mass and vice-versa during the step. This mechanism is strongly influenced by spatio-temporal gait (locomotion) parameters such as step length and preferred walking speed, which, in turn, may be severely altered in patients with chronic low back pain. However, much remains to be understood about the effects of chronic low back pain on the individual's ability to practice an economic locomotion, because functional impairment may compromise the mechanical and energetic characteristics of this type of gait, making it more costly. Thus, there are indications that such changes may compromise the functional energy-minimizer mechanisms. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  5. Minimal access surgery in Castleman disease in a child, a case report

    Directory of Open Access Journals (Sweden)

    Jan F. Svensson

    2015-07-01

    Full Text Available This case report describes a child with Castleman disease. We present an overview of the disease, the investigation leading to the diagnosis, the laparoscopic approach for surgical treatment and the follow up. This rare entity must be considered in cases of long-standing abdominal pain, cross-sectional imaging is beneficial and we support the use of laparoscopic intervention in the treatment of unifocal abdominal Castleman disease.

  6. Assessing impulsivity changes in Alzheimer disease.

    Science.gov (United States)

    Rochat, Lucien; Delbeuck, Xavier; Billieux, Joël; d'Acremont, Mathieu; Van der Linden, Anne-Claude Juillerat; Van der Linden, Martial

    2008-01-01

    Impulsive behaviors are common in brain-damaged patients including those with neurodegenerative diseases such as Alzheimer disease (AD). The objective of this study was to develop and validate a short version of the UPPS Impulsive Behavior Scale assessing changes on 4 different dimensions of impulsivity, namely urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking, arising in the course of a neurodegenerative disease. To this end, caregivers of 83 probable AD patients completed a short questionnaire adapted from the UPPS Impulsive Behavior Scale. Exploratory and confirmatory factor analyses of the data were performed and revealed that a model with 4 distinct but related latent variables corresponding to 4 different dimensions of impulsivity fit the data best. Furthermore, the results showed that lack of perseverance, followed by lack of premeditation and urgency, increased after the onset of the disease, whereas sensation seeking decreased. Overall, the multifaceted nature of impulsivity was confirmed in a sample of AD patients, whose caregivers reported significant changes regarding each facet of impulsivity. Consequently, the short version of the UPPS Impulsive Behavior Scale opens up interesting prospects for a better comprehension of behavioral symptoms of dementia.

  7. Minimizing Climate Change Impacts through the Application of Green Building Principles

    OpenAIRE

    Baharuddin

    2014-01-01

    The presentation explains the climate change and the role of green building in minimising the impact of climate change. The presentation covers the emerging issues, sustainable building, green building certification which covers: sustainable site, water efficiency, energy and

  8. Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteria-poliomyelitis-vaccination

    Directory of Open Access Journals (Sweden)

    Clajus Christian

    2009-08-01

    Full Text Available Abstract Background The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS. In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. Case presentation A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l. About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. Conclusion Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.

  9. Chagas disease: changes in knowledge and management.

    Science.gov (United States)

    Lescure, François-Xavier; Le Loup, Guillaume; Freilij, Hector; Develoux, Michel; Paris, Luc; Brutus, Laurent; Pialoux, Gilles

    2010-08-01

    More than 100 years after the discovery of human American trypanosomiasis by Carlos Chagas, our knowledge and management of the disease are profoundly changing. Substantial progress made by disease control programmes in most endemic areas contrasts with persisting difficulties in the Gran Chaco region in South America and the recent emergence of the disease in non-endemic areas because of population movements. In terms of pathogenesis, major discoveries have been made about the life cycle and genomics of Trypanosoma cruzi, and the role of the parasite itself in the chronic phase of the disease. From a clinical perspective, a growing number of arguments have challenged the notion of an indeterminate phase, and suggest new approaches to manage patients. New methods such as standardised PCR will be necessary to ensure follow-up of this chronic infection. Although drugs for treatment of Chagas disease are limited, poorly tolerated, and not very effective, treatment indications are expanding. The results of the Benznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT) trial in 2012 will also help to inform treatment. Mobilisation of financial resources to fund research on diagnosis and randomised controlled trials of treatment are international health priorities.

  10. Lactacidosis in the neonate is minimized by prenatal detection of congenital heart disease

    NARCIS (Netherlands)

    Verheijen, PM; Lisowski, LA; Stoutenbeek, P; Hitchcock, JF; Bennink, GBWE; Meijboom, EJ

    2002-01-01

    Objectives To investigate the impact of prenatal detection of congenital heart disease on preventing severe preoperative lactacidosis. Design Patients operated upon for congenital heart disease during the first 31 days of life (n=209) were studied retrospectively, 21 were diagnosed prenatally and 18

  11. MINIMALLY INVASIVE SURGERY FOR GASTRIC CANCER: TIME TO CHANGE THE PARADIGM.

    Science.gov (United States)

    Barchi, Leandro Cardoso; Jacob, Carlos Eduardos; Bresciani, Cláudio José Caldas; Yagi, Osmar Kenji; Mucerino, Donato Roberto; Lopasso, Fábio Pinatel; Mester, Marcelo; Ribeiro-Júnior, Ulysses; Dias, André Roncon; Ramos, Marcus Fernando Kodama Pertille; Cecconello, Ivan; Zilberstein, Bruno

    2016-01-01

    Minimally invasive surgery widely used to treat benign disorders of the digestive system, has become the focus of intense study in recent years in the field of surgical oncology. Since then, the experience with this kind of approach has grown, aiming to provide the same oncological outcomes and survival to conventional surgery. Regarding gastric cancer, surgery is still considered the only curative treatment, considering the extent of resection and lymphadenectomy performed. Conventional surgery remains the main modality performed worldwide. Notwithstanding, the role of the minimally invasive access is yet to be clarified. To evaluate and summarize the current status of minimally invasive resection of gastric cancer. A literature review was performed using Medline/PubMed, Cochrane Library and SciELO with the following headings: gastric cancer, minimally invasive surgery, robotic gastrectomy, laparoscopic gastrectomy, stomach cancer. The language used for the research was English. 28 articles were considered, including randomized controlled trials, meta-analyzes, prospective and retrospective cohort studies. Minimally invasive gastrectomy may be considered as a technical option in the treatment of early gastric cancer. As for advanced cancer, recent studies have demonstrated the safety and feasibility of the laparoscopic approach. Robotic gastrectomy will probably improve outcomes obtained with laparoscopy. However, high cost is still a barrier to its use on a large scale. A cirurgia minimamente invasiva amplamente usada para tratar doenças benignas do aparelho digestivo, tornou-se o foco de intenso estudo nos últimos anos no campo da oncologia cirúrgica. Desde então, a experiência com este tipo de abordagem tem crescido, com o objetivo de fornecer os mesmos resultados oncológicos e sobrevivência à cirurgia convencional. Em relação ao câncer gástrico, o tratamento cirúrgico ainda é considerado o único tratamento curativo, considerando a extensão da

  12. Meningococcal disease: changes in epidemiology and prevention

    Directory of Open Access Journals (Sweden)

    Chang Q

    2012-09-01

    Full Text Available Qiuzhi Chang,1 Yih-Ling Tzeng,2 David S Stephens1–31Department of Epidemiology, Rollins School of Public Health, Emory University, 2Department of Medicine, Emory University School of Medicine, 3Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Atlanta, GAAbstract: The human bacterial pathogen Neisseria meningitidis remains a serious worldwide health threat, but progress is being made toward the control of meningococcal infections. This review summarizes current knowledge of the global epidemiology and the pathophysiology of meningococcal disease, as well as recent advances in prevention by new vaccines. Meningococcal disease patterns and incidence can vary dramatically, both geographically and over time in populations, influenced by differences in invasive meningococcal capsular serogroups and specific genotypes designated as ST clonal complexes. Serogroup A (ST-5, ST-7, B (ST-41/44, ST-32, ST-18, ST-269, ST-8, ST-35, C (ST-11, Y (ST-23, ST-167, W-135 (ST-11 and X (ST-181 meningococci currently cause almost all invasive disease. Serogroups B, C, and Y are responsible for the majority of cases in Europe, the Americas, and Oceania; serogroup A has been associated with the highest incidence (up to 1000 per 100,000 cases and large outbreaks of meningococcal disease in sub-Saharan Africa and previously Asia; and serogroups W-135 and X have emerged to cause major disease outbreaks in sub-Saharan Africa. Significant declines in meningococcal disease have occurred in the last decade in many developed countries. In part, the decline is related to the introduction of new meningococcal vaccines. Serogroup C polysaccharide-protein conjugate vaccines were introduced over a decade ago, first in the UK in a mass vaccination campaign, and are now widely used; multivalent meningococcal conjugate vaccines containing serogroups A, C, W-135, and/or Y were first used for adolescents in the US in 2005 and have now expanded

  13. Impact of climate change on waterborne diseases

    Directory of Open Access Journals (Sweden)

    Enzo Funari

    2012-12-01

    Full Text Available Change in climate and water cycle will challenge water availability but it will also increase the exposure to unsafe water. Floods, droughts, heavy storms, changes in rain pattern, increase of temperature and sea level, they all show an increasing trend worldwide and will affect biological, physical and chemical components of water through different paths thus enhancing the risk of waterborne diseases. This paper is intended, through reviewing the available literature, to highlight environmental changes and critical situations caused by floods, drought and warmer temperature that will lead to an increase of exposure to water related pathogens, chemical hazards and cyanotoxins. The final aim is provide knowledge-based elements for more focused adaptation measures.

  14. Impact of endoscopically minimal involvement on IL-8 mRnA expression in esophageal mucosa of Patients with non-erosive reflux disease

    Institute of Scientific and Technical Information of China (English)

    Yusei Kanazawa; Ikuo Murata; Shunichi Yamashita; Shigeru Kohno; Hajime Isomoto; Chun-Yang Wen; Ai-Ping Wang; Vladimir A Saenko; Akira Ohtsuru; Fuminao Takeshima; Katsuhisa Omagari; Yohei Mizuta

    2003-01-01

    AIM: Little has been known about the pathogenesis of nonerosive reflux disease (NERD). Recent studies have implicated interleukin 8 (IL-8) in the development and progression of gastroesophgeal reflux disease (GERD). The purpose of this study was to determine IL-8 RNA expression levels in NERD patients with or without subtle mucosal changes.METHODS: We studied 26 patients with NERD and 13 asymptomatic controls. Biopsy sample was taken from the esophagus 3 cm above the gastroesophageal junction and snap frozen for measurement of IL-8 mRNA levels by real-time quantitative polyrnerase chain reaction (PCR). We also examined mRNA expression of IL-8 receptors, CXCR-1 and -2 by reverse transcriptase PCR. The patients were endoscopically classified into grade M (mucosal color changes without visible mucosal break) and N (neither minimal involvement nor mucosal break) of the modified Los Angeles classification.RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of NERD patients than those in esophageal mucosa of the controls. There was a significant difference in IL-8 mRNA levels between grades M and N. The CXCR-1 and -2 mRNAs were constitutively expressed in esophageal mucosa.CONCLUSION: Our results suggest that high IL-8 levels in esophageal mucosa may be involved in the pathogenesis of NERD through interaction with its receptors. NERD seems to be composed of a heterogeneous population in terms of not only endoscopically minimal involvement but also immune and inflammatory processes.

  15. Minimal Pairs: Minimal Importance?

    Science.gov (United States)

    Brown, Adam

    1995-01-01

    This article argues that minimal pairs do not merit as much attention as they receive in pronunciation instruction. There are other aspects of pronunciation that are of greater importance, and there are other ways of teaching vowel and consonant pronunciation. (13 references) (VWL)

  16. Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

    Science.gov (United States)

    Tousseyn, Thomas; Bajsarowicz, Krystyna; Sánchez, Henry; Gheyara, Ania; Oehler, Abby; Geschwind, Michael; DeArmond, Bernadette; DeArmond, Stephen J.

    2016-01-01

    We examined the brains of 266 patients with prion diseases (PrionD) and found that 46 (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (Hu BrnAggs) to brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease (CJD) and found that the neurons in the Hu BrnAggs produced many β-amyloid (β42) inclusions, whereas uninfected, control-exposed Hu BrnAggs did not. Western blots of 20-pooled CJD-infected BrnAggs verified higher Aβ42 levels than controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrPSc), many Aβ42 intraneuronal inclusions, low APOE-4, and no significant nerve cell loss. Seven patients had high levels of PrPSc, low Aβ42, high APOE-4 and 40% nerve cell loss, suggesting that APOE-4 and PrPSc together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls and 2 controls had a few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to AD and suggest that PrionD are diseases of PrPSc, Aβ42, APOE-4 and abnormal tau. PMID:26226132

  17. 76 FR 30550 - Federal Management Regulation; Change in Consumer Price Index Minimal Value

    Science.gov (United States)

    2011-05-26

    ... ADMINISTRATION 41 CFR Part 102-42 RIN 3090-AJ12 Federal Management Regulation; Change in Consumer Price Index..., to reflect changes in the Consumer Price Index for the immediately preceding 3-year period. The... INFORMATION CONTACT: Mr. Robert Holcombe, Director, Asset Management Policy Division (202-501-3828...

  18. Minimal change of thermal continentality in Slovakia within the period 1961-2013

    Science.gov (United States)

    Vilček, Jozef; Škvarenina, Jaroslav; Vido, Jaroslav; Nalevanková, Paulína; Kandrík, Radoslav; Škvareninová, Jana

    2016-08-01

    Thermal continentality plays an important role not only in the basic characterisation of the climate in particular regions but also in the phytogeographic distribution of plants and ecosystem formation. Due to ongoing climate change, questions surrounding the changes of thermal continentality are very relevant. Therefore, the aim of this study is to investigate the characteristics of thermal continentality and its temporal changes in the Slovak Republic between the years of 1961 and 2013. The study was carried out on several meteorological stations selected in respect to the geographical and geomorphological heterogeneity of Slovakia. Our results show that the continentality of Slovakia increased in the period 1961 to 2013; however, this trend is not significant. These non-significant trends are confirmed at all the stations. Nevertheless, it is necessary to be aware of this signal, especially because these changes could cause changes in ecosystem formation in future.

  19. CLIMATE CHANGE IN KYIV: WAYS TO CONTERACT AND MINIMIZE NEGATIVE EFFECTS

    Directory of Open Access Journals (Sweden)

    V. Bazylevych

    2013-10-01

    Full Text Available ital issues of climate change in Kyiv are studied with elucidation of the need for developing a comprehensive research technique to analyse and assess a cumulative impact of the process. The study exposes anthropogenic and natural factors responsible for climate formation in Kyiv and the climatic changes. With an account for recent international experience the proposals are formulated how to make use of contemporary administrative, economic, legal and regulatory levers to forestall climatic changes in the capital and cope with the negative environmental aftermath.

  20. Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle Deformity Associated With Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Boffeli, Troy J; Tabatt, Jessica A

    2015-01-01

    Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in a predictable pattern of progressive bilateral lower extremity weakness, numbness, contracture, and deformity, including drop foot, loss of ankle eversion strength, dislocated hammertoes, and severe cavus foot deformity. Late stage reconstructive surgery will be often necessary if the deformity becomes unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for Charcot-Marie-Tooth deformity is generally extensive and sometimes staged. Traditional reconstructive surgery involves a combination of procedures, including tendon lengthening or transfer, osteotomy, and arthrodesis. The described technique highlights our early surgical approach, which involves limited intervention before the deformity becomes rigid, severe, or disabling. We present 2 cases to contrast our early minimally invasive technique with traditional late stage reconstruction. Charcot-Marie-Tooth disease affects different muscles at various stages of disease progression. As 1 muscle becomes weak, the antagonist will overpower it and cause progressive deformity. The focus of the early minimally invasive approach is to decrease the forces that cause progressive deformity yet maintain function, where possible. Our goal has been to maintain a functional and braceable foot and ankle, with the hope of avoiding or limiting the extent of future major reconstructive surgery. The presented cases highlight the patient selection criteria, the ideal timing of early surgical intervention, the procedure selection criteria, and operative pearls. The early minimally invasive approach includes plantar fasciotomy, Achilles tendon lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and Jones tendon transfer, and hammertoe repair of digits 1 to 5.

  1. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Büchi Stefan

    2008-07-01

    Full Text Available Abstract Background Interpretation of the Hospital Anxiety and Depression Scale (HADS, commonly used to assess anxiety and depression in COPD patients, is unclear. Since its minimal important difference has never been established, our aim was to determine it using several approaches. Methods 88 COPD patients with FEV1 ≤ 50% predicted completed the HADS and other patient-important outcome measures before and after an inpatient respiratory rehabilitation. For the anchor-based approach we determined the correlation between the HADS and the anchors that have an established minimal important difference (Chronic Respiratory Questionnaire [CRQ] and Feeling Thermometer. If correlations were ≥ 0.5 we performed linear regression analyses to predict the minimal important difference from the anchors. As distribution-based approach we used the Effect Size approach. Results Based on CRQ emotional function and mastery domain as well as on total scores, the minimal important difference was 1.41 (95% CI 1.18–1.63 and 1.57 (1.37–1.76 for the HADS anxiety score and 1.68 (1.48–1.87 and 1.60 (1.38–1.82 for the HADS total score. Correlations of the HADS depression score and CRQ domain and Feeling Thermometer scores were Conclusion The minimal important difference of the HADS is around 1.5 in COPD patients corresponding to a change from baseline of around 20%. It can be used for the planning and interpretation of trials.

  2. Treatment of patients with minimal stage IIIA Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Powlis, W.D.; Mauch, P.; Goffman, T.; Goodman, R.L.

    1987-10-01

    Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT.

  3. Management of diverticular disease is changing

    Institute of Scientific and Technical Information of China (English)

    Martin H Floch; Jonathan A White

    2006-01-01

    Diverticular disease of the colon is primarily a disease of humans living in westernized and industrialized countries. Sixty percent of humans living in industrialized countries will develop colonic diverticula. It is rare before the age of 40, but more prone to complications when it occurs in the young. By age 80, over 65% of humans have colonic diverticula. The cause remains uncertain, but epidemiologic studies attribute it to dietary fiber deficiency. The cause of diverticulitis remains uncertain, but new observations and hypotheses suggest that it is due to chronic inflammation in the bowel wall. Standard medical therapies of bowel rest and antibiotics are still the recommended treatment.However, changing concepts and new therapies indicate that anti-inflammatory agents such as mesalamine and possibly probiotics may be helpful in shortening the course and perhaps preventing recurrences. Standard surgical treatment for perforation for severe acute disease has developed so that two-stage procedures are recommended. In addition, laparoscopic surgery has proven safe and may slowly become the technique of choice.

  4. Changes in total ascorbic acid and carotenoids in minimally processed irradiated Arugula (Eruca sativa Mill) stored under refrigeration

    Science.gov (United States)

    Nunes, Tatiana Pacheco; Martins, Cecília Geraldes; Faria, Adelia Ferreira; Bíscola, Vanessa; de Oliveira Souza, Kátia Leani; Mercadante, Adriana Zerlotti; Cordenunsi, Beatriz Rosana; Landgraf, Mariza

    2013-09-01

    This work investigated the effects of irradiation (0, 1 and 2 kGy) on the content of bioactive compounds such as vitamin C and carotenoids with provitamin A activity in arugula during the storage at 5±1 °C for up to 13 and 16 days, respectively. The vitamin C content decreased in non-irradiated as well as irradiated (1 and 2 kGy) samples during the storage period. On the other hand, no significant change in the content of carotenoids with provitamin A activity was observed after irradiation or storage period. Thus, the irradiation had minimal detrimental effects on the contents of carotenoids in arugula.

  5. The response of Mediterranean thermohaline circulation to climate change: a minimal model

    OpenAIRE

    Meijer, P.Th.; H. A. Dijkstra

    2009-01-01

    Physics-based understanding of the effects of paleoclimate and paleogeography on the thermohaline circulation of the Mediterranean Sea requires an ocean model capable of long integrations and involving a minimum of assumptions about the atmospheric forcing. Here we examine the sensitivity of the deep circulation in the eastern Mediterranean basin to changes in atmospheric forcing, considered a key factor in the deposition of organic-rich sediments (sapropels). To this extent we explore the se...

  6. Minimal evidence for consistent changes in maize DNA methylation patterns following environmental stress.

    Directory of Open Access Journals (Sweden)

    Steven R Eichten

    2015-05-01

    Full Text Available DNA methylation is a chromatin modification that is sometimes associated with epigenetic regulation of gene expression. As DNA methylation can be reversible at some loci, it is possible that methylation patterns may change within an organism that is subjected to environmental stress. In order to assess the effects of abiotic stress on DNA methylation patterns in maize (Zea mays, seeding plants were subjected to heat, cold, and UV stress treatments. Tissue was later collected from individual adult plants that had been subjected to stress or control treatments and used to perform DNA methylation profiling to determine whether there were consistent changes in DNA methylation triggered by specific stress treatments. DNA methylation profiling was performed by immunoprecipitation of methylated DNA followed by microarray hybridization to allow for quantitative estimates of DNA methylation abundance throughout the low-copy portion of the maize genome. By comparing the DNA methylation profiles of each individual plant to the average of the control plants it was possible to identify regions of the genome with variable DNA methylation. However, we did not find evidence of consistent DNA methylation changes resulting from the stress treatments used in this study. Instead, the data suggest that there is a low-rate of stochastic variation that is present in both control and stressed plants.

  7. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma

    DEFF Research Database (Denmark)

    Kumar, Shaji; Paiva, Bruno; Anderson, Kenneth C;

    2016-01-01

    Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monocl...

  8. Minimally invasive biomarker confirms glial activation present in Alzheimer's disease: a preliminary study

    Directory of Open Access Journals (Sweden)

    Tran T

    2011-08-01

    Full Text Available Napapon Sailasuta, Kent Harris, Thao Tran, Brian RossClinical MR Unit, Huntington Medical Research Institutes, Pasadena, CA, USAAbstract: We applied 13C magnetic resonance spectroscopy (MRS, a nonradioactive, noninvasive brain imaging technique, to quantify the oxidation of [1-13C] acetate in a conventional clinical magnetic resonance imaging (MRI scanner in five consecutive elderly subjects at various clinical stages of Alzheimer's disease (AD progression. [1-13C] acetate entered the brain and was metabolized to [5-13C] glutamate and glutamine, as well as [1-13C] glutamate and glutamine, and the final glial oxidation product, 13C bicarbonate, at a linear rate. Calculation of the initial slope was similar in a single subject, examined twice, 1 month apart (test-re-test 8%. Mean rate of cerebral bicarbonate production in this elderly group was 0.040 ± 0.01 (n = 5. Assuming that the rate of conversion of acetate to bicarbonate is a reflection of glial metabolic rate and that glial metabolic rate is a surrogate marker for 'neuroinflammation', our preliminary results suggest that [1-13C] MRS may provide biomarkers for diseases, believed to involve microglia and other cells of the astrocyte series. Among these is AD, for which novel drugs which ameliorate the damaging effects of neuroinflammation before symptoms of dementia appear, are in advanced development. The value of 13C MRS as an early, noninvasive biomarker may lie in the conduct of cost-effective clinical trials.Keywords: Alzheimer's disease, noninvasive biomarker, glial activation

  9. [The use of minimally invasive instrumental spinal surgical technique in lumbar diseases of degenerative or traumatic origin].

    Science.gov (United States)

    Schwarcz, Attila; Kasó, Gábor; Büki, András; Dóczi, Tamás

    2013-03-30

    Paradigm change has recently taken place in spine surgery with the application of minimally invasive techniques. Minimally invasive techniques have several advantages over the open traditional techniques: less blood loss, preservation of spine muscle integrity, shorter hospitalization, early mobilization, reduced pain levels, lower risk of infection. The presented cases cover following lumbar pathologies: segmental spinal instability, LV-SI grade II. spondylolisthesis, degenerative spondylolisthesis, spine trauma. Unilateral or bilateral mini-open technique was employed in the degenerative cases, depending on symptoms and signes. If unilateral symptoms--pathology was identified, screws and rod were implanted percutaneously on the side contralateral to the pathology. The segmental fusion between vertebral bodies was always assured by a cage and autologous bone. The presented trauma case involved combined AO type A2 and B fractures. The anterior column was strengthened with vertebral body stents filled with bone cement, the posterior column was fixed with a percutaneously implanted screw rod system. Insertion of stents in the collapsed vertebra significantly increased the vertebral body height and also improved the stability of the spine. Minimally invasive spine surgery techniques appear more advantageous over the traditional open spine surgery that necessitates for large midline approaches.

  10. Celiac Disease Changes Everything | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Celiac Disease Celiac Disease Changes Everything Past Issues / Spring 2015 Table of ... your thoughts when you were told you had celiac disease? I was actually thrilled when I was finally ...

  11. Mapping Climate Change Vulnerabilities to Infectious Diseases in Europe

    National Research Council Canada - National Science Library

    Jan C. Semenza; Jonathan E. Suk; Virginia Estevez; Kristie L. Ebi; Elisabet Lindgren

    Background: The incidence, outbreak frequency, and distribution of many infectious diseases are generally expected to change as a consequence of climate change, yet there is limited regional information...

  12. Energy and environment in the 21st century : minimizing climate change.

    CERN Document Server

    CERN. Geneva

    2003-01-01

    Energy demand and economic output are coupled. Both are expected to vastly increase in this century, driven primarily by the economic and population growth of the developing world. If the present reliance on carbon-based fuels as primary energy sources continues, average global temperatures are projected to rise between 3° C and 6° C. Limiting climate change will require reduction in greenhouse gas emissions far beyond the Kyoto commitments. Time scales and options, including nuclear, will be reviewed.

  13. [TREATMENT OF POST-SPONDYLODESIS, ADJACENT-SEGMENT DISEASE WITH MINIMALLY INVASIVE, ANTEROLATERAL SURGERY ON THE LUMBAR SPINE: IS THERE IS NO NEED FOR DORSAL OPERATION?].

    Science.gov (United States)

    Schwarcz, Attila; Szakály, Péter; Büki, András; Dóczi, Tamás

    2015-07-30

    Adjacent segment disease (ASD) occurs with a probability of 30% in the lumbar spine following spinal fusion surgery. Usually advanced degenerative changes happen cranially to the fused lumbar segment. Thus, secondary spinal instability, stenosis, spodylolisthesis, foraminal stenosis can lead to the recurrence of the pain not always amenable to conservative measures. A typical surgical solution to treat ASD consists of posterior revision surgery including decompression, change or extension of the instrumentation and fusion to the rostral level. It results in a larger operation with considerable risk of complications. We present a typical case of ASD treated surgically with a new minimally invasive method not yet performed in Hungary. We use anterolateral abdominal muscle splitting approach to reach the lumbar spine through the retroperitoneum. A discectomy is performed by retracting the psoas muscle dorsally. The intervertebral bony fusion is achieved by implanting a cage with large volume that is stuffed with autologous bone or tricalcium phosphate. A cage with large volume results in excellent annulus fibrosus tension, immediate stability and provides large surface for bony fusion. A stand-alone cage construct can be supplemented with lateral screw/rod/plate fixation. The advantage of the new technique for the treatment of ASD includes minimal blood loss, short operation time, significantly less postoperative pain and much lower complication rate.

  14. Minimally invasive thoracotomy approach for double valve replacement for valvular heart diseases

    Directory of Open Access Journals (Sweden)

    Ab Gani Ahangar

    2014-01-01

    Full Text Available Background: Double valve replacement (DVR is usually done through median sternotomy. However, right anterolateral thoracotomy is an alternative approach. Aim: The aim of this study was to analyze the results of right anterolateral thoracotomy for DVR. Patients and Methods: This was a prospective study conducted on during the period from January 2009 to January 2012. This study consists of 56 patients who had a concomitant mitral and aortic valve disease and were subjected to DVR. Patients were studied according to their age and sex, New York Heart Association (NYHA class, valve pathology, concomitant procedures, urgent/elective, length of incision, surgical exposure, mean bypass time, operating time, hospital stay, and cosmesis. Results: Majority of the patients were in 3 rd and 4 th decade (61%. Postoperative length of stay was 7-12 days, 70% of patients were discharged by the 7 th day. The average size of incision in males was 7.5 cm and in females the size of incision was 7.25 cm with a mean of 7.3 cm in both genders. Rheumatic heart disease was responsible for 89.28% of cardiac valvular lesions, degenerative disease in 7.14% and endocarditis in 3.5%. Postoperatively at 2 months, there was a statistically significant improvement in the NYHA class with 94% of the survivors in class I-II. There was a statistically significant difference in the outcome in patients having higher ejection fraction as compared to those who had low ejection fraction preoperatively. Thirty days mortality was 1.78%. Over the first 24 postoperative hours, only about 30% of patients were pain free, and this proportion increased to about 50% by day 2, 60% by day 3, 70% by day 4, 75% by day 5 and stabilized. Postoperative length of stay was 7-12 days, 70% of patients were discharged by the 7 th day. Conclusion: DVR via thoracotomy appears to be associated with faster recover, early discharge and reduced use of rehabilitation facilities that translate into a shorter

  15. Minimally invasive coronary artery bypass grafting versus stenting for patients with proximal left anterior descending coronary artery disease.

    Science.gov (United States)

    Shirai, Kazuyuki; Lansky, Alexandra J; Mehran, Roxana; Dangas, George D; Costantini, Costantino O; Fahy, Martin; Slack, Steven; Mintz, Gary S; Stone, Gregg W; Leon, Martin B

    2004-04-15

    The purpose of this study was to compare the clinical outcomes of stenting and minimally invasive coronary artery bypass grafting (MIDCAB) in patients with proximal left anterior descending (LAD) coronary artery disease. The Patency, Outcome, Economics of Minimally invasive direct coronary bypass (POEM) study demonstrated that MIDCAB had similar safety and long-term efficacy for LAD revascularization compared with conventional coronary artery bypass grafting. Although LAD stenting is superior to conventional balloon angioplasty, whether it is comparable to MIDCAB is not known. We identified a matched population of 429 consecutive patients with 1-vessel disease who underwent elective proximal LAD stenting and compared their clinical outcomes with those of the 152 patients in the MIDCAB group of the POEM study. The in-hospital event rate was similar in both groups, except for a shorter length of hospital stay with LAD stenting compared with MIDCAB (2.68 vs 4.07 days, p <0.0001). At 6-month follow-up, the incidence of death and Q-wave myocardial infarction or that of cerebrovascular accident was not significantly different between these 2 groups. However, target vessel revascularization was significantly higher with LAD stenting than MIDCAB (13.3% vs 6.6%, p = 0.045). In the subgroup of patients without diabetes, all clinical events were similar in both groups, and the benefit of a shorter hospital stay associated with stenting was maintained. Compared with MIDCAB, LAD stenting is associated with higher repeat revascularization rates but offers the advantage of shorter hospitalization. For nondiabetics with proximal LAD disease, stenting may be the revascularization strategy of choice.

  16. Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction.

