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Sample records for minimal disease application

  1. Minimal change disease

    MedlinePlus

    ... seen under a very powerful microscope called an electron microscope. Minimal change disease is the most common ... biopsy and examination of the tissue with an electron microscope can show signs of minimal change disease.

  2. Minimal residual disease detection using flow cytometry: Applications in acute leukemia.

    PubMed

    Chatterjee, T; Mallhi, R S; Venkatesan, S

    2016-04-01

    Minimal residual disease (MRD) describes disease that can be diagnosed by methodologies other than conventional morphology, and includes molecular methods (like polymerase chain reaction (PCR)) or flow cytometry (FCM). Detection and monitoring of MRD is becoming the standard of care, considering its importance in predicting the treatment outcome. MRD aids in identifying high-risk patients and hence therapy can be intensified in them while deintensification of therapy can prevent long-term sequelae of chemotherapy in low-risk category. FCM is considered as a less labor-intensive and faster MRD technique as compared to PCR although it has its own share of disadvantages. Current immune-based methodologies for detection of MRD depend on establishing leukemia-associated aberrant immunophenotype (LAIP), at diagnosis or relapse and use this information at specified time points for detection of MRD, or apply a standardized panel of antibody combinations for all MRD cases, in a different-from-normal approach. This review highlights MRD detection by FCM and its application in acute leukemia.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Minimally Invasive Surgery for Inflammatory Bowel Disease

    PubMed Central

    Holder-Murray, Jennifer; Marsicovetere, Priscilla

    2015-01-01

    Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341

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

    PubMed

    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.

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

    PubMed

    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 minimal residual disease and 45 patients with high (> 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

  7. Minimal change disease: a CD80 podocytopathy?

    PubMed

    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.

  8. The application of CD73 in minimal residual disease monitoring using flow cytometry in B-cell acute lymphoblastic leukemia.

    PubMed

    Wang, Wei; Gao, Li; Li, Yan; Li, Zhen-Ling; Gong, Ming; Huang, Fan-Zhou; Chen, Yan-Rong; Zhang, Chun-Xia; Gao, Ya-Yue; Ma, Yi-Gai

    2016-05-01

    The expression of CD73 by flow cytometry (FC) in bone marrow (BM) specimens of B-cell acute lymphoblastic leukemia (B-ALL) with or without minimal residual disease (MRD) was studied, and its advantages were evaluated using the MRD assay. This study also detected the expression profile of CD73 in hematogones and mature B cells in BM specimens of 18 healthy donors. Results showed that the mean value of CD73 expression in MRD-positive B cells was 6-fold greater than that in the MRD negative ones. Also, 41.82% MRD-positive B-ALL cases expressed high CD73 and the sensitivity of CD73-based MRD detection reached 10(-4). Since the expression of CD73 increases with the maturation of normal B cells, it is better to mix it with CD34, CD10 and CD20 in one tube to prevent the disturbance of mature B cells. CD73 is recommended as an optional MRD marker for B-ALL patients by using FC.

  9. Multiple myeloma, immunotherapy and minimal residual disease.

    PubMed

    Kusenda, J; Kovarikova, A

    2016-01-01

    Multiple myeloma (MM) is an incurable heterogeneous hematological malignancy in which relapse is characterized by re-growth of residual tumor and immune suppression with a complex biology that affects many aspects of the disease and its response to treatment. The bone marrow microenvironment, including immune cells, plays a central role in MM pathogenesis, survival, and drug resistance. The advances in basic and translational research, introduction of novel agents, particularly combination therapies, improved indicators of quality of life and survival. Minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) has revolutionized monitoring of treatment response in MM. The importance of MFC methodology will be further strengthened by the ongoing international standardization efforts. Results of MRD testing provide unique and clinically important information and demonstrated the prognostic significance of MRD in patients, leading to regulate treatment intensity in many contemporary protocols. In this review, we will summarize the principal approaches in MM immunotherapy, focusing how new agents have potential in the treatment of MM and application of MRD detection by MFC as a surrogate endpoint would allow quicker evaluation of treatment outcomes and rapid identification of effective new therapies.

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

    PubMed

    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. PMID:27440038

  11. Minimal disease activity in Gaucher disease: criteria for definition.

    PubMed

    Di Rocco, Maja; Andria, Generoso; Bembi, Bruno; Carubbi, Francesca; Giona, Fiorina; Giuffrida, Gaetano; Linari, Silvia; Sibilio, Michelina; Spina, Vincenzo; Cappellini, Maria Domenica

    2012-11-01

    Gaucher disease type I is a metabolic disorder caused by a genetic deficiency of lysosomal β-glucocerebrosidase that leads to accumulation of glucocerebroside in macrophages, thus causing damage in different organ systems. Enzyme replacement therapy with imiglucerase improves organ impairment and clinical manifestations, but patients differ in response to treatment. While clinical remission is the most desirable therapeutic outcome, a more realistic goal in patients with high disease burden is reasonably good clinical status despite persistence of residual biochemical or imaging abnormalities. Therefore, the concept of minimal disease activity--used in certain haematological or rheumatologic conditions--needs to be introduced in Gaucher disease, with a level of disease activity that patients and physicians consider a useful treatment target. In this paper, we propose specific parameters and criteria for defining minimal disease activity in Gaucher disease and its stability over time, based on three major systemic domains typically involved: haematological, visceral, and skeletal. Biomarker parameters were not included as criteria, because currently they do not adequately reflect disease evolution in individual patients. Neurological and respiratory domains were also excluded, as their involvement per se indicates severe disease unlikely to respond to enzyme replacement therapy and achieve minimal disease status. Our goal in defining minimal disease activity and stability is to identify a tool to facilitate treatment decisions in clinical practice. PMID:22954583

  12. The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

    PubMed

    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

  13. The Challenge of Producing Skin Test Antigens with Minimal Resources Suitable for Human Application against a Neglected Tropical Disease; Leprosy

    PubMed Central

    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

  14. Minimal-change disease secondary to etanercept.

    PubMed

    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.

  15. Minimal residual disease in acute promyelocytic leukemia.

    PubMed

    Weil, S C

    2000-03-01

    In the last decade our understanding of acute promyelocytic leukemia (APL) has advanced tremendously. The recognition of all-trans retinoic acid (ATRA) as a powerful therapeutic agent paralleled the cloning of the t(15;17) breakpoint. RtPCR for the PML-RARA hybrid mRNA has become the hallmark of molecular diagnosis and molecular monitoring in APL. Current techniques are useful in predicting complete remission and a possible cure in many patients who repeatedly test negative by PCR. Standardizing techniques and improving the sensitivity of the assay are important. Doing this in a way so that clinically relevant minimal residual disease can be distinguished from "indolent disease" remains among the future challenges in APL. PMID:10702899

  16. Minimally invasive surgery for thyroid eye disease.

    PubMed

    Naik, Milind Neilkant; Nair, Akshay Gopinathan; Gupta, Adit; Kamal, Saurabh

    2015-11-01

    Thyroid eye disease (TED) can affect the eye in myriad ways: proptosis, strabismus, eyelid retraction, optic neuropathy, soft tissue changes around the eye and an unstable ocular surface. TED consists of two phases: active, and inactive. The active phase of TED is limited to a period of 12-18 months and is mainly managed medically with immunosuppression. The residual structural changes due to the resultant fibrosis are usually addressed with surgery, the mainstay of which is orbital decompression. These surgeries are performed during the inactive phase. The surgical rehabilitation of TED has evolved over the years: not only the surgical techniques, but also the concepts, and the surgical tools available. The indications for decompression surgery have also expanded in the recent past. This article discusses the technological and conceptual advances of minimally invasive surgery for TED that decrease complications and speed up recovery. Current surgical techniques offer predictable, consistent results with better esthetics.

  17. Technology applications for radioactive waste minimization

    SciTech Connect

    Devgun, J.S.

    1994-07-01

    The nuclear power industry has achieved one of the most successful examples of waste minimization. The annual volume of low-level radioactive waste shipped for disposal per reactor has decreased to approximately one-fifth the volume about a decade ago. In addition, the curie content of the total waste shipped for disposal has decreased. This paper will discuss the regulatory drivers and economic factors for waste minimization and describe the application of technologies for achieving waste minimization for low-level radioactive waste with examples from the nuclear power industry.

  18. [Significance of Minimal Residual Disease in Chronic Lymphocytic Leukemia].

    PubMed

    Doubek, M

    2015-01-01

    Newly introduced highly effective treatment options increase the importance of minimal residual disease measurement in chronic lymphocytic leukemia. Minimal residual disease is gaining interest mainly as a predictive marker; however, clinical significance of minimal residual dis-ease in chronic lymphocytic leukemia in many different situations remains unresolved. Factors with a possible impact on the clinical significance of minimal residual disease are as follows: technique for minimal residual disease quantification, treatment regimen, peripheral blood vs. bone marrow analysis or time -point for sampling. Highly sensitive methods now available to evaluate minimal residual disease can detect a single chronic lymphocytic leukemia cell in 10(-4)- 10(-5) leukocytes using either allele -specific oligonucleotide polymerase chain reaction or multicolor flow cytometry. Minimal residual disease quantification as a surrogate marker to assess treatment efficacy in routine hematological practice has to be further evaluated.

  19. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD, the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help clarifying the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  20. Application of Self-Quenched JH Consensus Primers for Real-Time Quantitative PCR of IGH Gene to Minimal Residual Disease Evaluation in Multiple Myeloma

    PubMed Central

    Martinez-Lopez, Joaquin; Martinez-Sanchez, Pilar; Garcia-Sanz, Ramon; Sarasquete, Maria Eugenia; Ayala, Rosa; Gonzalez, Marcos; Bautista, Jose Manuel; Gonzalez, David; Miguel, Jesus San; Garcia-Effron, Guillermo; Lahuerta, Juan Jose

    2006-01-01

    Monitoring multiple myeloma patients for relapse requires sensitive methods to measure minimal residual disease and to establish a more precise prognosis. The present study aimed to standardize a real-time quantitative polymerase chain reaction (PCR) test for the IgH gene with a JH consensus self-quenched fluorescence reverse primer and a VDJH or DJH allele-specific sense primer (self-quenched PCR). This method was compared with allele-specific real-time quantitative PCR test for the IgH gene using a TaqMan probe and a JH consensus primer (TaqMan PCR). We studied nine multiple myeloma patients from the Spanish group treated with the MM2000 therapeutic protocol. Self-quenched PCR demonstrated sensitivity of ≥10−4 or 16 genomes in most cases, efficiency was 1.71 to 2.14, and intra-assay and interassay reproducibilities were 1.18 and 0.75%, respectively. Sensitivity, efficiency, and residual disease detection were similar with both PCR methods. TaqMan PCR failed in one case because of a mutation in the JH primer binding site, and self-quenched PCR worked well in this case. In conclusion, self-quenched PCR is a sensitive and reproducible method for quantifying residual disease in multiple myeloma patients; it yields similar results to TaqMan PCR and may be more effective than the latter when somatic mutations are present in the JH intronic primer binding site. PMID:16825510

  1. Eliminating Hairy Cell Leukemia Minimal Residual Disease

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

  2. Prognostic relevance of minimal residual disease in colorectal cancer.

    PubMed

    Bork, Ulrich; Grützmann, Robert; Rahbari, Nuh N; Schölch, Sebastian; Distler, Marius; Reissfelder, Christoph; Koch, Moritz; Weitz, Jürgen

    2014-08-14

    Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options.

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

    PubMed

    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.

  4. [Evaluation of minimal residual disease using allele (mutation) -specific PCR].

    PubMed

    Matsuda, Kazuyuki

    2014-06-01

    For patients with hematological malignancies, monitoring minimal residual disease (MRD) provides useful information to evaluate the therapeutic response and risk of relapse. The currently available quantitative MRD assays are fluorescence in situ hybridization of chromosomal aberrations, multiparameter flow cytometry of leukemia-associated immunophenotypes, and quantitative polymerase chain reaction (qPCR) analysis of fusion genes, immunoglobulin/T-cell receptor gene rearrangements, genetic alterations, or over-expressed genes. Single nucleotide mutations associated with leukemogenesis can be considered as applicable MRD markers. Allele-specific qPCR (AS-qPCR) using primers including mismatched bases and locked nucleic acids (LNA) can quantify not only the insertion and duplication of several nucleotides, but also single nucleotide mutation in the presence of an excess amount of wild-type nucleotides. The AS-qPCR for analyzing single nucleotide mutations contributes to the monitoring of MRD in patients without recurrent fusion genes throughout the clinical course and, thus, broadens the spectrum of patients in whom MRD can be monitored. In addition to the evaluation of MRD, AS-qPCR can provide insight into the development of leukemia and the sequential acquisition of gene mutations.

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

    PubMed Central

    Zoccali, Marco; Fichera, Alessandro

    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. PMID:23239913

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

    PubMed

    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.

  7. Minimally invasive treatment of Peyronie's disease: evidence-based progress.

    PubMed

    Jordan, Gerald H; Carson, Culley C; Lipshultz, Larry I

    2014-07-01

    Peyronie's disease (PD) is often physically and psychologically devastating for patients, and the goal of treatment is to improve symptoms and sexual function without adding treatment-related morbidity. The potential for treatment-related morbidity after more invasive interventions, e.g. surgery, creates a need for effective minimally invasive treatments. We critically examined the available literature using levels of evidence to determine the reported support for each treatment. Most available minimally invasive treatments lack critical support for effectiveness due to the absence of randomised, placebo-controlled trials (RCTs) or non-significant results after RCTs. Iontophoresis, oral therapies (vitamin E, potassium para-aminobenzoate, tamoxifen, carnitine, and colchicine), extracorporeal shockwave therapy, and intralesional injection with verapamil or nicardipine have shown mixed or negative results. Treatments that have decreased penile curvature deformity in Level 1 or Level 2 evidence-based, placebo-controlled studies include intralesional injection with interferon α-2b or collagenase clostridium histolyticum.

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

    PubMed

    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.

  9. Cord-Blood Transplantation in Patients with Minimal Residual Disease.

    PubMed

    Milano, Filippo; Gooley, Ted; Wood, Brent; Woolfrey, Ann; Flowers, Mary E; Doney, Kristine; Witherspoon, Robert; Mielcarek, Marco; Deeg, Joachim H; Sorror, Mohamed; Dahlberg, Ann; Sandmaier, Brenda M; Salit, Rachel; Petersdorf, Effie; Appelbaum, Frederick R; Delaney, Colleen

    2016-09-01

    Background The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources. Methods In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98). Results The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P=0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P=0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P=0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P=0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P=0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P=0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P=0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P=0.46). Conclusions Our data suggest that among patients with pretransplantation minimal

  10. Cord-Blood Transplantation in Patients with Minimal Residual Disease.

    PubMed

    Milano, Filippo; Gooley, Ted; Wood, Brent; Woolfrey, Ann; Flowers, Mary E; Doney, Kristine; Witherspoon, Robert; Mielcarek, Marco; Deeg, Joachim H; Sorror, Mohamed; Dahlberg, Ann; Sandmaier, Brenda M; Salit, Rachel; Petersdorf, Effie; Appelbaum, Frederick R; Delaney, Colleen

    2016-09-01

    Background The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources. Methods In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98). Results The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P=0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P=0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P=0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P=0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P=0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P=0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P=0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P=0.46). Conclusions Our data suggest that among patients with pretransplantation minimal

  11. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    PubMed Central

    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. PMID:24527240

  12. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; 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 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. PMID:26258081

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

    PubMed

    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.

  14. Minimal change disease onset observed after bevacizumab administration.

    PubMed

    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.

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

    PubMed

    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.

  16. [Prognostic value of minimal residual disease detection in multiple myeloma].

    PubMed

    Takamatsu, Hiroyuki

    2015-01-01

    Minimal residual disease (MRD) detection methods are important for diagnosis, treatment, and prognosis in multiple myeloma (MM), and include serum free-light chain assay, multiparametric flow cytometry (with ≥ 4 colors; sensitivity ≤ 10(-4)), allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR; sensitivity 10(-5)), and next-generation sequencing (NGS; sensitivity ≤ 10(-6)). Although molecular complete remission in MM can be assessed by ASO-PCR, this technique requires preparation of clonotype-pecific primers for each individual, which is both labor- and time-consuming. The use of NGS for MRD detection in MM provides increased sensitivity and specificity, while overcoming the challenges associated with ASO-PCR. Furthermore, MRD-negativity revealed by NGS is more closely associated with durable remission of MM than that revealed by ASO -PCR.

  17. Should minimal residual disease guide therapy in AML?

    PubMed

    Paietta, Elisabeth

    2015-01-01

    The prognostic power of minimal residual disease after therapy for acute leukemias is not in question. It is only logical that the finding of leukemic blast cells after therapy predicts for impending relapse or at least the need for additional treatment. Which level of what is called minimal residual disease (MRD) is clinically relevant, however, depends on the efficacy of the initial treatment as well as the treatment strategies available to target MRD. There are a multitude of additional factors that can alter the clinical significance of MRD, including the genotype of the patient's leukemic cells. The fact that methodologies of MRD detection are not standardized and thresholds for defining MRD positivity vary depending upon MRD detection method and the operator's skills or convictions only add to the complexity of MRD interpretation. While enormous efforts are devoted to enhancing the sensitivity of MRD detection, eg, by next-generation sequencing, improvements of methods for detecting MRD per se will not automatically lead to a more reliable estimation of total tumor burden. Most importantly, even the best assay will yield accurate MRD results only if the tissue source for MRD determination is of good quality. Another aspect of potentially crucial importance is the heterogenous distribution of leukemic cells throughout the skeleton after treatment, recently demonstrated for acute myeloid leukemia (AML) by bone marrow imaging. Once technical difficulties of MRD measurement are resolved and better MRD-targeting drugs are developed, we still need to learn about alternate proposed mechanisms to explain MRD-independent prognostication, well described in acute lymphoid leukemia, before MRD can be included routinely in the guidance of therapy in AML.

  18. Minimal Residual Disease Assessment in the Context of Multiple Myeloma Treatment.

    PubMed

    Nishihori, Taiga; Song, Jinming; Shain, Kenneth H

    2016-04-01

    With contemporary therapeutic strategies in multiple myeloma, heretofore unseen depth and rate of responses are being achieved. These strategies have paralleled improvements in outcome of multiple myeloma patients. The integration of the next generation of proteasome inhibitors and antibody therapeutics promise continued improvements in therapy with the expectation of consistent depth of response not quantifiable by current clinical methods. As such, there is a growing need to develop adequate tools to evaluate deeper disease response after therapy and to refine the response criteria including the minimal residual disease. Several emerging techniques are being evaluated for these purposes including multi-parameter flow cytometry, allele-specific oligonucleotide polymerase chain reaction, next-generation sequencing, and imaging modalities. In this review, we highlight the recent developments and evaluate advantages and limitations of the current technologies to assess minimal residual disease. We also discuss future applications of these methodologies in potentially guiding multiple myeloma treatment decisions.

  19. Cell biology and genetics of minimal change disease.

    PubMed

    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.

  20. Cell biology and genetics of minimal change disease

    PubMed Central

    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

  1. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  2. MINIMAL RESIDUAL DISEASE QUANTITATION IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Shook, David; Coustan-Smith, Elaine; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Campana, Dario

    2009-01-01

    The prognosis for patients with acute myeloid leukemia (AML) is heterogeneous. A minority of patients has clinical and biologic features that are associated with a very high risk of relapse. For the remaining patients no clear prognostic factors can be identified at diagnosis. The degree of treatment response is likely to be an informative predictor of outcome for these patients. Modern assays to detect AML cells that are undetectable by conventional morphologic techniques, i.e. minimal residual disease (MRD), can potentially improve measurements of treatment response. It is plausible that modifications to treatment based on the results of these assays will improve clinical management and ultimately increase cure rates. Established MRD assays for AML are based on either polymerase chain reaction (PCR) amplification of genetic abnormalities or flow cytometric detection of abnormal immunophenotypes. Residual disease and treatment response can be measured by these assays in a manner that is much more sensitive and objective than that afforded by conventional morphologic examination. The expanding use of MRD testing is beginning to change the definition of treatment response and of remission. Other clinically informative uses of MRD testing include the detection of early relapse and the evaluation of the efficacy of new antileukemic agents. PMID:19778853

  3. Principles of minimal residual disease detection for hematopoietic neoplasms by flow cytometry.

    PubMed

    Wood, Brent L

    2016-01-01

    Flow cytometry has become an indispensible tool for the diagnosis and classification of hematopoietic neoplasms. The ability to rapidly distinguish cellular subpopulations via multiparametric assessment of quantitative differences in antigen expression on single cells and enumerate the relative sizes of the resulting subpopulations is a key feature of the technology. More recently, these capabilities have been expanded to include the identification and enumeration of rare subpopulations within complex cellular mixtures, for example, blood or bone marrow, leading to the application for post-therapeutic monitoring or minimal residual disease detection. This review will briefly present the principles to be considered in the construction and use of flow cytometric assays for minimal residual disease detection including the use of informative antibody combinations, the impact of immunophenotypic instability, enumeration, assay sensitivity, and reproducibility.

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

    PubMed

    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.

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

    PubMed

    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

    2016-03-01

    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. (clinicaltrials identifiers: 00209209 and 00209222).

  6. Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies.

    PubMed

    Ommen, Hans Beier

    2016-02-01

    Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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

  10. Minimal change disease in association with fire coral (Millepora species) exposure.

    PubMed

    Prasad, G V Ramesh; Vincent, Lloyd; Hamilton, Robert; Lim, Ki

    2006-01-01

    Numerous agents have been associated with minimal change disease. We describe a previously unreported association in a 45-year-old white woman of scuba diving exposure to fire coral (Millepora species) that was followed by the development of nephrotic syndrome, acute renal failure, pulmonary edema, and intubation. The renal biopsy specimen was consistent with minimal change disease. Institution of corticosteroid therapy resulted in symptomatic improvement and resolution of proteinuria. Physicians, particularly those in scuba-diving areas, should consider minimal change disease in exposed patients with proteinuria because a prompt diagnostic and therapeutic approach may potentially limit complications.

  11. 77 FR 14813 - Public Workshop on Minimal Residual Disease; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... HUMAN SERVICES Food and Drug Administration Public Workshop on Minimal Residual Disease; Public Workshop... residual disease (MRD) as a biomarker for evaluating new drugs for the treatment of acute lymphoblastic...., a measurable characteristic that is predictive of disease outcome) that can be used to...

  12. [THE COMPARISON OF RESULTS OF DETECTION OF MINIMAL RESIDUAL DISEASE IN PERIPHERAL BLOOD AND MARROW IN CHILDREN OF THE FIRST YEAR OF LIFE WITH ACUTE LYMPHOBLASTIC LEUCOSIS].

    PubMed

    Tsaur, G A; Riger, T O; Popov, A M; Nasedkina, T V; Kustanovich, A M; Solodovnikov, A G; Streneva, O V; Shorikov, E V; Tsvirenko, S V; Saveliev, L I; Fechina, L G

    2015-04-01

    The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic

  13. Critical methodological factors in diagnosing minimal residual disease in hematological malignancies using quantitative PCR.

    PubMed

    Nyvold, Charlotte Guldborg

    2015-05-01

    Hematological malignancies are a heterogeneous group of cancers with respect to both presentation and prognosis, and many subtypes are nowadays associated with aberrations that make up excellent molecular targets for the quantification of minimal residual disease. The quantitative PCR methodology is outstanding in terms of sensitivity, specificity and reproducibility and thus an excellent choice for minimal residual disease assessment. However, the methodology still has pitfalls that should be carefully considered when the technique is integrated in a clinical setting.

  14. Trial of a minimal-risk botanical compound to control the vector tick of Lyme disease.

    PubMed

    Rand, Peter W; Lacombe, Eleanor H; Elias, Susan P; Lubelczyk, Charles B; St Amand, Theodore; Smith, Robert P

    2010-07-01

    We compared the application of IC2, a minimal-risk (25B) botanical compound containing 10% rosemary oil, with bifenthrin, a commonly used synthetic compound, and with water for the control of Ixodes scapularis Say (= Ixodes dammini Spielman, Clifford, Piesman & Corwin), on tick-infested grids in Maine, in an area where Lyme disease is established and other tick-borne diseases are emerging. High-pressure sprays of IC2, bifenthrin, and water were applied during the peak nymphal (July) and adult (October) seasons of the vector tick. No ticks could be dragged on the IC2 grids within 2 wk of the July spray, and few adult ticks were found in October or the following April. Similarly, no adult ticks could be dragged 1.5 wk after the October IC2 spray, and few the following April. No ticks were found on the bifenthrin grids after either spray through the following April, whereas substantial numbers of ticks remained throughout on the grids sprayed with water. Thus, IC2 appears to be an effective, minimum-risk acaricide to control the vector tick of Lyme disease.

  15. A minimally invasive microchip for transdermal injection/sampling applications.

    PubMed

    Strambini, Lucanos M; Longo, Angela; Diligenti, Alessandro; Barillaro, Giuseppe

    2012-09-21

    The design, fabrication, and characterization of a minimally invasive silicon microchip for transdermal injection/sampling applications are reported and discussed. The microchip exploits an array of silicon-dioxide hollow microneedles with density of one million needles cm(-2) and lateral size of a few micrometers, protruding from the front-side chip surface for one hundred micrometers, to inject/draw fluids into/from the skin. The microneedles are in connection with independent reservoirs grooved on the back-side of the chip. Insertion experiments of the microchip in skin-like polymers (agarose hydrogels with concentrations of 2% and 4% wt) demonstrate that the microneedles successfully withstand penetration without breaking, despite their high density and small size, according to theoretical predictions. Operation of the microchip with different liquids of biomedical interest (deionized water, NaCl solution, and d-glucose solution) at different differential pressures, in the range 10-100 kPa, highlights that the flow-rate through the microneedles is linearly dependent on the pressure-drop, despite the small section area (about 13 μm(2)) of the microneedle bore, and can be finely controlled from a few ml min(-1) up to tens of ml min(-1). Evaporation (at room temperature) and acceleration (up to 80 g) losses through the microneedles are also investigated to quantify the ability of the chip in storing liquids (drug to be delivered or collected fluid) in the reservoir, and result to be of the order of 70 nl min(-1) and 1300 nl min(-1), respectively, at atmospheric pressure and room temperature. PMID:22773092

  16. A minimally invasive microchip for transdermal injection/sampling applications.

    PubMed

    Strambini, Lucanos M; Longo, Angela; Diligenti, Alessandro; Barillaro, Giuseppe

    2012-09-21

    The design, fabrication, and characterization of a minimally invasive silicon microchip for transdermal injection/sampling applications are reported and discussed. The microchip exploits an array of silicon-dioxide hollow microneedles with density of one million needles cm(-2) and lateral size of a few micrometers, protruding from the front-side chip surface for one hundred micrometers, to inject/draw fluids into/from the skin. The microneedles are in connection with independent reservoirs grooved on the back-side of the chip. Insertion experiments of the microchip in skin-like polymers (agarose hydrogels with concentrations of 2% and 4% wt) demonstrate that the microneedles successfully withstand penetration without breaking, despite their high density and small size, according to theoretical predictions. Operation of the microchip with different liquids of biomedical interest (deionized water, NaCl solution, and d-glucose solution) at different differential pressures, in the range 10-100 kPa, highlights that the flow-rate through the microneedles is linearly dependent on the pressure-drop, despite the small section area (about 13 μm(2)) of the microneedle bore, and can be finely controlled from a few ml min(-1) up to tens of ml min(-1). Evaporation (at room temperature) and acceleration (up to 80 g) losses through the microneedles are also investigated to quantify the ability of the chip in storing liquids (drug to be delivered or collected fluid) in the reservoir, and result to be of the order of 70 nl min(-1) and 1300 nl min(-1), respectively, at atmospheric pressure and room temperature.