    Science.gov (United States)

    Van Bree, L; Zhang, F; Schiffmann, S N; Halleux, P; Mailleux, P; Vanderhaeghen, J J

    1995-12-01

    A cortical infarct of 2 mm diameter was obtained in the parietal cortex after a craniotomy, disruption of the dura mater and topical application of 3 M KCl. It has been shown previously that the presence of a small cortical infarct induces an increase in immediate early gene messenger RNA expression followed by an increase in neuropeptide and glutamic acid decarboxylase messenger RNA expression. Glutamate, acting at N-methyl-D-aspartate receptors, is held responsible for these changes, since they are blocked by pretreatment with dizocilpine. In the present study, we have analysed the consequences of the dramatic changes in messenger RNA expression on the level of immediate early gene products c-fos and zif 268, and on that of neuropeptides by using immunohistochemistry. After just 1 h, an increase in c-fos- and zif 268-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct, and is no longer detected after 6 h. An increase in cholecystokinin octapeptide-, substance P-, neuropeptide Y- and somatostatin-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after 30 days. To investigate if these dramatic increases in neuropeptide immunoreactivities may have functional consequences, we studied the level of cholecystokinin receptors by autoradiographic binding using [125I]cholecystokinin-8S and in situ hybridization for the detection of cholecystokinin-b receptor messenger RNA. A decrease in cholecystokinin binding sites and cholecystokinin-b receptor messenger RNA is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after nine days. This study shows that a topical stimulation has diffuse effects, reaching regions far from the site of the lesion, and some of them are still strongly present after nine days. The increase in neuropeptide messenger RNAs is followed by an increase in the

  17. Effect of cyclosporin A and mycophenolate mofetil on levels of soluble urokinase type plasminogen activator receptor in children patients with minimal change disease%环孢素A与吗替麦考酚酯对微小病变型肾病患儿血浆可溶性尿激酶型纤溶酶原激活物受体水平的影响

    Institute of Scientific and Technical Information of China (English)

    王凯臣; 张赟; 刘恒昌; 晋学飞

    2015-01-01

    Objective To observe the level change of soluble urokinase type plasminogen activator receptor (suPAR) in the plasma of children with minimal change disease (MCD) caused by cyclosporin A (CsA) and mycophenolate mofetil (MMF) and investigate the role of suPAR in minimal change disease.Methods The 29 children with MCD were divided into two groups:CsA group (group A) and MMF group (group B),given CsA and MMF combined with prednisone for 12 months respectively.The plasma level of suPAR was determined by enzyme linked immunosorbent assay (ELISA).These children were followed up for at least 12 months to observe the curative effectiveness.Results After treatment for 12 months,suPAR levels in group B [(2 208.3 ±395.4) ng/L] were lower than those before treatment,and those in group A were significantly increased [(2 984.6 ± 804.7) ng/L],significantly higher than in group B (P <0.05).The urinary protein and 24-h urine protein after treatment in the two groups were significantly reduced as compared with those before treatment (P < 0.05),but there were no significant differences between two groups (P >0.05).The incidence of adverse reactions in group A was 57.14% (8/14),the total response rate was 85.71% (12/14),and the recurrence rate was 14.29% (2/14),and those in group B were 35.71% (5/14),78.57% (11/14),and 35.71% (5/14) respectively,with the difference being not significant between two groups.Conclusion The curative efficacy of CsA and MMF on MCD was good.Both CsA and MMF had the opposite effect on suPAR and GFR,but had no significant effect on urinary protein and 24-h urine protein.%目的 观察环孢素A(CsA)与吗替麦考酚酯(MMF)对微小病变型肾病(MCD)患儿血浆中可溶性尿激酶型纤溶酶原激活物受体(suPAR)水平变化的影响,及探讨suPAR在微小病变型肾病中的作用.方法 将29例MCD患儿随机分为CsA组(A组)和MMF组(B组),分别给予CsA和MMF联合强的松治疗12个月,采用酶联免疫吸附试验

  18. Minimizing the cost of keeping options open for conservation in a changing climate

    Science.gov (United States)

    Mills, Morena; Nicol, Samuel; Wells, Jessie A.; Lahoz-Monfort, José J.; Wintle, Brendan; Bode, Michael; Wardrop, Martin; Walshe, Terry; Probert, William J. M.; Runge, Michael C.; Possingham, Hugh P.; McDonald Madden, Eve

    2014-01-01

    Policy documents advocate that managers should keep their options open while planning to protect coastal ecosystems from climate-change impacts. However, the actual costs and benefits of maintaining flexibility remain largely unexplored, and alternative approaches for decision making under uncertainty may lead to better joint outcomes for conservation and other societal goals. For example, keeping options open for coastal ecosystems incurs opportunity costs for developers. We devised a decision framework that integrates these costs and benefits with probabilistic forecasts for the extent of sea-level rise to find a balance between coastal ecosystem protection and moderate coastal development. Here, we suggest that instead of keeping their options open managers should incorporate uncertain sea-level rise predictions into a decision-making framework that evaluates the benefits and costs of conservation and development. In our example, based on plausible scenarios for sea-level rise and assuming a risk-neutral decision maker, we found that substantial development could be accommodated with negligible loss of environmental assets. Characterization of the Pareto efficiency of conservation and development outcomes provides valuable insight into the intensity of trade-offs between development and conservation. However, additional work is required to improve understanding of the consequences of alternative spatial plans and the value judgments and risk preferences of decision makers and stakeholders.

  19. Minimizing the cost of keeping options open for conservation in a changing climate.

    Science.gov (United States)

    Mills, Morena; Nicol, Sam; Wells, Jessie A; Lahoz-Monfort, José J; Wintle, Brendan; Bode, Michael; Wardrop, Martin; Walshe, Terry; Probert, William J M; Runge, Michael C; Possingham, Hugh P; Madden, Eve McDonald

    2014-06-01

    Policy documents advocate that managers should keep their options open while planning to protect coastal ecosystems from climate-change impacts. However, the actual costs and benefits of maintaining flexibility remain largely unexplored, and alternative approaches for decision making under uncertainty may lead to better joint outcomes for conservation and other societal goals. For example, keeping options open for coastal ecosystems incurs opportunity costs for developers. We devised a decision framework that integrates these costs and benefits with probabilistic forecasts for the extent of sea-level rise to find a balance between coastal ecosystem protection and moderate coastal development. Here, we suggest that instead of keeping their options open managers should incorporate uncertain sea-level rise predictions into a decision-making framework that evaluates the benefits and costs of conservation and development. In our example, based on plausible scenarios for sea-level rise and assuming a risk-neutral decision maker, we found that substantial development could be accommodated with negligible loss of environmental assets. Characterization of the Pareto efficiency of conservation and development outcomes provides valuable insight into the intensity of trade-offs between development and conservation. However, additional work is required to improve understanding of the consequences of alternative spatial plans and the value judgments and risk preferences of decision makers and stakeholders. © 2014 Society for Conservation Biology.

  20. Structures of minimal catalytic fragments of topoisomerase V reveals conformational changes relevant for DNA binding.

    Science.gov (United States)

    Rajan, Rakhi; Taneja, Bhupesh; Mondragón, Alfonso

    2010-07-14

    Topoisomerase V is an archaeal type I topoisomerase that is unique among topoisomerases due to presence of both topoisomerase and DNA repair activities in the same protein. It is organized as an N-terminal topoisomerase domain followed by 24 tandem helix-hairpin-helix (HhH) motifs. Structural studies have shown that the active site is buried by the (HhH) motifs. Here we show that the N-terminal domain can relax DNA in the absence of any HhH motifs and that the HhH motifs are required for stable protein-DNA complex formation. Crystal structures of various topoisomerase V fragments show changes in the relative orientation of the domains mediated by a long bent linker helix, and these movements are essential for the DNA to enter the active site. Phosphate ions bound to the protein near the active site helped model DNA in the topoisomerase domain and show how topoisomerase V may interact with DNA.

  1. Changes in ion transport in inflammatory disease

    Directory of Open Access Journals (Sweden)

    Eisenhut Michael

    2006-03-01

    Full Text Available Abstract Ion transport is essential for maintenance of transmembranous and transcellular electric potential, fluid transport and cellular volume. Disturbance of ion transport has been associated with cellular dysfunction, intra and extracellular edema and abnormalities of epithelial surface liquid volume. There is increasing evidence that conditions characterized by an intense local or systemic inflammatory response are associated with abnormal ion transport. This abnormal ion transport has been involved in the pathogenesis of conditions like hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal diseases, electrolyte abnormalites in pyelonephritis of early infancy, septicemia induced pulmonary edema, and in hypersecretion and edema induced by inflammatory reactions of the mucosa of the upper respiratory tract. Components of membranous ion transport systems, which have been shown to undergo a change in function during an inflammatory response include the sodium potassium ATPase, the epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance Regulator and calcium activated chloride channels and the sodium potassium chloride co-transporter. Inflammatory mediators, which influence ion transport are tumor necrosis factor, gamma interferon, interleukins, transforming growth factor, leukotrienes and bradykinin. They trigger the release of specific messengers like prostaglandins, nitric oxide and histamine which alter ion transport system function through specific receptors, intracellular second messengers and protein kinases. This review summarizes data on in vivo measurements of changes in ion transport in acute inflammatory conditions and in vitro studies, which have explored the underlying mechanisms. Potential interventions directed at a correction of the observed abnormalities are discussed.

  2. Twins Bed Rest Project: LBNP/Exercise Minimizes Changes in Lean Leg Mass, Strength and Endurance

    Science.gov (United States)

    Amorim, Fabiano T.; Schneider, Suzanne M.; Lee, Stuart M. C.; Boda, Wanda L.; Watenpaugh, Donald E.; Hargens, Alan R.

    2006-01-01

    Decreases in muscle strength and endurance frequently are observed in non-weightbearing conditions such as bed rest (BR), spaceflight or limb immobilization. Purpose: Ow purpose was to determine if supine treadmill exercise against simulated gravity, by application of lower body negative pressure (LBNP), prevents loss of lean leg mass, strength and endurance during 30 d of 6deg head-down bed rest (BR). Methods: Fifteen pairs of monozygous twins (8 male, 7 female pairs; 26+/-4 yrs; 170+/-12 cm; 62.6+/-11.3 kg; mean+/-SD) were subjects in the present study. One sibling of each pair of twins was randomly assigned to either an exercise (EX) or non-exercise (CON) group. The EX twin walked/jogged on a vertical treadmill within LBNP chamber 6 d/wk using a 40-min interval exercise protocol at 40-80% of pre-BR VO(sub 2peak). LBNP was adjusted individually for each subject such that footward force was between 1.0 and 1.2 times body weight (-53+/-5 mmHg LBNP). The CON twin performed no exercise during BR. Subjects performed isokinetic knee (60 and 120deg/s) and ankle (60deg/s) testing to assess strength and endurance (End) before and after BR. They also had their lean leg mass (L(sub mass)) evaluated by DEXA before and after BR. Results: Changes in peak torque (T(sub pk)) were smaller for flexion (flex) than for extension (ext) after BR and did not differ between groups. The CON group had larger decreases (P<0.05) in L(sub mass), knee and ankle ext T(sub pk), and knee ext End.

  3. Minimally Important Differences and Change Across Time in Patients Treated Surgically and Non-Surgically for Full-Thickness Rotator Cuff Tears

    Science.gov (United States)

    Miller, Bruce S.; Robbins, Christopher; Gagnier, Joel Joseph

    2016-01-01

    Objectives: The minimally important difference (MID) is the smallest change in an outcome measure that is perceived by patients as beneficial. The MIDs for the ASES and WORC scores have not been established in a homogenous population of patients with rotator cuff tears. The objective of the present study was to establish the MIDs for patients with known cuff tears who were treated both surgically and non-surgically, and to compare the MIDs over time. Methods: We included 209 subjects with known full-thickness rotator cuff tears who were followed prospectively for two years. The WORC and ASES scores were collected at baseline, 4, 8, 16, 32, and 48 weeks, 1 year and 2 years. At the final follow-up point patients filled out an end-of-study form which included questions regarding change in their condition after treatment. Results: For those that indicated being minimally better, the change from baseline for the ASES score was -20.57 (-2.94 to -38.20) and for the WORC was 418.60 (70.39 to 766.81); both indicated improvement in outcomes. When converted to the percentage change score the WORC change represented 19.93%. The plots of these new MID values for the ASES and WORC indicate that not only does the operative group improve more than the non-operative group but it does so to an extent that is greater than the MID. The non-operative group also improved across time, but the magnitude did not exceed the MID for either the WORC or the ASES. Conclusion: We found that the ASES and the WORC MIDs in patients with rotator cuff tears is different from that previously reported, and that the operative group change was greater than the non-operative group change. This information will directly improve our ability to: (1) Determine when patients with RCTs are changing in a meaningful manner; (2) Accurately power clinical studies using these outcome measures; (3) Make more informed choices of treatments in these patients. This is the first study to report MIDs for the ASES and WORC

  4. The change and significance of vancomycin minimal inhibitory concentration against methicillin-resistant Staphylococcus aureus isolates from inpatients with lower respiratory tract infection

    Institute of Scientific and Technical Information of China (English)

    杨薇

    2013-01-01

    Objective To investigate the change and significance of vancomycin minimal inhibitory concentration(MIC) against methicillin-resistant Staphylococcus aureus(MRSA)isolates.Methods We analyzed the data of

  5. Bone changes in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Alcoholism has been associated with growth impairment,osteomalacia, delayed fracture healing, and asepticnecrosis (primarily necrosis of the femoral head), butthe main alterations observed in the bones of alcoholicpatients are osteoporosis and an increased risk offractures. Decreased bone mass is a hallmark of osteoporosis,and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanolmay affect both mechanisms. It is generally acceptedthat ethanol decreases bone synthesis, and most authorshave reported decreased osteocalcin levels (a "marker" ofbone synthesis), but some controversy exists regardingthe effect of alcohol on bone breakdown, and, indeed,disparate results have been reported for telopeptideand other biochemical markers of bone resorption.In addition to the direct effect of ethanol, systemicalterations such as malnutrition, malabsorption, liverdisease, increased levels of proinflammatory cytokines,alcoholic myopathy and neuropathy, low testosteronelevels, and an increased risk of trauma, play contributoryroles. The treatment of alcoholic bone disease should beaimed towards increasing bone formation and decreasingbone degradation. In this sense, vitamin D and calciumsupplementation, together with biphosphonates areessential, but alcohol abstinence and nutritional improvementare equally important. In this review we study thepathogenesis of bone changes in alcoholic liver diseaseand discuss potential therapies.

  6. Lyme disease ecology in a changing world

    DEFF Research Database (Denmark)

    Kilpatrick, A. Marm; Dobson, Andrew D.M.; Levi, Taal

    2017-01-01

    Lyme disease is the most common tick-borne disease in temperate regions of North America, Europe and Asia, and the number of reported cases has increased in many regions as landscapes have been altered. Although there has been extensive work on the ecology and epidemiology of this disease in both...... insights into the drivers and dynamics of this emblematic multi-host-vector-borne zoonotic disease.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'....

  7. Interferon α: the salvage therapy for patients with unsatisfactory response to minimal residual disease-directed modified donor lymphocyte infusion

    Institute of Scientific and Technical Information of China (English)

    Mo Xiaodong; Zhao Xiangyu; Xu Lanping; Liu Daihong; Zhang Xiaohui; Chen Huan; Wang Yu

    2014-01-01

    Background Minimal residual disease (MRD)-directedmodified donor lymphocyte infusion (mDLI) is used to treat relapse after hematopoietic stem cell transplantation (HSCT).For patients who experience an unsatisfactory response tomDLI,relapse is usually inevitable.Therefore,we sought to evaluate the efficacy ofinterferon α therapy in these patients.Methods Regular MRD monitoring was carried out after the HSCT.The patients who were MRD-positive underwent mDLI.Patients with an unsatisfactory response to mDLI received interferon α therapy (3 million units,twice weekly) with regular monitoring of MRD.To ensure the immunomodulatory effects of interferon α,immunosuppressant treatment would be stopped before interferon α treatment.Results Five patients with an unsatisfactory response to mDLI treatment received interferon α (3 had t(8;21) chromosomal translocation acute myeloid leukemia,and 2 had common acute leukemia).They had significantly reduced or resolved MRD.Four patients developed chronic graft-versus-host disease.Two of the 5 patients reported transient fevers,and no significant bone marrow suppression was observed.All of them were in continuous complete remission after interferon α treatment.The median survival time was 469 days (range 368-948 days).Conclusions In patients with an unsatisfactory response to MRD-directed mDLI,interferon α may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD.

  8. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    Science.gov (United States)

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  9. Impact of Minimal Residual Disease, Detected by Flow Cytometry, on Outcome of Myeloablative Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Merav Bar

    2014-01-01

    Full Text Available In this retrospective study, we evaluated the impact of pre- and posttransplant minimal residual disease (MRD detected by multiparametric flow cytometry (MFC on outcome in 160 patients with ALL who underwent myeloablative allogeneic hematopoietic cell transplantation (HCT. MRD was defined as detection of abnormal B or T cells by MFC with no evidence of leukemia by morphology (<5% blasts in marrow and no evidence of extramedullary disease. Among 153 patients who had pre-HCT flow data within 50 days before transplant, MRD pre-HCT increased the risk of relapse (hazard ratio (HR = 3.64; 95% confidence interval (CI, 1.87–7.09; P=.0001 and mortality (HR = 2.39; 95% CI, 1.46–3.90, P=.0005. Three-year estimates of relapse were 17% and 38% and estimated 3-year OS was 68% and 40% for patients without and with MRD pre-HCT, respectively. 144 patients had at least one flow value post-HCT, and the risk of relapse among those with MRD was higher than that among those without MRD (HR = 7.47; 95% CI, 3.30–16.92, P<.0001. The risk of mortality was also increased (HR = 3.00; 95% CI, 1.44–6.28, P=.004. These data suggest that pre- or post-HCT MRD, as detected by MFC, is associated with an increased risk of relapse and death after myeloablative HCT for ALL.

  10. Effects of minimal exercise and cognitive behavior modification on adherence, emotion change, self-image, and physical change in obese women.

    Science.gov (United States)

    Annesi, J J

    2000-08-01

    The present investigation tested a 12-wk. treatment protocol which employed low intensity cardiovascular and resistance exercise as well as cognitive-behavior modification on 13 obese, previously sedentary women. Separate analyses were conducted on program maintenance, emotional change, and physiological change. Although self motivation was lower in the treatment group than in the control group (n=35), measures of exercise maintenance were significantly higher. Analyses within the treatment group only indicated significant improvements in measures of State Anxiety, Depression, Anger, Fatigue, Tension, and Vigor, also Health Evaluation, Body Area Satisfaction, and heightened Overweight Preoccupation, over the 12 weeks. Their feelings after individual bouts of exercise indicated significantly increased Positive Engagement, Revitalization, and Tranquility, and reduced Physical Exhaustion. Maximum volume of oxygen uptake (VO2max) significantly increased (2nd to 10th percentile), but not resting heart rate. No significant correlation was found between cardiorespiratory change and change in scores on depression and anxiety. No significant association was found between physiological change and change in body image. Preliminary evaluation of the minimal exercise treatment was given. The need to replicate findings with larger and different samples was emphasized.

  11. Mapping Climate Change Vulnerabilities to Infectious Diseases in Europe

    National Research Council Canada - National Science Library

    Jan C. Semenza; Jonathan E. Suk; Virginia Estevez; Kristie L. Ebi; Elisabet Lindgren

    ...: In 2007 and 2009/2010, national infectious disease experts from 30 European Economic Area countries were surveyed about recent and projected infectious disease patterns in relation to climate change...

  12. Climate change-related migration and infectious disease.

    Science.gov (United States)

    McMichael, Celia

    2015-01-01

    Anthropogenic climate change will have significant impacts on both human migration and population health, including infectious disease. It will amplify and alter migration pathways, and will contribute to the changing ecology and transmission dynamics of infectious disease. However there has been limited consideration of the intersections between migration and health in the context of a changing climate. This article argues that climate-change related migration - in conjunction with other drivers of migration - will contribute to changing profiles of infectious disease. It considers infectious disease risks for different climate-related migration pathways, including: forced displacement, slow-onset migration particularly to urban-poor areas, planned resettlement, and labor migration associated with climate change adaptation initiatives. Migration can reduce vulnerability to climate change, but it is critical to better understand and respond to health impacts - including infectious diseases - for migrant populations and host communities.

  13. New insight into the pathogenesis of minimal change nephrotic syndrome: Role of the persistence of respiratory tract virus in immune disorders.

    Science.gov (United States)

    Zhang, Hui; Wang, Zheng; Dong, Liqun; Guo, Yannan; Wu, Jin; Zhai, Songhui

    2016-07-01

    The pathogenesis of minimal change nephrotic syndrome (MCNS) is a complex clinical problem which, unfortunately, has been in need of significant breakthroughs for decades. Improved understanding of the mechanisms is important to develop effective treatment strategies. To our knowledge, the pathogenesis of MCNS is multifactorial, involving both intrinsic and extrinsic factors, reasonable to be regarded as a "long chain" cascade reaction. Current studies implicating that the disease could probably be caused by immune disorders, however, have focused merely on the middle or terminal of this "long chain". It remains unclear what really triggers the immune disorders. It is noteworthy that the close association of respiratory tract infection with the occurrence, relapse and aggravation of nephrotic syndrome has been confirmed for over two decades. Derived from what we demonstrated in earlier studies, that the persistence of respiratory tract virus may contribute to the onset and development of MCNS, this review summarizes current evidence investigating the possible mechanisms of viral persistence, and discusses the role of viral persistence in the pathogenesis of MCNS. The key point is: whether the persistence of respiratory tract virus results in immune disorders. The available evidence under review also highlight the fact that the background of genetic susceptibility to the disease was found in many patients, which could be triggered by extrinsic factors, e.g. by the infection of respiratory tract virus.

  14. Retrospective monitoring of minimal residual disease using hairpin-shaped clone specific primers in B-cell lymphoma affected dogs.

    Science.gov (United States)

    Gentilini, Fabio; Turba, Maria E; Forni, Monica

    2013-06-15

    Lymphoma is one of the most common forms of cancer in dogs as it is in humans but, unlike humans, the cure rates in canines are still very low. Despite the fact that high grade B-cell lymphomas are considered to be chemotherapy responsive, almost all treated dogs ultimately relapse and die due to the residual malignant lymphocytes, namely minimal residual disease (MRD). It would be extremely valuable for clinicians to detect, monitor and quantify MRD for risk group stratification, effective treatment intervention and outcome prediction. The PCRs targeting the Ig gene rearrangements constitute one of the most reliable tools to this end. We have recently validated a method which exploits hairpin-shaped primers for quantifying MRD. In the present study, that method is conveniently used for retrospectively monitoring MRD in the peripheral blood of 8 dogs diagnosed with B-cell lymphoma who underwent chemotherapy. All dogs attained complete remission. The median disease-free interval was 254.5 days (range 63-774) while the median survival time was 313.5 days (range 143-817 days). At admission, all dogs, except one which had already been treated with prednisone, had circulating neoplastic cells. All dogs attained complete remission (CR) which was almost always matched with a complete MRD response. The persistence of MRD despite apparent CR indicated a worse prognosis and a short duration of CR. Finally, the relapse is consistently anticipated by the reappearance of MRD in the peripheral blood. The study confirmed the suitability of an MRD monitoring assay as a clinical decision-making tool.

  15. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Ravandi, Farhad; Jorgensen, Jeffrey L; O'Brien, Susan M; Jabbour, Elias; Thomas, Deborah A; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M

    2016-02-01

    The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.

  16. Common themes in changing vector-borne disease scenarios.

    Science.gov (United States)

    Molyneux, David H

    2003-01-01

    The impact of climate change on disease patterns is controversial. However, global burden of disease studies suggest that infectious diseases will contribute a proportionately smaller burden of disease over the next 2 decades as non-communicable diseases emerge as public health problems. However, infectious diseases contribute proportionately more in the poorest quintile of the population. Notwithstanding the different views of the impact of global warming on vector-borne infections this paper reviews the conditions which drive the changing epidemiology of these infections and suggests that such change is linked by common themes including interactions of generalist vectors and reservoir hosts at interfaces with humans, reduced biodiversity associated with anthropogenic environmental changes, increases in Plasmodium falciparum: P. vivax ratios and well-described land use changes such as hydrological, urbanization, agricultural, mining and forest-associated impacts (extractive activities, road building, deforestation and migration) which are seen on a global scale.

  17. Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome

    DEFF Research Database (Denmark)

    Nyvold, Charlotte; Madsen, Hans O; Ryder, Lars P

    2002-01-01

    The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlat......The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant...

  18. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

    Science.gov (United States)

    Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

    2016-01-01

    The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.

  19. Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

    Science.gov (United States)

    Pochon, Cécile; Oger, Emmanuel; Michel, Gérard; Dalle, Jean-Hugues; Salmon, Alexandra; Nelken, Brigitte; Bertrand, Yves; Cavé, Hélène; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rohrlich, Pierre; Paillard, Catherine; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Eliaou, Jean-François; Semana, Gilbert; Drunat, Séverine; Jonveaux, Philippe; Bordigoni, Pierre; Gandemer, Virginie

    2015-04-01

    Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention. © 2014 John Wiley & Sons Ltd.

  20. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia.

    Science.gov (United States)

    Jourdan, Eric; Boissel, Nicolas; Chevret, Sylvie; Delabesse, Eric; Renneville, Aline; Cornillet, Pascale; Blanchet, Odile; Cayuela, Jean-Michel; Recher, Christian; Raffoux, Emmanuel; Delaunay, Jacques; Pigneux, Arnaud; Bulabois, Claude-Eric; Berthon, Céline; Pautas, Cécile; Vey, Norbert; Lioure, Bruno; Thomas, Xavier; Luquet, Isabelle; Terré, Christine; Guardiola, Philippe; Béné, Marie C; Preudhomme, Claude; Ifrah, Norbert; Dombret, Hervé

    2013-03-21

    Not all patients with core binding factor acute myeloid leukemia (CBF-AML) display a good outcome. Modern risk factors include KIT and/or FLT3 gene mutations and minimal residual disease (MRD) levels, but their respective values have never been prospectively assessed. A total of 198 CBF-AML patients were randomized between a reinforced and a standard induction course, followed by 3 high-dose cytarabine consolidation courses. MRD levels were monitored prospectively. Gene mutations were screened at diagnosis. Despite a more rapid MRD decrease after reinforced induction, induction arm did not influence relapse-free survival (RFS) (64% in both arms; P = .91). Higher WBC, KIT, and/or FLT3-ITD/TKD gene mutations, and a less than 3-log MRD reduction after first consolidation, were associated with a higher specific hazard of relapse, but MRD remained the sole prognostic factor in multivariate analysis. At 36 months, cumulative incidence of relapse and RFS were 22% vs 54% (P gene mutations, should be used for future treatment stratifications in CBF-AML patients. This trial was registered at EudraCT as #2006-005163-26 and at www.clinicaltrials.gov as #NCT 00428558.

  1. Flow Cytometry and Polymerase Chain Reaction-Based Analyses of Minimal Residual Disease in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Sabrina Uhrmacher

    2010-01-01

    Full Text Available New therapeutic strategies developed recently for chronic lymphocytic leukemia (CLL have led to remarkable treatment response rates and complete hematological remissions. This means highly sensitive and specific techniques are increasingly needed to evaluate minimal residual disease (MRD in CLL patients. Quantitative MRD levels can be used as prognostic markers, where total MRD eradication is associated with prolonged survival. Nowadays, PCR and flow cytometry techniques used to detect MRD in CLL patients can generate reliable and quantitative results with the highest sensitivity. MRD Flow is based on four-color flow cytometry using specific antibody combinations. For allele specific oligonucleotide real-time quantification (ASO RQ PCR individual primers are designed to detect a specific immunoglobulin heavy chain (IgH rearrangement in each patient clone. Five comprehensive studies investigated and compared the sensitivity and specificity of both methods. Groups of patients receiving different therapies were analyzed at different time points to generate quantitative MRD levels and MRD kinetics. All studies confirmed that both methods generate equivalent results with regard to sensitivity and MRD quantification, although each method has advantages and disadvantages in the daily routine of a standard hematological laboratory. Here, we review these investigations and compare their results in the light of modern therapies.

  2. Is There a Role for Minimal Residual Disease Monitoring in Follicular Lymphoma in the Chemo-Immunotherapy Era?

    Science.gov (United States)

    Gritti, Giuseppe; Pavoni, Chiara; Rambaldi, Alessandro

    2017-01-01

    After 25 years, evaluation of minimal residual disease (MRD) in follicular lymphoma (FL) has become a standardized technique frequently integrated into clinical trials for its consistent and independent prognostic significance. Achievement of a sustained MRD negativity is a marker of treatment sensibility that has been associated with excellent clinical outcome in terms of clinical response and progression-free survival, independently from the employed therapy. However, no survival advantages has been reported for MRD negative patients and despite the compelling results of clinical trials, MRD evaluation has currently no role in clinical practice. Ongoing clinical trials will help in clarifying the potential setting in which MRD monitoring may have a routine clinical application i.e. allowing de-escalation of standard maintenance therapy in very low risk patients. In this review the clinical implications of MRD monitoring in Rituximab-era are discussed in light of the current treatment paradigms most aimed at reducing toxicities, and the response definition that now routinely integrates PET scan. PMID:28101314

  3. Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2015-01-01

    Full Text Available 191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188, 36 (n = 191, and 85 (n = 187 of remission induction. Minimal residual disease (MRD was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001: 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 % belonged to group with poor outcome (EFS 56.7 ± 9.0 %. At the end of remission induction (day 36 36 children (18.85 % with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001. From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.

  4. Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma

    OpenAIRE

    Bickel, Angelika; Koneth, Irene; Enzler-Tschudy, Annette; Neuweiler, Jörg; Flatz, Lukas; Früh, Martin

    2016-01-01

    Background Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis. Case presentation We describe a 62-year old patient diagnosed with malignant pleural mesothelioma who experienced ten days after the second dose...

  5. Elastomer Change Out - Justification for minimizing the removal of elastomers in order to prevent cross contamination in a multiproduct facility.

    Science.gov (United States)

    Parks, Michael; O'Dwyer, Niamh; Bollinger, Jeremy; Johnson, Alan; Goss, Brian; Wyman, Ned; Arroyo, Adeyma; Wood, Joseph; Willison-Parry, Derek

    2017-09-19

    The primary objective of any Biopharmaceutical Product Changeover (PCO) program is to employ control strategies before, during, and after the manufacturing process, as well as from the beginning of the lifecycle approach for the equipment and validation, which will minimize the opportunity for cross- contamination when switching between products. Evaluation of the need for an Elastomer Change Out (ECO) should be considered as a segment of an overall changeover assessment. Lifecycle systems (e.g. Preventive Maintenance (PM), Cleanability Coupon Testing, Good Engineering Practices, etc.) and procedures should be in place and data should be generated demonstrating the soft parts do not harbor residues from the previous product campaign(s). The determination of whether or not to replace elastomers/soft parts should be made in the context of all of these systems along with the proper assessment of Risk. By understanding the actual value of ECO in terms of the overall PCO program, and the other systems and procedures that are in place that protect against cross contamination, the need for ECO for every product changeover is not necessary. The purpose of this paper is to review the practice of ECO at product changeover, evaluate the need for an ECO using a risk based approach, and provide rationale for justifying the reduction or elimination of ECO at product changeover. Copyright © 2017, Parenteral Drug Association.

  6. Electroencephalographic Changes Associated with Antinociceptive Actions of Lidocaine, Ketamine, Meloxicam, and Morphine Administration in Minimally Anaesthetized Dogs

    Directory of Open Access Journals (Sweden)

    Ubedullah Kaka

    2015-01-01

    Full Text Available Effects of ketamine and lidocaine on electroencephalographic (EEG changes were evaluated in minimally anaesthetized dogs, subjected to electric stimulus. Six dogs were subjected to six treatments in a crossover design with a washout period of one week. Dogs were subjected to intravenous boluses of lidocaine 2 mg/kg, ketamine 3 mg/kg, meloxicam 0.2 mg/kg, morphine 0.2 mg/kg and loading doses of lidocaine 2 mg/kg followed by continuous rate infusion (CRI of 50 and 100 mcg/kg/min, and ketamine 3 mg/kg followed by CRI of 10 and 50 mcg/kg/min. Electroencephalogram was recorded during electrical stimulation prior to any drug treatment (before treatment and during electrical stimulation following treatment with the drugs (after treatment under anaesthesia. Anaesthesia was induced with propofol and maintained with halothane at a stable concentration between 0.85 and 0.95%. Pretreatment median frequency was evidently increased (P<0.05 for all treatment groups. Lidocaine, ketamine, and morphine depressed the median frequency resulting from the posttreatment stimulation. The depression of median frequency suggested evident antinociceptive effects of these treatments in dogs. It is therefore concluded that lidocaine and ketamine can be used in the analgesic protocol for the postoperative pain management in dogs.