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

    PubMed Central

    Castro, Josué Viana; Melo, Emanuel Carvalho; Silva, Juliana Fernandes; Rebouças, Leonardo Lemos; Corrêa, Larissa Chagas; Germano, Amanda de Queiroz; Machado, João José Aquino

    2014-01-01

    Background Minimally invasive cardiovascular procedures have been progressively used in heart surgery. Objective To describe the techniques and immediate results of minimally invasive procedures in 5 years. Methods 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. Results 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. Conclusion 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. PMID:24553983

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

    PubMed Central

    Neumann, Philipp-Alexander; Rijcken, Emile

    2016-01-01

    Patients with inflammatory bowel disease (IBD) comprise 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 best postoperative 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, interenteric fistula, abscesses, malnutrition, repetitive surgeries, 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. PMID:27158537

  19. Minimally invasive surgery for paediatric inflammatory bowel disease: Personal experience and literature review

    PubMed Central

    Pini-Prato, Alessio; Faticato, Maria Grazia; Barabino, Arrigo; Arrigo, Serena; Gandullia, Paolo; Mazzola, Cinzia; Disma, Nicola; Montobbio, Giovanni; Mattioli, Girolamo

    2015-01-01

    The incidence of paediatric inflammatory bowel disease (PIBD) has dramatically increased in the last 20 years. Although first reported in mid 1970s’, diagnostic laparoscopy has started to be routinely adopted in paediatric surgical practice since late 1990s’. Minimally invasive surgery was first limited to diagnostic purposes. After 2002 it was also applied to the radical treatment of PIBD, either Crohn’s disease (CD) or Ulcerative colitis. During the last decade minimally invasive approaches to PIBD have gained popularity and have recently became the “gold standard” for the treatment of such invalidating and troublesome chronic diseases. The authors describe and track the historical evolution of minimally invasive surgery for PIBD and address all available opportunities, including most recent advancements such as robotic surgery, single port approaches and minimally invasive treatment of perianal fistulising CD. A systematic review of all series of PIBD treated with minimally invasive approaches published so far is provided in order to determine the incidence and type of patients’ complications reported up to present days. The authors also describe their experience with minimally invasive surgery for PIBD and will report the results of 104 laparoscopic procedures performed in a series of 61 patients between January 2006 and December 2014. PMID:26525138

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

    PubMed

    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. Effective chromatic texture coding for robust skin disease minimal descriptor quantification

    NASA Astrophysics Data System (ADS)

    Fiorini, Rodolfo A.; Crivellini, M.; Codagnone, G.; Dacquino, Gianfranco F.; Libertini, M.; Morresi, A.

    1997-04-01

    Among the various skin diseases skin tumors are the most serious ones and skin melanoma is particularly dangerous. Its malignant evolution lasts about 5 or 6 years and ends with the death of the patient. Early diagnosis is a powerful means of preventing this evolution allowing sudden intervention which increases probability of recover and survival. Purpose of this paper is to present an active support system (ASS) able to reveal and quantify the stage of disease evolution. The work focuses the problem encountered in chromatic information encoding the morphological aspects quantification. A new method is proposed which permits robust and reliable quantification of image data obtained via a digital epiluminescence dermatoscopy apparatus (DELM) designed and built with interesting new features. The image information extraction is based on minimal descriptor set of parameters in order to classify chromatic texture and morphological features. The active support systems is based on DELM technique, taking advantage of polarized light guided by optical fibers. In the purpose to discriminate between malignant and benign melanocytic lesions, several dermatoscopical features have been proposed by different research groups. Nevertheless many are the attempts to reach a reliable and objective classification procedure. We adopt, as reference, the approach used by Stanganelli and Kenet. Through a bioengineering analysis we can organize reference grids that offer the possibility to extract the maximum information content from dermatological data. The classification takes into account the Spread and Intrinsic Descriptors and correspond to the best operative description. Therefore these grids are the more suitable tools for application which require ASS for diagnosis. In fact it is possible to obtain quantitative evaluations too. We propose a method based on geometrical synthetical descriptors. All that permits a reliable early diagnosis of melanotic disease and to follow its

  2. Applications of minimal physiologically-based pharmacokinetic models

    PubMed Central

    Cao, Yanguang

    2012-01-01

    Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available. Such models depend on the quality of the drug disposition data and have vague biological features. An alternative minimal-physiologically-based PK (minimal-PBPK) modeling approach is proposed which inherits and lumps major physiologic attributes from whole-body PBPK models. The body and model are represented as actual blood and tissue usually total body weight) volumes, fractions (fd) of cardiac output with Fick’s Law of Perfusion, tissue/blood partitioning (Kp), and systemic or intrinsic clearance. Analyzing only blood or plasma concentrations versus time, the minimal-PBPK models parsimoniously generate physiologically-relevant PK parameters which are more easily interpreted than those from mam-millary models. The minimal-PBPK models were applied to four types of therapeutic agents and conditions. The models well captured the human PK profiles of 22 selected beta-lactam antibiotics allowing comparison of fitted and calculated Kp values. Adding a classical hepatic compartment with hepatic blood flow allowed joint fitting of oral and intravenous (IV) data for four hepatic elimination drugs (dihydrocodeine, verapamil, repaglinide, midazolam) providing separate estimates of hepatic intrinsic clearance, non-hepatic clearance, and pre-hepatic bioavailability. The basic model was integrated with allometric scaling principles to simultaneously describe moxifloxacin PK in five species with common Kp and fd values. A basic model assigning clearance to the tissue compartment well characterized plasma concentrations of six monoclonal antibodies in human subjects, providing good concordance of predictions with expected tissue kinetics. The proposed minimal-PBPK modeling approach offers an alternative and more rational basis for assessing PK than compartmental models. PMID:23179857

  3. Epizootic Infection of a Minimal Disease Swine Herd with a Herpesvirus

    PubMed Central

    Orr, James P.; Althouse, Elizabeth; Dulac, Gilles C.; Durham, Peter J.K.

    1988-01-01

    A totally confined, farrow-to-finish, closed, minimal disease herd of pigs experienced high death and reproductive losses during a disease outbreak lasting five weeks, and during the ensuing three months. The losses were caused by infection of pigs of all ages with a herpesvirus, with devastating effects on the lungs of immature pigs and on the reproductive performance of the sows. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:17422946

  4. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia.

    PubMed

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-07-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348.

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

    PubMed Central

    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

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

    PubMed

    Martinez-Lopez, Joaquin; 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

    2014-05-15

    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).

  7. Minimal residual disease in canine lymphoma: An objective marker to assess tumour cell burden in remission.

    PubMed

    Sato, Masahiko; Yamazaki, Jumpei; Goto-Koshino, Yuko; Setoguchi, Asuka; Takahashi, Masashi; Baba, Kenji; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

    2016-09-01

    Lymphoma is the most common haematopoietic malignancy in dogs. Since a high proportion of dogs with lymphoma achieve remission soon after initiation of chemotherapy, an objective marker assessing treatment efficacy is required. Following clinical remission, the residual population of tumour cells can be referred to as the minimal residual disease (MRD). MRD traditionally has been detected by cytology and flow cytometry; however, if the burden of malignant cells is low, these methods might not be sufficiently sensitive to detect MRD. As an extension of the development of PCR for antigen receptor gene rearrangements (PARR) in dogs, there has been recent progress in the application of real-time quantitative PCR (RT-qPCR) to canine lymphoma. With the RT-qPCR system, a very high sensitivity (1 cell per 10,000 cells) has been achieved by preparing allele-specific oligonucleotide primers and probes designed from neoplastic clones of each dog. A series of MRD diagnostics studies employing the RT-qPCR system has revealed its usefulness as a prognostic indicator, an objective marker of treatment efficacy and a predictor of relapse for dogs with lymphoma receiving chemotherapy. Introduction of the MRD monitoring system will provide an innovative scientific tool in the development of superior treatments and monitoring strategies for canine lymphoma.

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

    PubMed Central

    van der Velden, Vincent H. J.; Brüggemann, Monika; Orfao, Alberto

    2015-01-01

    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. PMID:25999452

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

    PubMed

    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 < 0.05). The prevalence of GERD in asthmatic patients (69.2%) was higher than that in 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.

  10. Minimizing masses in explosively driven two-shockwave physics applications

    NASA Astrophysics Data System (ADS)

    Buttler, William; Cherne, Frank; Furlanetto, Michael; Payton, Jeremy; Stone, Joseph; Tabaka, Leonard; Vincent, Samuel

    2015-06-01

    We have experimentally investigated different two-shockwave high-explosives (HE) physics package designs to maximize the variability of the second shockwave peak stress, while minimizing the total HE load of the physics tool. A critical requirement is to also have a large radial diameter of the second shockwave to maintain its value as an HE driven two-shockwave drive. We have previously shown that we could vary the peak-stress of the second-shockwave with a 76 mm diameter HE lens driving different composite boosters of PBX 9501 and TNT. Here we report on our results with a 56- and 50-mm diameter HE lens driving Baritol. The results indicate that the 56-mm diameter HE lens works well, as does the Baritol, giving total HE loads of about 250 mg TNT equivalent explosives.

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

    SciTech Connect

    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. )

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  15. Minimal form factor digital-image sensor for endoscopic applications

    NASA Astrophysics Data System (ADS)

    Wäny, Martin; Voltz, Stephan; Gaspar, Fabio; Chen, Lei

    2009-02-01

    This paper presents a digital image sensor SOC featuring a total chip area (including dicing tolerances) of 0.34mm2 for endoscopic applications. Due to this extremely small form factor the sensor enables integration in endoscopes, guide wires and locater devices of less than 1mm outer diameter. The sensor embeds a pixel matrix of 10'000 pixels with a pitch of 3um x 3um covered with RGB filters in Bayer pattern. The sensor operates fully autonomous, controlled by an on chip ring oscillator and readout state machine, which controls integration AD conversion and data transmission, thus the sensor only requires 4 pin's for power supply and data communication. The sensor provides a frame rate of 40Frames per second over a LVDS serial data link. The endoscopic application requires that the sensor must work without any local power decoupling capacitances at the end of up to 2m cabling and be able to sustain data communication over the same wire length without deteriorating image quality. This has been achieved by implementation of a current mode successive approximation ADC and current steering LVDS data transmission. An band gap circuit with -40dB PSRR at the data frequency was implemented as on chip reference to improve robustness against power supply ringing due to the high series inductance of the long cables. The B&W versions of the sensor provides a conversion gain of 30DN/nJ/cm2 at 550nm with a read noise in dark of 1.2DN when operated at 2m cable. Using the photon transfer method according to EMVA1288 standard the full well capacity was determined to be 18ke-. According to our knowledge the presented work is the currently world smallest fully digital image sensor. The chip was designed along with a aspheric single surface lens to assemble on the chip without increasing the form factor. The extremely small form factor of the resulting camera permit's to provide visualization with much higher than state of the art spatial resolution in sub 1mm endoscopic

  16. Minimal Technologies Application Project, Hohenfels Training Area, Germany: Final report

    SciTech Connect

    Zellmer, S.D.; Hinchman, R.R.; Johnson, D.O.; Severinghaus, W.D.; Brent, J.J.

    1991-12-01

    At the US Army Hohenfels Training Area in Germany, more than 30 years of continuous and intensive tactical training has caused extensive environmental damage because of the loss of vegetative cover and accelerated soil erosion. A project was conducted to evaluate the cost-effectiveness and relative benefits of various revegetation procedures. These procedures involved amendment and seedbed preparation options that were combined with three different durations of site closure. The point-intercept method was used to measure the types and amounts of vegetation established and changes in the vegetative community. Over three growing seasons, applications of fertilizer and seed increased the percent grass, legume, and total vegetative cover. The duration of site closure had no influence on the types or amounts of ground cover established. Materials made up only 10% of the total cost of the fertilization and seeding operations. The results of the research indicate that less expensive methods of amendment application should be evaluated. The data also show that site closure is not practical, economical, or necessary. The results of this project suggest that a regular maintenance program consisting of seeding and fertilization is required to maintain adequate vegetative cover and control erosion on tactical training areas.

  17. Virtual reality applications in improving postural control and minimizing falls.

    PubMed

    Virk, Sumandeep; McConville, Kristiina M Valter

    2006-01-01

    Maintaining balance under all conditions is an absolute requirement for humans. Orientation in space and balance maintenance requires inputs from the vestibular, the visual, the proprioceptive and the somatosensory systems. All the cues coming from these systems are integrated by the central nervous system (CNS) to employ different strategies for orientation and balance. How the CNS integrates all the inputs and makes cognitive decisions about balance strategies has been an area of interest for biomedical engineers for a long time. More interesting is the fact that in the absence of one or more cues, or when the input from one of the sensors is skewed, the CNS "adapts" to the new environment and gives less weight to the conflicting inputs [1]. The focus of this paper is a review of different strategies and models put forward by researchers to explain the integration of these sensory cues. Also, the paper compares the different approaches used by young and old adults in maintaining balance. Since with age the musculoskeletal, visual and vestibular system deteriorates, the older subjects have to compensate for these impaired sensory cues for postural stability. The paper also discusses the applications of virtual reality in rehabilitation programs not only for balance in the elderly but also in occupational falls. Virtual reality has profound applications in the field of balance rehabilitation and training because of its relatively low cost. Studies will be conducted to evaluate the effectiveness of virtual reality training in modifying the head and eye movement strategies, and determine the role of these responses in the maintenance of balance. PMID:17946975

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

    PubMed

    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.

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

    PubMed

    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.

  20. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL.

    PubMed

    Thompson, Philip A; Wierda, William G

    2016-01-21

    Deep remission and prolonged disease-free survival can be achieved with first-line chemoimmunotherapy (CIT), such as combined fludarabine, cyclophosphamide, and rituximab, in the majority of patients with chronic lymphocytic leukemia (CLL). More modest results are reported with less intense regimens like obinutuzumab plus chlorambucil. Clinical assessment has limited sensitivity in detecting residual disease responsible for subsequent relapse, even including morphologic bone marrow (BM) evaluation. Multicolor flow cytometry and polymerase chain reaction (PCR)-based methods can detect minimal residual disease (MRD) to a sensitivity of ≥1:10,000 (10(-4)). Achieving BM MRD-negative complete remission (CR) is associated with superior progression-free survival (PFS) and overall survival; MRD status is the single best posttreatment predictor of long-term outcomes after CIT. Newer oral B-cell receptor signaling pathway inhibitors are highly effective at controlling disease, but best monotherapy responses are typically partial remission, and patients must remain on treatment to maintain disease control. Therapeutic progress is still needed for CLL. We propose that targeting MRD provides opportunity to realize this progress. Achieving BM MRD-negative CR is a prerequisite for long-term unmaintained disease-free survival and potential for cure. We review available methodologies for detecting MRD and correlations with posttreatment outcomes. We discuss the potential utility of MRD to direct individualized therapy. Finally, we discuss the importance of MRD-negative status as a surrogate marker for longer PFS in clinical studies to allow more rapid determination of clinical benefit.

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

    PubMed

    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).

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

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

    2016-01-01

    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.

  5. [Shared decision making and minimal disruptive medicine in the management of chronic diseases].

    PubMed

    Zeballos-Palacios, Claudia; Morey-Vargas, Oscar L; Brito, Juan P; Montori, Víctor M

    2014-01-01

    Chronic diseases are the leading cause of morbidity and mortality worldwide. These conditions require considerable time investment and resources from the health system in Peru, as well as from patients and their families. Paradoxically, the developed medical strategies for managing these conditions generate a constant and increasing burden for the patient and their environment, which affects quality of life and therapeutic results. In this article, the role of shared decision making and minimal disruptive medicine will be described as strategies to address these problems. PMID:24718535

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

    PubMed

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

    2016-01-01

    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. PMID:27629965

  7. A new multiple-drug applicator with minimal drug cross-talk, leakage, and consumption.

    PubMed

    Fujita, Yosuke; Shimomura, Takeshi; Hosoguchi, Masafumi; Kano, Masanobu; Fukurotani, Kenkichi; Tabata, Toshihide

    2010-04-01

    The relative effects of multiple drugs give an important clue to dissect a neuronal mechanism and to seek for a candidate neurotherapeutical agent. Here we have devised a "flute" applicator which can deliver several drugs to a neural cell preparation. The applicator stands by, cleaning itself with bath perfusate and delivers drugs only during test applications. This minimizes drug cross-talk in and leakage from the applicator and drug consumption. Using the applicator, we successfully compared the relative effects of widely different doses of an agonist in single neurons. The flute applicator would be a useful tool for pharmacological analyses.

  8. A new multiple-drug applicator with minimal drug cross-talk, leakage, and consumption.

    PubMed

    Fujita, Yosuke; Shimomura, Takeshi; Hosoguchi, Masafumi; Kano, Masanobu; Fukurotani, Kenkichi; Tabata, Toshihide

    2010-04-01

    The relative effects of multiple drugs give an important clue to dissect a neuronal mechanism and to seek for a candidate neurotherapeutical agent. Here we have devised a "flute" applicator which can deliver several drugs to a neural cell preparation. The applicator stands by, cleaning itself with bath perfusate and delivers drugs only during test applications. This minimizes drug cross-talk in and leakage from the applicator and drug consumption. Using the applicator, we successfully compared the relative effects of widely different doses of an agonist in single neurons. The flute applicator would be a useful tool for pharmacological analyses. PMID:20060427

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

    PubMed

    Kumar, Shaji; Paiva, Bruno; Anderson, Kenneth C; Durie, Brian; Landgren, Ola; Moreau, Philippe; Munshi, Nikhil; Lonial, Sagar; Bladé, Joan; Mateos, Maria-Victoria; Dimopoulos, Meletios; Kastritis, Efstathios; Boccadoro, Mario; Orlowski, Robert; Goldschmidt, Hartmut; Spencer, Andrew; Hou, Jian; Chng, Wee Joo; Usmani, Saad Z; Zamagni, Elena; Shimizu, Kazuyuki; Jagannath, Sundar; Johnsen, Hans E; Terpos, Evangelos; Reiman, Anthony; Kyle, Robert A; Sonneveld, Pieter; Richardson, Paul G; McCarthy, Philip; Ludwig, Heinz; Chen, Wenming; Cavo, Michele; Harousseau, Jean-Luc; Lentzsch, Suzanne; Hillengass, Jens; Palumbo, Antonio; Orfao, Alberto; Rajkumar, S Vincent; San Miguel, Jesus; Avet-Loiseau, Herve

    2016-08-01

    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 monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments. PMID:27511158

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

    PubMed

    Kumar, Shaji; Paiva, Bruno; Anderson, Kenneth C; Durie, Brian; Landgren, Ola; Moreau, Philippe; Munshi, Nikhil; Lonial, Sagar; Bladé, Joan; Mateos, Maria-Victoria; Dimopoulos, Meletios; Kastritis, Efstathios; Boccadoro, Mario; Orlowski, Robert; Goldschmidt, Hartmut; Spencer, Andrew; Hou, Jian; Chng, Wee Joo; Usmani, Saad Z; Zamagni, Elena; Shimizu, Kazuyuki; Jagannath, Sundar; Johnsen, Hans E; Terpos, Evangelos; Reiman, Anthony; Kyle, Robert A; Sonneveld, Pieter; Richardson, Paul G; McCarthy, Philip; Ludwig, Heinz; Chen, Wenming; Cavo, Michele; Harousseau, Jean-Luc; Lentzsch, Suzanne; Hillengass, Jens; Palumbo, Antonio; Orfao, Alberto; Rajkumar, S Vincent; San Miguel, Jesus; Avet-Loiseau, Herve

    2016-08-01

    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 monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.

  11. Minimal Clinically Important Difference on Parkinson's Disease Sleep Scale 2nd Version.

    PubMed

    Horváth, Krisztina; Aschermann, Zsuzsanna; Ács, Péter; Deli, Gabriella; Janszky, József; Komoly, Sámuel; Karádi, Kázmér; Kovács, Márton; Makkos, Attila; Faludi, Béla; Kovács, Norbert

    2015-01-01

    Background and Aims. The aim of the present study was to determine the estimates of minimal clinically important difference for Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score and dimensions. Methods. The subject population consisted of 413 PD patients. At baseline, MDS-UPDRS, Hoehn-Yahr Scale, Mattis Dementia Rating Scale, and PDSS-2 were assessed. Nine months later the PDSS-2 was reevaluated with the Patient-Reported Global Impression Improvement Scale. Both anchor-based techniques (within patients' score change method and sensitivity- and specificity-based method by receiver operating characteristic analysis) and distribution-based approaches (effect size calculations) were utilized to determine the magnitude of minimal clinically important difference. Results. According to our results, any improvements larger than -3.44 points or worsening larger than 2.07 points can represent clinically important changes for the patients. These thresholds have the effect size of 0.21 and -0.21, respectively. Conclusions. Minimal clinically important differences are the smallest change of scores that are subjectively meaningful to patients. Studies using the PDSS-2 as outcome measure should utilize the threshold of -3.44 points for detecting improvement or the threshold of 2.07 points for observing worsening.

  12. Barlow’s mitral valve disease: results of conventional and minimally invasive repair approaches

    PubMed Central

    Melnitchouk, Serguei I.; Seeburger, Joerg; Kaeding, Anna F.; Misfeld, Martin; Mohr, Friedrich W.

    2013-01-01

    Barlow’s valve is a clinically important form of degenerative mitral valve (MV) disease that is characterized by unique clinical, echocardiographic and pathological features. Successful and durable repair of Barlow’s MV represents a clinical challenge for most cardiac surgeons. An armamentarium of different MV repair techniques may be required, resectional, neochordal or plicational techniques. Although conventional sternotomy remains the mainstay approach for MV surgery in the majority of cardiac surgery centers, minimally invasive surgery (MIS) is becoming increasingly accepted amongst patients, referring physicians and practicing cardiac surgeons. As surgical approaches, instrumentation and operative experience develop, select centers are now performing MIS MV surgery for nearly all MV patients. Although successful Barlow’s MV repair is more complex than that for most degenerative pathologies, several centers have published relatively large series of MIS MV repair for Barlow’s disease. In this review article, we highlight and compare the early and long-term results of conventional and minimally invasive approaches to Barlow’s and bileaflet mitral prolapse disease. Recent studies from various large volume centers around the world have demonstrated equivalent safety and efficacy outcomes of the MIS approach compared to conventional sternotomy surgery. In addition, MIS MV surgery may allow patients to benefit from a cosmetically appealing incision, a faster recovery and a quicker return to normal activities. However, a definite learning curve has been demonstrated for MIS MV surgery. If a patient with Barlow’s disease or other complex MV pathology desires to undergo MIS MV surgery, referral to a center and/or surgeon with extensive experience in MIS MV surgery is recommended. PMID:24349980

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

    PubMed

    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.

  14. Determination of minimal clinically important change in early and advanced Parkinson's disease.

    PubMed

    Hauser, Robert A; Auinger, Peggy

    2011-04-01

    Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies.

  15. Minimally invasive treatment of pilonidal disease: crystallized phenol and laser depilation.

    PubMed

    Girgin, Mustafa; Kanat, Burhan Hakan; Ayten, Refik; Cetinkaya, Ziya; Kanat, Zekiye; Bozdağ, Ahmet; Turkoglu, Ahmet; Ilhan, Yavuz Selim

    2012-01-01

    Pilonidal disease has been treated surgically and by various other methods for many years. The most important problem associated with such treatment is recurrence, but cosmetic outcome is another important issue that cannot be ignored. Today, crystallized phenol is recognized as a treatment option associated with good medical and cosmetic outcomes. We hypothesized that the addition of laser depilation to crystallized phenol treatment of pilonidal disease might increase the rate of success, and this study aimed to determine if the hypothesis was true. Patients who were treated with crystallized phenol and 755-nm alexandrite laser depilation were retrospectively analyzed. In total, 42 (31 male and 11 female) patients were treated with crystallized phenol and alexandrite laser depilation and were followed up between January 2009 and January 2012. In all, 38 patients (90.5%) had chronic disease and 4 (9.5%) had recurrent disease. Among the patients, 26 (61.9%) recovered following 1 crystallized phenol treatment, and the remaining patients had complete remission following repeated treatment. Some patients needed multiple treatments, even up to 8 times. None of the patients had a recurrence during a mean 24 months (range, 6-30 months) of follow-up. Whatever method of treatment is used for pilonidal disease, hair cleaning positively affects treatment outcome. The present results support the hypothesis that the addition of laser depilation (which provides more permanent and effective depilation than other methods) to crystallized phenol treatment (a non-radical, minimally invasive method associated with very good cosmetic results) can increase the effectiveness of the treatment and also reduce the recurrence rate of the disease. PMID:23294066

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27189371

  19. Minimally Invasive Treatment of the Thoracic Spine Disease: Completely Percutaneous and Hybrid Approaches

    PubMed Central

    Francesco Ciro, Tamburrelli; Laura, Scaramuzzo; Maurizio, Genitiempo; 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. PMID:24455233

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

    PubMed

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

    PubMed

    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.

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

    PubMed

    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.

  3. [Minimal-change disease with mesangial IgA deposits associated with Sjogren syndrome].

    PubMed

    Mon, C; Sánchez Hernández, R; Fernández Reyes, M J; Estébanez, C; Ortiz, M; Alvarez-Ude, F; Mampaso, F

    2002-01-01

    Sjögren's syndrome may be accompanied by a dysregulation of IgA system implying the presence of increased serum polymeric IgA or circulating immune complexes and their consequent deposition within the kidney. In this context IgA nephropathy may only represent one of the complications brought by IgA deposition. Glomerular involvement and primary Sjögren's syndrome has been described previously only in isolated case reports, membranous nephropathy and membranoproliferative glomerulonephritis have been reported. We have not found any case of minimal change disease and glomerular IgA deposition associated with Sjögren's syndrome. In this patient nephrotic syndrome was related to serum increase of CA 19-9; this association has been reported in only three previous cases.