  7. Climate change and infectious diseases in the Arctic

    DEFF Research Database (Denmark)

    Parkinson, Alan J; Evengard, Birgitta; Semenza, Jan C

    2014-01-01

    distribution of a range of infectious diseases. Many infectious diseases are climate sensitive, where their emergence in a region is dependent on climate-related ecological changes. Most are zoonotic diseases, and can be spread between humans and animals by arthropod vectors, water, soil, wild or domestic...

  8. Stability and Change in Patterns of Coping with Parkinson's Disease

    Science.gov (United States)

    Frazier, Leslie D.

    2002-01-01

    This study examined how Parkinson's disease patients cope with disease-related stressors over time. Of interest was whether patterns of coping would support a dispositional model of coping (i.e., stability) or a contextual model of coping (i.e., change). The influence of stability and change in coping on mental and physical health outcomes was…

  9. Huntington's disease : quantifying structural brain changes

    NARCIS (Netherlands)

    Bogaard, Simon Johannes Adrianus van den

    2012-01-01

    The aim of this thesis was to find potential MRI biomarkers for Huntington’s disease (HD). Therefore, after an overview of the current literature on MRI biomarkers, followed by examinations of volumetric MRI, magnetization transfer imaging (MTI), diffusion tensor imaging (DTI) and magnetic resonance

  10. Managing marine disease emergencies in an era of rapid change.

    Science.gov (United States)

    Groner, Maya L; Maynard, Jeffrey; Breyta, Rachel; Carnegie, Ryan B; Dobson, Andy; Friedman, Carolyn S; Froelich, Brett; Garren, Melissa; Gulland, Frances M D; Heron, Scott F; Noble, Rachel T; Revie, Crawford W; Shields, Jeffrey D; Vanderstichel, Raphaël; Weil, Ernesto; Wyllie-Echeverria, Sandy; Harvell, C Drew

    2016-03-05

    Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. © 2016 The Author(s).

  11. Managing marine disease emergencies in an era of rapid change

    Science.gov (United States)

    Maynard, Jeffrey; Breyta, Rachel; Carnegie, Ryan B.; Dobson, Andy; Friedman, Carolyn S.; Froelich, Brett; Garren, Melissa; Gulland, Frances M. D.; Heron, Scott F.; Noble, Rachel T.; Revie, Crawford W.; Shields, Jeffrey D.; Vanderstichel, Raphaël; Weil, Ernesto; Wyllie-Echeverria, Sandy; Harvell, C. Drew

    2016-01-01

    Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. PMID:26880835

  12. Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.

    Science.gov (United States)

    Paiva, Bruno; Corchete, Luis A; Vidriales, Maria-Belen; Puig, Noemi; Maiso, Patricia; Rodriguez, Idoia; Alignani, Diego; Burgos, Leire; Sanchez, Maria-Luz; Barcena, Paloma; Echeveste, Maria-Asuncion; Hernandez, Miguel T; García-Sanz, Ramón; Ocio, Enrique M; Oriol, Albert; Gironella, Mercedes; Palomera, Luis; De Arriba, Felipe; Gonzalez, Yolanda; Johnson, Sarah K; Epstein, Joshua; Barlogie, Bart; Lahuerta, Juan José; Blade, Joan; Orfao, Alberto; Mateos, María-Victoria; San Miguel, Jesús F

    2016-04-14

    Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) is associated with inferior survival in multiple myeloma (MM). Thus, characterization of the minor MRD subclone may represent a unique model to understand chemoresistance, but to our knowledge, the phenotypic and genetic features of the MRD subclone have never been investigated. Here, we compared the antigenic profile of MRD vs diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study and showed that the MRD subclone is enriched in cells overexpressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4), and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs diagnostic PCs was performed in 12 patients; 3 of them showed identical copy number alterations (CNAs), in another 3 cases, MRD clonal PCs displayed all genetic alterations detected at diagnosis plus additional CNAs that emerged at the MRD stage, whereas in the remaining 6 patients, there were CNAs present at diagnosis that were undetectable in MRD clonal PCs, but also a selected number of genetic alterations that became apparent only at the MRD stage. The MRD subclone showed significant downregulation of genes related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and may identify chemoresistant PCs in vitro. Altogether, our results suggest that therapy-induced clonal selection could be already present at the MRD stage, where chemoresistant PCs show a singular phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles. This trial was registered atwww.clinicaltrials.gov as #NCT01237249.

  13. Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining.

    Science.gov (United States)

    Jacobson, Samuel G; Cideciyan, Artur V; Aleman, Tomas S; Sumaroka, Alexander; Roman, Alejandro J; Swider, Malgorzata; Schwartz, Sharon B; Banin, Eyal; Stone, Edwin M

    2011-01-05

    To determine the human retinal phenotype caused by mutations in the gene encoding AIPL1 (Aryl hydrocarbon receptor-interacting protein-like 1) now that there are proof-of-concept results for gene therapy success in Aipl1-deficient mice. Leber congenital amaurosis (LCA) patients (n = 10) and one patient with a later-onset retinal degeneration (RD) and AIPL1 mutations were studied by ocular examination, retinal imaging, perimetry, full-field sensitivity testing, and pupillometry. The LCA patients had severe visual acuity loss early in life, nondetectable electroretinograms (ERGs), and little or no detectable visual fields. Hallmarks of retinal degeneration were present in a wide region, including the macula and midperiphery; there was some apparent peripheral retinal sparing. Cross-sectional imaging showed foveal cone photoreceptor loss with a ring of minimally preserved paracentral photoreceptor nuclear layer. Features of retinal remodeling were present eccentric to the region of detectable photoreceptors. Full-field sensitivity was reduced by at least 2 log units, and chromatic stimuli, by psychophysics and pupillometry, revealed retained but impaired rod function. The RD patient, examined serially over two decades (ages, 45-67 years), retained an ERG in the fifth decade of life with abnormal rod and cone signals; and there was progressive loss of central and peripheral function. AIPL1-LCA, unlike some other forms of LCA with equally severe visual disturbance, shows profound loss of foveal as well as extrafoveal photoreceptors. The more unusual late-onset and slower form of AIPL1 disease may be better suited to gene augmentation therapy and is worthy of detection and further study.

  14. [Case of goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS) in a patient with rheumatoid arthritis (RA)].

    Science.gov (United States)

    Takeda, Yoko; Abe, Aya; Toki, Takeshi; Komaba, Hirotaka; Abe, Takaya; Umezu, Michio; Joh, Kensuke; Fukagawa, Masafumi

    2009-01-01

    In early June 2004, a 50-year-old female was admitted to the hospital for slight fever, general fatigue, hemoptysis, dyspnea, and renal dysfunction (serum creatinine[Cr] : 6.05 mg/dL). She had been treated with prednisolone (PSL : 10-20 mg/day) for RA. She was diagnosed with Goodpasture syndrome based on a high titer of anti-glomerular basement membrane antibody (87 EU), and pulmonary hemorrhage. The renal and pulmonary impairments were markedly improved by the pulse therapy, plasma exchange and temporary hemodialysis. However, the Cr level remained at 2.0 mg/dL, indicating nephrotic syndrome. Light microscopy with Periodic acid-Shiff(PAS) staining demonstrated global sclerosis in three of ten glomeruli. Five glomeruli showed the formation of cellular, and fibrocellular crescents, and the formation of fibrous crescents. Tubular damage and interstitial fibrosis were severe. Immunofluorescence microscopy disclosed major depositions of IgG in a linear pattern along the glomerular basement membrane(GBM). Electron microscopy revealed foot process effacement (>50%)and no electron-dense deposits. Therefore, we diagnosed Goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS). Some reports have dealt with the association of RA and Goodpasture syndrome with D-penicillamine, and of RA and antineutrophil cytoplasmic antibodies (ANCA)-related vasculitis with pulmonary hemorrhage, but none has dealt with cases complicated with RA and Goodpasture syndrome associated with MCNS. Accordingly, whether or not there is a causal relationship between RA and Goodpasture syndrome remains obscure, but since the number of reported cases is small, experience with more cases is necessary to clarify this matter.

  15. Progressive changes in patients with skeletal Class III malocclusion treated by 2-jaw surgery with minimal and conventional presurgical orthodontics: A comparative study.

    Science.gov (United States)

    Zhou, Yang; Li, Zili; Wang, Xiaoxia; Zou, Bingshuang; Zhou, Yanheng

    2016-02-01

    In this study, we aimed to compare treatment efficacy and postsurgical stability between minimal presurgical orthodontics and conventional presurgical orthodontics for patients with skeletal Class III malocclusion. Forty patients received minimal presurgical orthodontics (n = 20) or conventional presurgical orthodontics (n = 20). Lateral cephalograms were obtained before treatment, before orthognathic surgery, and at 1 week, 3 months, 6 months, and 12 months after surgery. Changes of overjet and mandibular incisal angle before surgery were greater in the conventional presurgical orthodontics group than in the minimal presurgical orthodontics group. Postsurgical horizontal changes in Points A and B, overjet, and mandibular incisal angle showed significant differences among the time points. Most of the horizontal and vertical relapses in the maxilla and the mandible occurred within the first 6 months in both groups. Minimal presurgical orthodontics and conventional presurgical orthodontics showed similar extents and directions of skeletal changes in patients with Class III malocclusion. However, orthodontists and surgeons should preoperatively consider the postsurgical counterclockwise rotation of the mandible when using minimal presurgical orthodontics. Close and frequent observations are recommended in the early postsurgical stages. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  16. Blood pressure in children with minimal change nephrotic syndrome during oedema and after steroid therapy: the influence of familial essential hypertension.

    Science.gov (United States)

    Kontchou, Laure Monthe; Liccioli, Giulia; Pela, Ivana

    2009-01-01

    To verify the variations of blood pressure in children with minimal change nephrotic syndrome and to correlate the blood pressure with familial history of essential hypertension. We measured blood pressure in 49 prepubertal nephrotic children, 17 females and 32 males, in the first week of oedema, and after 4 weeks of ISKDC (International Study of Kidney Disease in Children) standard steroid therapy. The children were divided into two groups: one with and the other without familial history of essential hypertension. Among all the patients, 65% showed systolic and/or diastolic blood pressure higher than the 90th percentile at the first assessment. Among the children with a familial history of essential hypertension, in the oedematous phase of the nephrotic syndrome, 88% showed blood pressure higher than the 90th percentile and no children showed blood pressure lower than the 75th percentile. After therapy, the percentage of children with blood pressure higher than the 90th percentile was 52%. In the group with a negative familial history, at the onset 53% showed blood pressure over the 90th percentile. After 4 weeks of therapy, the percentage of children with blood pressure higher than the 90th percentile was 34%. Our study reveals the influence of familial essential hypertension in the oedematous phase of the nephrotic syndrome in children. (c) 2009 S. Karger AG, Basel.

  17. A minimally invasive approach to spleen histopathology in dogs: A new method for follow-up studies of spleen changes in the course of Leishmania infantum infection.

    Science.gov (United States)

    Santos, Silvana Ornelas; Fontes, Jonathan L M; Laranjeira, Daniela F; Vassallo, José; Barrouin-Melo, Stella Maria; Dos-Santos, Washington L C

    2016-10-01

    Severe forms of zoonotic visceral leishmaniosis (ZVL) are associated with disruption of the spleen structure. However, the study of spleen histology requires splenectomy or necropsy. In this work, we present a minimally invasive cell-block technique for studying spleen tissue histology in dogs with ZVL. We examined 13 dogs with and seven dogs without Leishmania infantum infection. The dogs with Leishmania infection had a lower frequency of lymphoid follicles (2/13, Fisher's test, P<0.02) and a higher density of plasma cells (score 3, Fisher's test, P<0.02) than uninfected dogs (5/7 exhibiting lymphoid follicles and a plasma cell score of 1). The dogs with Leishmania infection also presented with granulomas (8/13) and infected macrophages (5/13). These differences in the histological presentations of spleen tissue from infected and uninfected dogs corresponded to changes observed in conventional histology. Hence, the cell-block technique described here may be used in the follow-up care and study of dogs with ZVL and other diseases in both clinical practice and research.

  18. Comparing minimally invasive and open transforaminal lumbar interbody fusion for treatment of degenerative lumbar disease: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    SUN Zhi-jian; LI Wen-jing; ZHAO Yu; QIU Gui-xing

    2013-01-01

    Background Transforaminal lumbar interbody fusion (TLIF) through a minimally invasive approach (mTLIF) was introduced to reduce soft tissue injury and speed recovery.Studies with small numbers of patients have been carried out,comparing mTLIF with traditional open TLIF (oTLIF),but inconsistent outcomes were reported.Methods We conducted a meta-analysis to evaluate the effectiveness of mTLIF and oTLIF in the treatment of degenerative lumbar disease.We searched PubMed,Embase and Cochrane Database of Systematic Reviews in March 2013 for studies directly comparing mTLIF and oTLIF.Patient characteristics,interventions,surgical-related messages,early recovery parameters,long-term clinical outcomes,and complications were extracted and relevant results were pooled.Results Twelve cohort studies with a total of 830 patients were identified.No significant difference regarding average operating time was observed when comparing mTLIF group with oTLIF group (-0.35 minute,95% confidence interval (C/):-20.82 to 20.13 minutes).Intraoperative blood loss (-232.91 ml,95% CI:-322.48 to-143.33 ml) and postoperative drainage (-111.24.ml,95% CI:-177.43 to-45.05 ml) were significantly lower in the mTLIF group.A shorter hospital stay by about two days was observed in patients who underwent mTLIF (-2.11 days,95% CI:-2.76 to-1.45 days).With regard to long-term clinical outcomes,no significant difference in visual analog scale score (-0.25,95% CI:-0.63 to 0.13) was observed; however,there was a slight improvement in Oswestry Disability Index (-1.42,95% CI:-2.79 to-0.04) during a minimum of 1-year follow-up between the two groups.The incidence of complications did not differ significantly between the procedures (RR=1.06,95% CI:0.7 to 1.59).Reoperation was more common in patients in mTLIF group than in oTLIF group (5% vs.2.9%),but this difference was not significant (RR=1.62,95% CI:0.75 to 3.51).Conclusion Current evidence suggests that,compared with traditional open surgery

  19. Introducing the Concept of the Minimally Important Difference to Determine a Clinically Relevant Change on Patient-Reported Outcome Measures in Patients with Intermittent Claudication

    NARCIS (Netherlands)

    A.P. Conijn (Anne P.); W. Jonkers (Wilma); E.V. Rouwet (Ellen); A. Vahl (Anco); J.A. Reekers (Jim); M.J. Koelemay

    2015-01-01

    textabstractPurpose: The minimally important difference (MID) represents the smallest change in score on patient-reported outcome measures that is relevant to patients. The aim of this study was to introduce the MID for the Vascular Quality of Life Questionnaire (VascuQol) and the walking impairment

  20. Developmental changes in maternal education and minimal exposure effects on vocabulary in English- and Spanish-learning toddlers.

    Science.gov (United States)

    Friend, Margaret; DeAnda, Stephanie; Arias-Trejo, Natalia; Poulin-Dubois, Diane; Zesiger, Pascal

    2017-12-01

    The current research follows up on two previous findings: that children with minimal dual-language exposure have smaller receptive vocabularies at 16months of age and that maternal education is a predictor of vocabulary when the dominant language is English but not when it is Spanish. The current study extends this research to 22-month-olds to assess the developmental effects of minimal exposure and maternal education on direct and parent-report measures of vocabulary size. The effects of minimal exposure on vocabulary size are no longer present at 22months of age, whereas maternal education effects remain but only for English speakers. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Climate change effects on plant disease: Genomes to ecosystems

    OpenAIRE

    Garrett, Karen A.; Dendy, S.P.; Frank, E.E.; Rouse, M. N.; Travers, S.E.

    2006-01-01

    We have reviewed the potential effects of climate change on plant disease, considering processes within plants as well as larger scale processes. LTRA-4 (Practices and Strategies for Vulnerable Agro-Ecosystems)

  2. Climate change effects on plant disease: Genomes to ecosystems

    OpenAIRE

    Garrett, Karen A.; Dendy, S.P.; Frank, E.E.; Rouse, M. N.; Travers, S.E.

    2006-01-01

    We have reviewed the potential effects of climate change on plant disease, considering processes within plants as well as larger scale processes. LTRA-4 (Practices and Strategies for Vulnerable Agro-Ecosystems)

  3. Is proliferative colonic disease presentation changing?

    Institute of Scientific and Technical Information of China (English)

    Vito D Corleto; Cristiano Pagnini; Maria Sofia Cattaruzza; Ermira Zykaj; Emilio Di Giulio; Giovanna Margagnoni; Emanuela Pilozzi

    2012-01-01

    AIM:To compare the site,age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome,Italy,during two periods.METHODS:CRC data were collected from surgery/pathology registers,and polyp data from colonoscopy reports.Patients who met the criteria for familial adenomatous polyposis,hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study.Overlap of patients between the two groups (cancers and polyps) was carefully avoided.Thex2 statistical test and a regression analysis were performed.RESULTS:Data from a total of 768 patients (352 and 416 patients,respectively,in periods A and B) who underwent surgery for cancer were collected.During the same time periods,a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B).A proximal shift in cancer occurred during the latter years for both sexes,but particularly in males.Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31,95%CI:2.00-5.47; P <0.0001).A similar proximal shift was observed for polyps,particularly in males (OR 1.87,95%CI:1.23-2.87;P < 0.0038),but also in females (OR 1.62,95%CI:0.96-2.73; P < 0.07).CONCLUSION:The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade,particularly in males.

  4. Sublingual Microvascular Changes in Patients With Cerebral Small Vessel Disease

    NARCIS (Netherlands)

    M. Khalilzada; K. Dogan; C. Ince; J. Stam

    2011-01-01

    Background and Purpose-It is unknown whether changes in cerebral small vessel disease (SVD) are limited to the brain or part of a generalized vascular disorder. Methods-We examined the sublingual microcirculation of 10 healthy controls, 10 patients with large vessel disease, and 8 with SVD, with sid

  5. [The prognostic value of evaluation of minimal residual disease using technique of flow cytofluorometry during application of therapy of chronic lymphatic leukemia].

    Science.gov (United States)

    Kisilichina, D G; Lugovskaia, C A; Naumova, E V; Pochtar', M E; Nikitin, E A; Dolgov, V V

    2014-11-01

    The achievement of molecular remission is associated with increasing of survival of patients with chronic lymphatic leukemia. The important direction of research is seeking of parameters applicable to forecast of response to therapy. The purpose of the study was evaluating prognostic significance of indicator of minimal residual disease detected by technique of flow cytofluorometry of peripheral blood of patients with chronic lymphatic leukemia during therapy application. The sampling included 112 patients with chronic lymphatic leukemia aged from 43 to 82 years. All patients were given treatment consisted of 6 courses of immune chemotherapy combined with fludarabine with cyclophosphan and rituximab. The samples of peripheral blood were analyzed after 3 courses during therapy and after 6 courses after completion of treatment. The cells were analyzed using 5 and 6 color flow cytometry for the purpose of detection of immune phenotype associated with chronic lymphatic leukemia. The evaluation of minimal residual disease was implemented according international standardized protocol (Rawstron A.C. et al. 2007; 21 (5): 956-64). The minimal residual disease negative status was reached in 87 (78%) patients during evaluation of response after 6th course of treatment. The implementation of indicators of residual disease after 3 courses with fludarabine, cyclophosphan and rituximab permitted to sort out two groups of patients with chronic lymphatic leukemia i.e 67 patients with low ( 0.12%) level of tumor cells. The rate of molecular remission after completion of treatment. in the given groups consisted 100% and 44% correspondingly. The study demonstrates possibilities of early immune phenotype evaluation of minimal residual disease to forecast differences in response to treatment in patients with chronic lymphatic leukemia that makes it possible to avoid undesirable toxicity of therapy or to choose method of consolidation.

  6. Assessment of the trauma degree and spinal cord function of para-median minimally invasive and open TLIF for single segmental lumbar degenerative disease

    Institute of Scientific and Technical Information of China (English)

    Zheng Bo-long; He Bao-rong; Yang Xiao-bin; Yang Ming; Yan Liang; Bai Xiao-fan; Hao Ding-jun

    2016-01-01

    Objective:To study the trauma degree of para-median minimally invasive and open TLIF for single segmental lumbar degenerative disease and the effect on spinal cord function.Methods:A total of 78 cases of patients with single segmental lumbar disc herniation who received TLIF treatment in our hospital were selected as the research subjects and randomly divided into two groups, minimally invasive group received para-median minimally invasive TLIF and open group received open TLIF. Perioperative serum levels of oxidative stress indicators and pain mediators as well as spinal cord function were compared between two groups.Results: 1 d and 3 d after operation, serum SOD, GSH-Px and SP levels of minimally invasive group were significantly higher than those of open group, and MDA, AOPP, NO,β-EP, PGE2 and CGRP levels were significantly lower than those of open group; 1 week after operation, NCV and DL of common peroneal nerve and tibial nerve of two groups were not different from those before operation; 4 weeks and 16 weeks after operation, NCV of common peroneal nerve and tibial nerve of both groups were higher than those before operation while DL were lower than those before operation, and NCV of common peroneal nerve and tibial nerve of minimally invasive group were significantly higher than those of open group while DL were significantly lower than those of open group.Conclusion:The trauma degree of para-median minimally invasive TLIF for single segmental lumbar degenerative disease is less and the postoperative spinal cord function recovery is more ideal.

  7. 3. Early outcomes of minimally invasive versus conventional mitral valve surgery in mitral valve diseases. A single institutional experience

    Directory of Open Access Journals (Sweden)

    E. Nourelden

    2016-07-01

    Full Text Available Minimally invasive techniques in cardiac surgery gained popularity due to many advantages like less postoperative pain, minimal blood loss, less hospital stay, less cost. Minimally invasive mitral valve surgery through right anterolateral mini thoracotomy became safe technique. In our study we compared mini-MV surgery with conventional technique regarding cross clamp time, bypass time, total blood loss, reopening for bleeding, and hospital and ICU length of stay. In our institution between 2010 and 2015, 147patients underwent minimally invasive mitral surgery through right lateral minithoracotomy 8 cm incision and 118 patient underwent conventional mitral valve surgery through median sternotomy in minimally invasive technique: mean age was 38 ± 20 vs 59 ± 21, 70.7% were female (n = 104 vs 39.8% (n = 47, 23.8% were associated with tricuspid valve regurgitation (n = 33 vs 55% in conventional technique (n = 65, 0.08% were able to use endovascular clamp (n = 12, mean Euroscore predected risk of mortality 14.7 ± 13.6% vs 8.7 ± 10.9%. Minimally invasive mitral valve repair surgery was accomplished in 77.5% (n = 114 vs 46.15% (n = 55 and replacement of mitral valve in 22.4% (n = 30 vs 53.8% (n = 64 , concomitant procedures consists of tricuspid valve surgery in 23.8% (n = 35 vs 55% (n = 65, primary mitral valve repair included implantation of rigid annuloplasty ring in 79.6% vs 38.9% (n = 46, duration of cardiopulmonary bypass in minimally invasive surgery was 123 ± 64 min vs 116 ± 62 min, cross clamp time was 64 ± 27 min vs 59 ± 23 min, postoperative mechanical ventilation time 4 ± 1.5 h vs 6.5 ± 2 h, ICU lenght of stay (LOS was 48 ± 12 h vs 3 ± 1 days. Minimally invasive mitral surgery can be performed very safely with excellent early results. mini-MV surgery can be performed with a reasonable operative time, good perioperative course with decrease in postoperative ICU and hospital

  8. Changing patterns of recurrent disease in colorectal cancer

    NARCIS (Netherlands)

    Grossmann, I.; Doornbos, P. M.; Klaase, J. M.; de Bock, G. H.; Wiggers, T.

    2014-01-01

    Background: Due to changes in staging, (neo)-adjuvant treatment and surgical techniques for colorectal cancer (CRC), it is expected that the recurrence pattern will change as well. This study aims to report the current incidence of, and time to recurrent disease (RD), further the localization(s) and

  9. White matter changes in Wilson's disease: A radiological enigma

    Directory of Open Access Journals (Sweden)

    Soumava Mukherjee

    2016-01-01

    Full Text Available Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease.

  10. White matter changes in Wilson's disease: A radiological enigma.

    Science.gov (United States)

    Mukherjee, Soumava; Solanki, Bhavesh; Guha, Goutam; Saha, Shankar Prasad

    2016-01-01

    Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease.

  11. Bovine Ephemeral Fever As A Disease Related To Climate Change

    Directory of Open Access Journals (Sweden)

    Indrawati Sendow

    2013-06-01

    Full Text Available Bovine Ephemeral Fever (BEF is one of arbovirus diseases infecting in ruminants especially cattle and buffaloes, which is transmitted by mosquito vectors. In general, vector borne disease is also related to climate change, that mosquito as a vector will significantly increase when the environment temperature increases. The disease was found in many countries in Asia, Africa and Australia. The clinical sign of the disease such as fever to paralysis causes economical impact to the farmer, eventhough the mortality is very low. This review will discuss the disease in relation to climate change, which affects vector population that spread the disease. The more population of vector is the higher chance of animal to be infected. This condition describes that the spread of BEF will depend on some factors included the increase of vectors, the availability of susceptible host and vector media facilities, climate condition and supportive ecology. This paper will discuss the feature of BEF, mode of transmission, the impact of environment and climate change, disease prevention and control, and other aspects to prevent further economical impact. It will also discuss how to the transmission, prevention and control of disease BEF. The information can be taken as an input for policy makers to prevent BEF infection in Indonesia.

  12. Global climate change and vector-borne diseases

    Science.gov (United States)

    Ginsberg, H.S.

    2002-01-01

    Global warming will have different effects on different diseases because of the complex and idiosynchratic interactions between vectors, hosts, and pathogens that influence transmission dynamics of each pathogen. Human activities, including urbanization, rapid global travel, and vector management, have profound effects on disease transmission that can operate on more rapid time scales than does global climate change. The general concern about global warming encouraging the spread of tropical diseases is legitimate, but the effects vary among diseases, and the ecological implications are difficult to predict.

  13. Early postural changes in individuals with idiopathic Parkinson's disease.

    Science.gov (United States)

    Khallaf, Mohamed Elsayed; Fayed, Eman Elsayed

    2015-01-01

    Background and Objectives. Postural changes are frequent and disabling complications of Parkinson's disease (PD). Many contributing factors have been evident either related to disease pathology or to adaptive changes. This study aimed at studying the postural changes in subjects with Parkinson's disease and its relation to duration of illness and disease severity. Methods. Eighteen patients with PD and 18 healthy matched volunteers represented the sample of the study. The patients were at stage 1 or 1.5 according to the Modified Hoehn and Yahr Staging with duration of illness between 18 and 36 months. Three-dimensional analysis of the back surface was conducted to explore the postural changes in the sagittal and frontal planes in both the patients and the healthy subjects. Results. Kyphotic angle, lordotic angle, fleche cervicale, fleche lombaire, scoliotic angle, and associated vertebral rotation and pelvic obliquity were significantly increased in patients with PD compared to the healthy subjects (P ≤ 0.05). There was no association between the measured postural changes and duration of illness as well as the severity of the IPD (P ≤ 0.05). Conclusion. Postural changes start in the early stages of idiopathic PD and they have no relationship to the duration of illness and disease severity.

  14. Aeroallergens, allergic disease, and climate change: impacts and adaptation.

    Science.gov (United States)

    Reid, Colleen E; Gamble, Janet L

    2009-09-01

    Recent research has shown that there are many effects of climate change on aeroallergens and thus allergic diseases in humans. Increased atmospheric carbon dioxide concentration acts as a fertilizer for plant growth. The fertilizing effects of carbon dioxide, as well as increased temperatures from climate change, increase pollen production and the allergen content of pollen grains. In addition, higher temperatures are changing the timing and duration of the pollen season. As regional climates change, plants can move into new areas and changes in atmospheric circulation can blow pollen- and spore-containing dust to new areas, thus introducing people to allergens to which they have not been exposed previously. Climate change also influences the concentrations of airborne pollutants, which alone, and in conjunction with aeroallergens, can exacerbate asthma or other respiratory illnesses. The few epidemiological analyses of meteorological factors, aeroallergens, and allergic diseases demonstrate the pathways through which climate can exert its influence on aeroallergens and allergic diseases. In addition to the need for more research, there is the imperative to take preventive and adaptive actions to address the onset and exacerbation of allergic diseases associated with climate variability and change.

  15. Definition of Nonresponse to Analgesic Treatment of Arthritic Pain: An Analytical Literature Review of the Smallest Detectable Difference, the Minimal Detectable Change, and the Minimal Clinically Important Difference on the Pain Visual Analog Scale

    Directory of Open Access Journals (Sweden)

    Melissa E. Stauffer

    2011-01-01

    Full Text Available Our objective was to develop a working definition of nonresponse to analgesic treatment of arthritis, focusing on the measurement of pain on the 0–100 mm pain visual analog scale (VAS. We reviewed the literature to assess the smallest detectable difference (SDD, the minimal detectable change (MDC, and the minimal clinically important difference (MCID. The SDD for improvement reported in three studies of rheumatoid arthritis was 18.6, 19.0, and 20.0. The median MDC was 25.4 for 7 studies of osteoarthritis and 5 studies of rheumatoid arthritis (calculated for a reliability coefficient of 0.85. The MCID increased with increasing baseline pain score. For baseline VAS tertiles defined by scores of 30–49, 50–65, and >65, the MCID for improvement was, respectively, 7–11 units, 19–27 units, and 29–37 units. Nonresponse can thus be defined in terms of the MDC for low baseline pain scores and in terms of the MCID for high baseline scores.

  16. Infectious Diseases, Urbanization and Climate Change: Challenges in Future China.

    Science.gov (United States)

    Tong, Michael Xiaoliang; Hansen, Alana; Hanson-Easey, Scott; Cameron, Scott; Xiang, Jianjun; Liu, Qiyong; Sun, Yehuan; Weinstein, Philip; Han, Gil-Soo; Williams, Craig; Bi, Peng

    2015-09-07

    China is one of the largest countries in the world with nearly 20% of the world's population. There have been significant improvements in economy, education and technology over the last three decades. Due to substantial investments from all levels of government, the public health system in China has been improved since the 2003 severe acute respiratory syndrome (SARS) outbreak. However, infectious diseases still remain a major population health issue and this may be exacerbated by rapid urbanization and unprecedented impacts of climate change. This commentary aims to explore China's current capacity to manage infectious diseases which impair population health. It discusses the existing disease surveillance system and underscores the critical importance of strengthening the system. It also explores how the growing migrant population, dramatic changes in the natural landscape following rapid urbanization, and changing climatic conditions can contribute to the emergence and re-emergence of infectious disease. Continuing research on infectious diseases, urbanization and climate change may inform the country's capacity to deal with emerging and re-emerging infectious diseases in the future.

  17. Climate change and animal diseases: making the case for adaptation.

    Science.gov (United States)

    Cáceres, Sigfrido Burgos

    2012-12-01

    The exponential expansion of the human population has led to overexploitation of resources and overproduction of items that have caused a series of potentially devastating effects, including ocean acidification, ozone depletion, biodiversity loss, the spread of invasive flora and fauna and climatic changes - along with the emergence of new diseases in animals and humans. Climate change occurs as a result of imbalances between incoming and outgoing radiation in the atmosphere. This process generates heat. As concentrations of atmospheric gases reach record levels, global temperatures are expected to increase significantly. The hydrologic cycle will be altered, since warmer air can retain more moisture than cooler air. This means that some geographic areas will have more rainfall, whereas others have more drought and severe weather. The potential consequences of significant and permanent climatic changes are altered patterns of diseases in animal and human populations, including the emergence of new disease syndromes and changes in the prevalence of existing diseases. A wider geographic distribution of known vectors and the recruitment of new strains to the vector pool could result in infections spreading to more and potentially new species of hosts. If these predictions turn out to be accurate, there will be a need for policymakers to consider alternatives, such as adaptation. This review explores the linkages between climate change and animal diseases, and examines interrelated issues that arise from altered biological dynamics. Its aim is to consider various risks and vulnerabilities and to make the case for policies favoring adaptation.