  4. Minimal residual disease of leukemia and the quality of cryopreserved human ovarian tissue in vitro.

    PubMed

    Asadi-Azarbaijani, Babak; Sheikhi, Mona; Nurmio, Mirja; Tinkanen, Helena; Juvonen, Vesa; Dunkel, Leo; Hovatta, Outi; Oskam, Irma C; Jahnukainen, Kirsi

    2016-01-01

    Auto-transplant of cryopreserved ovarian tissue in leukemia patients carries a risk to reintroduce malignant cells. Maturation of ovarian follicles in vitro is a promising strategy to overcome the leukemic cell contamination. The follicle development and survival in 14 cryopreserved ovarian tissues with leukemia-specific PCR marker was evaluated after 7 or 14 days culture. Minimal residual disease (MRD) quantification was assessed by real-time quantitative PCR in order to identify the MRD positive (n = 6) and negative (n = 8) samples and to monitor levels of MRD before and after culture. The morphology of ovarian follicles were studied by light microscopy. After culture, no statistical significant differences were detected in follicle densities between MRD positive- and negative samples. Ovarian MRD either decreased below undetectable or fluctuated near the baseline level after 7 and 14 days in culture. This study provides quantitative in vitro evidence that leukemia contamination does not affect the follicle survival in cryopreserved ovarian tissue.

  5. Assessment of minimal residual disease in myeloma and the need for a consensus approach.

    PubMed

    Rawstron, Andy C; Paiva, Bruno; Stetler-Stevenson, Maryalice

    2016-01-01

    Treatment options for myeloma continue to develop at a rapid pace, and it is becoming increasingly challenging to determine the optimal therapeutic approaches because demonstrating a clear survival benefit now requires many years of follow-up. The detection of minimal residual disease (MRD) is recognized as a sensitive and rapid approach to evaluate treatment efficacy that predicts progression-free and overall survival independent of categorical response assessment and patients' biology. The benefit of MRD analysis is reflected in the many different techniques (multiparameter flow cytometry, quantitative polymerase chain reaction, and high-throughput sequencing) and collaborative groups (including EMN, ESCCA, ICCS, EuroFlow, and EuroMRD) that have performed collaborative projects to harmonize quantitative MRD detection. The time has come to adopt a consensus approach, and this report reviews the benefits and disadvantages of different strategies for MRD detection in myeloma and highlights the requirements for a sensitive, reproducible, and clinically meaningful cellular analytical approach.

  6. ROLE OF MINIMAL RESIDUAL DISEASE MONITORING IN ADULT AND PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Campana, Dario

    2009-01-01

    SYNOPSIS Assays that measure minimal residual disease (MRD) can determine the response to treatment in patients with acute lymphoblastic leukemia (ALL) much more precisely than morphological screening of bone marrow smears. The clinical significance of MRD detected by flow cytometry or polymerase chain reaction-based methods in childhood ALL has been conclusively established. Hence, MRD is being used in several clinical trials to adjust treatment intensity. Similar findings have been gathered in adult patients with ALL, making MRD one of the most powerful and informative parameters to guide clinical management. This article discusses practical issues related to MRD methodologies and the evidence supporting the use of MRD for risk assignment in clinical trials. PMID:19825454

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

    PubMed Central

    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

    2016-01-01

    Abstract 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

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

    PubMed

    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.

  9. Minimal residual disease in cancer therapy--Small things make all the difference.

    PubMed

    Blatter, Sohvi; Rottenberg, Sven

    2015-01-01

    Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer

  10. The role of multiparametric flow cytometry in the detection of minimal residual disease in acute leukaemia.

    PubMed

    Lee, Denise; Grigoriadis, George; Westerman, David

    2015-12-01

    Flow cytometry is the most accessible method for minimal residual disease (MRD) detection due to its availability in most haematological centres. Using a precise combination of different antibodies, immunophenotypic detection of MRD in acute leukaemia can be performed by identifying abnormal combinations or expressions of antigens on malignant cells at diagnosis, during and post treatment. These abnormal phenotypes, referred to as leukaemia-associated immunophenotypes (LAIPs) are either absent or expressed at low frequency in normal bone marrow (BM) cells and are used to monitor the behaviour and quantitate the amount of residual disease following treatment. In paediatric acute lymphoblastic leukaemia (ALL), the level of MRD by multiparametric flow cytometry (MPFC) during therapy is recognised as an important predictor of outcome. Although less extensively studied, adult ALL and adult and paediatric acute myeloid leukaemia (AML) have also demonstrated similar findings. The challenge now is incorporating this information for risk-stratification so that therapy can be tailored individually and ultimately improve outcome while also limiting treatment-related toxicity. In this review we will elaborate on the current and future role of MPFC in MRD in acute leukaemia while also addressing its limitations.

  11. Is this the time to introduce minimal residual disease in multiple myeloma clinical practice?

    PubMed

    Paiva, Bruno; Puig, Noemi; García-Sanz, Ramón; San Miguel, Jesús F

    2015-05-01

    Increasing therapeutic options and prolonged survival in multiple myeloma have raised interest in the concept of depth of response and its importance to predict patients' outcomes. Although the efficacy of current treatment approaches has greatly improved in the past decade, the definition of complete response (CR) remains unaltered and continues to use conventional serological and morphologic techniques. That notwithstanding, there is growing interest in minimal residual disease (MRD) monitoring, which has emerged in recent years as one of the most relevant prognostic factors in multiple myeloma. MRD can be assessed both inside (e.g., immunophenotypic and molecular techniques) and outside the bone marrow (e.g., PET/CT). Here, we focus on flow- and molecular-based assays by which different cooperative groups have demonstrated the efficacy of MRD assessment to predict outcomes even among patients in CR, and irrespectively of disease risk. Although further standardization is still required, the time has come to implement MRD monitoring in prospective clinical trials as a sensitive tool to evaluate treatment efficacy and for risk-adapted treatment, particularly in the consolidation and maintenance settings. Here, we present a comprehensive and critical review on the methodologic aspects, specific characteristics, and clinical significance of MRD monitoring by flow cytometry, PCR, and next-generation sequencing. PMID:25754350

  12. Cyclin D1, a novel molecular marker of minimal residual disease, in metastatic neuroblastoma.

    PubMed

    Cheung, Irene Y; Feng, Yi; Vickers, Andrew; Gerald, William; Cheung, Nai-Kong V

    2007-04-01

    Accurate monitoring of minimal residual disease (MRD) is critical for the management of metastatic neuroblastoma (NB). We evaluated cyclin D1 (CCND1), a cell-cycle control gene, as a novel MRD marker of NB. Using quantitative reverse transcriptase-polymerase chain reaction, we studied CCND1 expression in 133 solid tumors of different histological types, including 39 NB tumors, and examined its potential clinical utility as an early response marker in the bone marrows before and after treatment of 118 stage 4 patients enrolled after induction chemotherapy in an immunotherapy protocol. Based on 40 normal marrow and peripheral blood samples, a CCND1 transcript value greater than the mean + 2 SD was defined as positive. Sensitivity of this assay was one NB cell in 10(6) normal mononuclear cells. CCND1 transcript levels were high in NB, breast cancer, and Ewing family tumors. Among the NB patients evaluated, early (2.5 months from protocol entry) marrow response was strongly associated with both progression-free (P=0.0001) and overall survival (P=0.0006). CCND1 response remained predictive of survival among a subset of 66 patients who had no histological evidence of marrow disease before immunotherapy. We conclude that CCND1 has potential clinical utility as a novel molecular marker of MRD in the bone marrow of patients with metastatic NB.

  13. Seasonal Relapsing Minimal Change Disease: A Novel Strategy for Avoiding Long-Term Immunosuppression

    PubMed Central

    Lawrence, Christopher; Cook, H. Terry; Lightstone, Liz

    2012-01-01

    Background We describe the case of a young woman with seasonal allergic rhinitis who presented with signs of a lower respiratory tract infection, acute renal impairment and the nephrotic syndrome, demonstrated on biopsy to be due to minimal change disease (MCD) with acute tubular injury. Following initiation of high-dose corticosteroids, her respiratory symptoms and renal impairment improved, and the nephrotic syndrome went rapidly into remission, but relapsed, off treatment, in a seasonal fashion. Management In view of significant side effects related to corticosteroids, relapses were treated with the calcineurin inhibitor tacrolimus with excellent effect, but the patient was keen to avoid the complications of medium-term immunosuppression and so the drug was weaned early. She relapsed for the second time, whilst off tacrolimus, at the same time of year as at her initial presentation. In subsequent years we have successfully managed this patient with seasonal relapsing MCD with seasonal prophylactic tacrolimus therapy. Discussion We discuss the natural history of MCD and treatment options and demonstrate the utility of a clear understanding of the natural history of the condition in order to predict disease relapse and tailor therapy to the individual patient. PMID:23197964

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

    PubMed Central

    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

  15. Usability factors of mobile health application for chronic diseases

    NASA Astrophysics Data System (ADS)

    Zahra, Fatima; Hussain, Azham; Mohd, Haslina

    2016-08-01

    M-health has changed the conventional delivery system of health-care, permitting continuous, pervasive Health-care anywhere, anytime. Chronic disease apps are increasing, as many health workers, patients and clinicians already embracing smartphones in their comprehensive and diverse practices. There are lots of challenges and requirements that need to be addressed for mobile health applications to prevent or eliminate design problems and minimize potential threats for users, the proposed factors for chronic disease mobile applications can be used as a guide for app developers While, the usability testing, and evaluations of chronic disease apps have not yet touched the accuracy level of other web based applications. This study is being conducted to learn about challenges of m-health apps and to identify the factors that affect the usability of such applications.

  16. Minimal Residual Disease Detection and Evolved IGH Clones Analysis in Acute B Lymphoblastic Leukemia Using IGH Deep Sequencing

    PubMed Central

    Wu, Jinghua; Jia, Shan; Wang, Changxi; Zhang, Wei; Liu, Sixi; Zeng, Xiaojing; Mai, Huirong; Yuan, Xiuli; Du, Yuanping; Wang, Xiaodong; Hong, Xueyu; Li, Xuemei; Wen, Feiqiu; Xu, Xun; Pan, Jianhua; Li, Changgang; Liu, Xiao

    2016-01-01

    Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients. We identified leukemic IGH clones in 92.2% of the diagnostic samples and nearly half of the patients were polyclonal. About one-third of the leukemic clones have correct open reading frame in the complementarity determining region 3 (CDR3) of IGH, which demonstrates that the leukemic B cells were in the early developmental stage. We also demonstrated the higher sensitivity of HTS in MRD detection and investigated the clinical value of using peripheral blood in MRD detection and monitoring the clonal IGH evolution. In addition, we found leukemic clones were extensively undergoing continuous clonal IGH evolution by variable gene replacement. Dynamic frequency change and newly emerged evolved IGH clones were identified upon the pressure of chemotherapy. In summary, we confirmed the high sensitivity and universal applicability of HTS in MRD detection. We also reported the ubiquitous evolved IGH clones in B-ALL samples and their response to chemotherapy during treatment. PMID:27757113

  17. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: A Clinical Evidence Review

    PubMed Central

    2016-01-01

    Background Leukemia accounts for nearly a third of childhood cancers in Canada, with acute lymphoblastic leukemia (ALL) comprising nearly 80% of cases. Identification of prognostic factors that allow risk stratification and tailored treatment have improved overall survival. However, nearly a quarter of patients considered standard risk on the basis of conventional prognostic factors still relapse, and relapse is associated with increased morbidity and mortality. Relapse is thought to result from extremely low levels of leukemic cells left over once complete remission is reached, termed minimal residual disease (MRD). Poor event-free survival (EFS) as well as overall survival for those who are classified as MRD-positive have been substantiated in seminal studies demonstrating the prognostic value of MRD for EFS in the past few decades. This review sought to further elucidate the relationship between MRD and EFS by looking at relapse, the primary determinant of EFS and the biological mechanism through which MRD is thought to act. This evidence review aimed to ascertain whether MRD is an independent prognostic factor for relapse and to assess the effect of MRD-directed treatment on patient-important outcomes in childhood ALL. Methods Large prospective cohort studies with a priori multivariable analysis that includes potential confounders are required to draw confirmatory conclusions about the independence of a prognostic factor. Data on the prognostic value of MRD for relapse measured by molecular methods (polymerase chain reaction [PCR] of immunoglobulin or T-cell receptor rearrangements) or flow cytometry for leukemia-associated immunophenotypes or difference-from-normal approach were abstracted from included studies. Relevant data on relapse, EFS, and overall survival were abstracted from randomized controlled trials (RCTs) evaluating the effect of MRD-directed treatment. Results A total of 2,832 citations were reviewed, of which 12 studies were included in this

  18. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

    PubMed

    Beldjord, Kheira; Chevret, Sylvie; Asnafi, Vahid; Huguet, Françoise; Boulland, Marie-Laure; Leguay, Thibaut; Thomas, Xavier; Cayuela, Jean-Michel; Grardel, Nathalie; Chalandon, Yves; Boissel, Nicolas; Schaefer, Beat; Delabesse, Eric; Cavé, Hélène; Chevallier, Patrice; Buzyn, Agnès; Fest, Thierry; Reman, Oumedaly; Vernant, Jean-Paul; Lhéritier, Véronique; Béné, Marie C; Lafage, Marina; Macintyre, Elizabeth; Ifrah, Norbert; Dombret, Hervé

    2014-06-12

    With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. PMID:24740809

  19. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

    PubMed

    Beldjord, Kheira; Chevret, Sylvie; Asnafi, Vahid; Huguet, Françoise; Boulland, Marie-Laure; Leguay, Thibaut; Thomas, Xavier; Cayuela, Jean-Michel; Grardel, Nathalie; Chalandon, Yves; Boissel, Nicolas; Schaefer, Beat; Delabesse, Eric; Cavé, Hélène; Chevallier, Patrice; Buzyn, Agnès; Fest, Thierry; Reman, Oumedaly; Vernant, Jean-Paul; Lhéritier, Véronique; Béné, Marie C; Lafage, Marina; Macintyre, Elizabeth; Ifrah, Norbert; Dombret, Hervé

    2014-06-12

    With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:27781205

  2. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10−3 a 10−5), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  3. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10(-3) a 10(-5)), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  4. High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia.