  18. High applicability of ASO-RQPCR for detection of minimal residual disease in multiple myeloma by entirely patient-specific primers/probes

    Directory of Open Access Journals (Sweden)

    Yinlei Bai

    2016-10-01

    Full Text Available Abstract Allele-specific oligonucleotide real-time quantitative PCR (ASO-RQPCR is a standardized technique for detection and monitoring of minimal residual disease (MRD in acute lymphoblastic leukemia (ALL but not multiple myeloma (MM due to a low applicability inherent with presence of somatic hypermutation. Herein, by a staged PCR approach and sequencing, clonality and tumor-specific complementarity-determining region 3 (CDR3 sequence were identified in 13/13 MM by sequential PCR of IgH VDJ (n = 10, IgH DJ (n = 2, or IgK VJ (n = 1. Using consensus primers/probes conventionally employed in ALL, ASO-RQPCR worked in three (23.1 % cases only. Conversely, using entirely patient-specific primers/probes, ASO-RQPCR was applicable in eight (61.5 % cases with a sensitivity of 5 × 10−4–10−5. Moreover, using standard curves constructed by serial dilution of plasmids cloned with patient-specific CDR3, ASO-RQPCR was successful in 12 (92.3 % cases with a sensitivity of 10−4–10−5, but not in a case lacking an N region, in which design of a tumor-specific ASO primer was precluded. Finally, in a patient in complete response (CR, further reduction of MRD after autologous stem cell transplantation (ASCT was demonstrated. In summary, using entirely patient-specific primers/probes, ASO-RQPCR was applicable in >90 % MM patients and enabled detection of dynamic changes of MRD before and after ASCT despite conventional CR.

  19. Effect of climatic changes on the prevalence of zoonotic diseases

    Directory of Open Access Journals (Sweden)

    Neelam Sachan and V.P.Singh

    Full Text Available Combustion of fossil fuels and human activities has led to sharp increase in greenhouse gases in the atmosphere. These climate changes have tremendous effect on prevalence of zoonotic diseases. The changes in climate may increase the insect vectors, prolong transmission cycles or increase the importation of vectors or animal reservoirs. It may also have an adverse effect on biodiversity, distribution of animals and microflora which may lead to emergence of zoonotic disease outbreaks. A historical perspective on major vector-borne diseases such as arboviral encephalitides, dengue fever and Rift Valley fever, Lyme disease, West Nile virus, malaria, plague, hantavirus pulmonary syndrome and dengue fever have been shown to have a distinct seasonal pattern and in some instances their frequency has been shown to be weather sensitive. Because of the sensitivities of the vectors and animal hosts of these diseases to climactic factors, climate change-driven ecological changes such as variations in rainfall and temperature could significantly alter the range, seasonality and human incidence of many zoonotic and vector-borne diseases. The evolution of emerging zoonotic diseases globally during the period 1996 to 2007 was Ebola haemorrhagic fever, Rift Valley fever, avian influenza H5N1, plague and Nipah virus. Whereas, bird flu and swine flu like diseases are still creating havoc for human and animal health worldwide. It is a today’s and tomorrow’s demand that interdisciplinary communication between health professionals, veterinarians, environmental scientists, ecologists, geographers and economists seeking to understand climate change will be key to protecting people in India and worldwide against these threats. Rigorous cross-disciplinary studies using a variety of methodological tools will enable us to predict the transmission dynamics of diseases under different climate scenarios and estimate the cost-effectiveness of mitigation strategies. In this

  20. Personality changes in dementia: are they disease specific and universal?

    Science.gov (United States)

    Torrente, Fernando; Pose, Mariángeles; Gleichgerrcht, Ezequiel; Torralva, Teresa; López, Pablo; Cetkovich-Bakmas, Marcelo; Manes, Facundo

    2014-01-01

    Previous studies about personality changes in dementia suggest that they may be due to the disruption of the biological basis of personality traits, and hence, that they are disease specific and universal. However, evidence about its specificity is still limited and scarce regarding culturally diverse populations. Accordingly, our aim was to compare personality changes in Argentinean patients with Alzheimer disease, behavioral variant of frontotemporal dementia, and primary progressive aphasia. The closest living relatives of patients diagnosed with Alzheimer disease (n=19), behavioral variant of frontotemporal dementia (n=16), and primary progressive aphasia (n=15) were asked to complete 2 versions of the personality inventory NEO Personality Inventory-Revised, one for assessing patients' premorbid personality traits, and the other for assessing current traits. All groups showed changes in several domains and facets of the NEO Personality Inventory-Revised. Globally, the observed pattern of changes was fairly consistent with previous studies based on the same model of personality. Nevertheless, our results regarding disease-specificity were less conclusive. Even if there were some indicators of specific differences between groups, most traits varied similarly across the 3 groups, revealing a pattern of generalized changes in personality expression after illness onset. More studies are needed that help to distinguish real personality changes from other affective or cognitive symptoms that accompany dementia, as well as further data from culturally diverse populations.

  1. 生殖相关输卵管疾病的微创手术进展%Progress of Minimally Invasive Surgery for Reproductive Related Tubal Diseases

    Institute of Scientific and Technical Information of China (English)

    张松英; 林小娜; 徐文治

    2014-01-01

    The goal of infertile couples are to achieve pregnancy via exploring all reasonable attempts. The infertile couples who are due to tubal disease, account for more than 20%of all infertile couples, have two options to achieve this goal:minimally invasive tubal surgery and in vitro fertilization (IVF). In most cases, the decision-making process requires detailed and effective discussion on the curative effect, side effect and cost of the procedures. The available evidence shows that tubal surgery can be more effective for cases of tubal adhesions, mild distal tubal occlusion, proximal obstruction and ectopic pregnancy. A successful tubal reconstructive surgery can not only make infertile couples to avoid further treatment, but also obtain the psychological advantage to conceive naturally. Before or during IVF treatment, individualized minimally invasive surgery treatment which according to tubal pathological changes, can improve the curative effect of IVF, intrauterine pregnancy rate and live birth rates. The incidence of ectopic pregnancy (EP) in IVF cycle is higher than that of natural population, minimally invasive surgery treatment for EP not only less trauma, but also can reduce the impact on subsequent IVF as far as possible. Now the most pragmatic viewpoint is to consider reproductive surgery and in vitro fertilization as complementary options that are directed towards increasing the overall probability of achieving a pregnancy in the most efficient manner.%任何不孕夫妇都希望通过寻求一切合理的治疗手段来实现妊娠。其中20%以上夫妇是由于输卵管因素导致的不孕,这部分患者面临的治疗选择有:微创手术和体外受精(IVF)。大多数情况下,在这一决策过程中必须切实有效地比较这两种方法的疗效、不良反应及费用。目前证据显示,微创手术对于输卵管疏松粘连、轻微的远端输卵管梗阻、近端输卵管梗阻及输卵管妊娠的治疗更加有效。

  2. [Severe behavioral changes in a patient with Fahr's disease].

    Science.gov (United States)

    Kümmer, Arthur; de Castro, Maila; Caramelli, Paulo; Cardoso, Francisco; Teixeira, Antônio Lúcio

    2006-09-01

    We report on a case of a 40 year-old man with Fahrs disease, defined by idiopathic bilateral basal ganglia calcification, who developed depressive disorder, motor and phonic tics, stereotyped behaviors such as punding and personality changes with significant social and familiar implications. We discuss about the psychopathology of Fahrs disease and the relevance of the basal ganglia in the determination of humans behavior.

  3. Extramammary paget disease of scrotum with oncocytic changes.

    Science.gov (United States)

    Aneiros-Fernandez, J; Arias-Santiago, S; Husein-ElAhmed, H; Nicolae, Alina; Ravassa, F O'valle; Serrano-Ortega, S; Fernandez, F Nogales; Cachaza, J Aneiros

    2010-10-01

    We report an unusual case of primary scrotal extramammary Paget disease that infiltrated reticular dermis and lymph vessels, with metastasis in inguinal lymph node. The 67-year-old patient died at 14 months due to systemic metastases. The tumor, which was located in epidermis and infiltrated the dermis, comprised cells with wide, granular, and eosinophilic cytoplasm and intense positivity for antimitochondrial antibody. This seems to be the first report of oncocytic changes in extramammary Paget disease.

  4. Assessing the Stroke-Specific Quality of Life for Outcome Measurement in Stroke Rehabilitation: Minimal Detectable Change and Clinically Important Difference

    Directory of Open Access Journals (Sweden)

    Wu Ching-yi

    2011-01-01

    Full Text Available Abstract Background This study was conducted to establish the minimal detectable change (MDC and clinically important differences (CIDs of the physical category of the Stroke-Specific Quality of Life Scale in patients with stroke. Methods MDC and CIDs scores were calculated from the data of 74 participants enrolled in randomized controlled trials investigating the effects of two rehabilitation programs in patients with stroke. These participants received treatments for 3 weeks and underwent clinical assessment before and after treatment. To obtain test-retest reliability for calculating MDC, another 25 patients with chronic stroke were recruited. The MDC was calculated from the standard error of measurement (SEM to indicate a real change with 95% confidence for individual patients (MDC95. Distribution-based and anchor-based methods were adopted to triangulate the ranges of minimal CIDs. The percentage of scale width was calculated by dividing the MDC and CIDs by the total score range of each physical category. The percentage of patients exceeding MDC95 and minimal CIDs was also reported. Results The MDC95 of the mobility, self-care, and upper extremity (UE function subscales were 5.9, 4.0, and 5.3 respectively. The minimal CID ranges for these 3 subscales were 1.5 to 2.4, 1.2 to 1.9, and 1.2 to 1.8. The percentage of patients exceeding MDC95 and minimal CIDs of the mobility, self-care, and UE function subscales were 9.5% to 28.4%, 6.8% to 28.4%, and 12.2% to 33.8%, respectively. Conclusions The change score of an individual patient has to reach 5.9, 4.0, and 5.3 on the 3 subscales to indicate a true change. The mean change scores of a group of patients with stroke on these subscales should reach the lower bound of CID ranges of 1.5 (6.3% scale width, 1.2 (6.0% scale width, and 1.2 (6.0% scale width to be regarded as clinically important change. This information may facilitate interpretations of patient-reported outcomes after stroke

  5. Pancreatic endocrine and exocrine changes in celiac disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Although there is a great deal of information on celiac disease and associated involvement of other nonintestinal sites, data on concomitant changes in the structure and function of the pancreas is limited. The present review critically examines pancreatic endocrine changes that have been well documented in the literature, including insulin-dependent diabetes mellitus. Pancreatic exocrine alterations may also occur, and if severe, marked malnutrition with pancreatic failure and ductal calcification have been observed. Finally, other pancreatic disorders have been recorded with celiac disease.

  6. Declining Prevalence of Disease Vectors Under Climate Change

    Science.gov (United States)

    Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato; Lepe-Lopez, Manuel A.; Craft, Meggan E.; Borbor-Cordova, Mercy J.; Svenning, Jens-Christian

    2016-12-01

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.

  7. The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study

    Directory of Open Access Journals (Sweden)

    Sara Galimberti

    2017-06-01

    Full Text Available R-Bendamustine is an effective treatment for follicular lymphoma (FL. Previous large trials demonstrated the prognostic role of the molecular minimal residual disease (MRD during the most frequently adopted chemotherapeutic regimens, but there are not yet conclusive data about the effect of combination of rituximab (R and bendamustine in terms of MRD clearance. Thus, the aim of this retrospective study was to assess if and in what extent the combination of rituximab and bendamustine would exert a significant reduction of the molecular disease in 48 previously untreated FL patients. The molecular marker at baseline was found in the 62.5% of cases; no significant differences were observed between patients with or without the molecular marker in respect of the main clinical features. Moreover, the quantization of the baseline molecular tumor burden showed a great variability: the median value was 1.4 × 10−2 copies, ranging from 3 × 10−5 to 4 × 104. The initial molecular tumor burden did not correlate with clinical features and did not impact on the subsequent quality of response. After treatment, 93% of cases became MRD-negative; the median reduction of the BCL2/JH load was 4 logs. The 2-years PFS was 85%; it was significantly longer for patients in complete than for those in partial response (91 vs. 57%; p = 0.002, and for cases with lower FLIPI-2 score (88 vs. 60%; p = 0.004. On the contrary, PFS did not differ between patients with or without the molecular marker at baseline; a molecular tumor burden 15 times higher was observed in the relapsed subgroup in comparison to the relapse-free one, but this difference did not change the PFS length. The 2-years OS was 93.6%; the only variable that significantly impacted on it was the FLIPI-2 score; the presence of the molecular marker at baseline or its behavior after treatment did not impact on survival. This study, even if retrospective and conducted on a small series of patients, would

  8. Epigenetic changes in Alzheimer's disease: decrements in DNA methylation

    OpenAIRE

    Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul D.; Rogers, Joseph

    2008-01-01

    DNA methylation is a vital component of the epigenetic machinery that orchestrates changes in multiple genes and helps regulate gene expression in all known vertebrates. We evaluated immunoreactivity for two markers of DNA methylation and eight methylation maintenance factors in entorhinal cortex layer II, a region exhibiting substantial Alzheimer's disease (AD) pathology in which expression changes have been reported for a wide variety of genes. We show, for the first time, neuronal immunore...

  9. Using ROC curves to choose minimally important change thresholds when sensitivity and specificity are valued equally: the forgotten lesson of pythagoras. theoretical considerations and an example application of change in health status.

    Directory of Open Access Journals (Sweden)

    Robert Froud

    Full Text Available Receiver Operator Characteristic (ROC curves are being used to identify Minimally Important Change (MIC thresholds on scales that measure a change in health status. In quasi-continuous patient reported outcome measures, such as those that measure changes in chronic diseases with variable clinical trajectories, sensitivity and specificity are often valued equally. Notwithstanding methodologists agreeing that these should be valued equally, different approaches have been taken to estimating MIC thresholds using ROC curves.We aimed to compare the different approaches used with a new approach, exploring the extent to which the methods choose different thresholds, and considering the effect of differences on conclusions in responder analyses.Using graphical methods, hypothetical data, and data from a large randomised controlled trial of manual therapy for low back pain, we compared two existing approaches with a new approach that is based on the addition of the sums of squares of 1-sensitivity and 1-specificity.There can be divergence in the thresholds chosen by different estimators. The cut-point selected by different estimators is dependent on the relationship between the cut-points in ROC space and the different contours described by the estimators. In particular, asymmetry and the number of possible cut-points affects threshold selection.Choice of MIC estimator is important. Different methods for choosing cut-points can lead to materially different MIC thresholds and thus affect results of responder analyses and trial conclusions. An estimator based on the smallest sum of squares of 1-sensitivity and 1-specificity is preferable when sensitivity and specificity are valued equally. Unlike other methods currently in use, the cut-point chosen by the sum of squares method always and efficiently chooses the cut-point closest to the top-left corner of ROC space, regardless of the shape of the ROC curve.

  10. [Analysis of clinical pathway in changing and disabling neurological diseases].

    Science.gov (United States)

    Cordesse, V; Jametal, T; Guy, C; Lefebvre, S; Roussel, M; Ruggeri, J; Schimmel, P; Holstein, J; Meininger, V

    2013-01-01

    Neurological diseases are characterized by the complexity of care and by a constant and changing disability. More and more frequently, their impact on the clinical pathway remains unknown. Seven postgraduate rehabilitation students (Master coordination du handicap, université Pierre-et-Marie-Curie, Paris) reconstructed the clinical pathway of 123 patients with various neurological diseases: multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis, spinal trauma, Parkinson disease and brain tumors. There was a significant correlation between disease duration and the number of specialists involved in care, the number of prescribed drugs and the number of short-term hospitalizations; there was no correlation with age. This result suggests that with time an increasing number of complications related to the initial neurological disease developed. Hospitalization in rehabilitation units was highly correlated with the degree of disability and also with the help received by the patients during the course of their disease. This result suggests that these hospitalizations were a direct consequence of burn out among relatives. General practitioners (GP) were highly involved only during the initial part of the pathway, and their involvement rapidly declined thereafter, suggesting a probable relation with the specificities and the complexity of care for neurological diseases which induces a progressive transfer of responsibilities from the GP to the hospital. Social care was always incomplete and occurred too late during the course of the disease. The feeling by the patients that their care pathway was chaotic was highly correlated with the quality of the information given to the patient at the time of the announcement of their disease. This study confirms that cares for neurological diseases is highly specific and that expert centers and coordination networks are in a key position to ensure an efficient care pathway.

  11. Climate change, vector-borne diseases and working population.

    Science.gov (United States)

    Vonesch, Nicoletta; D'Ovidio, Maria Concetta; Melis, Paola; Remoli, Maria Elena; Ciufolini, Maria Grazia; Tomao, Paola

    2016-01-01

    Risks associated with climate change are increasing worldwide and the global effects include altered weather and precipitation patterns, rising temperatures and others; human health can be affected directly and indirectly. This paper is an overview of literature regarding climate changes, their interaction with vector-borne diseases and impact on working population. Articles regarding climate changes as drivers of vector-borne diseases and evidences of occupational cases have been picked up by public databank. Technical documents were also included in the study. Evidences regarding the impact of climate changes on vector-borne diseases in Europe, provided by the analysis of the literature, are presented. Climate-sensitive vector-borne diseases are likely to be emerging due to climate modifications, with impacts on public and occupational health. However, other environmental and anthropogenic drivers such as increasing travelling and trade, deforestation and reforestation, altered land use and urbanization can influence their spread. Further studies are necessary to better understand the phenomenon and implementation of adaptation strategies to protect human health should be accelerated and strengthened.

  12. Climate change effects on plant disease: genomes to ecosystems.

    Science.gov (United States)

    Garrett, K A; Dendy, S P; Frank, E E; Rouse, M N; Travers, S E

    2006-01-01

    Research in the effects of climate change on plant disease continues to be limited, but some striking progress has been made. At the genomic level, advances in technologies for the high-throughput analysis of gene expression have made it possible to begin discriminating responses to different biotic and abiotic stressors and potential trade-offs in responses. At the scale of the individual plant, enough experiments have been performed to begin synthesizing the effects of climate variables on infection rates, though pathosystem-specific characteristics make synthesis challenging. Models of plant disease have now been developed to incorporate more sophisticated climate predictions. At the population level, the adaptive potential of plant and pathogen populations may prove to be one of the most important predictors of the magnitude of climate change effects. Ecosystem ecologists are now addressing the role of plant disease in ecosystem processes and the challenge of scaling up from individual infection probabilities to epidemics and broader impacts.

  13. Application of minimally invasive technique in surgical treatment of pancreatic diseases%微创技术在胰腺疾病外科治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    张轶西; 乔昕; 刘斌; 乔士兴

    2015-01-01

    近年来,伴随着微创理念的发展,从腹腔镜手术运用于临床到3D 腹腔镜技术的纷至沓来,再到目前发展势头迅猛的外科手术机器人,疾病的治疗模式已发生了颠覆性的转变。胰腺疾病包含多种病变,各自的预后大为不同,再选择一种合理的手术方式,在满足病灶根治性的大前提下,尽可能保留患者脏器功能,最大限度的减少对患者的创伤,使微创技术在胰腺疾病外科治疗中的应用意义更加重大。%In recent years,with the rapid development of minimally invasive concept,from laparoscopic operation to three -dimension lapa-roscopic technique and to robotic surgical system,treatment modalities have changed a lot.Pancreatic diseases,including multiple lesions, have different prognoses.An appropriate surgical procedure should be selected while ensuring the radical treatment of disease,so as to mini-mize the injury to patients and the impairment of organ function.Minimally invasive technique is of great significance in the surgical treat-ment of pancreatic diseases.

  14. [Changes in the epidemiology of inflammatory bowel diseases].

    Science.gov (United States)

    Lakatos, László; Lakatos, Péter László

    2007-02-04

    Significant changes have been observed in the epidemiology of inflammatory bowel diseases (IBD) in the last two decades. Traditionally, the incidence of IBD was higher in the developed, industrialized countries, in contrast, nowadays it became more prevalent in the previously low incidence areas. In particular, the incidence of ulcerative colitis (UC) is similar to that observed in North America and Western Europe, while the incidence of Crohn's disease (CD) in developing countries is still low, suggesting that the environmental factors may act faster or differently in UC than in CD. In Europe, the North to South gradient disappeared, and also the West to East gradient is diminishing. Smoking and appendectomy may be considered as important environmental factors in both UC and CD, however, with opposite effects. In addition, the use of oral contraceptives is associated to disease susceptibility in both diseases. The role of diet, perinatal events, stress and nonsteroidal anti-inflammatory drugs in the pathogenesis is still controversial.

  15. Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Bernal, Teresa; Diez-Campelo, María; Godoy, Vicky; Rojas, Silvia; Colado, Enrique; Alcoceba, Miguel; González, Marcos; Vidriales, Belén; Sánchez-Guijo, Fermín M; López-Corral, Lucía; Luño, Elisa; del Cañizo, Consuelo

    2014-05-01

    We evaluated the impact of detection of minimal residual disease by flow cytometry (FCMRD) and CD3 chimerism in relapse in a cohort of 87 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing stem cell transplantation. Patients with a positive FCMRD at day +100 after transplantation showed higher relapse rates and worse overall survival. In multivariate analysis, a positive FCMRD after transplantation was a significant predictor of relapse. Mixed chimerism showed a trend to statistical signification. We conclude that FCMRD at day 100 after SCT is the best predictor of relapse after SCT in patients with aggressive myeloid malignancies.

  16. Cognitive and behavioral changes in Huntington disease before diagnosis.

    Science.gov (United States)

    Paulsen, Jane S; Miller, Amanda C; Hayes, Terry; Shaw, Emily

    2017-01-01

    Phenotypic manifestations of Huntington disease (HD) can be detected at least 15 years prior to the time when a motor diagnosis is given. Advances in clinical care and future research will require consistent use of HD definitions and HD premanifest (prodromal) stages being used across clinics, sites, and countries. Cognitive and behavioral (psychiatric) changes in HD are summarized and implications for ongoing advancement in our knowledge of prodromal HD are suggested. The earliest detected cognitive changes are observed in the Symbol Digit Modalities Test, Stroop Interference, Stroop Color and Word Test-interference condition, and Trail Making Test. Cognitive changes in the middle and near motor diagnostic stages of prodromal HD involve nearly every cognitive test administered and the greatest changes over time (i.e., slopes) are found in those prodromal HD participants who are nearest to motor diagnosis. Psychiatric changes demonstrate significant worsening over time and remain elevated compared with healthy controls throughout the prodromal disease course. Psychiatric and behavior changes in prodromal HD are much lower than that obtained using cognitive assessment, although the psychiatric and behavioral changes represent symptoms most debilitating to independent capacity and wellness. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Biodiversity decreases disease through predictable changes in host community competence.

    Science.gov (United States)

    Johnson, Pieter T J; Preston, Daniel L; Hoverman, Jason T; Richgels, Katherine L D

    2013-02-14

    Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in biodiversity affect disease outcomes. Over the past decade, a growing number of studies have reported negative correlations between host biodiversity and disease risk, prompting suggestions that biodiversity conservation could promote human and wildlife health. Yet the generality of the diversity-disease linkage remains conjectural, in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity-disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.

  18. Fatigue in Parkinson's disease: The contribution of cerebral metabolic changes.

    Science.gov (United States)

    Cho, Sang Soo; Aminian, Kelly; Li, Crystal; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2017-01-01

    Fatigue is a common and disabling non-motor symptom in Parkinson's disease associated with a feeling of overwhelming lack of energy. The aim of this study was to identify the neural substrates that may contribute to the development of fatigue in Parkinson's disease. Twenty-three Parkinson's disease patients meeting UK Brain Bank criteria for the diagnosis of idiopathic Parkinson's disease were recruited and completed the 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG)-PET scan. The metabolic activities of Parkinson's disease patients with fatigue were compared to those without fatigue using statistical parametric mapping analysis. The Parkinson's disease group exhibiting higher level of fatigue showed anti-correlated metabolic changes in cortical regions associated with the salience (i.e., right insular region) and default (i.e., bilateral posterior cingulate cortex) networks. The metabolic abnormalities detected in these brain regions displayed a significant correlation with level of fatigue and were associated with a disruption of the functional correlations with different cortical areas. These observations suggest that fatigue in Parkinson's disease may be the expression of metabolic abnormalities and impaired functional interactions between brain regions linked to the salience network and other neural networks. Hum Brain Mapp 38:283-292, 2017. © 2016 Wiley Periodicals, Inc.

  19. Modeling seasonal behavior changes and disease transmission with application to chronic wasting disease.

    Science.gov (United States)

    Oraby, Tamer; Vasilyeva, Olga; Krewski, Daniel; Lutscher, Frithjof

    2014-01-07

    Behavior and habitat of wildlife animals change seasonally according to environmental conditions. Mathematical models need to represent this seasonality to be able to make realistic predictions about the future of a population and the effectiveness of human interventions. Managing and modeling disease in wild animal populations requires particular care in that disease transmission dynamics is a critical consideration in the etiology of both human and animal diseases, with different transmission paradigms requiring different disease risk management strategies. Since transmission of infectious diseases among wildlife depends strongly on social behavior, mechanisms of disease transmission could also change seasonally. A specific consideration in this regard confronted by modellers is whether the contact rate between individuals is density-dependent or frequency-dependent. We argue that seasonal behavior changes could lead to a seasonal shift between density and frequency dependence. This hypothesis is explored in the case of chronic wasting disease (CWD), a fatal disease that affects deer, elk and moose in many areas of North America. Specifically, we introduce a strategic CWD risk model based on direct disease transmission that accounts for the seasonal change in the transmission dynamics and habitats occupied, guided by information derived from cervid ecology. The model is composed of summer and winter susceptible-infected (SI) equations, with frequency-dependent and density-dependent transmission dynamics, respectively. The model includes impulsive birth events with density-dependent birth rate. We determine the basic reproduction number as a weighted average of two seasonal reproduction numbers. We parameterize the model from data derived from the scientific literature on CWD and deer ecology, and conduct global and local sensitivity analyses of the basic reproduction number. We explore the effectiveness of different culling strategies for the management of CWD

  20. Reliability, Agreement and Minimal Detectable Change of the Timed Up & Go and the 10-Meter Walk Tests in Older Patients with COPD.

    Science.gov (United States)

    Marques, Alda; Cruz, Joana; Quina, Sara; Regêncio, Maria; Jácome, Cristina

    2016-06-01

    This study aimed to determine the interrater and intrarater reliability and agreement and the minimal detectable change (MDC) of the Timed Up & Go (TUG) test and the 10-Meter Walk Test (10MWT) in older patients with Chronic Obstructive Pulmonary Disease (COPD). Patients (≥ 60 years old) living in the community were asked to attend 2 sessions with 48-72-hour interval. In session 1, participants completed the TUG and 10MWT twice (2 trials) and were assessed by 2 raters. In session 2, they repeated the tests twice and were assessed by 1 rater. Interrater and intrarater reliability were calculated for the exact scores (using data from trial 1) and mean scores (mean of 2 trials) using Intraclass Correlation Coefficients (ICC2,1 and ICC2,2, respectively). Interrater and intrarater agreement were explored with the Bland & Altman method. The MDC95 was calculated from the standard error of measurement. Sixty participants (72.43 ± 6.90 years old) completed session 1 and 41 participants session 2. Excellent ICC values were found for the TUG test (interrater: ICC2,1 = 0.997 ICC2,2 = 0.999; intrarater: ICC2,1 = 0.921 ICC2,2 = 0.964) and 10MWT (interrater: ICC2,1 = 0.992 ICC2,2 = 0.997; intrarater: ICC2,1 = 0.903 ICC2,2 = 0.946). Good interrater and intrarater agreement was also found for both tests. The MDC95 was 2.68 s and 1.84 s for the TUG and 0.40 m/s and 0.30 m/s for the 10MWT considering the exact and mean scores, respectively. Findings suggest that the TUG test and the 10MWT are reliable and have acceptable measurement error. Therefore, these measures may be used to assess functional balance (TUG) and gait (10MWT) deficits in older patients with COPD.

  1. Prostate resection - minimally invasive

    Science.gov (United States)

    ... invasive URL of this page: //medlineplus.gov/ency/article/007415.htm Prostate resection - minimally invasive To use ... into your bladder instead of out through the urethra ( retrograde ... on New Developments in Prostate Cancer and Prostate Diseases. Evaluation and treatment of lower ...

  2. Optimized oral cholera vaccine distribution strategies to minimize disease incidence: A mixed integer programming model and analysis of a Bangladesh scenario.

    Science.gov (United States)

    Smalley, Hannah K; Keskinocak, Pinar; Swann, Julie; Hinman, Alan

    2015-11-17

    In addition to improved sanitation, hygiene, and better access to safe water, oral cholera vaccines can help to control the spread of cholera in the short term. However, there is currently no systematic method for determining the best allocation of oral cholera vaccines to minimize disease incidence in a population where the disease is endemic and resources are limited. We present a mathematical model for optimally allocating vaccines in a region under varying levels of demographic and incidence data availability. The model addresses the questions of where, when, and how many doses of vaccines to send. Considering vaccine efficacies (which may vary based on age and the number of years since vaccination), we analyze distribution strategies which allocate vaccines over multiple years. Results indicate that, given appropriate surveillance data, targeting age groups and regions with the highest disease incidence should be the first priority, followed by other groups primarily in order of disease incidence, as this approach is the most life-saving and cost-effective. A lack of detailed incidence data results in distribution strategies which are not cost-effective and can lead to thousands more deaths from the disease. The mathematical model allows for what-if analysis for various vaccine distribution strategies by providing the ability to easily vary parameters such as numbers and sizes of regions and age groups, risk levels, vaccine price, vaccine efficacy, production capacity and budget.

  3. Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes.

    Science.gov (United States)

    Brammer, J E; Saliba, R M; Jorgensen, J L; Ledesma, C; Gaballa, S; Poon, M; Maziarz, R T; Champlin, R E; Hosing, C; Kebriaei, P

    2017-01-01

    This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.

  4. Linking species- and ecosystem-level impacts of climate change in lakes with a complex and a minimal model

    NARCIS (Netherlands)

    Mooij, W.M.; De Senerpont Domis, L.N.; Janse, J.H.

    2009-01-01

    To study the interaction between species- and ecosystem-level impacts of climate change, we focus on the question of how climate-induced shifts in key species affect the positive feedback loops that lock shallow lakes either in a transparent, macrophyte-dominated state or, alternatively, in a turbid

  5. Common handling procedures conducted in preclinical safety studies result in minimal hepatic gene expression changes in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Yudong D He

    Full Text Available Gene expression profiling is a tool to gain mechanistic understanding of adverse effects in response to compound exposure. However, little is known about how the common handling procedures of experimental animals during a preclinical study alter baseline gene expression. We report gene expression changes in the livers of female Sprague-Dawley rats following common handling procedures. Baseline gene expression changes identified in this study provide insight on how these changes may affect interpretation of gene expression profiles following compound exposure. Rats were divided into three groups. One group was not subjected to handling procedures and served as controls for both handled groups. Animals in the other two groups were weighed, subjected to restraint in Broome restrainers, and administered water via oral gavage daily for 1 or 4 days with tail vein blood collections at 1, 2, 4, and 8 hours postdose on days 1 and 4. Significantly altered genes were identified in livers of animals following 1 or 4 days of handling when compared to the unhandled animals. Gene changes in animals handled for 4 days were similar to those handled for 1 day, suggesting a lack of habituation. The altered genes were primarily immune function related genes. These findings, along with a correlating increase in corticosterone levels suggest that common handling procedures may cause a minor immune system perturbance.

  6. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma.

    Science.gov (United States)

    Damm-Welk, Christine; Mussolin, Lara; Zimmermann, Martin; Pillon, Marta; Klapper, Wolfram; Oschlies, Ilske; d'Amore, Emanuele S G; Reiter, Alfred; Woessmann, Wilhelm; Rosolen, Angelo

    2014-01-16

    Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% ± 8%) was significantly higher than the CIR of 26 MDD-positive/MRD-negative (31% ± 9%) and 77 MDD-negative patients (15% ± 5%) (P NPM-ALK-positive ALCL identifies patients with a very high relapse risk and inferior survival.

  7. Climate change, air pollution, and allergic respiratory diseases: an update.

    Science.gov (United States)

    D'Amato, Gennaro; Vitale, Carolina; Lanza, Maurizia; Molino, Antonio; D'Amato, Maria

    2016-10-01

    The rising trend in prevalence of allergic respiratory disease and bronchial asthma, observed over the last decades, can be explained by changes occurring in the environment, with increasing presence of biologic, such as allergens, and chemical atmospheric trigger factors able to stimulate the sensitization and symptoms of these diseases. Many studies have shown changes in production, dispersion, and allergen content of pollen and spores because of climate change with an increasing effect of aeroallergens on allergic patients. Over the last 50 years, global earth's temperature has markedly risen likely because of growing emission of anthropogenic greenhouse gas concentrations. Major changes involving the atmosphere and the climate, including global warming induced by human activity, have a major impact on the biosphere and human environment.Urbanization and high levels of vehicle emissions are correlated to an increase in the frequency of pollen-induced respiratory allergy prevalent in people who live in urban areas compared with those who live in rural areas. Measures of mitigation need to be applied for reducing future impacts of climate change on our planet, but until global emissions continue to rise, adaptation to the impacts of future climate variability will also be required.

  8. Sleep-wake changes and cognition in neurodegenerative disease.

    Science.gov (United States)

    Naismith, Sharon L; Lewis, Simon J G; Rogers, Naomi L

    2011-01-01

    With the increasing aging population, neurodegenerative disorders will become more common in clinical practice. These disorders involve multiple pathophysiological mechanisms that differentially affect cognition, mood, and physical functions. Possibly due to the involvement of common underlying neurobiological circuits, sleep and/or circadian (sleep-wake) changes are also common in this disease group. Of significance, sleep-wake changes are often a prodromal feature and are predictive of cognitive decline, psychiatric symptoms, quality of life, need for institutional care, and caregiver burden. Unfortunately, in neurodegenerative disease, few studies have included detailed polysomnography or neuropsychological assessments although some data indicate that sleep and neurocognitive features are related. Further studies are also required to address the effects of pharmacological and nonpharmacological treatments on cognitive functioning. Such research will hopefully lead to targeted early intervention approaches for cognitive decline in older people.

  9. Minimally invasive treatments for perforator vein insufficiency.

    Science.gov (United States)

    Kuyumcu, Gokhan; Salazar, Gloria Maria; Prabhakar, Anand M; Ganguli, Suvranu

    2016-12-01

    Incompetent superficial veins are the most common cause of lower extremity superficial venous reflux and varicose veins; however, incompetent or insufficient perforator veins are the most common cause of recurrent varicose veins after treatment, often unrecognized. Perforator vein insufficiency can result in pain, skin changes, and skin ulcers, and often merit intervention. Minimally invasive treatments have replaced traditional surgical treatments for incompetent perforator veins. Current minimally invasive treatment options include ultrasound guided sclerotherapy (USGS) and endovascular thermal ablation (EVTA) with either laser or radiofrequency energy sources. Advantages and disadvantages of each modality and knowledge on these treatments are required to adequately address perforator venous disease.

  10. Changes of pituitary gland volume in Kennedy disease.

    Science.gov (United States)

    Pieper, C C; Teismann, I K; Konrad, C; Heindel, W L; Schiffbauer, H

    2013-12-01

    Kennedy disease is a rare X-linked neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the androgen-receptor gene. Apart from neurologic signs, this mutation can cause a partial androgen insensitivity syndrome with typical alterations of gonadotropic hormones produced by the pituitary gland. The aim of the present study was therefore to evaluate the impact of Kennedy disease on pituitary gland volume under the hypothesis that endocrinologic changes caused by partial androgen insensitivity may lead to morphologic changes (ie, hypertrophy) of the pituitary gland. Pituitary gland volume was measured in sagittal sections of 3D T1-weighted 3T-MR imaging data of 8 patients with genetically proven Kennedy disease and compared with 16 healthy age-matched control subjects by use of Multitracer by a blinded, experienced radiologist. The results were analyzed by a univariant ANOVA with total brain volume as a covariant. Furthermore, correlation and linear regression analyses were performed for pituitary volume, patient age, disease duration, and CAG repeat expansion length. Intraobserver reliability was evaluated by means of the Pearson correlation coefficient. Pituitary volume was significantly larger in patients with Kennedy disease (636 [±90] mm(3)) than in healthy control subjects (534 [±91] mm(3)) (P = .041). There was no significant difference in total brain volume (P = .379). Control subjects showed a significant decrease in volume with age (r = -0.712, P = .002), whereas there was a trend to increasing gland volume in patients with Kennedy disease (r = 0.443, P = .272). Gland volume correlated with CAG repeat expansion length in patients (r = 0.630, P = .047). The correlation coefficient for intraobserver reliability was 0.94 (P pituitary volume that correlated with the CAG repeat expansion length. This could reflect hypertrophy as the result of elevated gonadotropic hormone secretion caused by the androgen receptor mutation with partial

  11. Balance in Parkinson's disease patients changing the visual input

    OpenAIRE

    Suarez,Hamlet; Geisinger, Dario; Ferreira,Enrique D.; Nogueira,Santiago; Arocena,Sofia; Roman,Cecilia San; Suarez,Alejo

    2011-01-01

    The description of the postural responses in Parkinson's disease patients when visual information changes from a stable to a moving visual field analyzing the impact on balance in these patients. METHODS (CLINICAL): Limits of Stability, Body center of pressure and balance functional reserve were measured by means of the force platform in 24 Parkinson´s patients in stages 1 and 2 of the Boher classification and 19 volunteers as a control group. Both groups were stimulated with 1-Static visual ...

  12. The impact of climate change on infectious disease transmission: perceptions of CDC health professionals in Shanxi Province, China.

    Directory of Open Access Journals (Sweden)

    Junni Wei

    Full Text Available There have been increasing concerns about the challenge of emerging and re-emerging infectious diseases due to climate change, especially in developing countries including China. Health professionals play a significant role in the battle to control and prevent infectious diseases. This study therefore aims to investigate the perceptions and attitudes of health professionals at the Centers for Disease Control and Prevention (CDC in different levels in China, and to consider adaptation measures to deal with the challenge of climate change. In 2013, a cross-sectional questionnaire survey was undertaken among 314 staff in CDCs in Shanxi Province, China, whose routine work involves disease control and prevention. Data were analyzed using descriptive methods and logistic regression. A majority of the CDC staff were aware of the health risks from climate change, especially its impacts on infectious disease transmission in their jurisdictions, and believed climate change might bring about both temporal and spatial change in transmission patterns. It was thought that adaptation measures should be established including: strengthening/improving currently existing disease surveillance systems and vector monitoring; building CDC capacity in terms of infrastructure and in-house health professional training; development and refinement of relevant legislation, policies and guidelines; better coordination among various government departments; the involvement of the community in infectious disease interventions; and collaborative research with other institutions. This study provides a snapshot of the understanding of CDC staff regarding climate change risks relevant to infectious diseases and adaptation in China. Results may help inform future efforts to develop adaptation measures to minimize infectious disease risks due to climate change.

  13. The impact of climate change on infectious disease transmission: perceptions of CDC health professionals in Shanxi Province, China.

    Science.gov (United States)

    Wei, Junni; Hansen, Alana; Zhang, Ying; Li, Hong; Liu, Qiyong; Sun, Yehuan; Xue, Shulian; Zhao, Shufang; Bi, Peng

    2014-01-01

    There have been increasing concerns about the challenge of emerging and re-emerging infectious diseases due to climate change, especially in developing countries including China. Health professionals play a significant role in the battle to control and prevent infectious diseases. This study therefore aims to investigate the perceptions and attitudes of health professionals at the Centers for Disease Control and Prevention (CDC) in different levels in China, and to consider adaptation measures to deal with the challenge of climate change. In 2013, a cross-sectional questionnaire survey was undertaken among 314 staff in CDCs in Shanxi Province, China, whose routine work involves disease control and prevention. Data were analyzed using descriptive methods and logistic regression. A majority of the CDC staff were aware of the health risks from climate change, especially its impacts on infectious disease transmission in their jurisdictions, and believed climate change might bring about both temporal and spatial change in transmission patterns. It was thought that adaptation measures should be established including: strengthening/improving currently existing disease surveillance systems and vector monitoring; building CDC capacity in terms of infrastructure and in-house health professional training; development and refinement of relevant legislation, policies and guidelines; better coordination among various government departments; the involvement of the community in infectious disease interventions; and collaborative research with other institutions. This study provides a snapshot of the understanding of CDC staff regarding climate change risks relevant to infectious diseases and adaptation in China. Results may help inform future efforts to develop adaptation measures to minimize infectious disease risks due to climate change.

  14. Inflammatory bowel disease course in Crohn's disease: is the natural history changing?

    Science.gov (United States)

    Golovics, Petra A; Mandel, Michael D; Lovasz, Barbara D; Lakatos, Peter L

    2014-03-28

    Crohn's disease (CD) is a multifactorial potentially debilitating disease. It has a variable disease course, but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability. Studies on the natural history of CD provide invaluable data on its course and clinical predictors, and may help to identify patient subsets based on clinical phenotype. Most data are available from referral centers, however these outcomes may be different from those in population-based cohorts. New data suggest the possibility of a change in the natural history in Crohn's disease, with an increasing percentage of patients diagnosed with inflammatory disease behavior. Hospitalization rates remain high, while surgery rates seem to have decreased in the last decade. In addition, mortality rates still exceed that of the general population. The impact of changes in treatment strategy, including increased, earlier use of immunosuppressives, biological therapy, and patient monitoring on the natural history of the disease are still conflictive. In this review article, the authors summarize the available evidence on the natural history, current trends, and predictive factors for evaluating the disease course of CD.

  15. Changes of the cytokine profile in inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Gy(o)rgyi Müzes; Béla Molnár; Zsolt Tulassay; Ferenc Sipos

    2012-01-01

    Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut homeostasis.An imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases (IBD).Although Crohn's disease (CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis (UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been changed.The inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological settings.None the less there are many common immunological responses in IBD that are mediated by cytokines.Although they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the disease.Our aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and CD.The better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

  16. Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Gholamreza Hassanzadeh

    2015-01-01

    Full Text Available Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease (AD of sporadic origin. The expression of DHCR24 (Seladin-1, marker for neuronal oxidative stress and degeneration, has been reported to be altered in the brains of AD patients. In the present study, we investigated the effect of trimetazidine (TMZ on the hippocampal oxidative parameters and the expression of DHCR24 (Seladin-1 in an animal model of sporadic AD. Male rats were pre-treated with TMZ (25 mg/kg after which injected with intracerebroventricular-streptozotocin (ICV-STZ/Saline. Following 2, 7 and 14 days, animals of different groups were sacrificed with their brain excised to detect the hippocampal lipid peroxidation, superoxide dismutase (SOD, catalase activity, DHCR24 (Seladin-1 expression and possible histopathological changes. ICV-STZ administration induced significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment showed to ameliorate the oxidative stress, which was demonstrated by a significant rise in the hippocampal SOD and catalase activity, as well as a significant decrease in the malondialdehyde (MDA level. TMZ administration also increased the expression of DHCR24 (Seladin-1 gene in the hippocampus. In conclusion, our findings indicated a neuroprotective effect of TMZ possibly related to its antioxidant activity resulting in the up-regulation of DHCR24 (Seladin-1. Such TMZ effects may be beneficial in minimizing oxidative stress in sporadic Alzheimer's disease and possible prevention of disease progression.

  17. Effect of biodiversity changes in disease risk: exploring disease emergence in a plant-virus system.

    Directory of Open Access Journals (Sweden)

    Israel Pagán

    Full Text Available The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect, and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect. Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species.

  18. Effect of biodiversity changes in disease risk: exploring disease emergence in a plant-virus system.

    Science.gov (United States)

    Pagán, Israel; González-Jara, Pablo; Moreno-Letelier, Alejandra; Rodelo-Urrego, Manuel; Fraile, Aurora; Piñero, Daniel; García-Arenal, Fernando

    2012-01-01

    The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species.

  19. Minimal cosmography

    CERN Document Server

    Piazza, Federico

    2015-01-01

    The minimal requirement for cosmography - a nondynamical description of the universe - is a prescription for calculating null geodesics, and timelike geodesics as a function of their proper time. In this paper, we consider the most general linear connection compatible with homogeneity and isotropy, but not necessarily with a metric. A light-cone structure is assigned by choosing a set of geodesics representing light rays. This defines a "scale factor" and a local notion of distance, as that travelled by light in a given proper time interval. We find that the velocities and relativistic energies of free-falling bodies decrease in time as a consequence of cosmic expansion, but at a rate that can be different than that dictated by the usual metric framework. By extrapolating this behavior to photons redshift, we find that the latter is in principle independent of the "scale factor". Interestingly, redshift-distance relations and other standard geometric observables are modified in this extended framework, in a w...

  20. Minimal cosmography

    Science.gov (United States)

    Piazza, Federico; Schücker, Thomas

    2016-04-01

    The minimal requirement for cosmography—a non-dynamical description of the universe—is a prescription for calculating null geodesics, and time-like geodesics as a function of their proper time. In this paper, we consider the most general linear connection compatible with homogeneity and isotropy, but not necessarily with a metric. A light-cone structure is assigned by choosing a set of geodesics representing light rays. This defines a "scale factor" and a local notion of distance, as that travelled by light in a given proper time interval. We find that the velocities and relativistic energies of free-falling bodies decrease in time as a consequence of cosmic expansion, but at a rate that can be different than that dictated by the usual metric framework. By extrapolating this behavior to photons' redshift, we find that the latter is in principle independent of the "scale factor". Interestingly, redshift-distance relations and other standard geometric observables are modified in this extended framework, in a way that could be experimentally tested. An extremely tight constraint on the model, however, is represented by the blackbody-ness of the cosmic microwave background. Finally, as a check, we also consider the effects of a non-metric connection in a different set-up, namely, that of a static, spherically symmetric spacetime.

  1. Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos; Zsofia Czegledi; Tamas Szamosi; Janos Banai; Gyula David; Ferenc Zsigmond; Tunde Pandur; Zsuzsanna Erdelyi; Orsolya Gemela; Janos Papp; Laszlo Lakatos

    2009-01-01

    AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/ biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location ( P = 0.001), presence of perianal disease ( P < 0.001), prior steroid use ( P = 0.006), early AZA ( P = 0.005) or AZA/biological therapy ( P = 0.002), or smoking ( P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

  2. Reliability and minimal detectable change of three functional tests: forward-lunge, step-up-over and sit-to-stand.

    Science.gov (United States)

    Luque-Siles, Carmen; Gallego-Izquierdo, Tomas; Jímenez-Rejano, Jose Jesus; de-la-Orden, Susana Granados; Plaza-Manzano, Gustavo; López-Illescas-Ruiz, Africa; Ferragut-Garcías, Alejandro; Romero-Franco, Natalia; Martín-Casas, Patricia; Pecos-Martín, Daniel

    2016-12-01

    [Purpose] To examine the intrasession and intersession reliability and the absolute reliability of three functional dynamic tests-forward-lunge, step-up-over and sit-to-stand tests-using computerized dynamic posturography. [Subjects and Methods] An intra-test and test-retest, repeated measure study was designed. Forty-five healthy subjects twice carried out the forward-lunge test, step-up-over test, and sit-to-stand test on two days, one week apart. The intrasession and intersession reliabilities as judged by the intraclass correlation coefficient (ICC) and the minimal detectable change of the three functional tests were calculated. [Results] Excellent to very good intrasession reliability of the forward-lunge test (ICC range of 0.9-0.8) was found. Very good to good intrasession reliability of the step-up-over test (ICC range of 0.9-0.5) was found and very good intrasession reliability of the sit-to-stand test (ICC range of 0.8-0.7) was found. The minimal detectable change at the 95% confidence level of most of the measures was lower than 30%. [Conclusion] The forward-lunge, step-up-over and sit-to-stand tests are reliable measurement tools.

  3. Age-related changes in dynamic postural control and attentional demands are minimally affected by local muscle fatigue.

    Directory of Open Access Journals (Sweden)

    Anthony eRemaud

    2016-01-01

    Full Text Available Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Participants (young adults: n=15; healthy seniors: n=13 performed a dynamic postural task along the antero-posterior and the medio-lateral axes, with and without the addition of a simple reaction time task. The dynamic postural task consisted in following a moving circle on a computer screen with the representation of the center of pressure (COP. This protocol was repeated before and after a fatigue task where ankle plantarflexor muscles were targeted. The mean COP-target distance and the mean COP velocity were calculated for each trial. Cross-correlation analyses between the COP and target displacements were also performed. Reaction times were recorded during dual-task trials. Results showed that while young adults adopted an anticipatory control mode to move their COP as close as possible to the target center, seniors adopted a reactive control mode, lagging behind the target center. This resulted in longer COP-target distance and higher COP velocity in the latter group. Concurrently, reaction time increased more in seniors when switching from static stance to dynamic postural conditions, suggesting potential alterations in the central nervous system functions. Finally, plantar flexor muscle fatigue and dual-tasking had only minor effects on dynamic postural control of both young adults and seniors. Future studies should investigate why the fatigue-induced changes in quiet standing postural control do not seem to transfer to dynamic balance tasks.

  4. ELECTROCARDIOGRAPHIC CHANGES OBSERVED IN HAEMORRHAGIC AND ISCHAEMIC CEREBROVASCULAR DISEASES

    Directory of Open Access Journals (Sweden)

    Channappa

    2016-03-01

    Full Text Available INTRODUCTION Cardiac abnormalities are relatively common after acute neurologic injury. Disturbances can vary in severity from transient ECG abnormalities to profound myocardial injury and dysfunction. CNS is involved in the generation of cardiac arrhythmias and dysfunction even in an otherwise normal myocardium. AIM To find out proportion of ECG changes observed in ischaemic and haemorrhagic stroke. MATERIALS AND METHODS The Electrocardiographs of 100 patients with acute stroke were studied to find out the types of ECG abnormalities among different types of stroke. RESULTS In our study, the most common ECG abnormalities associated with stroke were prolonged QTc interval, ST-T segment abnormalities, prominent U wave and arrhythmias. Trop-I was positive in 12.8% patients with ECG changes. Statistical significance was found in association with Trop-I positivity and ST depression. CONCLUSION Usually patients with heart disease present with arrhythmias and Ischaemic like ECG changes. But these changes are also seen most often in the patients with presenting with stroke who didn’t have any past history of heart disease. This shows that arrhythmias and ischaemic ECG abnormalities are primarily evolved due to central nervous system disorders.

  5. Regional brain stiffness changes across the Alzheimer's disease spectrum.

    Science.gov (United States)

    Murphy, Matthew C; Jones, David T; Jack, Clifford R; Glaser, Kevin J; Senjem, Matthew L; Manduca, Armando; Felmlee, Joel P; Carter, Rickey E; Ehman, Richard L; Huston, John

    2016-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

  6. Minimal flavour violation in the quark and lepton sector and the impact of extra dimensions on flavour changing neutral currents and electroweak symmetry breaking

    Energy Technology Data Exchange (ETDEWEB)

    Weiler, A.

    2007-01-16

    We study flavor-changing decays of hadrons and leptons and an extra-dimensional approach to electroweak symmetry breaking. Specifically we study the framework of Minimal Flavour Violation (MFV) as an explanation of the flavour problem. We discuss the impact of a specific extra-dimensional model of the MFV class on flavour changing neutral currents. We derive model-independent upper bounds on rare decays. -We discuss the extension of the MFV framework from the quark to the lepton sector and show how baryogenesis through leptogenesis can be achieved and examine if possible correlations with charged lepton flavour violation exist. We discuss the dynamical breaking of the electroweak symmetry in extra dimensions by unifying gauge and Higgs fields and we show that realistic models are possible once the extra dimension is strongly curved. (orig.)

  7. Ages of celiac disease: from changing environment to improved diagnostics.

    Science.gov (United States)

    Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro

    2011-08-28

    From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.

  8. The Challenge of Producing Skin Test Antigens with Minimal Resources Suitable for Human Application against a Neglected Tropical Disease; Leprosy

    Science.gov (United States)

    Rivoire, Becky L.; TerLouw, Stephen; Groathouse, Nathan A.; Brennan, Patrick J.

    2014-01-01

    True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3–10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial. PMID:24874086

  9. The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

    Directory of Open Access Journals (Sweden)

    Becky L Rivoire

    Full Text Available True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan and MLCwA (M. leprae cell wall antigens. In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.

  10. Approaches to predicting potential impacts of climate change on forest disease: An example with Armillaria root disease

    Science.gov (United States)

    Ned B. Klopfenstein; Mee-Sook Kim; John W. Hanna; Bryce A. Richardson; John E. Lundquist

    2011-01-01

    Climate change will likely have dramatic impacts on forest health because many forest trees could become maladapted to climate. Furthermore, climate change will have additional impacts on forest health through changes in the distribution and severity of forest disease. Methods are needed to predict the influence of climate change on forest disease so that appropriate...

  11. Percutaneous internal jugular venous cannulation for extracorporeal circulation during minimally invasive technique in children with congenital heart disease: operative technique and results.

    Science.gov (United States)

    Vida, Vladimiro L; Tiberio, Ivo; Gallo, Michele; Guariento, Alvise; Suti, Emirjeta; Pittarello, Demetrio; Stellin, Giovanni

    2016-10-01

    The aim of this study was to evaluate the safety and efficacy of the percutaneous cannulation of the internal jugular venous (PCIJV) for extracorporeal circulation during minimally invasive cardiac surgery (MICS) in children with simple congenital heart disease. From September 2007, 83 children (<16 years) underwent PCIJV for extracorporeal circulation. Primary outcome of the study was to evaluate the safety and advantages of PCIJV technique. Technical steps and pitfalls of PCIJV technique are described. Median age at surgery was 9 years (range 3.5-16 years) and median body weight was 31 kilograms (range 13-72 kilograms); 32 patients (40%) had a body weight less than 30 kilograms. The PCIJV was achieved with a 14 French cannula in 61 pts (73%), with a 17 Fr cannula in 22 (23%). The PIJVC was judged difficult in 2 patients (2.4%); in both of them cannulation was achieved at a different venous site There were no procedure-related complications and no flow disturbances during the extracorporeal circulation. The PCIJV during MICS is an effective and reproducible technique for achieving peripheral CPB in children with simple CHDs. We progressively expanded the use of this technique in smaller children and this allows us to further minimize surgical trauma without experiencing venous drainage's problems.

  12. NPM1 mutation is a stable marker for minimal residual disease monitoring in acute myeloid leukaemia patients with increased sensitivity compared to WT1 expression*

    DEFF Research Database (Denmark)

    Kristensen, Thomas; Møller, Michael B; Friis, Lone;

    2011-01-01

    Mutation in the NPM1 gene occurs in 60% of acute myeloid leukaemia (AML) patients with normal karyotype. NPM1 mutation is potentially a superior minimal residual disease (MRD) marker compared to WT1 gene overexpression by being specific to the malignant clone, although experimental evidence...... published so far includes very limited numbers of relapsed cases. Also, the stability of the NPM1 mutation has been questioned by reports of the mutation being lost at relapse. In the present study we compared NPM1 mutation and WT1 overexpression as MRD markers in 20 cases of relapsed AML. The 20 patients...... experienced a total of 28 morphological relapses. Karyotypic evolution was detected in 56% of relapses. All relapses were accompanied by high levels of NPM1 mutation, along with high WT1 mRNA levels, thus demonstrating complete stability of both markers during relapse. Detectable NPM1 mutation following...

  13. Changing options for the control of deciduous fruit tree diseases.

    Science.gov (United States)

    Sutton, T B

    1996-01-01

    The evolution of disease management programs for deciduous fruit trees in the United States over the past 50 years has been influenced by factors that include public concern over pesticide residues on fruit and in the environment, the development of resistance of many important tree pathogens to fungicides and bactericides, the loss of fungicide registrations and restrictions on their use due to concern for human health and the environment and/or marketing decisions by the manufacturers, and changes in cultural practices and marketing objectives. These factors have led to wider use of forecasting models and cultural controls, the development of resistance management strategies, and the introduction of new equipment and methods for pesticide application. These same factors will most likely continue to drive the fruit industry to adopt disease management programs that rely less on pesticides in the future.

  14. The reliability, minimal detectable change and concurrent validity of a gravity-based bubble inclinometer and iphone application for measuring standing lumbar lordosis.

    Science.gov (United States)

    Salamh, Paul A; Kolber, Morey

    2014-01-01

    To investigate the reliability, minimal detectable change (MDC90) and concurrent validity of a gravity-based bubble inclinometer (inclinometer) and iPhone® application for measuring standing lumbar lordosis. Two investigators used both an inclinometer and an iPhone® with an inclinometer application to measure lumbar lordosis of 30 asymptomatic participants. ICC models 3,k and 2,k were used for the intrarater and interrater analysis, respectively. Good interrater and intrarater reliability was present for the inclinometer with Intraclass Correlation Coefficients (ICC) of 0.90 and 0.85, respectively and the iPhone® application with ICC values of 0.96 and 0.81. The minimal detectable change (MDC90) indicates that a change greater than or equal to 7° and 6° is needed to exceed the threshold of error using the iPhone® and inclinometer, respectively. The concurrent validity between the two instruments was good with a Pearson product-moment coefficient of correlation (r) of 0.86 for both raters. Ninety-five percent limits of agreement identified differences ranging from 9° greater in regards to the iPhone® to 8° less regarding the inclinometer. Both the inclinometer and iPhone® application possess good interrater reliability, intrarater reliability and concurrent validity for measuring standing lumbar lordosis. This investigation provides preliminary evidence to suggest that smart phone applications may offer clinical utility comparable to inclinometry for quantifying standing lumbar lordosis. Clinicians should recognize potential individual differences when using these devices interchangeably.

  15. Facial biometrics of peri-oral changes in Crohn's disease.

    Science.gov (United States)

    Zou, L; Adegun, O K; Willis, A; Fortune, Farida

    2014-05-01

    Crohn's disease is a chronic relapsing and remitting inflammatory condition which affects any part of the gastrointestinal tract. In the oro-facial region, patients can present peri-oral swellings which results in severe facial disfigurement. To date, assessing the degree of facial changes and evaluation of treatment outcomes relies on clinical observation and semi-quantitative methods. In this paper, we describe the development of a robust and reproducible measurement strategy using 3-D facial biometrics to objectively quantify the extent and progression of oro-facial Crohn's disease. Using facial laser scanning, 32 serial images from 13 Crohn's patients attending the Oral Medicine clinic were acquired during relapse, remission, and post-treatment phases. Utilising theories of coordinate metrology, the facial images were subjected to registration, regions of interest identification, and reproducible repositioning prior to obtaining volume measurements. To quantify the changes in tissue volume, scan images from consecutive appointments were compared to the baseline (first scan image). Reproducibility test was performed to ascertain the degree of uncertainty in volume measurements. 3-D facial biometric imaging is a reliable method to identify and quantify peri-oral swelling in Crohn's patients. Comparison of facial scan images at different phases of the disease revealed precisely profile and volume changes. The volume measurements were highly reproducible as adjudged from the 1% standard deviation. 3-D facial biometrics measurements in Crohn's patients with oro-facial involvement offers a quick, robust, economical and objective approach for guided therapeutic intervention and routine assessment of treatment efficacy on the clinic.

  16. Influenza SIRS with Minimal Pneumonitis.

    Science.gov (United States)

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  17. Climate change and diarrhoeal disease: Perspectives for development policies

    DEFF Research Database (Denmark)

    Halsnæs, Kirsten; Føyn, Tullik Helene Ystanes

    2010-01-01

    This paper points to the key role of health in development programmes and illustrates through diarrhoeal diseases as a case example, how climate change can impose increasing risks, which particularly will hit young children and the poor. The increased incidence can both be expected to emerge from...... that can help to reduce these risks. An attempt to start such a process i.e. has been done by the Danish Overseas Development Assistance Programme, Danida, which has conducted a climate screening of programme activities in Bangladesh. The paper presents a number of conclusions from this climate screening...

  18. A Selective Role for Dopamine in Learning to Maximize Reward But Not to Minimize Effort: Evidence from Patients with Parkinson's Disease.

    Science.gov (United States)

    Skvortsova, Vasilisa; Degos, Bertrand; Welter, Marie-Laure; Vidailhet, Marie; Pessiglione, Mathias

    2017-06-21

    Instrumental learning is a fundamental process through which agents optimize their choices, taking into account various dimensions of available options such as the possible reward or punishment outcomes and the costs associated with potential actions. Although the implication of dopamine in learning from choice outcomes is well established, less is known about its role in learning the action costs such as effort. Here, we tested the ability of patients with Parkinson's disease (PD) to maximize monetary rewards and minimize physical efforts in a probabilistic instrumental learning task. The implication of dopamine was assessed by comparing performance ON and OFF prodopaminergic medication. In a first sample of PD patients (n = 15), we observed that reward learning, but not effort learning, was selectively impaired in the absence of treatment, with a significant interaction between learning condition (reward vs effort) and medication status (OFF vs ON). These results were replicated in a second, independent sample of PD patients (n = 20) using a simplified version of the task. According to Bayesian model selection, the best account for medication effects in both studies was a specific amplification of reward magnitude in a Q-learning algorithm. These results suggest that learning to avoid physical effort is independent from dopaminergic circuits and strengthen the general idea that dopaminergic signaling amplifies the effects of reward expectation or obtainment on instrumental behavior.SIGNIFICANCE STATEMENT Theoretically, maximizing reward and minimizing effort could involve the same computations and therefore rely on the same brain circuits. Here, we tested whether dopamine, a key component of reward-related circuitry, is also implicated in effort learning. We found that patients suffering from dopamine depletion due to Parkinson's disease were selectively impaired in reward learning, but not effort learning. Moreover, anti-parkinsonian medication restored the

  19. Adaptive Alternating Minimization Algorithms

    CERN Document Server

    Niesen, Urs; Wornell, Gregory

    2007-01-01

    The classical alternating minimization (or projection) algorithm has been successful in the context of solving optimization problems over two variables or equivalently of finding a point in the intersection of two sets. The iterative nature and simplicity of the algorithm has led to its application to many areas such as signal processing, information theory, control, and finance. A general set of sufficient conditions for the convergence and correctness of the algorithm is quite well-known when the underlying problem parameters are fixed. In many practical situations, however, the underlying problem parameters are changing over time, and the use of an adaptive algorithm is more appropriate. In this paper, we study such an adaptive version of the alternating minimization algorithm. As a main result of this paper, we provide a general set of sufficient conditions for the convergence and correctness of the adaptive algorithm. Perhaps surprisingly, these conditions seem to be the minimal ones one would expect in ...