    PubMed

    Wu, David; Sherwood, Anna; Fromm, Jonathan R; Winter, Stuart S; Dunsmore, Kimberly P; Loh, Mignon L; Greisman, Harvey A; Sabath, Daniel E; Wood, Brent L; Robins, Harlan

    2012-05-16

    High-throughput sequencing (HTS) of lymphoid receptor genes is an emerging technology that can comprehensively assess the diversity of the immune system. Here, we applied HTS to the diagnosis of T-lineage acute lymphoblastic leukemia/lymphoma. Using 43 paired patient samples, we then assessed minimal residual disease (MRD) at day 29 after treatment. The variable regions of TCRB and TCRG were sequenced using an Illumina HiSeq platform after performance of multiplexed polymerase chain reaction, which targeted all potential V-J rearrangement combinations. Pretreatment samples were used to define clonal T cell receptor (TCR) complementarity-determining region 3 (CDR3) sequences, and paired posttreatment samples were evaluated for MRD. Abnormal T lymphoblast identification by multiparametric flow cytometry was concurrently performed for comparison. We found that TCRB and TCRG HTS not only identified clonality at diagnosis in most cases (31 of 43 for TCRB and 27 of 43 for TCRG) but also detected subsequent MRD. As expected, HTS of TCRB and TCRG identified MRD that was not detected by flow cytometry in a subset of cases (25 of 35 HTS compared with 13 of 35, respectively), which highlights the potential of this technology to define lower detection thresholds for MRD that could affect clinical treatment decisions. Thus, next-generation sequencing of lymphoid receptor gene repertoire may improve clinical diagnosis and subsequent MRD monitoring of lymphoproliferative disorders.

  5. Minimal residual disease monitoring and preemptive immunotherapy in myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Qin, Ya-Zhen; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-08-01

    This study investigated the efficacy of minimal residual disease (MRD) monitoring and MRD-directed preemptive immunotherapy in high-risk myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT). MRD assessment consisted of Wilms' tumor gene 1 (WT1) detection with PCR and leukemia-associated immunophenotypic pattern examination with multiparameter flow cytometry (FCM). Post-HSCT, 31 patients were positive for WT1, and 8, for FCM; positivity for WT1 (18.6 vs. 6.1 %, P = 0.040) or FCM (62.5 vs. 3.6 %, P < 0.001) indicated a higher 2-year relapse rate. Twenty-one patients met our combined criteria for MRD, and the presence of MRD was associated with a higher 2-year relapse rate (27.3 vs. 4.5 %, P = 0.003). Preferentially expressed antigen of melanoma (PRAME) expression alone was not an appropriate MRD marker; however, it suggested that the MRD-positive patients may fail to respond to preemptive immunotherapy. In patients positive for both PRAME and MRD, the relapse rate was 60 % despite preemptive immunotherapy. Multivariate analysis confirmed the association between the increased relapse rate and positivity for both PRAME and MRD (hazard ratio = 42.8, P = 0.001). MRD monitoring predicted relapse in high-risk MDS post-HSCT patients, and PRAME- and MRD-positive patients did not benefit from preemptive immunotherapy.

  6. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

    SciTech Connect

    Lockwood, A.H.; Yap, E.W.; Rhoades, H.M.; Wong, W.H. )

    1991-03-01

    We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.

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

    PubMed

    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.

  8. Timing of foliar Zn application plays a vital role in minimizing Cd accumulation in wheat.

    PubMed

    Saifullah; Javed, Hina; Naeem, Asif; Rengel, Zed; Dahlawi, Saad

    2016-08-01

    Due to chemical and biochemical similarities between cadmium (Cd) and zinc (Zn), application of Zn may minimize Cd uptake by plants and ameliorate its toxicity. However, there is poor understanding of the comparative effectiveness of the foliar Zn application at different growth stages on Cd toxicity and accumulation in wheat. The present study was carried out to compare the effectiveness of foliarly applied Zn at different stages of plant growth to minimize Cd accumulation in wheat grains. Wheat (cv AARI-2011) was grown at three levels of soil Cd (0, 2.5, and 5.0 mg kg(-1)). Foliar application of Zn was carried out at either tillering, jointing, booting, heading, or grain filling stage using 0.05 % w/v aqueous solution of ZnSO4 · 7H2O. Increasing soil Cd had a negative effect on growth and yield attributes, including tiller production, root length and dry weight, plant height, 100-grain weight and grain and straw yield. Zinc foliar spray increased grain yield by increasing tiller production; importantly, an application at booting was more effective than at other stages. Foliarly applied Zn decreased Cd concentration in the roots, straw, and grain. Similar to grain yield, the largest decrease (74 %) in Cd concentration was associated with Zn foliar spray at booting. Grain yield was negatively related to grain Cd concentration which in turn showed a negative relationship with Zn concentration in leaves and grains. It is concluded that the booting stage is the suitable time for foliar application of Zn to (i) effectively minimize a Cd-induced loss in grain yield and (ii) decrease grain Cd concentration.

  9. Timing of foliar Zn application plays a vital role in minimizing Cd accumulation in wheat.

    PubMed

    Saifullah; Javed, Hina; Naeem, Asif; Rengel, Zed; Dahlawi, Saad

    2016-08-01

    Due to chemical and biochemical similarities between cadmium (Cd) and zinc (Zn), application of Zn may minimize Cd uptake by plants and ameliorate its toxicity. However, there is poor understanding of the comparative effectiveness of the foliar Zn application at different growth stages on Cd toxicity and accumulation in wheat. The present study was carried out to compare the effectiveness of foliarly applied Zn at different stages of plant growth to minimize Cd accumulation in wheat grains. Wheat (cv AARI-2011) was grown at three levels of soil Cd (0, 2.5, and 5.0 mg kg(-1)). Foliar application of Zn was carried out at either tillering, jointing, booting, heading, or grain filling stage using 0.05 % w/v aqueous solution of ZnSO4 · 7H2O. Increasing soil Cd had a negative effect on growth and yield attributes, including tiller production, root length and dry weight, plant height, 100-grain weight and grain and straw yield. Zinc foliar spray increased grain yield by increasing tiller production; importantly, an application at booting was more effective than at other stages. Foliarly applied Zn decreased Cd concentration in the roots, straw, and grain. Similar to grain yield, the largest decrease (74 %) in Cd concentration was associated with Zn foliar spray at booting. Grain yield was negatively related to grain Cd concentration which in turn showed a negative relationship with Zn concentration in leaves and grains. It is concluded that the booting stage is the suitable time for foliar application of Zn to (i) effectively minimize a Cd-induced loss in grain yield and (ii) decrease grain Cd concentration. PMID:27164881

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

    PubMed

    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.

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

    PubMed

    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.

  12. Safety margin of minimized contrast volume during percutaneous coronary intervention in patients with chronic kidney disease.

    PubMed

    Ogata, Nobuhiko; Ikari, Yuji; Nanasato, Mamoru; Okutsu, Masaaki; Kametani, Ryosuke; Abe, Mitsuru; Uehara, Yoshiki; Sumitsuji, Satoru

    2014-07-01

    Maximum allowable contrast dose (MACD) calculated as body weight × 5/serum creatinine has been a standard contrast dye volume (CV) used to decrease contrast-induced acute kidney injury. Recent advances in intravascular ultrasound-guided percutaneous coronary intervention (PCI) can dramatically minimize CV. The safe threshold when using an extremely low-dose CV is unknown. This study was designed as a multicenter, retrospective study of chronic kidney disease (CKD) patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m(2) undergoing elective PCI. We divided the patients into three groups according to following criteria: (1) low dose, CV/eGFR ratio <1.0; (2) medium dose, CV/eGFR ratio ≥1 and

  13. Evaluation of Minimal Residual Disease in Acute Myeloid Leukemia with NPM1 Marker

    PubMed Central

    Alizad Ghandforoush, Nasrin; Chahardouli, Bahram; Rostami, Shahrbano; Ghadimi, Habibeh; Ghasemi, Ali; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Nadali, Fatemeh

    2016-01-01

    Background: Minimal residual disease (MRD) tests provide early identification of hematologic relapse and timely management of acute myeloid leukemia (AML) patients. Approximately, 50% of AML patients do not have clonal chromosomal aberrations and categorize as a cytogenetically normal acute myeloid leukemia (CN-AML). About 60% of adult CN-AML has a mutation in exon 12 of NPM1 gene. This mutation is specific for malignant clone and potentially is a good marker of MRD. In this retrospective study, we set up a quantitative test for quantifying NPM1 type A mutation and AML patients carrying this mutation at the time of diagnosis, were followed-up. Materials and Methods : We prepared plasmids containing a cDNA fragment of NPM1 and ABL genes by PCR cloning. The plasmids were used to construct standard curves. Eleven patients were analyzed using established method. Serial PB and/or BM samples (n=71) were taken in 1-3 months intervals (mean 1.5-month intervals) and median follow-up duration after chemotherapy was 11 months (5-28.5 months). Results: In this study, we developed RNA-based RQ-PCR to quantitation of NPM1 mutation A with sensitivities of 10(-5). The percent of NPMmut/ABL level showed a range between 132 and 757 with median of 383.5 in samples at diagnosis. The median NPMmut transcript level log reduction was 3 logs. Relapse occurred in 54.5% of patients (n=6), all cases at diagnosis demonstrated the same mutation at relapse. In patients who experienced relapse, log reduction levels of NPM1 mRNA transcript after therapy were 4 (n=2), 3 (n=2) and 1 log (n=2). Totally, NPMmut level showed less than 5 log reduction in all of them, whereas this reduction was 5-6 logs in other patients. Conclusion: Despite the limitations of this study in terms of sample size and duration of follow-up, it showed the accuracy of set up for detection of mutation and this marker has worth for following-up at different stages of disease. Because of high frequency, stability, specificity

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

    SciTech Connect

    Duprez, Frederic; Madani, Indira; Morbee, Lieve; Bonte, Katrien; Deron, Philippe; Domjan, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

    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

  15. Detection of minimal residual disease in NPM1-mutated acute myeloid leukemia by next-generation sequencing.

    PubMed

    Salipante, Stephen J; Fromm, Jonathan R; Shendure, Jay; Wood, Brent L; Wu, David

    2014-11-01

    Detection of minimal residual disease predicts adverse outcome in patients with acute myeloid leukemia. Currently, minimal residual disease may be detected by RQ-PCR or flow cytometry, both of which have practical and diagnostic limitations. Here, we describe a next-generation sequencing assay for minimal residual disease detection in NPM1-mutated acute myeloid leukemia, which encompasses ∼60% of patients with normal karyotype acute myeloid leukemia. Exon 12 of NPM1 was PCR amplified using sequencing adaptor-linked primers and deep sequenced to enable detection of low-prevalence, acute myeloid leukemia-specific activating mutations. We benchmarked our results against flow cytometry, the standard of care for acute myeloid leukemia minimal residual disease diagnosis at our institution. The performance of both approaches was evaluated using defined dilutions of an NPM1 mutation-positive cell line and longitudinal clinical samples from acute myeloid leukemia patients. Using defined control material, we found this assay sensitive to approximately 0.001% mutant cells, outperforming flow cytometry by an order of magnitude. Next-generation sequencing was precise and semiquantitative over four orders of magnitude. In 22 longitudinal samples from six acute myeloid leukemia patients, next-generation sequencing detected minimal residual disease in all samples deemed negative by flow cytometry. Further, in one-third of patients, sequencing detected alternate NPM1 mutations in addition to the patient's index mutation, consistent with tumor heterogeneity. Next-generation sequencing provides information without prior knowledge of NPM1 mutation subtype or validation of allele-specific probes as required for RQ-PCR assays, and without generation and interpretation of complex multidimensional flow cytometry data. This approach may complement current technologies to enhance patient-specific clinical decision-making.

  16. Ecological applications for flood hazard minimization in the Siwaliks region of Nepal

    NASA Astrophysics Data System (ADS)

    Dhital, Y. P.; Tang, Q.

    2015-12-01

    Water-induced disaster problems including soil erosion, debris flow, landslides and flooding are common due to the unstable landscape of Siwaliks region of Nepal. Ecological applications especially focused on soil bioengineering techniques have been used in Nepal for nearly four decades to deal with erosion problems on slopes, in high way construction and riverbank stabilization. In this study, both vegetative check dams and wire net check dams along with vegetation were used for flood hazard minimization. After three growing seasons, the banks of the ephemeral stream were almost fully stabilized. Vegetation based solutions are found to be more effective than the mechanical methods of stream bank stabilization. Bamboo combinations for check dam construction and planting of bamboo behind check dam are both very useful for stream bank stabilization. Vegetation application on flood damaged bare ground was also found to be very successful. Furthermore, some plants species showed almost equal growth performances on both flood-affected and unaffected bare ground. However, more scientific implementation of ecological applications for flood hazard minimization in those affected areas is essential in future.

  17. Application of Sequential Quadratic Programming to Minimize Smart Active Flap Rotor Hub Loads

    NASA Technical Reports Server (NTRS)

    Kottapalli, Sesi; Leyland, Jane

    2014-01-01

    In an analytical study, SMART active flap rotor hub loads have been minimized using nonlinear programming constrained optimization methodology. The recently developed NLPQLP system (Schittkowski, 2010) that employs Sequential Quadratic Programming (SQP) as its core algorithm was embedded into a driver code (NLP10x10) specifically designed to minimize active flap rotor hub loads (Leyland, 2014). Three types of practical constraints on the flap deflections have been considered. To validate the current application, two other optimization methods have been used: i) the standard, linear unconstrained method, and ii) the nonlinear Generalized Reduced Gradient (GRG) method with constraints. The new software code NLP10x10 has been systematically checked out. It has been verified that NLP10x10 is functioning as desired. The following are briefly covered in this paper: relevant optimization theory; implementation of the capability of minimizing a metric of all, or a subset, of the hub loads as well as the capability of using all, or a subset, of the flap harmonics; and finally, solutions for the SMART rotor. The eventual goal is to implement NLP10x10 in a real-time wind tunnel environment.

  18. Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis

    PubMed Central

    Fernandez-Juarez, Gema; Villacorta, Javier; Ruiz-Roso, Gloria; Panizo, Nayara; Martinez-Marín, Isabel; Marco, Helena; Arrizabalaga, Pilar; Díaz, Montserrat; Perez-Gómez, Vanessa; Vaca, Marco; Rodríguez, Eva; Cobelo, Carmen; Fernandez, Loreto; Avila, Ana; Praga, Manuel; Quereda, Carlos; Ortiz, Alberto

    2016-01-01

    Background Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. Methods Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. Results We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95

  19. Application of microarray technology in pulmonary diseases

    PubMed Central

    Tzouvelekis, Argyris; Patlakas, George; Bouros, Demosthenes

    2004-01-01

    Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives. PMID:15585067

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

    PubMed

    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 (<10(-5); n = 54, 34%), MRD positive (between <10(-4) and ≥10(-5); n = 20, 12%), and MRD positive (≥10(-4); n = 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P = .007) and overall survival (OS) (HR, 3.1; P = .04), with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10(-4) and ≥10(-5) vs ≥10(-4) (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >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

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

    PubMed Central

    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

  2. Minimizing losses in bio-electrochemical systems: the road to applications.

    PubMed

    Clauwaert, Peter; Aelterman, Peter; Pham, The Hai; De Schamphelaire, Liesje; Carballa, Marta; Rabaey, Korneel; Verstraete, Willy

    2008-07-01

    Bio-electrochemical systems (BESs) enable microbial catalysis of electrochemical reactions. Plain electrical power production combined with wastewater treatment by microbial fuel cells (MFCs) has been the primary application purpose for BESs. However, large-scale power production and a high chemical oxygen demand conversion rates must be achieved at a benchmark cost to make MFCs economical competitive in this context. Recently, a number of valuable oxidation or reduction reactions demonstrating the versatility of BESs have been described. Indeed, BESs can produce hydrogen, bring about denitrification, or reductive dehalogenation. Moreover, BESs also appear to be promising in the field of online biosensors. To effectively apply BESs in practice, both biological and electrochemical losses need to be further minimized. At present, the costs of reactor materials have to be decreased, and the volumetric biocatalyst activity in the systems has to be increased substantially. Furthermore, both the ohmic cell resistance and the pH gradients need to be minimized. In this review, these losses and constraints are discussed from an electrochemical viewpoint. Finally, an overview of potential applications and innovative research lines is given for BESs.

  3. Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: are we ready?

    PubMed

    Boyiadzis, Michael; Whiteside, Theresa L

    2016-06-01

    The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse has introduced the potential for more sensitive non-invasive monitoring of leukemia patients based on the molecular and genetic analysis of the exosome cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes in patients' plasma that associate with leukemic relapse can be identified. The diagnostic/prognostic value of these profiles could then be validated in prospective clinical studies. Here, we consider the potential of exosomes to fulfill the role of future biomarkers of minimal residual disease in AML. The rationale for developing exosome-based methodology for minimal residual disease detection is based on promising early observations. However, standards need to be established for evaluating exosome identity, isolation from body fluids, and assessment methods. The rapidly expanding knowledge of the exosome biology suggests that the exosome status as potential biomarkers may become clarified in the near future.

  4. Secondary histiocytic sarcoma may cause apparent persistence or recurrence of minimal residual disease in childhood acute lymphoblastic leukemia.

    PubMed

    Alten, Julia; Klapper, Wolfram; Leuschner, Ivo; Eckert, Cornelia; Beier, Rita; Vallo, Elisabeth; Krause, Martin; Claviez, Alexander; Vieth, Simon; Bleckmann, Kirsten; Möricke, Anja; Schrappe, Martin; Cario, Gunnar

    2015-09-01

    Histiocytic sarcoma (HS) is a rare disease with poor prognosis which may develop subsequent to acute lymphoblastic leukemia (ALL). Here we report two children treated within the AIEOP-BFM ALL 2009 trial: one patient succumbed to fulminant hemophagocytic lymphohistiocytosis triggered by HS during ALL maintenance therapy, the other patient had a smoldering course of HS for over 2 years, and subsequently died after allogeneic stem cell transplantation. In both cases, HS and ALL were clonally related and apparent return of minimal residual disease (MRD) was detected by qPCR in bone marrow. Thus, HS should be considered in ALL when MRD appears to persist or reappear.

  5. Bipolar radiofrequency-induced thermotherapy of haemorrhoids: a new minimally invasive method for haemorrhoidal disease treatment. Early results of a pilot study

    PubMed Central

    Duben, Jiri; Hnatek, Lukas; Dudesek, Bohumil; Humpolicek, Petr

    2012-01-01

    Introduction Haemorrhoidal disease is the most frequent benign anorectal disease. Conservative, minimally invasive and surgical methods are used in the treatment of haemorrhoidal disease. Radiofrequency thermoablation is a popular new technique in the treatment of varicose veins. Aim Assessment of the use of the method in the treatment of haemorrhoidal disease using bipolar radiofrequency-induced thermotherapy (RFITT or so-called Celon method). Material and methods We used the CelonLab PRECISION (Celon AG medical instruments, Teltow, Germany) with the bipolar RFITT applicator Celon ProBREATH for the treatment of haemorrhoidal disease stages III and IV. Results In the Department of Surgery at the Atlas Hospital in Zlin, Czech Republic, a total of 71 patients were treated from 9/2007 to 10/2010 with this new treatment approach. The success rate was 100%, local recurrence rate was 2.8%, and medium-term satisfaction of patients who underwent the procedure was 99.5%. Complications appeared in 4.26% of cases. Conclusions The new RFITTH technique for treatment of advanced stages of haemorrhoidal disease is a new treatment modality with good curative response, low level of complications, minimum pain and quick return of patients to their usual activities. PMID:23630553

  6. Minimizing crop damage through understanding relationships between pyrethrum phenology and ray blight disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The most damaging foliar disease of pyrethrum in Australia is ray blight caused by Stagonosporopsis tanaceti. The probability of growers incurring economic losses caused by this disease has been substantially reduced by the implementation of a prophylactically-applied spring fungicide program. Th...

  7. Insights into Spared Memory Capacity in Amnestic MCI and Alzheimer's Disease via Minimal Interference

    ERIC Educational Resources Information Center

    Dewar, Michaela; Pesallaccia, Martina; Cowan, Nelson; Provinciali, Leandro; Della Sala, Sergio

    2012-01-01

    Impairment on standard tests of delayed recall is often already maximal in the aMCI stage of Alzheimer's Disease. Neuropathological work shows that the neural substrates of memory function continue to deteriorate throughout the progression of the disease, hinting that further changes in memory performance could be tracked by a more sensitive test…

  8. Global error minimization in image mosaicing using graph connectivity and its applications in microscopy.

    PubMed

    Khurd, Parmeshwar; Grady, Leo; Oketokoun, Rafiou; Sundar, Hari; Gajera, Tejas; Gibbs-Strauss, Summer; Frangioni, John V; Kamen, Ali

    2011-01-01

    Several applications such as multiprojector displays and microscopy require the mosaicing of images (tiles) acquired by a camera as it traverses an unknown trajectory in 3D space. A homography relates the image coordinates of a point in each tile to those of a reference tile provided the 3D scene is planar. Our approach in such applications is to first perform pairwise alignment of the tiles that have imaged common regions in order to recover a homography relating the tile pair. We then find the global set of homographies relating each individual tile to a reference tile such that the homographies relating all tile pairs are kept as consistent as possible. Using these global homographies, one can generate a mosaic of the entire scene. We derive a general analytical solution for the global homographies by representing the pair-wise homographies on a connectivity graph. Our solution can accommodate imprecise prior information regarding the global homographies whenever such information is available. We also derive equations for the special case of translation estimation of an X-Y microscopy stage used in histology imaging and present examples of stitched microscopy slices of specimens obtained after radical prostatectomy or prostate biopsy. In addition, we demonstrate the superiority of our approach over tree-structured approaches for global error minimization.

  9. Design and fabrication of an IPMC-embedded tube for minimally invasive surgery applications

    NASA Astrophysics Data System (ADS)

    Liu, Jiayu; Wang, Yanjie; Zhao, Dongxu; Zhang, Chi; Chen, Hualing; Li, Dichen

    2014-03-01

    Minimally Invasive Surgery (MIS) is receiving much attention for a number of reasons, including less trauma, faster recovery and enhanced precision. The traditional robotic actuators do not have the capabilities required to fulfill the demand for new applications in MIS. Ionic Polymer-Metal Composite (IPMC), one of the most promising smart materials, has extensive desirable characteristics such as low actuation voltage, large bending deformation and high functionality. Compared with traditional actuators, IPMCs can mimic biological muscle and are highly promising for actuation in robotic surgery. In this paper, a new approach which involves molding and integrating IPMC actuators into a soft silicone tube to create an active actuating tube capable of multi-degree-of-freedom motion is presented. First, according to the structure and performance requirements of the actuating tube, the biaxial bending IPMC actuators fabricated by using solution casting method have been implemented. The silicone was cured at a suitable temperature to form a flexible tube using molds fabricated by 3D Printing technology. Then an assembly based fabrication process was used to mold or integrate biaxial bending IPMC actuators into the soft silicone material to create an active control tube. The IPMC-embedded tube can generate multi-degree-of-freedom motions by controlling each IPMC actuator. Furthermore, the basic performance of the actuators was analyzed, including the displacement and the response speed. Experimental results indicate that IPMC-embedded tubes are promising for applications in MIS.

  10. A 4-DOF haptic master using ER fluid for minimally invasive surgery system application

    NASA Astrophysics Data System (ADS)

    Oh, Jong-Seok; Han, Young-Min; Lee, Sang-Rock; Choi, Seung-Bok

    2013-04-01

    This paper presents a novel 4-degrees-of-freedom (4-DOF) haptic master using a electrorheological (ER) fluid which is applicable to minimally invasive surgery (MIS) systems. By adopting a controllable ER fluid, the master can easily generate 4-DOF repulsive forces with the advantages of a simple mechanism and continuous force control capability. The proposed master consists of two actuators: an ER spherical joint for 3-DOF rotational motion and an ER piston device for 1-DOF translational motion. The generated torque/force models are mathematically derived by analyzing the mechanism geometry and using the Bingham characteristics of an ER Fluid. The haptic master is optimally designed and manufactured based on the mathematical torque/force models. The repulsive torque/force responses are experimentally evaluated and expressed by the first-order and second-order dynamic equations for each motion. A sliding mode controller (SMC), which is known to be robust to uncertainties, is then designed and empirically implemented to achieve the desired torque/force trajectories. It is demonstrated by presenting torque/force tracking results of both rotational and translational motions that the proposed 4-DOF ER haptic master integrated with the SMC can provide an effective haptic control performance for MIS applications.

  11. [Economic impact of Alzheimer's Disease in Brazil: is it possible to improve care and minimize costs?].

    PubMed

    Gutierrez, Beatriz Aparecida Ozello; Silva, Henrique Salmazo da; Guimarães, Cristina; Campino, Antonio Carlos

    2014-11-01

    The scope of this study is to discuss data relating to the costs involved with Alzheimer's Disease and the initiatives in terms of care in order to reduce costs and help family members and caregivers to cope with the disease. The biggest cost for people with mild Alzheimer's Disease is the cost of time spent by the unremunerated caregiver, and for those at the advanced stages of the disease it is the cost of institutional care. In this respect, the literature proposes the adoption of models of care that maximize the functional independence of the elderly and maintain their skills, such as Day Care Centers for the Elderly and rehabilitation programs and support offered to the elderly and their family members. These models of care need to be discussed, structured and deployed in the context of the Brazilian reality. PMID:25351314

  12. Using population viability criteria to assess strategies to minimize disease threats for an endangered carnivore.

    PubMed

    Doak, Daniel F; Bakker, Victoria J; Vickers, Winston

    2013-04-01

    Outbreaks of infectious disease represent serious threats to the viability of many vertebrate populations, but few studies have included quantitative evaluations of alternative approaches to the management of disease. The most prevalent management approach is monitoring for and rapid response to an epizootic. An alternative is vaccination of a subset of the free-living population (i.e., a "vaccinated core") such that some individuals are partially or fully immune in the event of an epizootic. We developed a simulation model describing epizootic dynamics, which we then embedded in a demographic simulation to assess these alternative approaches to managing rabies epizootics in the island fox (Urocyon littoralis), a species composed of only 6 small populations on the California Channel Islands. Although the monitor and respond approach was superior to the vaccinated-core approach for some transmission models and parameter values, this type of reactive management did not protect the population from rabies under many disease-transmission assumptions. In contrast, a logistically feasible program of prophylactic vaccination for part of the wild population yielded low extinction probabilities across all likely disease-transmission scenarios, even with recurrent disease introductions. Our use of a single metric of successful management-probability of extreme endangerment (i.e., quasi extinction)-to compare very different management approaches allowed an objective assessment of alternative strategies for controlling the threats posed by infectious disease outbreaks.