  20. 微小病变性肾病综合征激素抵抗的多因素分析%Multiple factors analysis of steroid resistance of minimal change nephrotic syndrome

    Institute of Scientific and Technical Information of China (English)

    王明军; 张金荣; 徐婉梅; 黎伟; 张影华; 张元元; 何建静; 廖蕴华

    2015-01-01

    Aim:To evaluate risk factors of steroid-resistant minimal change nephrotic syndrome. Methods:retrospectively analysed 68 patients who were confirmed as minimal-change nephritic syndrome by renal biopsies,and divided as group steroid-resistant group(n =30)and non steroid-resistant group(n=38).A univariate analysis was performed firstly.Then the significant ones were performed a multivari-ate analysis by using binary Logistic regression model.Lastly,the sensitivity,the specificity,and the best threshold value of the indexes,which as indicating the steroid-resistant minimal change disease,was testi-fied by drawing a receiver operating characteristic curve(ROC).Results:(1)combined infection(P =0.014),red blood cell count(P =0.005 ),total cholesterol (P =0.015 ),24 h urinary protein (P = 0.000),serum albumin(P =0.011),high urine uric acid(P =0.045),C4 decrease(P =0.028)were all the risk factors of steroid-resistant minimal change disease(P 3.5 /HP,24 h u-rinary protein >5.57 g/d total cholesterol >9.49 mmol /L were the best threshold value indicating ster-oid-resistant minimal change disease.Conclusion:(1)infection,hematuria,24 h urinary protein quanti-tative is independent risk factors of Steroid-resistant minimal change nephrotic syndrome.(2)when Oc-cur hematuria,24 h urinary proteind≥5.57 g/d,total cholesterol≥9.49 mmol /L,,Should be alert to the occurrence of Steroid-resistant minimal change nephrotic syndrome.%目的:探讨微小病变性肾病综合征激素抵抗的相关危险因素.方法:回顾性调查68例经肾组织活检确诊为微小病变性肾小球肾炎患者临床资料,实验室检查结果及随访情况,将患者分为激素抵抗组(30例)及非抵抗组(38例),采用 SPSS17.0软件,进行单因素分析,对有意义的单因素采用二分类 Logistic 回归进行多因素分析,绘制受试者工作特性曲线(ROC)评价检验指标在预测微小病变性肾病综合征激素抵抗时的敏感度,特异

  1. Imaging changes associated with cognitive abnormalities in Parkinson's disease.

    Science.gov (United States)

    Koshimori, Yuko; Segura, Barbara; Christopher, Leigh; Lobaugh, Nancy; Duff-Canning, Sarah; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E; Aminian, Kelly; Houle, Sylvain; Strafella, Antonio P

    2015-07-01

    The current study investigates both gray and white matter changes in non-demented Parkinson's disease (PD) patients with varying degrees of mild cognitive deficits and elucidates the relationships between the structural changes and clinical sequelae of PD. Twenty-six PD patients and 15 healthy controls (HCs) were enrolled in the study. Participants underwent T1-weighted and diffusion tensor imaging (DTI) scans. Their cognition was assessed using a neuropsychological battery. Compared with HCs, PD patients showed significant cortical thinning in sensorimotor (left pre- and postcentral gyri) and cognitive (left dorsolateral superior frontal gyrus [DLSFG]) regions. The DLSFG cortical thinning correlated with executive and global cognitive impairment in PD patients. PD patients showed white matter abnormalities as well, primarily in bilateral frontal and temporal regions, which also correlated with executive and global cognitive impairment. These results seem to suggest that both gray and white matter changes in the frontal regions may constitute an early pathological substrate of cognitive impairment of PD providing a sensitive biomarker for brain changes in PD.

  2. Analysis of Biopsies From Duodenal Bulbs of All Endoscopy Patients Increases Detection of Abnormalities but has a Minimal Effect on Diagnosis of Celiac Disease.

    Science.gov (United States)

    Stoven, Samantha A; Choung, Rok Seon; Rubio-Tapia, Alberto; Absah, Imad; Lam-Himlin, Dora M; Harris, Lucinda A; Ngamruengphong, Saowanee; Vazquez Roque, Maria I; Wu, Tsung-Teh; Murray, Joseph A

    2016-11-01

    In patients with positive results from serologic tests for celiac disease, analysis of tissues samples from the duodenal bulb, in addition to those from other parts of the small bowel, might increase the diagnostic yield. However, biopsies are not routinely collected from the duodenal bulb because of concerns that villous atrophy detected there could be caused by other disorders (Brunner glands or peptic duodenitis, gastric metaplasia, shorter villi, or lymphoid follicles). We investigated whether analysis of biopsies from duodenal bulbs of all patients undergoing endoscopy (a population with a low probability for celiac disease) increases diagnoses of celiac disease. We performed a retrospective analysis of data from 679 patients (63% female; mean age, 50 years) from whom duodenal bulb and small bowel biopsies were collected during endoscopy at 3 Mayo Clinic sites, from January 1, 2011 through December 31, 2011. Records were reviewed for age, sex, pathology findings, serology test results (HLA DQ2 or DQ), indications for biopsy analyses, and adherence to a gluten-free diet. Patients with celiac disease were identified on the basis of increased intraepithelial lymphocytosis, with or without villous atrophy and crypt hyperplasia, and results from serology tests. Findings from duodenal bulbs were compared with diagnoses using the Fisher exact test. Of all patients undergoing endoscopy, 16 patients (2%) were found to have celiac disease. Analysis of the duodenal bulb biopsies identified 1 patient (0.1%) with celiac disease limited to this region. Of 399 patients whose celiac serology was not known before endoscopic examination, only 2 patients had histologic changes consistent with celiac disease but not limited to duodenal bulb. Abnormal duodenal histology was detected in 265 patients (39%), most commonly in the bulb (n = 241; P celiac disease detection. Abnormal histologic findings are more commonly detected in the duodenal bulb; although they do not seem to impair

  3. Serotonergic mediated body mass index changes in Parkinson's disease.

    Science.gov (United States)

    Politis, Marios; Loane, Clare; Wu, Kit; Brooks, David J; Piccini, Paola

    2011-09-01

    More than 50% of patients with Parkinson's disease (PD) are expected to show abnormalities with their weight in a process that starts several years before the diagnosis. The serotonergic (5-HT) system has been proposed to regulate appetite and the 5-HT transporter (SERT) is a key modulator of 5-HT metabolism. Here, we hypothesized that a dysfunctional 5-HT system could be responsible for alterations of weight in PD and we sought to investigate this in vivo. Thirty four PD patients had Body Mass Index (BMI) changes monitored over a 12-month period and one positron emission tomography (PET) brain scan with (11)C-DASB, a selective marker of SERT availability, during their second clinical assessment. Results were compared with those of a group of 10 normal controls. Half (17) of the PD patients showed abnormal BMI changes over the 12-month period; 12 lost while 5 gained weight. PD patients with abnormal BMI changes showed significantly raised (11)C-DASB binding in rostral raphe nuclei, hypothalamus, caudate nucleus and ventral striatum compared to cases with no significant BMI changes. (11)C-DASB binding in other regions was similarly decreased in the PD BMI subgroups compared to normal controls. BMI gainers showed significantly raised (11)C-DASB binding in anterior cingulate cortex (ACC) compared to BMI losers. Our findings suggest that abnormal BMI changes over a 12-month period are linked with relatively raised SERT availability in PD on an overall background of decreased 5-HT function. The regions implicated are the rostral raphe nuclei and its connections to limbic and cognitive areas. It is conceivable that 5-HT agents could help alleviate abnormal changes in BMI in PD.

  4. Alcoholic liver disease and changes in bone mineral density

    Directory of Open Access Journals (Sweden)

    Germán López-Larramona

    2013-12-01

    Full Text Available Osteoporosis and osteopenia are alterations in bone mineral density (BMD that frequently occur in the context of chronic liver disease (CLD. These alterations have been studied predominantly in chronic cholestatic disease and cirrhosis of the liver. Alcohol consumption is an independent risk factor for the onset of osteoporosis, whose estimated prevalence in patients with alcoholic liver disease (ALD ranges between 5 % and 40 %. The loss of BMD in ALD is the result of an imbalance between bone formation and resorption. Its pathogenesis is multifactorial and includes the toxic effects of alcohol on bone and endocrine and nutritional disorders secondary to alcoholism and a deficiency of osteocalcin, vitamin D and insulin growth factor-1. The diagnosis of BMD alterations in ALD is based on its measurement using bone densitometry. Treatment includes smoking and alcohol cessation and general measures such as changes in nutrition and exercise. Calcium and vitamin D supplements are recommended in all patients with ALD and osteoporosis. Bisphosphonates are the most commonly prescribed drugs for the specific treatment of this condition. Alternatives include raloxifene, hormone replacement therapy and calcitonin. This review will address the most important aspects involved in the clinical management of abnormal BMD in the context of ALD, including its prevalence, pathogenesis and diagnosis. We will also review the treatment of osteoporosis in CLD in general, focusing on specific aspects related to bone loss in ALD.

  5. Identifying early changes in myocardial microstructure in hypertensive heart disease.

    Directory of Open Access Journals (Sweden)

    Pranoti Hiremath

    Full Text Available The transition from healthy myocardium to hypertensive heart disease is characterized by a series of poorly understood changes in myocardial tissue microstructure. Incremental alterations in the orientation and integrity of myocardial fibers can be assessed using advanced ultrasonic image analysis. We used a modified algorithm to investigate left ventricular myocardial microstructure based on analysis of the reflection intensity at the myocardial-pericardial interface on B-mode echocardiographic images. We evaluated the extent to which the novel algorithm can differentiate between normal myocardium and hypertensive heart disease in humans as well as in a mouse model of afterload resistance. The algorithm significantly differentiated between individuals with uncomplicated essential hypertension (N = 30 and healthy controls (N = 28, even after adjusting for age and sex (P = 0.025. There was a trend in higher relative wall thickness in hypertensive individuals compared to controls (P = 0.08, but no difference between groups in left ventricular mass (P = 0.98 or total wall thickness (P = 0.37. In mice, algorithm measurements (P = 0.026 compared with left ventricular mass (P = 0.053 more clearly differentiated between animal groups that underwent fixed aortic banding, temporary aortic banding, or sham procedure, on echocardiography at 7 weeks after surgery. Based on sonographic signal intensity analysis, a novel imaging algorithm provides an accessible, non-invasive measure that appears to differentiate normal left ventricular microstructure from myocardium exposed to chronic afterload stress. The algorithm may represent a particularly sensitive measure of the myocardial changes that occur early in the course of disease progression.

  6. Identifying early changes in myocardial microstructure in hypertensive heart disease.

    Science.gov (United States)

    Hiremath, Pranoti; Bauer, Michael; Aguirre, Aaron D; Cheng, Hui-Wen; Unno, Kazumasa; Patel, Ravi B; Harvey, Bethany W; Chang, Wei-Ting; Groarke, John D; Liao, Ronglih; Cheng, Susan

    2014-01-01

    The transition from healthy myocardium to hypertensive heart disease is characterized by a series of poorly understood changes in myocardial tissue microstructure. Incremental alterations in the orientation and integrity of myocardial fibers can be assessed using advanced ultrasonic image analysis. We used a modified algorithm to investigate left ventricular myocardial microstructure based on analysis of the reflection intensity at the myocardial-pericardial interface on B-mode echocardiographic images. We evaluated the extent to which the novel algorithm can differentiate between normal myocardium and hypertensive heart disease in humans as well as in a mouse model of afterload resistance. The algorithm significantly differentiated between individuals with uncomplicated essential hypertension (N = 30) and healthy controls (N = 28), even after adjusting for age and sex (P = 0.025). There was a trend in higher relative wall thickness in hypertensive individuals compared to controls (P = 0.08), but no difference between groups in left ventricular mass (P = 0.98) or total wall thickness (P = 0.37). In mice, algorithm measurements (P = 0.026) compared with left ventricular mass (P = 0.053) more clearly differentiated between animal groups that underwent fixed aortic banding, temporary aortic banding, or sham procedure, on echocardiography at 7 weeks after surgery. Based on sonographic signal intensity analysis, a novel imaging algorithm provides an accessible, non-invasive measure that appears to differentiate normal left ventricular microstructure from myocardium exposed to chronic afterload stress. The algorithm may represent a particularly sensitive measure of the myocardial changes that occur early in the course of disease progression.

  7. The reliability and minimal detectable change of Timed Up and Go test in individuals with grade 1-3 knee osteoarthritis.

    Science.gov (United States)

    Alghadir, Ahmad; Anwer, Shahnawaz; Brismée, Jean-Michel

    2015-07-30

    The Timed Up and Go (TUG) test is quick and easy tests to assess patients' functional mobility. However, its reliability in individuals with knee osteoarthritis (OA) has not been well established. The aims of this study were to determine the reliability and minimal detectable change of the TUG test in individuals with doubtful to moderate (Grade 1-3) knee OA. Sixty-five subjects (25 male, 40 female), aged 45-70 years, with knee OA participated. Inter-rater reliability was assessed using two observers at different times of the same day in an alternating order. Intra-rater reliability was assessed on two consecutive visits with a 2-day interval. The standard error of measurement (SEM) and the minimum detectable change (MDC) were calculated to determine statistically meaningful changes. Intra-rater and inter-rater reliability were 0.97 (95% confidence interval [CI], 0.95 - 0.98) and 0.96 (95% confidence interval [CI], 0.94 - 0.97), respectively. The MDC, based on measurements by a single rater and between raters, was 1.10 and 1.14 seconds, respectively. The TUG is a reliable test with adequate MDC for clinical use in individuals with doubtful to moderate knee OA.

  8. Predictive role of minimal residual disease and log clearance in acute myeloid leukemia: a comparison between multiparameter flow cytometry and Wilm's tumor 1 levels.

    Science.gov (United States)

    Rossi, Giovanni; Minervini, Maria Marta; Melillo, Lorella; di Nardo, Francesco; de Waure, Chiara; Scalzulli, Potito Rosario; Perla, Gianni; Valente, Daniela; Sinisi, Nicola; Cascavilla, Nicola

    2014-07-01

    In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) as well as the degree of log clearance similarly identifies patients with poor prognosis. No comparison was provided between the two approaches in order to identify the best one to monitor follow-up patients. In this study, MRD and clearance were assessed by both multiparameter flow cytometry (MFC) and WT1 expression at different time points on 45 AML patients achieving complete remission. Our results by WT1 expression showed that log clearance lower than 1.96 after induction predicted the recurrence better than MRD higher than 77.0 copies WT1/10(4) ABL. Conversely, on MFC, MRD higher than 0.2 % after consolidation was more predictive than log clearance below 2.64. At univariate and multivariate analysis, positive MRD values and log clearance below the optimal cutoffs were associated with a shorter disease-free survival (DFS). At the univariate analysis, positive MRD values were also associated with overall survival (OS). Therefore, post-induction log clearance by WT1 and post-consolidation MRD by MFC represented the most informative approaches to identify the relapse. At the optimal timing of assessment, positive MRD and log-clearance values lower than calculated thresholds similarly predicted an adverse prognosis in AML.

  9. Molecular monitoring of minimal residual disease in two patients with MLL-rearranged acute myeloid leukemia and haploidentical transplantation after relapse

    Directory of Open Access Journals (Sweden)

    Burmeister Thomas

    2012-04-01

    Full Text Available Abstract This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11(p11.2;q23 with MLL-AF10 and the second a t(11;19(q23;p13.1 with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis. Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD, based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, both patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.

  10. Effects of intensive induction and consolidation chemotherapy with idarubicin and high dose cytarabine on minimal residual disease levels in newly diagnosed adult precursor-B acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Kenneth F. Bradstock

    2016-12-01

    Full Text Available An intensive induction regimen, consisting of idarubicin and high dose cytarabine, was assessed in 19 adult patients, median age 44 years, with newly diagnosed precursor-B acute lymphoblastic leukemia (ALL. Patients achieving a complete response (CR were given an attenuated consolidation course. The primary endpoints were induction death rate and incidence of serious non-hematological toxicity. Grades 3–4 diarrhoea occurred in 47% of patients during induction. Two patients (11% died during induction therapy, and 2 were withdrawn due to resistant disease or prolonged marrow hypoplasia. Fifteen patients achieved CR (79%, but levels of minimal residual disease (MRD after induction were comparable with those previously observed using a modified pediatric protocol. Overall survival at 5 years was 36.8% while leukemia-free survival was 44.1%. An intensive AML protocol used in adults with ALL resulted in substantial toxicity and provided similar levels of cytoreduction to conventional ALL protocols, without improving long-term outcomes.

  11. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.

    LENUS (Irish Health Repository)

    Rawstron, A C

    2016-04-01

    In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10(-5)). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.

  12. Ages of celiac disease: From changing environment to improved diagnostics

    Institute of Scientific and Technical Information of China (English)

    Alberto Tommasini; Tarcisio Not; Alessandro Ventura

    2011-01-01

    From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into manyages, each driven by a diagnostic advance and a deeperknowledge of disease pathogenesis. At the same time,these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the diseasein population. In the beginning, CD was considered a chronic indigestion, even if the causative food was notknown; later, the disease was proven to depend on anintolerance to wheat gliadin, leading to typical mucosalchanges in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten(AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presenta-tion. More recently, the characterization of autoantibod-ies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disor-ders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further devel-opments for the next celiac age will be proposed.

  13. Dietary change, nutrition education and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Brug, Johannes; Schols, Annemie; Mesters, Ilse

    2004-03-01

    Chronic obstructive pulmonary disease (COPD) is a prevalent and serious condition. Nutrition might play a role in COPD prevention and is definitely important in COPD management. There are some indications from epidemiological studies that dietary factors such as ample consumption of fruit and fish may decrease COPD risk. The available evidence is, however, not substantial enough to warrant dietary recommendations for primary prevention of COPD. Substantial evidence does point to the conclusion that, regardless of disease severity, weight loss is related to decreased exercise capacity, health status and mortality as well as to increased morbidity among patients with moderate to severe COPD. Current nutritional support strategies have primarily focussed on treatment of severely underweight and disabled patients. In an in-patient setting or when incorporated in a pulmonary rehabilitation programme, nutritional support has proved effective in inducing weight gain and related functional improvements. However, such interventions are only feasible for a selected group of patients and are very laborious. Therefore, opportunities for dietary and nutrition interventions in COPD management should be explored, aiming at early detection, prevention and early treatment of involuntary weight loss. This means expanding the target group to include COPD out-patients and primary care patients before they have become underweight, and putting more emphasis on dietary change than on medically prescribed supplementation. Successful intervention assumes (voluntary) adjustment of dietary behaviour, and health professionals may play an essential role in encouraging patients to make and maintain these changes. Achieving dietary change among COPD patients may require a combination of diet counselling and self-management. A model for such a combination is presented.

  14. Interactions of Climate Change and Nitrogen Management for Optimizing Crop Productivity and Food Security while Minimizing Nitrogen Pollution and Greenhouse Gas Emissions

    Science.gov (United States)

    Davidson, E. A.; Suddick, E. C.

    2012-12-01

    Producing food, transportation, and energy for seven billion people has led to huge increases in use of synthetic nitrogen (N) fertilizers and fossil fuels, resulting in large releases of N as air and water pollution. In its numerous chemical forms, N plays a critical role in all aspects of climate change, including mitigation, adaptation, and impacts. Here we report on a multi-authored, interdisciplinary technical report on climate-nitrogen interactions submitted to the US National Climate Assessment as part of a Research Coordination Network activity. Management of the N cycle not only affects emissions of nitrous oxide (N2O) and nitrogen oxides (NOX), but also impacts carbon dioxide (CO2) and methane (CH4), through effects on carbon cycling processes in forests and soils and the effects on atmospheric reactions of ozone (O3) and CH4. While some of these direct and indirect N effects have a short-term cooling effect, the warming effects of N2O dominate at long time scales. The challenges of mitigating N2O emissions are substantially different from those for CO2 and CH4, because N is essential for food production, and over 80% of anthropogenic N2O emissions are from the agricultural sector. On one hand, improved agricultural nutrient management can confer some adaptive capacity of crops to climatic variability, but, on the other hand, increased climatic variability will render the task more difficult to manage nutrients for the optimization of crop productivity while minimizing N losses to the environment. Higher air temperatures will result in a "climate penalty" for air quality mitigation efforts, because larger NOX emissions reductions will be needed to achieve the same reductions of O3 pollution under higher temperatures, thus imposing further challenges to avoid harmful impacts on human health and crop productivity. Changes in river discharge, due to summer drought and to extreme precipitation events, will affect the transport of N from agricultural fields to

  15. Salivary changes related to systemic diseases in the edentulous patients

    Science.gov (United States)

    Preoteasa, E; Tâncu, AM; Iosif, L; Melescanu Imre, M; Murariu-Măgureanu, C; Preoteasa, CT

    2014-01-01

    Introduction: The relatively frequent systemic comorbidities of geriatric patients can be linked to salivary changes, which may induce oral alteration and discomfort with the removable prosthesis. The aim of the study was to evaluate the salivary parameters in completely edentulous patients treated by removable prosthesis, in relation to their general health status. Material and method: A cross-sectional study was performed on 30 completely edentulous patients, 53% male and 47% female, aged between 53 and 84. The evaluation of the salivary parameters (oral hydration index, pH and salivary flow, viscosity and saliva buffer capacity) was performed with the Saliva Check Buffer kit (GC Corporation). Results: The salivary changes encountered were the following: low hydration level (63%), high saliva viscosity (57%), below-average pH (27%), reduced salivary flow (77%) and low saliva buffer capacity (80%). A reduced salivary flow and saliva buffer capacity was found in women. A lower buffer capacity of the saliva was found in patients with respiratory and gastro-intestinal disease. Conclusions: The alterations of the salivary flow are relatively frequent in geriatric patients, removable denture wearers, with compromised systemic status. These changes may be a risk factor for denture stomatitis and oral candidiasis, with a negative effect on the patient’s comfort and quality of life. PMID:25713626

  16. [Climate changes and emerging diseases. What new infectious diseases and health problem can be expected?].

    Science.gov (United States)

    Stark, K; Niedrig, M; Biederbick, W; Merkert, H; Hacker, J

    2009-07-01

    Increasing temperatures, but also other climatic factors, will have an impact on human health. Apart from the direct consequences of extreme weather conditions (e.g., heat-related fatalities), indirect health consequences in the long-term are also of great importance. In addition to a likely increase in allergic diseases and additional complications in the course of cardiovascular and respiratory diseases, infectious diseases are of particular interest. In Germany, endemic pathogens, such as hantavirus (with its reservoir in small rodents), tick-borne pathogens (Borrelia burgdorferi, tick-borne encephalitis virus), and certain food- and water-borne pathogens, are of concern. Mild winters favor rodent populations and may result in hantavirus epidemics in the subsequent summer period. Statistical analyses show a significant association between temperature and campylobacter incidence in Germany. An outbreak of rodent-borne leptospirosis among strawberry harvesters enhanced by heavy rainfalls illustrates how weather conditions may influence disease occurrence. Pathogens that are non-endemic in Germany but are imported by humans, vectors, and reservoir animals pose an additional risk to the population. Increasing temperatures improve the conditions for establishment of new vectors and for autochthonous transmission of some pathogens (e.g., chikungunya, dengue, West Nile virus, malaria, or leishmaniasis). Climatic and ecologic conditions in Germany currently do not favor autochthonous outbreaks for most of these pathogens. However, if temperatures increase, as expected, such outbreaks will become more likely. Germany should enhance its research in public health activities in the field of climate change and infectious diseases.

  17. Skeletal muscle function: role of ionic changes in fatigue, damage and disease.

    Science.gov (United States)

    Allen, D G

    2004-08-01

    1. Repeated activity of skeletal muscle causes a variety of changes in its properties: muscles become weaker with intense use (fatigue), may feel sore and weak after repeated contractions involving stretch and can degenerate in some disease conditions. The present review considers the role of early ionic changes in the development of each of these conditions. 2. Single fibre preparations of mouse muscle were used to measure ionic changes following activity induced changes in function. Single fibres were dissected with intact tendons and stimulated to produce force. Fluorescent indicators were microinjected into the fibres to allow simultaneous ionic measurements with determination of mechanical performance. 3. One theory to explain muscle fatigue is that fatigue is caused by the accumulation of lactic acid, producing an intracellular acidosis that inhibits the myofibrillar proteins. In contrast, we found that during repeated tetani there was little or no pH change, but that failure of calcium release was a major contributor to fatigue. Currently, it is proposed that precipitation of calcium and phosphate in the sarcoplasmic reticulum contributes to the failure of calcium release. 4. Muscles can be used to shorten and produce force or they can be used to de-accelerate loads (stretched or eccentric contractions). One day after intense exercise involving stretched contractions, muscles are weak, sore and tender, and this damage can take a week to recover. In this condition, sarcomeres are disorganized and there are increases in resting intracellular Ca2+ and Na+. Recently, we demonstrated that the elevation of Na+ occurs through a stretch-activated channel that can be blocked by either gadolinium or streptomycin. Preventing the increase in [Na+]i with gadolinium also prevented part of the muscle weakness after stretched contractions. 5. Duchenne muscular dystrophy is a lethal degenerative disease of muscles in which the protein dystrophin is absent. Dystrophic muscles

  18. Changing concepts in lipid nutrition in health and disease.

    Science.gov (United States)

    Chandrasekharan, N

    1999-09-01

    serum HDL cholesterol, raise serum LDL cholesterol and when substituted for saturated fatty acids, increase lipoprotein Lp (a) level, an independent risk factor for the development of coronary heart disease. The idea of which foods, nutrients and supplements are "healthy" is often being amended as new scientific data is presented and then simplified for the consumers. What was once perceived as a healthy diet is often no longer considered as such and vice versa. Dietary recommendations have to change with time and the evidence available. Nutritional recommendations should encourage eating a great variety of nutrient sources within our food supply in moderation. Various lifestyle options to improve health should also be promoted.

  19. Responsiveness and Minimal Important Changes of the Western Ontario and McMaster Universities Osteoarthritis Index in Subjects Undergoing Rehabilitation Following Hip Fracture.

    Science.gov (United States)

    Monticone, Marco; Ambrosini, Emilia; Secci, Claudio; Rocca, Barbara; Ferrante, Simona; Capone, Antonio

    2017-05-01

    To evaluate the responsiveness and minimal important changes (MICs) for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and its subscales in subjects with hip fractures. At the beginning and end of a 2-month rehabilitation program, 106 patients completed the WOMAC. After the program, the global perceived effect (GPE) was analyzed to produce a dichotomous outcome (improved vs. stable). Responsiveness for the WOMAC and its subscales were calculated by distribution (effect size; standardized response mean) and anchor-based methods (receiver operating characteristic curves; correlations between change scores of the WOMAC and its subscales and GPE). Receiver operating characteristic curves were also used in order to compute the best cutoff levels between improved and stable subjects (MICs). The effect size ranged from 0.64 to 11.10 and the standardized response mean from 0.79 to 2.65. The receiver operating characteristic analyses revealed an MIC value (area under the curve, sensitivity, specificity) for the WOMAC of 29 (0.817, 92, 78); values of 35 (0.820, 77, 76) 44 (0.625, 25, 95), and 24 (0.707, 100, 76) were found for pain, stiffness, and physical function subscales, respectively. Correlations between change scores of the WOMAC and its subscales and GPE were low (0.240, for stiffness subscale) to moderate (0.438-0.570 for the other subscales and the WOMAC). The WOMAC and its subscales (all but stiffness) were sensitive in detecting clinical changes in subjects with hip fracture undergoing rehabilitation. We recommend taking the MICs provided into account when assessing patients' improvement or planning studies in this clinical context.

  20. Assessing Minimal Detectable Changes and Test-Retest Reliability of the Timed Up and Go Test and the 2-Minute Walk Test in Patients With Total Knee Arthroplasty.

    Science.gov (United States)

    Yuksel, Ertugrul; Kalkan, Serpil; Cekmece, Senol; Unver, Bayram; Karatosun, Vasfi

    2017-02-01

    Two-minute walk test (2MWT) and the Timed Up and Go test (TUG) are simple, quick, and can be applied in a short time as part of the routine medical examination. They were shown to be reliable and valid tests in many patient groups. The aims of the present study were: (1) to determine test-retest reliability of data for the TUG and 2MWT and (2) to determine minimal detectable change (MDC) scores for the TUG and 2MWT in patients with TKA. Forty-eight patients with total knee arthroplasty, operated by the same surgeon, were included in this study. Patients performed trials for TUG and 2MWT twice on the same day. Between the first and second trials, patients waited for an hour on sitting position to prevent fatigue. The TUG and 2MWT showed an excellent test-retest reliability in this study. Intraclass correlation coefficient [ICC(2,1)] for TUG and 2MWT were 0.98 and 0.97, respectively. Standard error of measurement and MDC95 for TUG were 0.82 and 2.27, respectively. Standard error of measurement and MDC95 for 2MWT were 5.40 and 14.96, respectively. The TUG and 2MWT have an excellent test-retest reliability in patients with TKA. Clinicians and researchers can be confident that changes in TUG time above 2.27 seconds and changes in 2MWT distances above 14.96 meters, represent a "real" clinical change in an individual patient with TKA. We, therefore, recommend the use of these 2 tests as complementary outcome measures for functional evaluation in patients TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Modelling impacts of climate change on arable crop diseases: progress, challenges and applications.

    Science.gov (United States)

    Newbery, Fay; Qi, Aiming; Fitt, Bruce Dl

    2016-08-01

    Combining climate change, crop growth and crop disease models to predict impacts of climate change on crop diseases can guide planning of climate change adaptation strategies to ensure future food security. This review summarises recent developments in modelling climate change impacts on crop diseases, emphasises some major challenges and highlights recent trends. The use of multi-model ensembles in climate change modelling and crop modelling is contributing towards measures of uncertainty in climate change impact projections but other aspects of uncertainty remain largely unexplored. Impact assessments are still concentrated on few crops and few diseases but are beginning to investigate arable crop disease dynamics at the landscape level.

  2. Adult and paediatric patients with minimal change nephrotic syndrome show no major alterations in glomerular expression of sulphated heparan sulphate domains.

    Science.gov (United States)

    Wijnhoven, Tessa J M; Geelen, Joyce M; Bakker, Marinka; Lensen, Joost F M; Rops, Angelique L W M M; Kramer, Andrea B; Navis, Gerjan; van den Hoven, Mabel J W; van der Vlag, Johan; Berden, Jo H M; Wetzels, Jack F M; van den Heuvel, Lambert P W J; Monnens, Leo A H; van Kuppevelt, Toin H

    2007-10-01

    Minimal change nephrotic syndrome (MCNS) is the most frequent form of nephrotic syndrome in childhood. In the glomerular basement membrane (GBM) of adult patients with MCNS, a reduced expression of a specific heparan sulphate (HS) domain has been reported. In children with MCNS, urinary activity of the HS-degrading enzyme heparanase was increased. It is, therefore, possible that a decreased GBM HS expression is associated with the pathogenesis of proteinuria in patients with MCNS. In this study, HS in glomeruli of five adult and six paediatric patients with MCNS were analysed by immunofluorescence staining using four different antibodies, each defining a specific sulphated HS domain. The pediatric patients were subdivided into three groups depending on the presence or absence of podocyte foot process effacement, the level of proteinuria and prednisone administration at the time of the biopsy. In addition, kidneys of rats with adriamycin nephropathy (ADRN), a model for MCNS, were included in the study. Expression of sulphated HS domains was not aberrant in adult or paediatric patients compared with control subjects. Children with and without proteinuria had the same HS content. In contrast, rats with ADRN showed a decreased glomerular expression of sulphated HS domains. These results suggest that in patients with MCNS proteinuria is not associated with major changes in glomerular expression of sulphated HS domains.

  3. Structural changes in the minimal spanning tree and the hierarchical network in the Korean stock market around the global financial crisis

    Science.gov (United States)

    Nobi, Ashadun; Maeng, Seong Eun; Ha, Gyeong Gyun; Lee, Jae Woo

    2015-04-01

    This paper considers stock prices in the Korean stock market during the 2008 global financial crisis by focusing on three time periods: before, during, and after the crisis. Complex networks are extracted from cross-correlation coefficients between the normalized logarithmic return of the stock price time series of firms. The minimal spanning trees (MSTs) and the hierarchical network (HN) are generated from cross-correlation coefficients. Before and after the crisis, securities firms are located at the center of the MST. During the crisis, however, the center of the MST changes to a firm in heavy industry and construction. During the crisis, the MST shrinks in comparison to that before and that after the crisis. This topological change in the MST during the crisis reflects a distinct effect of the global financial crisis. The cophenetic correlation coefficient increases during the crisis, indicating an increase in the hierarchical structure during in this period. When crisis hits the market, firms behave synchronously, and their correlations are higher than those during a normal period.

  4. Changes of Regulatory T Cells in Graves' Disease

    Institute of Scientific and Technical Information of China (English)

    WANG Hongxiang; ZHAO Shi; TANG Xiaoqiong; LI Jingyuan

    2006-01-01

    The immune mechanism of Graves' diseases (GD) and the roles of regulator T cells were investigated. In 32 patients with GD (GD group) and 20 healthy volunteers (control group), flow cytometry was used to detect the proportion of CD4+CD25+ cells, MACS to isolate CD4+ CD25+ cells,RT-PCR to assay the expression of FOXP3, and ELISA to test the level of IL-10, respectively. It was found that there was no significant change in the proportion of CD4+CD25+ T cells between GD group and control group (P>0.05), while secretion of IL-10 and expression of FOXP3 in GD group were lower than control group (P<0.01 and P<0.05, respectively). In conclusion, though the proportion of regulatory T cells of peripheral blood lymphocytes in the patients with GD, the functions of them were significantly weakened, which might be a pathogenic factor in GD.

  5. Venous hemodynamic changes in lower limb venous disease

    DEFF Research Database (Denmark)

    Lee, Byung Boong; Nicolaides, Andrew N; Myers, Kenneth

    2016-01-01

    ). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various......There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due...... not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect...

  6. The association of income with health behavior change and disease monitoring among patients with chronic disease.

    Directory of Open Access Journals (Sweden)

    David J T Campbell

    Full Text Available BACKGROUND: Management of chronic diseases requires patients to adhere to recommended health behavior change and complete tests for monitoring. While studies have shown an association between low income and lack of adherence, the reasons why people with low income may be less likely to adhere are unclear. We sought to determine the association between household income and receipt of health behavior change advice, adherence to advice, receipt of recommended monitoring tests, and self-reported reasons for non-adherence/non-receipt. METHODS: We conducted a population-weighted survey, with 1849 respondents with cardiovascular-related chronic diseases (heart disease, hypertension, diabetes, stroke from Western Canada (n = 1849. We used log-binomial regression to examine the association between household income and the outcome variables of interest: receipt of advice for and adherence to health behavior change (sodium reduction, dietary improvement, increased physical activity, smoking cessation, weight loss, reasons for non-adherence, receipt of recommended monitoring tests (cholesterol, blood glucose, blood pressure, and reasons for non-receipt of tests. RESULTS: Behavior change advice was received equally by both low and high income respondents. Low income respondents were more likely than those with high income to not adhere to recommendations regarding smoking cessation (adjusted prevalence rate ratio (PRR: 1.55, 95%CI: 1.09-2.20, and more likely to not receive measurements of blood cholesterol (PRR: 1.72, 95%CI 1.24-2.40 or glucose (PRR: 1.80, 95%CI: 1.26-2.58. Those with low income were less likely to state that non-adherence/non-receipt was due to personal choice, and more likely to state that it was due to an extrinsic factor, such as cost or lack of accessibility. CONCLUSIONS: There are important income-related differences in the patterns of health behavior change and disease monitoring, as well as reasons for non-adherence or non

  7. Disease related tissue damage and subsequent changes in fillet structure

    DEFF Research Database (Denmark)

    Fish meat quality is influenced by many biological and physical factors like e.g. rearing, feeding, slaughtering, processing and storage. Observations from practical fish farming indicate that infections in e.g. salmon caused by Moritella viscosus or Pancreas Disease (PD) results in downgrading o......-regulation of immune-related genes followed by a regenerative phase with regulation of genes coding for muscle growth and synthesis of connective tissue....... of the fish and subsequent a reduction in price. Despite this, the impact of infectious diseases on the meat quality and the mechanisms behind are poorly investigated. Wound repair is a dynamic, interactive response to tissue injury that involves a complex interaction and cross talk of various cell types......, extracellular matrix molecules, soluble mediators and cytokines. In order to describe the molecular mechanisms and processes of wound repair, a panel of genes covering immunological factors and tissue regeneration were used to measure changes at the mRNA level following mechanical tissue damage in rainbow trout...

  8. Comparative study of calcified changes in aortic valvular diseases.

    Science.gov (United States)

    Togashi, Mayuko; Tamura, Koichi; Masuda, Yukinari; Fukuda, Yuh

    2008-06-01

    Calcification of the aortic valve leads to stenosis or regurgitation or both. To clarify the mechanism of heart valve calcification, comparative studies using histological and ultrastructural examinations were performed of calcified aortic valves. These valves were obtained at valve replacement surgery from 11 patients with rheumatic aortic valvular disease (RAVD), 10 patients with degenerative aortic valve disease (DAVD), and 10 patients with congenitally bicuspid aortic valves (CBAV). For electron microscopic study, 5 cases were selected from each group. In RAVD, histological examination revealed calcification in a degenerated amorphous area at the center of fibrous thickened regions and in laminar fibrous thickened areas near the valve surface. In DAVD, calcification was observed mainly in the fibrosa near the valve ring. In CBAV, basic pathological changes were similar to those in DAVD; however, additional severe calcification of the raphe was observed, if the raphe was present. Ultrastructural examinations showed deposition of electron-dense materials in two patterns in all three groups; one pattern was observed in the interfibrillar spaces of collagen fibrils, and the other pattern was widespread macular deposition unrelated to the preexisting structure. In RAVD, microfibril-like fibrillar structures were found in the areas of deposition of electron-dense materials. These findings suggest that newly formed connective tissue degraded and became necrotic because of nutritional deprivation, especially in the thickened central area, causing calcium deposition. In DAVD and CBAV, numerous lipid vacuoles were found in the electron-dense deposition areas similar to lipid deposition in aortic atherosclerosis. Localized calcium deposition in the fibrosa suggests that the stress of valvular motion and pressure load induces sclerotic changes with the degeneration of collagen fibers, providing a core for calcification. In CBAV, the raphe was the main location of

  9. Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo‐Controlled Study

    Science.gov (United States)

    van der Heijde, Désirée; Beutler, Anna; Gladman, Dafna; Mease, Philip; Krueger, Gerald G.; McInnes, Iain B.; Helliwell, Philip; Coates, Laura C.; Xu, Stephen

    2016-01-01

    Objective To evaluate long‐term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO‐REVEAL trial. Methods The GO‐REVEAL trial was a phase III, randomized, double‐blind trial with placebo‐control through week 24 followed by an open‐label extension of golimumab 50/100 mg treatment up to 5 years. In these post‐hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0–100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point). Results Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P golimumab‐treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1‐unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321–0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290–0.795]; P = 0.004) consecutive visits. Conclusion Among golimumab‐treated PsA patients, better long‐term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA. PMID:25779603

  10. Epigenetic changes in Alzheimer's disease: decrements in DNA methylation

    Science.gov (United States)

    Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul D.; Rogers, Joseph

    2010-01-01

    DNA methylation is a vital component of the epigenetic machinery that orchestrates changes in multiple genes and helps regulate gene expression in all known vertebrates. We evaluated immunoreactivity for two markers of DNA methylation and eight methylation maintenance factors in entorhinal cortex layer II, a region exhibiting substantial Alzheimer's disease (AD) pathology in which expression changes have been reported for a wide variety of genes. We show, for the first time, neuronal immunoreactivity for all 10 of the epigenetic markers and factors, with highly significant decrements in AD cases. These decrements were particularly marked in PHF1/PS396 immunoreactive, neurofibrillary tangle-bearing neurons. In addition, two of the DNA methylation maintenance factors, DNMT1 and MBD2, have been reported also to interact with ribosomal RNAs and ribosome synthesis. Consistent with these findings, DNMT1 and MBD2, as well as p66α, exhibited punctate cytoplasmic immunoreactivity that co-localized with the ribosome markers RPL26 and 5.8s rRNA in ND neurons. By contrast, AD neurons generally lacked such staining, and there was a qualitative decrease in RPL26 and 5.8s rRNA immunoreactivity. Collectively, these findings suggest epigenetic dysfunction in AD-vulnerable neurons. PMID:19117641

  11. Endocarditis infecciosa: Una enfermedad cambiante Infective endocarditis: A changing disease

    Directory of Open Access Journals (Sweden)

    José Horacio Casabé

    2008-04-01

    Full Text Available A pesar de los avances en el diagnóstico y en el tratamiento antibiótico y quirúrgico, la endocarditis infecciosa sigue siendo una enfermedad con una mortalidad elevada. Los estudios llevados a cabo en nuestro país y en otros países demostraron que el perfil clínico del paciente ha cambiado. Existe mayor prevalencia de pacientes añosos con enfermedad degenerativa valvular, las endocarditis protésicas y nosocomiales son más frecuentes y aumentó la presencia del Staphylococcus aureus. Estos cambios podrían justificar la ausencia de disminución en la mortalidad de esta enfermedad y plantean la necesidad de encarar enfoques más agresivos de tratamiento mediante la confección de estudios prospectivos bien diseñados y controlados.In spite of the advance in diagnosis and antibiotic and surgical treatment, mortality of infective endocarditis remains high. Recent studies in various countries and in Argentina have shown that the clinical profile of infective endocarditis has changed. Currently the patients are older with higher frequency of degenerative valve disease and prosthetic valve and nosocomial endocarditis. The incidence of Staphylococcus aureus as etiological agent has increased. These changes may justify the absence of decrease in mortality and suggests that more aggressive measures are needed based on prospective, well designed and controlled trials.

  12. Grey matter changes in cognitively impaired Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Irena Rektorova

    Full Text Available BACKGROUND: Cortical changes associated with cognitive decline in Parkinson's disease (PD are not fully explored and require investigations with established diagnostic classification criteria. OBJECTIVE: We used MRI source-based morphometry to evaluate specific differences in grey matter volume patterns across 4 groups of subjects: healthy controls (HC, PD with normal cognition (PD-NC, PD with mild cognitive impairment (MCI-PD and PD with dementia (PDD. METHODS: We examined 151 consecutive subjects: 25 HC, 75 PD-NC, 29 MCI-PD, and 22 PDD at an Italian and Czech movement disorder centre. Operational diagnostic criteria were applied to classify MCI-PD and PDD. All structural MRI images were processed together in the Czech centre. The spatial independent component analysis was used to assess group differences of local grey matter volume. RESULTS: We identified two independent patterns of grey matter volume deviations: a Reductions in the hippocampus and temporal lobes; b Decreases in fronto-parietal regions and increases in the midbrain/cerebellum. Both patterns differentiated PDD from all other groups and correlated with visuospatial deficits and letter verbal fluency, respectively. Only the second pattern additionally differentiated PD-NC from HC. CONCLUSION: Grey matter changes in PDD involve areas associated with Alzheimer-like pathology while fronto-parietal abnormalities are possibly an early marker of PD cognitive decline. These findings are consistent with a non-linear cognitive progression in PD.

  13. Gray Matter Changes in Demyelinating Disease: Correlations with Clinical Scores.

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    Onu, Mihaela; Aroceanu, Adina; Ferastraoaru, Victor; Bajenaru, Ovidiu

    2015-09-01

    Recent MR studies have shown that, in multiple sclerosis, selective regional, but not global gray matter atrophy occurs in multiple sclerosis. Our aim was to identify specific areas of gray matter volume changes and explore the relationship between atrophy and clinical motor outcomes. Nine patients with relapsing remitting MS and 9 matched healthy controls were recruited. The Multiple Sclerosis Functional Composite was administered. For MR acquisitions, a GE- Genesis- Signa, 1.5T MR system, was used. A voxel-based morphometry (VBM), subcortical structures segmentation (FIRST) and volumetric (SIENAx) FSL tools were used in the study. Group comparison showed atrophy for several gray matter regions. The most important volume reductions were found for subcortical deep gray matter areas. Correlations with clinical scores were checked and specific gray matter areas showed significant volume reductions associated with motor scores (9-hole peg time and 25-feet walk time) and EDSS (Expanded Disability Status Scale). We performed a voxelwise analysis of gray matter changes in MS and found a more prominent atrophy for the subcortical structures than for cortical gray matter. Using an additional analysis (FIRST and SIENAx segmentation/volumetry) we were able to confirm the VBM results and to quantify the degree of atrophy in specific structures. Specific gray matter regions which volume reductions correlate with 25-feet walk, 9-hole peg times and EDSS suggest that 25-feet walk time is the best predictor of disease progression in terms of gray matter reduction.

  14. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease

    NARCIS (Netherlands)

    Smeets, B.; Stucker, F.; Wetzels, J.; Brocheriou, I.; Ronco, P.; Grone, H.J.; D'Agati, V.; Fogo, A.B.; Kuppevelt, T.H. van; Fischer, H.P.; Boor, P.; Floege, J.; Ostendorf, T.; Moeller, M.J.

    2014-01-01

    In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of i

  15. Introducing the Concept of the Minimally Important Difference to Determine a Clinically Relevant Change on Patient-Reported Outcome Measures in Patients with Intermittent Claudication

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    Conijn, Anne P., E-mail: a.p.conijn@amc.nl [Academic Medical Center, Departments of Vascular Surgery and Interventional Radiology (Netherlands); Jonkers, Wilma, E-mail: wilma.jonkers@achmea.nl [Achmea Insurances, Division of Health Care (Netherlands); Rouwet, Ellen V., E-mail: e.rouwet@erasmusmc.nl [Erasmus Medical Center, Department of Vascular Surgery (Netherlands); Vahl, Anco C., E-mail: a.c.vahl@olvg.nl [Onze Lieve Vrouwe Gasthuis, Department of Vascular Surgery (Netherlands); Reekers, Jim A., E-mail: j.a.reekers@amc.nl [Academic Medical Center, Department of Radiology (Netherlands); Koelemay, Mark J. W., E-mail: m.j.koelemaij@amc.nl [Academic Medical Center, Department of vascular surgery (Netherlands)

    2015-10-15

    PurposeThe minimally important difference (MID) represents the smallest change in score on patient-reported outcome measures that is relevant to patients. The aim of this study was to introduce the MID for the Vascular Quality of Life Questionnaire (VascuQol) and the walking impairment questionnaire (WIQ) for patients with intermittent claudication (IC).MethodsIn this multicenter study, we recruited 294 patients with IC between July and October 2012. Patients completed the VascuQol, with scores ranging from 1 to 7 (worst to best), and the WIQ, with scores ranging from 0 to 1 (worst to best) at first visit and after 4 months follow-up. In addition, patients answered an anchor-question rating their health status compared to baseline, as being improved, unchanged, or deteriorated. The MID for improvement and deterioration was calculated by an anchor-based approach, and determined with the upper and lower limits of the 95 % confidence interval of the mean change of the group who had not changed according to the anchor-question.ResultsFor the MID analyses of the VascuQol and WIQ, 163 and 134 patients were included, respectively. The MID values for the VascuQol (mean baseline score 4.25) were 0.87 for improvement and 0.23 for deterioration. For the WIQ (mean baseline score 0.39), we found MID values of 0.11 and −0.03 for improvement and deterioration, respectively.ConclusionIn this study, we calculated the MID for the VascuQol and the WIQ. Applying these MID facilitates better interpretation of treatment outcomes and can help to set treatment goals for individual care.

  16. High prognostic value of minimal residual disease detected by flow-cytometry-enhanced fluorescence in situ hybridization in core-binding factor acute myeloid leukemia (CBF-AML).

    Science.gov (United States)

    Wang, Libing; Gao, Lei; Xu, Sheng; Gong, Shenglan; Liu, Min; Qiu, Huiying; Xu, Xiaoqian; Ni, Xiong; Chen, Li; Lu, Shuqing; Chen, Jie; Song, Xianmin; Zhang, Weiping; Yang, Jianmin; Hu, Xiaoxia; Wang, Jianmin

    2014-10-01

    Acute myeloid leukemia (AML) is generally regarded as a disorder of stem cells, known as leukemic initiating cells (LICs), which initiate the disease and contribute to relapses. Although the phenotype of these cells remains unclear in most patients, they are enriched within the CD34(+)CD38(-) population. In core-binding factor (CBF) AML, the cytogenetic abnormalities also exist in LIC. The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy. Thirty-six patients under 65 years of age with de novo CBF-AML treated with intensive chemotherapy were retrospectively included in this study. Correlations with relapse-free survival (RFS) and overall survival were evaluated with univariate and multivariate analyses. FISH efficiently identified LICs in the CD34(+)CD38(-) population. The presence of FISH(+)CD34(+)CD38(-) cells before consolidation was negatively associated with cumulative incidence of relapse (64 vs 18 %, P = .012), which showed prognostic value for RFS (12 vs 68 %, P = .008) and OS (11 vs 75 %, P = .0005), and retained prognostic significance for RFS in multivariate analysis. The detection of FISH(+)CD34(+)CD38(-) cells before consolidation therapy significantly correlated with long-term survival. Fluorescence-activated cell sorting (FACS)-FISH could be potentially adopted as a MRD monitor approach in clinical practice to identify CBF-AML patients at risk of treatment failure during therapy.

  17. Quantification of minimal residual disease levels by flow cytometry at time of transplant predicts outcome after myeloablative allogeneic transplantation in ALL.

    Science.gov (United States)

    Sanchez-Garcia, J; Serrano, J; Serrano-Lopez, J; Gomez-Garcia, P; Martinez, F; Garcia-Castellano, J M; Rojas, R; Martin, C; Rodriguez-Villa, A; Molina-Hurtado, J R; Alvarez, M A; Casaño, J; Torres-Gomez, A

    2013-03-01

    The potential impact on patient outcome of different Minimal residual disease (MRD) levels at time of transplant in patients with lymphoblastic leukemia undergoing allogeneic hematopoietic SCT (HSCT) remains uncertain. In this study, we quantified MRD levels at time of transplant using multiparameter flow cytometry (MFC). Mononuclear cells from marrow aspirates were obtained from 102 adult and child patients before their conditioning regimen. Quantification of MRD levels was carried out by detecting patient-specific leukemia-associated immunophenotypes using four-color MFC. Thirty patients exhibited measurable levels of MRD at the time of transplant, with low levels (0.01 to 0.1%) in 12 cases, intermediate levels (>0.1 to 1%) in 8 cases and high levels (>1%) in 10 cases. The leukemia-free survival (LFS) rates were 65.9±7.0%, 42.9±15.7% and 0% for negative, low levels 0.1% and intermediate-high levels >0.1%, respectively (P0.1%, respectively (P<0.001, log-rank test). Multivariate Cox analysis confirmed that detection of leukemia cells by flow cytometry at transplant was the most significantly adverse factor for OS, LFS and EFS after transplant.

  18. Minimally invasive percutaneous endovascular therapies in the management of complications of non-alcoholic fatty liver disease (NAFLD): A case report.

    Science.gov (United States)

    Salsamendi, Jason; Pereira, Keith; Kang, Kyungmin; Fan, Ji

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from simple steatosis to inflammation leading to fibrosis, cirrhosis, and even hepatocellular carcinoma. With the progressive epidemics of obesity and diabetes, major risk factors in the development and pathogenesis of NAFLD, the prevalence of NAFLD and its associated complications including liver failure and hepatocellular carcinoma is expected to increase by 2030 with an enormous health and economic impact. We present a patient who developed Hepatocellular carcinoma (HCC) from nonalcoholic steatohepatitis (NASH) cirrhosis. Due to morbid obesity, she was not an optimal transplant candidate and was not initially listed. After attempts for lifestyle modifications failed to lead to weight reduction, a transarterial embolization of the left gastric artery was performed. This is the sixth such procedure in humans in literature. Subsequently she had a meaningful drop in BMI from 42 to 36 over the following 6 months ultimately leading to her being listed for transplant. During this time, the left hepatic HCC was treated with chemoembolization without evidence of recurrence. In this article, we wish to highlight the use of minimally invasive percutaneous endovascular therapies such as transarterial chemoembolization (TACE) in the comprehensive management of the NAFLD spectrum and percutaneous transarterial embolization of the left gastric artery (LGA), a novel method, for the management of obesity.

  19. Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects With Alzheimer Disease.

    Science.gov (United States)

    Williams, Erik A; McGuone, Declan; Frosch, Matthew P; Hyman, Bradley T; Laver, Nora; Stemmer-Rachamimov, Anat

    2017-05-01

    Alzheimer disease (AD) is the most common cause of dementia in the elderly, and is characterized by extracellular deposition of β-amyloid and intracellular accumulation of hyperphosphorylated tau protein in the brain. These pathologic findings are identified postmortem. Various visual deficits in AD have been reported and there have been conflicting reports, through imaging and pathology studies, regarding the presence of changes in the globe that mirror Alzheimer changes in the brain. Moreover, both macular degeneration and glaucoma have been variously characterized as having AD-related features. We examined one or both eyes from 19 autopsy cases, 17 of which had varying degrees of AD-related changes, and 2 of which were age-matched controls. Three cases had glaucoma and 4 had macular degeneration. Immunohistochemistry for tau, β-amyloid, TDP-43, ubiquitin, and α-synuclein showed no evidence of inclusions, deposits or other protein accumulation in any case, in any part of the globe. This finding suggests that regardless of the severity of changes seen in the brain in AD, there are no similar changes in the globe. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  20. Overweight, hypertension and cardiovascular disease: focus on adipocytokines, insulin, weight changes and natriuretic peptides.

    Science.gov (United States)

    Seven, Ekim

    2015-11-01

    Paper I: In the prevalent model including leptin, CRP, adiponectin, sex, age, lifestyle risk factors, lipids, insulin, haemoglobin A1c, and in the incident model which also included baseline heart rate and blood pressure, only leptin of the three candidate intermediates was significantly associated with both prevalent and incident hypertension. Paper II: Five-year weight changes were associated with blood pressure alterations and had a substantial impact on both fasting and two-hour post-glucose serum insulin levels. However, in multivariable regression analyses, additional adjustments for insulin values only attenuated the associations between weight changes and blood pressure minimally. Paper III: Higher serum concentrations of NT-proBNP associated with prevalent hypertension whereas lower concentrations associated with incident hypertension. Paper IV: Among 6,502 participants with a mean follow-up time of 11.4 years, 527 participants experienced one or multiple cardio-vascular events. Among adiponectin, leptin and CRP, only CRP were significantly positive associated with CVD in all models.   Regarding the pathophysiology of overweight-related hypertension and CVD, our results indicate that:   • Leptin is possibly an independent risk factor for the development of hypertension.   • Albeit weight loss improves insulin-profile, the effect of insulin on blood pressure changes seems minimal, indicating that insulin does not play a major direct role in the early development of hypertension.   • A deficiency of the natriuretic peptides, resulting in reduced vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.   • Since adjustment for CRP decreased the BMI-associated CVD risk markedly, our data indirectly suggest that IL-6 originating from fat tissue could play a role in overweight and obesity-related cardiovascular disease.

  1. Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease.

    Directory of Open Access Journals (Sweden)

    Alhelí Rodríguez-Cortés

    Full Text Available Visceral leishmaniasis (VL is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease.

  2. Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease

    Science.gov (United States)

    Carrillo, Eugenia; Martorell, Susanna; Todolí, Felicitat; Martínez-Flórez, Alba; Urniza, Alicia; Moreno, Javier

    2016-01-01

    Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease. PMID:27171409

  3. Do the chaotic features of gait change in Parkinson's disease?

    Science.gov (United States)

    Sarbaz, Yashar; Towhidkhah, Farzad; Jafari, Ayyoob; Gharibzadeh, Shahriar

    2012-08-21

    Some previous studies have focused on chaotic properties of Parkinson's disease (PD). It seems that considering PD from dynamical systems perspective is a relevant method that may lead to better understanding of the disease. There is some ambiguity about chaotic nature in PD symptoms and normal behaviour. Some studies claim that normal gait has somehow a chaotic behaviour and disturbed gait in PD has decreased chaotic nature. However, it is worth noting that the basis of this idea is the difference of fractal behaviour in gait of normal and PD patients, which is concluded from Long Range Correlation (LRC) indices. Our primary calculations show that a large number of normal persons and patients have similar LRC. It seems that chaotic studies on PD need a different view. Because of short time recording of symptoms, accurate calculation of chaotic features is tough. On the other hand, long time recording of symptoms is experimentally difficult. In this research, we have first designed a physiologically plausible model for normal and PD gait. Then, after validating the model with neural network classifier, we used the model for extracting long time simulation of stride in normal and PD persons. These long time simulations were then used for calculating the chaotic features of gait. According to change of phase space behaviour and alteration of three largest lyapunov exponents, it was observed that simulated normal persons act as chaotic systems in stride production, but simulated PD does not have chaotic dynamics and is stochastic. Based on our results, it may be claimed that normal gait has chaotic nature which is disturbed in PD state. Surely, long time real recordings from gait signal in normal persons and PD patients are necessary to warranty this hypothesis.

  4. Hemodynamic changes after vascular reconstructive surgery for moyamoya disease

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    Kuyama, Hideyuki; Niimi, Hitohisa; Kawauchi, Masamitsu; Tanimoto, Takaho; Murota, Takenobu; Kinugasa, Kazushi; Asari, Shoji; Nishimoto, Akira; Nagao, Seigo.

    1988-06-01

    The regional cerebral blood flow (rCBF) was measured in eight juvenile cases with moyamoya disease before and after vascular reconstructive surgery consisting either of encephalo-duro-arterio-synangiosis (EDAS) or of encephalo-duro-arterio-myo-synangiosis (EDAMS). The rCBF was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon-emission computed tomography. A patient with a completed stroke showed a low value of the mean hemispheric blood flow on the lesion side. There was no significant difference in the mean hemispheric blood flow between the two hemispheres in the patients with a transient ischemic attack. The variation in the rCBF versus the mean hemispheric blood flow was studied before and after the operation. The preoperative rCBF was relatively high in the basal ganglia and occipital regions and low in the frontal region. One month after the operation, the rCBF in each region was not significantly changed in comparison with the preoperative rCBF. Six months after the operation, however, the rCBF was significantly reduced in the basal ganglia and significantly increased in the temporal region. On the other hand, the rCBF was almost identical with the mean hemispheric blood flow in the frontal and occipital regions. These results may be explained by the angiographic findings, which showed a diminution in the moyamoya vessels and a good filling of the middle cerebral artery area via the external carotid artery on the postoperative angiogram. Vascular reconstructive surgery for moyamoya disease in children may, therefore, be thought to be an effective procedure for smoothing the cerebral-blood-flow distribution.

  5. Repeatability and Minimal Detectable Change in Longitudinal Median Nerve Excursion Measures During Upper Limb Neurodynamic Techniques in a Mixed Population: A Pilot Study Using Musculoskeletal Ultrasound Imaging.

    Science.gov (United States)

    Paquette, Philippe; Lamontagne, Martin; Higgins, Johanne; Gagnon, Dany H

    2015-07-01

    This study determined test-retest reliability and minimum detectable change in longitudinal median nerve excursion during upper limb neurodynamic tests (ULNTs). Seven participants with unilateral or bilateral carpal tunnel syndrome and 11 healthy participants were randomly tested with two ULNTs (i.e., tensioner and slider). Each ULNT was performed three times each at 45° and 90° of shoulder abduction on two separate visits. Video sequences of median nerve excursion, recorded by a physical therapist using ultrasound imaging, were quantified using computer software. The generalizability theory, encompassing a G-Study and a D-study, measured the dependability coefficient (Φ) along with standard error of measurement (SEM) accuracy and allowed various testing protocols to be proposed. The highest reliability (Φ = 0.84) and lowest minimal measurement error (SEM = 0.58 mm) of the longitudinal median nerve excursion were reached during the ULNT-slider performed with 45° of shoulder abduction and when measures obtained from three different image sequences recorded during a single visit were averaged. It is recommended that longitudinal median nerve excursion measures computed from three separate image sequences recorded during a single visit be averaged in clinical practice. Ideally, adding a second visit (six image sequences) is also suggested in research protocols.

  6. Minimal hepatic encephalopathy.

    Science.gov (United States)

    Zamora Nava, Luis Eduardo; Torre Delgadillo, Aldo

    2011-06-01

    The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.

  7. Influenza SIRS with minimal pneumonitis

    Directory of Open Access Journals (Sweden)

    Shruti Erramilli

    2016-08-01

    Full Text Available While systemic inflammatory response syndrome (SIRS, is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  8. New therapies for hereditary angioedema: disease outlook changes dramatically.

    Science.gov (United States)

    Frank, Michael M; Jiang, Haixiang

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease associated with episodic attacks of nonpitting edema that may affect any external or mucosal body surface. Attacks most often affect the extremities, causing local swelling, the GI tract, leading to severe abdominal pain, and the mouth and throat, at times causing asphyxiation. Most patients with HAE have low levels of the plasma serine protease inhibitor C1 inhibitor. The edema in these patients is caused by unregulated generation of bradykinin. Effective chronic therapy of patients with impeded androgens or plasmin inhibitors has been available for decades, but in the United States, we do not have therapy for acute attacks. Five companies have completed or are in the process of conducting phase 3 clinical trials, double-blind, placebo-controlled studies of products designed to terminate acute attacks or to be used in prophylaxis. Two companies, Lev Pharmaceuticals and CSL Behring, have preparations of C1 inhibitor purified from plasma that have been used in Europe for decades (trade names Cinryze and Berinert P, respectively). One company, Pharming, has developed a recombinant C1 inhibitor preparation. One company, Dyax, is testing a kallikrein inhibitor (ecallantide), and one company, Jerini, is completing testing of a bradykinin type 2 receptor antagonist (Icatibant). Although little has been published thus far, all of these products may prove effective. It is likely that HAE treatment will change dramatically within the next few years.

  9. [Meningococcal disease: always present. Serogroup changes in the Southern Cone].

    Science.gov (United States)

    López, Eduardo Luis; Debbag, Roberto

    2012-12-01

    Meningococcal disease (MD) caused by Neisseria meningitidis is a condition with high mortality rates in childhood. Serogroup W135 N. meningitidis (MenW135) is usually associated with 1 to 8% of MD cases worldwide, and with a low carriage rate. During March 2000, an increase in the number of cases of MenW135 in Saudi Arabia was reported that coincided with the Hajj pilgrimage (Hajj-2000 strain). Mayer et al studied MenW135 strains from outbreaks related with this pilgrimage and found that all had been caused by the same hypervirulent clone (ST-11/complex ET-37). The circulation of this strain could also be documented in Latin America. In the last years, changes in serogroup prevalence have been observed in the region, the increase of MenW135 in the Southern Cone being the most significant. N. meningitidis infections of several serogroups including MenW135 may be prevented with chemoprophylaxis with antibiotics and quadrivalent vaccines. Better knowledge of the global epidemiology through the new molecular techniques, jointly with the availability of vaccines are the most relevant tools to control hyperendemic or epidemic periods of MD.

  10. Timing of critical genetic changes in human breast disease.

    Science.gov (United States)

    Ellsworth, Rachel E; Ellsworth, Darrell L; Deyarmin, Brenda; Hoffman, Laurel R; Love, Brad; Hooke, Jeffrey A; Shriver, Craig D

    2005-12-01

    Breast cancer development has been characterized as a nonobligatory sequence of histological changes from normal epithelium through invasive malignancy. Although genetic alterations are thought to accumulate stochastically during tumorigenesis, little is known about the timing of critical mutations. This study examined allelic imbalance (AI) in tissue samples representing a continuum of breast cancer development to examine the evolution of genomic instability. Laser-microdissected DNA samples were collected from histologically normal breast specimens (n = 25), atypical ductal hyperplasia (ADH, n = 16), ductal carcinoma-in-situ (DCIS, n = 37), and stage I to III invasive carcinomas (n = 72). Fifty-two microsatellite markers representing 26 chromosomal regions commonly deleted in breast cancer were used to assess patterns of AI. AI frequencies were .0001). DCIS lesions contain levels of genomic instability that are characteristic of advanced invasive tumors, and this suggests that the biology of a developing carcinoma may already be predetermined by the in situ stage. Observations that levels of AI in ADH lesions are similar to those in disease-free tissues provide a genomic rationale for why prevention strategies at the ADH level are successful and why cases with ADH involving surgical margins do not require further resection.

  11. Personality Changes after Deep Brain Stimulation in Parkinson's Disease

    Science.gov (United States)

    Pham, Uyen; Solbakk, Anne-Kristin; Skogseid, Inger-Marie; Pripp, Are Hugo; Konglund, Ane Eidahl; Andersson, Stein; Haraldsen, Ira Ronit; Aarsland, Dag; Dietrichs, Espen; Malt, Ulrik Fredrik

    2015-01-01

    Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson's disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P = 0.006; P = 0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P = 0.027). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity. PMID:25705545

  12. Minimal intervention concept: a new paradigm for operative dentistry.

    Science.gov (United States)

    Dalli, Mehmet; Çolak, Hakan; Mustafa Hamidi, M

    2012-08-01

    The current treatment philosophy is to prevent and detect dental disease at the earliest stage in order to avoid invasive treatment. With the current understanding of the nature of dental disease and its process, the treatment philosophy is now changing to a more conservative approach and the concept of minimal intervention is gaining popularity in modern dentistry throughout the world. It is now established that demineralized but non-cavitated enamel and dentine can be healed and traditional surgical approach of drilling and filling may no longer be necessary as this only treats the symptoms of the disease and not the cause. However, when surgical intervention is indicated, the least invasive techniques such as preventive resin restoration and minimal cavity preparation are utilized. The aim of this article is to give dental professionals an overview of the concepts of minimal intervention dentistry and recent innovations in dental technology in both the diagnosis and treatment of dental caries.

  13. Changes in adult neurogenesis in neurodegenerative diseases: Cause or consequence?

    NARCIS (Netherlands)

    Thompson, A.; Boekhoorn, K.; van Dam, A.-M.; Lucassen, P.J.

    2008-01-01

    This review addresses the role of adult hippocampal neurogenesis and stem cells in some of the most common neurodegenerative disorders and their related animal models. We discuss recent literature in relation to Alzheimer's disease and dementia, Parkinson's disease, Huntington's disease, amyotrophic

  14. Declining Prevalence of Disease Vectors Under Climate Change

    DEFF Research Database (Denmark)

    Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato

    2016-01-01

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian...

  15. Changes in adult neurogenesis in neurodegenerative diseases: Cause or consequence?

    NARCIS (Netherlands)

    Thompson, A.; Boekhoorn, K.; van Dam, A.-M.; Lucassen, P.J.

    2008-01-01

    This review addresses the role of adult hippocampal neurogenesis and stem cells in some of the most common neurodegenerative disorders and their related animal models. We discuss recent literature in relation to Alzheimer's disease and dementia, Parkinson's disease, Huntington's disease, amyotrophic

  16. Virus disease in wheat predicted to increase with a changing climate.

    Science.gov (United States)

    Trębicki, Piotr; Nancarrow, Narelle; Cole, Ellen; Bosque-Pérez, Nilsa A; Constable, Fiona E; Freeman, Angela J; Rodoni, Brendan; Yen, Alan L; Luck, Jo E; Fitzgerald, Glenn J

    2015-09-01

    Current atmospheric CO2 levels are about 400 μmol mol(-1) and are predicted to rise to 650 μmol mol(-1) later this century. Although the positive and negative impacts of CO2 on plants are well documented, little is known about interactions with pests and diseases. If disease severity increases under future environmental conditions, then it becomes imperative to understand the impacts of pathogens on crop production in order to minimize crop losses and maximize food production. Barley yellow dwarf virus (BYDV) adversely affects the yield and quality of economically important crops including wheat, barley and oats. It is transmitted by numerous aphid species and causes a serious disease of cereal crops worldwide. This study examined the effects of ambient (aCO2 ; 400 μmol mol(-1) ) and elevated CO2 (eCO2 ; 650 μmol mol(-1) ) on noninfected and BYDV-infected wheat. Using a RT-qPCR technique, we measured virus titre from aCO2 and eCO2 treatments. BYDV titre increased significantly by 36.8% in leaves of wheat grown under eCO2 conditions compared to aCO2 . Plant growth parameters including height, tiller number, leaf area and biomass were generally higher in plants exposed to higher CO2 levels but increased growth did not explain the increase in BYDV titre in these plants. High virus titre in plants has been shown to have a significant negative effect on plant yield and causes earlier and more pronounced symptom expression increasing the probability of virus spread by insects. The combination of these factors could negatively impact food production in Australia and worldwide under future climate conditions. This is the first quantitative evidence that BYDV titre increases in plants grown under elevated CO2 levels. © 2015 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  17. Minimally invasive dentistry: a review and update.

    Science.gov (United States)

    Brostek, Andrew M; Bochenek, Andrew J; Walsh, Laurence J

    2006-06-01

    The term "Minimal Invasive (MI) Dentistry" can best be defined as the management of caries with a biological approach, rather than with a traditional (surgical) operative dentistry approach. Where operative dentistry is required, this is now carried out in the most conservative manner with minimal destruction of tooth structure. This new approach to caries management changes the emphasis from diagnosing carious lesions as cavities (and a repeating cycle of restorations), to one of diagnosing the oral ecological imbalance and effecting biological changes in the biofilm. The goal of MI is to stop the disease process and then to restore lost tooth structure and function, maximizing the healing potential of the tooth. The thought process which underpins this new minimal invasive approach can be organized into three main categories: (1) Recognize, which means identify patient caries risk, (2) Remineralize, which means prevent caries and reverse non-cavitated caries, and (3) Repair, which means control caries activity, maximize healing and repair the damage. The disease of dental caries is not just demineralization, but a process of repeated demineralization cycles caused by an imbalance in the ecological and chemical equilibrium of the biofilm /tooth interface (the ecological plaque hypothesis). Dietary and lifestyle patterns, especially carbohydrate frequency, water intake and smoking, play an important role in changing the biofilm ecology and pathogenicity. Tools for chairside assessment of saliva and plaque, allow risk to be assessed and patient compliance monitored. The remineralizing properties of saliva can be enhanced using materials which release biologically available calcium, phosphate and fluoride ions (CPP-ACP and CPP-ACFP). Use of biocides can also alter the pathogenic properties of plaque. Use of these MI treatment protocols, can repair early lesions and improve patient understanding and compliance. This review article introduces some of the key concepts

  18. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study.

    NARCIS (Netherlands)

    Cilloni, D.; Renneville, A.; Hermitte, F.; Hills, R.K.; Daly, S.; Jovanovic, J.V.; Gottardi, E.; Fava, M.; Schnittger, S.; Weiss, T.; Izzo, B.; Nomdedeu, J.; Heijden, A. van der; Reijden, B.A. van der; Jansen, J.H.; Velden, V.H. van der; Ommen, H.; Preudhomme, C.; Saglio, G.; Grimwade, D.

    2009-01-01

    PURPOSE: Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteristics. It remains to be established whether relapse risk can be better predicted through assessment of minimal residual disease (MRD). One proposed marker is the Wilms tumor gene WT1, which is o

  19. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

    NARCIS (Netherlands)

    Biondi, A; Valsecchi, MG; Seriu, T; D'Aniello, E; Willemse, MJ; Fasching, K; Pannunzio, A; Gadner, H; Schrappe, M; Kamps, WA; Bartram, CR; van Dongen, JJM; Panzer-Grumayer, ER

    2000-01-01

    The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case

  20. Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease.

    Science.gov (United States)

    Bachanova, V; Marks, D I; Zhang, M-J; Wang, H; de Lima, M; Aljurf, M D; Arellano, M; Artz, A S; Bacher, U; Cahn, J-Y; Chen, Y-B; Copelan, E A; Drobyski, W R; Gale, R P; Greer, J P; Gupta, V; Hale, G A; Kebriaei, P; Lazarus, H M; Lewis, I D; Lewis, V A; Liesveld, J L; Litzow, M R; Loren, A W; Miller, A M; Norkin, M; Oran, B; Pidala, J; Rowe, J M; Savani, B N; Saber, W; Vij, R; Waller, E K; Wiernik, P H; Weisdorf, D J

    2014-03-01

    The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P=0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P=0.62). Patients MRD(pos) pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P=0.057), but absence of pre-HCT TKI (HR 1.88; P=0.018), RIC (HR 1.891; P=0.054) and pre-HCT MRD(pos) (HR 1.6; P=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRD(neg) status is preferred pre-HCT.

  1. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

    Science.gov (United States)

    Dawidowska, Małgorzata; Kosmalska, Maria; Sędek, Łukasz; Szczepankiewicz, Aleksandra; Twardoch, Magdalena; Sonsala, Alicja; Szarzyńska-Zawadzka, Bronisława; Derwich, Katarzyna; Lejman, Monika; Pawelec, Katarzyna; Obitko-Płudowska, Agnieszka; Pawińska-Wąsikowska, Katarzyna; Kwiecińska, Kinga; Kołtan, Andrzej; Dyla, Agnieszka; Grzeszczak, Władysław; Kowalczyk, Jerzy R; Szczepański, Tomasz; Ziętkiewicz, Ewa; Witt, Michał

    2016-07-18

    Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07-5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05-3.52, P = 0.03, MRD-day33 and MRD-week12, P RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28-12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61-28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.

  2. Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.

    Science.gov (United States)

    Takamatsu, Hiroyuki; Ogawa, Yoshiyasu; Kobayashi, Noriko; Obata, Kazue; Narisawa, Tadashi; Nakayama, Kouji; Munemoto, Saori; Aoki, Go; Ohata, Kinya; Kumano, Yoshihisa; Ozaki, Jun; Murata, Ryoichi; Kondo, Yukio; Terasaki, Yasushi; Kurokawa, Toshiro; Miyamoto, Toshihiro; Shimizu, Naomi; Fukushima, Toshihiro; Yoshida, Akira; Ueda, Takanori; Yoshida, Takashi; Nakao, Shinji

    2013-10-01

    Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

  3. Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study.

    Science.gov (United States)

    Yeoh, Allen Eng Juh; Ariffin, Hany; Chai, Elaine Li Leng; Kwok, Cecilia Sze Nga; Chan, Yiong Huak; Ponnudurai, Kuperan; Campana, Dario; Tan, Poh Lin; Chan, Mei Yoke; Kham, Shirley Kow Yin; Chong, Lee Ai; Tan, Ah Moy; Lin, Hai Peng; Quah, Thuan Chong

    2012-07-01

    To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement. Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients. Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%). Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

  4. Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis.

    Science.gov (United States)

    Mussolin, L; Damm-Welk, C; Pillon, M; Zimmermann, M; Franceschetto, G; Pulford, K; Reiter, A; Rosolen, A; Woessmann, W

    2013-02-01

    We studied the prognostic value of minimal disseminated disease (MDD) and anti-ALK immune response in children with NPM-ALK-positive anaplastic-large cell lymphoma (ALCL) and evaluated their potential for risk stratification. NPM-ALK transcripts were analyzed by RT-PCR in bone marrow/peripheral blood of 128 ALCL patients at diagnosis, whereas ALK antibody titers in plasma were assessed using an immunocytochemical approach. MDD was positive in 59% of patients and 96% showed an anti-ALK response. Using MDD and antibody titer results, patients could be divided into three biological risk groups (bRG) with different prognosis: high risk (bHR): MDD-positive and antibody titer ≤ 1/750, 26/128 (20%); low risk (bLR): MDD negative and antibody titer >1/750, 40/128 (31%); intermediate risk (bIR): all remaining patients, 62/128 (48%). Progression-free survival was 28% (s.e., 9%), 68% (s.e., 6%) and 93% (s.e., 4%) for bHR, bIR and bLR, respectively (P<0.0001). Survival was 71% (s.e., 9%), 83% (s.e., 5%) and 98% (s.e., 2%) for bHR, bIR and bLR (P=0.02). Only bHR and histology other than common type were predictive of higher risk of failure (hazard ratio 4.9 and 2.7, respectively) in multivariate analysis. Stratification of ALCL patients based on MDD and anti-ALK titer should be considered in future ALCL trials to optimize treatment.

  5. Prospective comparison of two flow cytometry methodologies for monitoring minimal residual disease in a multicenter treatment protocol of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Luria, Drorit; Rosenthal, Eti; Steinberg, David; Kodman, Yona; Safanaiev, Marina; Amariglio, Ninette; Avigad, Smadar; Stark, Batia; Izraeli, Shai

    2010-11-01

    Minimal residual disease (MRD) is a powerful prognostic indicator in childhood acute lymphoblastic leukemia (ALL). Multiparametric flow cytometry (FC) is a rapid and sensitive methodology for detection of MRD, applicable for most patients and is being incorporated in multicenter treatment protocols. The influence of different techniques and of individual interpretation of data on the interlaboratory variability in FC-MRD determinations has not been described. We compared FC-MRD of identical bone marrow samples processed as either Ficoll separated mononuclear cells or lyse and wash nucleated cells (NC) in two central laboratories of a national multicenter childhood ALL study. A total of 290 samples at diagnosis and 494 follow-up samples (Day-15 n = 261; Day-33 n = 233) were analyzed. A group of 52 paired list mode data (LMD) of D-15 and D-33 samples was blindly reanalyzed by both laboratories. Pearson correlations for all samples of D-15 (n = 261) and D-33 (n = 233) were 0.875 and 0.82, respectively (P < 0.001), being lower for T-ALL 0.716 and 0.719, respectively. Quantitative concordance defined as less than 0.5 log difference in MRD measured by the two methodologies was 80.8% at D-15 but only in 57.9% at D-33. Reanalysis of LMD revealed that data interpretation explained half of the discordance. FC-MRD analysis of childhood ALL is a robust method during the earliest phases of induction therapy in a multicentric setting. Standardization of data analysis could improve about half of the discordance between different technical approaches. © 2010 International Clinical Cytometry Society.

  6. A novel approach to investigation of the pathogenesis of active minimal-change nephrotic syndrome using subtracted cDNA library screening.

    Science.gov (United States)

    Sahali, Djillali; Pawlak, André; Valanciuté, Asta; Grimbert, Philippe; Lang, Philippe; Remy, Philippe; Bensman, Albert; Guellaën, Georges

    2002-05-01

    Clinical and experimental observations suggest that minimal-change nephrotic syndrome (MCNS) results from T cell dysfunction, via unknown mechanisms. For the identification of genes that are potentially involved in MCNS, a subtractive cDNA library was constructed from cDNA from T cell-enriched peripheral blood mononuclear cells obtained from the same patient during relapse versus remission ("relapse minus remission"). This library was screened by differential hybridization with forward ("relapse minus remission") and reverse ("remission minus relapse") subtractive cDNAs probes, as well as unsubtracted probes from relapse and remission, and irrelevant nephrotic syndrome (membranous nephropathy). A total of 84 transcripts were isolated, of which 12 matched proteins of unknown function and 30 were unknown clones. Among the 42 known transcripts, at least 18 are closely involved in the T cell receptor-mediated complex signaling cascade, including genes encoding components of the T cell receptor and proteins associated with the cytoskeletal scaffold, as well as transcription factors. In particular, it was demonstrated that the expression levels of Fyb/Slap, L-plastin, and grancalcin were increased during relapse, suggesting that the integration of proximal signaling after T cell engagement involves the preferential recruitment of these cytoskeleton-associated proteins in MCNS. Because very low levels of interleukin-12 receptor beta2 mRNA were detected in relapse samples, the interleukin-12 signaling pathway might be defective, suggesting that, in MCNS, T cell activation evolves toward a T helper 2 phenotype. Therefore, the combination of subtractive cloning and differential screening constitutes an efficient approach to the identification of genes that are likely to be involved in the pathophysiologic processes of MCNS.

  7. Climate change and infectious diseases in Australia: future prospects, adaptation options, and research priorities.

    Science.gov (United States)

    Harley, David; Bi, Peng; Hall, Gillian; Swaminathan, Ashwin; Tong, Shilu; Williams, Craig

    2011-03-01

    Climate change will have significant and diverse impacts on human health. These impacts will include changes in infectious disease incidence. In this article, the authors review the current situation and potential future climate change impacts for respiratory, diarrheal, and vector-borne diseases in Australia. Based on this review, the authors suggest adaptive strategies within the health sector and also recommend future research priorities.

  8. Subtle changes among presymptomatic carriers of the Huntington's disease gene

    OpenAIRE

    S. Kirkwood; Siemers, E.; Hodes, M; Conneally, P; Christian, J.; Foroud, T

    2000-01-01

    OBJECTIVES—To compare the neurological and psychometric characteristics of presymptomatic gene carriers and non-gene carriers who are at risk for developing Huntington's disease so as to characterise early signs of disease and to identify markers of neurological function that could be used to assess the impact of experimental therapies on the progression of disease, even among those who are clinically presymptomatic.
METHODS—A sample of people at risk for Huntington's dis...

  9. Procedural learning changes in patients with Wilson's disease

    Institute of Scientific and Technical Information of China (English)

    Yumei Jiang; Xiang Shen; Xiaoping Wang; Wenjie Li

    2011-01-01

    In the present study, we compared explicit memory performance, using the Wechsler Memory Scale, and implicit memory performance, using the Nissen software version of the serial reaction time task, in patients with Wilson's disease to normal controls. The Wilson's disease patients exhibited deficits in explicit memory tasks, such as figure recall and understanding memory. Moreover, the Wilson's disease patients exhibited deficits in implicit memory tasks, including significantly prolonged response times. These findings indicate that Wilson's disease patients have explicit and implicit partial memory impairments.

  10. Effects of climate change, invasive species, and disease on the distribution of native European crayfishes.

    Science.gov (United States)

    Capinha, César; Larson, Eric R; Tricarico, Elena; Olden, Julian D; Gherardi, Francesca

    2013-08-01

    Climate change will require species to adapt to new conditions or follow preferred climates to higher latitudes or elevations, but many dispersal-limited freshwater species may be unable to move due to barriers imposed by watershed boundaries. In addition, invasive nonnative species may expand into new regions under future climate conditions and contribute to the decline of native species. We evaluated future distributions for the threatened European crayfish fauna in response to climate change, watershed boundaries, and the spread of invasive crayfishes, which transmit the crayfish plague, a lethal disease for native European crayfishes. We used climate projections from general circulation models and statistical models based on Mahalanobis distance to predict climate-suitable regions for native and invasive crayfishes in the middle and at the end of the 21st century. We identified these suitable regions as accessible or inaccessible on the basis of major watershed boundaries and present occurrences and evaluated potential future overlap with 3 invasive North American crayfishes. Climate-suitable areas decreased for native crayfishes by 19% to 72%, and the majority of future suitable areas for most of these species were inaccessible relative to native and current distributions. Overlap with invasive crayfish plague-transmitting species was predicted to increase. Some native crayfish species (e.g., noble crayfish [Astacus astacus]) had no future refugia that were unsuitable for the modeled nonnative species. Our results emphasize the importance of preventing additional introductions and spread of invasive crayfishes in Europe to minimize interactions between the multiple stressors of climate change and invasive species, while suggesting candidate regions for the debatable management option of assisted colonization. © 2013 Society for Conservation Biology.

  11. Minimal residual disease in melanoma: circulating melanoma cells and predictive role of MCAM/MUC18/MelCAM/CD146

    Science.gov (United States)

    Rapanotti, Maria Cristina; Campione, Elena; Spallone, Giulia; Orlandi, Augusto; Bernardini, Sergio; Bianchi, Luca

    2017-01-01

    Circulating tumour cells (CTCs), identified in numerous cancers including melanoma, are unquestionably considered valuable and useful as diagnostic and prognostic markers. They can be detected at all melanoma stages and may persist long after treatment. A crucial step in metastatic processes is the intravascular invasion of neoplastic cells as circulating melanoma cells (CMCs). Only a small percentage of these released cells are efficient and capable of colonizing with a strong metastatic potential. CMCs' ability to survive in circulation express a variety of genes with continuous changes of signal pathways and proteins to escape immune surveillance. This makes it difficult to detect them; therefore, specific isolation, enrichment and characterization of CMC population could be useful to monitor disease status and patient clinical outcome. Overall and disease-free survival have been correlated with the presence of CMCs. Specific melanoma antigens, in particular MCAM (MUC18/MelCAM/CD146), could be a potentially useful tool to isolate CMCs as well as be a prognostic, predictive biomarker. These are the areas reviewed in the article. PMID:28280601

  12. Can we change the natural history of Crohn's disease with early immunomodulation?

    Science.gov (United States)

    Markowitz, James

    2014-01-01

    In both children and adults, the natural history of Crohn's disease (CD) is characterized by relapsing and remitting bouts of intestinal inflammation, often associated with a progressive shift from inflammatory to complicated stricturing or penetrating disease behavior. The past 2 decades have seen a dramatic shift in therapeutic approach with the increasingly common use of early thiopurine immunomodulation. These maintenance medications were initially introduced primarily as corticosteroid-sparing agents capable of minimizing recurrent flares of inflammatory disease and have proven to be quite efficacious. Increasing evidence suggests, however, that thiopurines may only delay rather than prevent the development of complicated disease behavior. Data from both adult and pediatric CD populations from around the world are reviewed in terms of the effect of early immunomodulation on progression to complicated disease behavior, need for surgery, and prevention of recurrent disease after resection. The effect of thiopurines on the growth of children is also reviewed.

  13. Minimally invasive surgery. Future developments.

    OpenAIRE

    1994-01-01

    The rapid development of minimally invasive surgery means that there will be fundamental changes in interventional treatment. Technological advances will allow new minimally invasive procedures to be developed. Application of robotics will allow some procedures to be done automatically, and coupling of slave robotic instruments with virtual reality images will allow surgeons to perform operations by remote control. Miniature motors and instruments designed by microengineering could be introdu...

  14. Outcomes of Children With BCR-ABL1–Like Acute Lymphoblastic Leukemia Treated With Risk-Directed Therapy Based on the Levels of Minimal Residual Disease

    Science.gov (United States)

    Roberts, Kathryn G.; Pei, Deqing; Campana, Dario; Payne-Turner, Debbie; Li, Yongjin; Cheng, Cheng; Sandlund, John T.; Jeha, Sima; Easton, John; Becksfort, Jared; Zhang, Jinghui; Coustan-Smith, Elaine; Raimondi, Susana C.; Leung, Wing H.; Relling, Mary V.; Evans, William E.; Downing, James R.; Mullighan, Charles G.; Pui, Ching-Hon

    2014-01-01

    Purpose BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL) subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction. Patients and Methods Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–like ALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL. Results Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% ± 4.7% [SE] v 88.4% ± 1.9% at 5 years; P = .41) or in overall survival (92.5% ± 4.2% v 95.1% ± 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL. Conclusion Patients who have BCR-ABL1–like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies. PMID:25049327

  15. Real-world validation of the minimal disease activity index in psoriatic arthritis: an analysis from a prospective, observational, biological treatment registry.

    Science.gov (United States)

    Rahman, Proton; Zummer, Michel; Bessette, Louis; Baer, Philip; Haraoui, Boulos; Chow, Andrew; Kelsall, John; Kapur, Suneil; Rampakakis, Emmanouil; Psaradellis, Eliofotisti; Lehman, Allen J; Nantel, Francois; Osborne, Brendan; Tkaczyk, Cathy

    2017-08-30

    To describe the minimal disease activity (MDA) rate over time in patients with psoriatic arthritis (PsA) receiving antitumour necrosis factor agents, evaluate prognostic factors of MDA achievement and identify the most common unmet criteria among MDA achievers. Biologic Treatment Registry Across Canada (BioTRAC): ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis or PsA with infliximab (IFX), golimumab (GLM) or ustekinumab. 46 primary-care Canadian rheumatology practices. 223 patients with PsA receiving IFX (enrolled since 2005) and GLM (enrolled since 2010) with available MDA information at baseline, 6 months and/or 12 months. MDA was defined as ≥5 of the following criteria: 28-item tender joint count (TJC28) ≤1, 28-item swollen joint count (SJC28) ≤1, Psoriasis Area and Severity Index (PASI) ≤1 or body surface area≤3, Pain Visual Analogue Scale (VAS) ≤15 mm, patient's global assessment (PtGA) (VAS) ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, tender entheseal points ≤1. Independent prognostic factors of MDA achievement were assessed with multivariate logistic regression. MDA was achieved by 11.7% of patients at baseline, 43.5% at 6 months, 44.8% at 12 months and 48.8% at either 6 or 12 months. Among MDA achievers at 6 months, 75.7% had sustained MDA at 12 months. Lower baseline HAQ (OR=0.210; 95% CI: 0.099 to 0.447) and lower TJC28 (OR=0.880; 95% CI: 0.804 to 0.964), were significant prognostic factors of MDA achievement over 12 months of treatment. The most commonly unmet MDA criteria among MDA achievers was patient reported pain (25%), PtGA (15%) and PASI (12%). Almost 50% of patients treated with IFX or GLM in routine clinical care achieved MDA within the first year of treatment. Lower baseline HAQ and lower TJC28, were identified as significant prognostic factors of MDA achievement. The most commonly unmet criteria in patients who achieved MDA were pain, PtGA and

  16. Major impact of an early bone marrow checkpoint (day 21) for minimal residual disease in flow cytometry in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Eveillard, Marion; Robillard, Nelly; Arnoux, Isabelle; Garand, Richard; Rialland, Fanny; Thomas, Caroline; Strullu, Marion; Michel, Gérard; Béné, Marie C; Fossat, Chantal; Loosveld, Marie

    2017-06-01

    The early persistence of minimal residual disease (MRD) is considered a poor prognostic factor indicative of chemoresistance in acute lymphoblastic leukemia. In French children, chemosensitivity is assessed at day 21 post-induction by cytomorphology. Here, it was investigated whether a more precise evaluation could be obtained at this time point with multiparameter flow cytometry (MFC). This study enrolled 123 children with de novo acute lymphoblastic leukemia. MRD0 was investigated at day 21 in MFC with a combination of antibodies based on the immunophenotype of diagnosis. It was also evaluated at day 35 by immunoglobulin/T-cell receptor quantitative real-time polymerase chain reaction (MRD1). Three risk groups could be delineated based on MRD0. Patients with MFC/MRD0 levels >10(-2) (n = 25) were considered high risk, those with levels between 10(-2) and 10(-4) (n = 46) intermediate risk, and those <10(-4) (n = 50) low risk. Overall survival (p = 0.048) and event-free survival (EFS, p = 0.00017) were significantly different between these three groups. EFS of the 14 corticoresistant patients strongly depended on their MRD0 level (p = 0.004). Similarly, both EFS (p = 0.0004) and overall survival (p = 0.02) were significantly different in the 109 chemosensitive patients, according to MRD0 levels. MRD0 and MRD1 levels, compared with 112 patients, were consistent (-/- or +/+) in 57.2% of the cases. Both MRD0+/MRD1+ and MRD0+/MRD1- patients had a significantly worse EFS (p = 0.0001) than those with undetectable MRD at both MRD0 and MRD1. This study confirms the usefulness and superiority of an early point of MRD detection by MFC. In addition, MRD0 in MFC identifies a subgroup of patients with poorer prognosis (MRD0+/MRD1-). Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Climate change and infectious diseases of wildlife: Altered interactions between pathogens, vectors and hosts

    Institute of Scientific and Technical Information of China (English)

    Milena GALLANA; Marie-Pierre RYSER-DEGIORGIS; Thomas WAHLI; Helmut SEGNER

    2013-01-01

    Infectious diseases result from the interactions of host,pathogens,and,in the case of vector-borne diseases,also vectors.The interactions involve physiological and ecological mechanisms and they have evolved under a given set of environmental conditions.Environmental change,therefore,will alter host-pathogen-vector interactions and,consequently,the distribution,intensity,and dynamics of infectious diseases.Here,we review how climate change may impact infectious diseases of aquatic and terrestrial wildlife.Climate change can have direct impacts on distribution,life cycle,and physiological status of hosts,pathogens and vectors.While a change in either host,pathogen or vector does not necessarily translate into an alteration of the disease,it is the impact of climate change on the interactions between the disease components which is particularly critical for altered disease risks.Finally,climate factors can modulate disease through modifying the ecological networks host-pathogen-vector systems are belonging to,and climate change can combine with other environmental stressors to induce cumulative effects on infectious diseases.Overall,the influence of climate change on infectious diseases involves different mechanisms,it can be modulated by phenotypic acclimation and/or genotypic adaptation,it depends on the ecological context of the host-pathogen-vector interactions,and it can be modulated by impacts of other stressors.As a consequence of this complexity,non-linear responses of disease systems under climate change are to be expected.To improve predictions on climate change impacts on infectious disease,we suggest that more emphasis should be given to the integration of biomedical and ecological research for studying both the physiological and ecological mechanisms which mediate climate change impacts on disease,and to the development of harmonized methods and approaches to obtain more comparable results,as this would support the discrimination of case-specific versus

  18. Climate change and vector-borne diseases of public health significance.

    Science.gov (United States)

    Ogden, Nicholas H

    2017-10-16

    There has been much debate as to whether or not climate change will have, or has had, any significant effect on risk from vector-borne diseases. The debate on the former has focused on the degree to which occurrence and levels of risk of vector-borne diseases are determined by climate-dependent or independent factors, while the debate on the latter has focused on whether changes in disease incidence are due to climate at all, and/or are attributable to recent climate change. Here I review possible effects of climate change on vector-borne diseases, methods used to predict these effects and the evidence to date of changes in vector-borne disease risks that can be attributed to recent climate change. Predictions have both over- and underestimated the effects of climate change. Mostly under-estimations of effects are due to a focus only on direct effects of climate on disease ecology while more distal effects on society's capacity to control and prevent vector-borne disease are ignored. There is increasing evidence for possible impacts of recent climate change on some vector-borne diseases but for the most part, observed data series are too short (or non-existent), and impacts of climate-independent factors too great, to confidently attribute changing risk to climate change. © Crown copyright 2017.

  19. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    Science.gov (United States)

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  20. Change in Reported Lyme Disease Incidence in the Northeast and Upper Midwest, 1991-2014

    Data.gov (United States)

    U.S. Environmental Protection Agency — This indicator shows how reported Lyme disease incidence has changed by state since 1991, based on the number of new cases per 100,000 people. The total change has...

  1. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease.

    Science.gov (United States)

    Sobol, Urszula; Rodriguez, Tulio; Smith, Scott; Go, Aileen; Vimr, Ross; Parthasarathy, Mala; Guo, Rong; Stiff, Patrick

    2014-06-01

    Abstract Allogeneic transplant using reduced intensity conditioning is a therapeutic option for patients with Hodgkin lymphoma (HL) who relapse after an autograft. This was a prospective study of 31 consecutive eligible patients with HL who relapsed after an autograft and underwent an allograft using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning. At a median follow-up of 7 years the progression-free survival (PFS) was 36% (95% confidence interval [CI] 19-54%) and overall survival (OS) was 42% (95% CI 23-59%). In multivariate analysis only residual disease at the time of transplant predicted outcome, with a 4-year PFS and OS of 62% and 75% for patients with minimal residual disease versus 8% and 8% for patients with gross residual disease, respectively (p = 0.005 and p = 0.001, respectively). This benefit seemed to be irrespective of chemosensitivity, with an OS for patients with chemorefractory yet minimal disease of 71% at 4 years. BEAM allogeneic transplant is effective in producing long-term remissions after autograft failure. Regardless of chemosensitivity, minimizing tumor burden pre-transplant may improve long-term outcome.

  2. Demographic, socioeconomic and environmental changes affecting circulation of neglected tropical diseases in Egypt.

    Science.gov (United States)

    Abou-El-Naga, Iman F

    2015-11-01

    Egypt has been plagued by many neglected tropical diseases since Pharaonic time. These diseases are Schistosomiasis, soil-transmitted helminthiasis, lymphatic filariasis, leishmaniasis and fascioliasis beside the epidermal parasitic skin diseases. Indeed, theses diseases still per