  13. Using population viability criteria to assess strategies to minimize disease threats for an endangered carnivore.

    PubMed

    Doak, Daniel F; Bakker, Victoria J; Vickers, Winston

    2013-04-01

    Outbreaks of infectious disease represent serious threats to the viability of many vertebrate populations, but few studies have included quantitative evaluations of alternative approaches to the management of disease. The most prevalent management approach is monitoring for and rapid response to an epizootic. An alternative is vaccination of a subset of the free-living population (i.e., a "vaccinated core") such that some individuals are partially or fully immune in the event of an epizootic. We developed a simulation model describing epizootic dynamics, which we then embedded in a demographic simulation to assess these alternative approaches to managing rabies epizootics in the island fox (Urocyon littoralis), a species composed of only 6 small populations on the California Channel Islands. Although the monitor and respond approach was superior to the vaccinated-core approach for some transmission models and parameter values, this type of reactive management did not protect the population from rabies under many disease-transmission assumptions. In contrast, a logistically feasible program of prophylactic vaccination for part of the wild population yielded low extinction probabilities across all likely disease-transmission scenarios, even with recurrent disease introductions. Our use of a single metric of successful management-probability of extreme endangerment (i.e., quasi extinction)-to compare very different management approaches allowed an objective assessment of alternative strategies for controlling the threats posed by infectious disease outbreaks. PMID:23521669

  14. Application of Ultrasound-Guided Core Biopsy to Minimal-Invasively Diagnose Supraclavicular Fossa Tumors and Minimize the Requirement of Invasive Diagnostic Surgery.

    PubMed

    Chen, Chun-Nan; Lin, Che-Yi; Chi, Fan-Hsiang; Chou, Chen-Han; Hsu, Ya-Ching; Kuo, Yen-Lin; Lin, Chih-Feng; Chen, Tseng-Cheng; Wang, Cheng-Ping; Lou, Pei-Jen; Ko, Jenq-Yuh; Hsiao, Tzu-Yu; Yang, Tsung-Lin

    2016-01-01

    Tumors of the supraclavicular fossa (SC) is clinically challenging because of anatomical complexity and tumor pathological diversity. Because of varied diseases entities and treatment choices of SC tumors, making the accurate decision among numerous differential diagnoses is imperative. Sampling by open biopsy (OB) remains the standard procedure for pathological confirmation. However, complicated anatomical structures of SC always render surgical intervention difficult to perform. Ultrasound-guided core biopsy (USCB) is a minimally invasive and office-based procedure for tissue sampling widely applied in many diseases of head and neck. This study aims to evaluate the clinical efficacy and utility of using USCB as the sampling method of SC tumors. From 2009 to 2014, consecutive patients who presented clinical symptoms and signs of supraclavicular tumors and were scheduled to receive sampling procedures for diagnostic confirmation were recruited. The patients received USCB or OB respectively in the initial tissue sampling. The accurate diagnostic rate based on pathological results was 90.2% for USCB, and 93.6% for OB. No significant difference was noted between USCB and OB groups in terms of diagnostic accuracy and the percentage of inadequate specimens. All cases in the USCB group had the sampling procedure completed within 10  minutes, but not in the OB group. No scars larger than 1  cm were found in USCB. Only patients in the OB groups had the need to receive general anesthesia and hospitalization and had scars postoperatively. Accordingly, USCB can serve as the first-line sampling tool for SC tumors with high diagnostic accuracy, minimal invasiveness, and low medical cost. PMID:26825877

  15. Minimal access surgery for hydatid cyst disease: laparoscopic, thoracoscopic, and retroperitoneoscopic approach.

    PubMed

    Chowbey, P K; Shah, S; Khullar, R; Sharma, A; Soni, V; Baijal, M; Vashistha, A; Dhir, A

    2003-06-01

    Surgery has remained the mainstay for the treatment of hydatid cyst. The rapid development of laparoscopic techniques has encouraged surgeons to replicate principles of conventional hydatid surgery using a minimally invasive approach. Several reports have confirmed the feasibility of laparoscopic hepatic hydatid surgery. We report the use of a laparoscopic approach for cysts located in the liver, lung, and retroperitoneum. Fifteen patients with hydatid cysts, including one patient with a recurrent cyst, of various organs, including the liver, lung, and retroperitoneum, were operated on laparoscopically. Sixteen hydatid cysts were drained in a total of 15 patients. The mean operative time was 84 +/- 6 minutes (60-125 minutes). The mean duration of the hospital stay was 2.3 days (1-6 days). The mean cyst diameter was 9.2 cm (6.4-13.5 cm). No conversions to open surgery were required. One complication, a trocar-induced bowel perforation, occurred, and there was no mortality. During 3 to 44 months (mean, 27 months) of follow-up, no recurrences developed. Minimal access surgery is a safe, effective, and viable option for the management of selected patients with hydatid cysts in various locations, such as the liver, lung, and retroperitoneum.

  16. SU-E-J-167: Dosimetric Consequences From Minimal Displacements in APBI with SAVI Applicators

    SciTech Connect

    Chandrasekara, S; Dumitru, N; Hyvarinen, M; Pella, S

    2015-06-15

    Purpose: To determine the importance of providing proper solid immobilization in every fraction of treatment in APBI with brachytherapy. Methods: 125 patients treated with APBI brachytherapy with SAVI applicators at SFRO Boca Raton, from 2013–2015 were considered for this retrospective study. The CT scans of each patient, which were taken before each treatment, were imported in to the Oncentra treatment planning system. Then they were compared with the initial CT scan which was used for the initial plan. Deviation in displacements in reference to ribs and skin surface was measured and dosimetric evaluations respective to the initial image were performed. Results: Small deviations in displacements were observed from the SAVI applicator to the ribs and the skin surface. Dosimetric evaluations revealed, very small changes in the inter-fractionation position make significant differences in the maximum dose to critical organs. Additionally, the volume of the cavity also changed between fractions. As a Result, the maximum dose manifested variance between 10% and 32% in ribs and skin surface respectively. Conclusion: It appears that taking a CT scan before each treatment is necessary to minimize the risk of delivering undesired high doses to the critical organs. This study indicates, in 30% of the cases re-planning was necessary between treatments. We conclude that, treatment planning teams should evaluate the placement of the device by analyzing the CT images before each treatment and they must be prepared for re-planning if needed. This study also reveals the urgent need of improving the immobilization methods with APBI when treating with the SAVI applicator.

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

    PubMed

    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.

  18. MINIMIZING THE RISK OF PREGNANCY, SEXUALLY TRANSMITTED DISEASES, AND HIV AMONG INCARCERATED ADOLESCENT GIRLS

    PubMed Central

    ST LAWRENCE, JANET S.; SNODGRASS, C. EDWARD; ROBERTSON, ANGELA; BAIRD-THOMAS, CONNIE

    2010-01-01

    Delinquent girls are at elevated risk for unplanned pregnancy and sexually transmitted diseases when compared with non-delinquent peers. Participants—234 incarcerated female juveniles—completed demographic, individual, partner, peer, and family measures and were tested for sexually transmitted diseases. Disease rates were as follows: chlamydia (20%), gonorrhea (4%), and syphilis (1%). Stepwise multiple linear regression analysis assessed the relationship of the predictor variable sets with sexual risk. Demographic and individual variables had the strongest associations with risk. Peer, partner, or family variables did not account for significant additional variance. The results suggest that an intervention could be delivered during the window of opportunity during the girls’ incarceration, changing their knowledge, attitudes, and skills that are implicated in risky sexual behavior before they are released back into the community. PMID:20585415

  19. Minimal Residual Disease and Childhood Leukemia: Standard of Care Recommendations From the Pediatric Oncology Group of Ontario MRD Working Group.

    PubMed

    Athale, Uma H; Gibson, Paul J; Bradley, Nicole M; Malkin, David M; Hitzler, Johann

    2016-06-01

    Minimal residual disease (MRD) is an independent predictor of relapse risk in children with leukemia and is widely used for risk-adapted treatment. This article summarizes current evidence supporting the use of MRD, including clinical significance, current international clinical practice, impact statement, and recommended indications. The proposed MRD recommendations have been endorsed by the MRD Working Group of the Pediatric Oncology Group of Ontario and provide the foundation for a strategy that aims at equitable access to MRD evaluation for children with leukemia.

  20. Borrelia burgdorferi has minimal impact on the Lyme disease reservoir host Peromyscus leucopus.

    PubMed

    Schwanz, Lisa E; Voordouw, Maarten J; Brisson, Dustin; Ostfeld, Richard S

    2011-02-01

    The epidemiology of vector-borne zoonotic diseases is determined by encounter rates between vectors and hosts. Alterations to the behavior of reservoir hosts caused by the infectious agent have the potential to dramatically alter disease transmission and human risk. We examined the effect of Borrelia burgdorferi, the etiological agent of Lyme disease, on one of its most important reservoir hosts, the white-footed mouse, Peromyscus leucopus. We mimic natural infections in mice using the vector (Black-legged ticks, Ixodes scapularis) and examine the immunological and behavioral responses of mouse hosts. Despite producing antibodies against B. burgdorferi, infected mice did not have elevated white blood cells compared with uninfected mice. In addition, infected and uninfected mice did not differ in their wheel-running activity. Our results suggest that infection with the spirochete B. burgdorferi has little impact on the field activity of white-footed mice. Lyme disease transmission appears to be uncomplicated by pathogen-altered behavior of this reservoir host. PMID:20569016

  1. Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment.

    PubMed

    Lindeboom, Jaap; Weinstein, Henry

    2004-04-19

    In this review, the neuropsychological symptoms of different diseases in the elderly are described. After a brief explanation of relevant principles in the neuropsychological assessment of older individuals, a summary of the complex relation between ageing and cognition is presented. It may be concluded that cognitive decline is not an inevitable outcome of ageing, and may well be the result of unrecognised pathology. The term mild cognitive impairment is reserved for patients whose impairment is objectively demonstrable but is not pronounced in more than one domain of cognition and does not seriously affect activities of daily living. The initial phase of Alzheimer's disease is marked by a progressive deterioration of episodic memory. When the process advances, the impairment spreads to other functions, such as semantic memory, language and visuo-spatial ability. Vascular dementia is the second most common type of dementia; however, it is increasingly being recognised that vascular dementia is actually a heterogeneous syndrome and that several vascular pathologies can lead to cognitive deterioration. In contrast to the striking deficits produced by cortical infarcts, lesions of the subcortical white matter are mainly associated with a non-specific slowing of behaviour. Cerebrovascular disease also plays an important role in forms of cognitive decline other than dementia, and as such, it appears to be no less prevalent in old age than Alzheimer's disease. Neuropsychology is an important asset to the study and treatment of cognitive decline, but must be embedded in a multi-disciplinary context.

  2. Borrelia burgdorferi has minimal impact on the Lyme disease reservoir host Peromyscus leucopus.

    PubMed

    Schwanz, Lisa E; Voordouw, Maarten J; Brisson, Dustin; Ostfeld, Richard S

    2011-02-01

    The epidemiology of vector-borne zoonotic diseases is determined by encounter rates between vectors and hosts. Alterations to the behavior of reservoir hosts caused by the infectious agent have the potential to dramatically alter disease transmission and human risk. We examined the effect of Borrelia burgdorferi, the etiological agent of Lyme disease, on one of its most important reservoir hosts, the white-footed mouse, Peromyscus leucopus. We mimic natural infections in mice using the vector (Black-legged ticks, Ixodes scapularis) and examine the immunological and behavioral responses of mouse hosts. Despite producing antibodies against B. burgdorferi, infected mice did not have elevated white blood cells compared with uninfected mice. In addition, infected and uninfected mice did not differ in their wheel-running activity. Our results suggest that infection with the spirochete B. burgdorferi has little impact on the field activity of white-footed mice. Lyme disease transmission appears to be uncomplicated by pathogen-altered behavior of this reservoir host.

  3. Minimal interference beam size/profile measurement techniques applicable to the Collider

    SciTech Connect

    Nexsen, W.; Dutt, S.; Kauffmann, S.; Lebedev, V.; Maschke, A.; Mokhov, N.; Richardson, R.; Tsyganov, E.; Zinchenko, A.

    1993-05-01

    The imaging of synchrotron radiation (SR) has been suggested as a technique for providing a continuous, non-interfering monitor of the beam profile in the Collider rings at the Superconducting Super Collider. A closer examination has raised questions concerning the applicability of SR imaging in this case because of the diffraction broadening of the image, the requirements for axial space and location in the lattice, and the complexity of the system. We have surveyed the known, alternative, minimal interference techniques for measuring beam size and have evaluated them for possible Collider usage. We conclude that of the approaches that appear feasible, all require at least some development for our usage and that the development of an electron beam probe offers the best promise. We recommend that flying wires be used for cross-checking and calibrating the electron beam probe diagnostic and for luminosity measurements when the highest accuracy is required, but flying wires should not be used as the primary diagnostic because of their limited lifetime.

  4. Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.

    PubMed

    Pettit, Kristen; Stock, Wendy; Walter, Roland B

    2016-07-01

    Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation.

  5. An unusual manifestation in a patient with adult-onset Still’s disease: Minimal glomerular lesion

    PubMed Central

    El Mezouar, Imane; Abourazzak, Fatima Zahra; Ghani, Najoua; Harzy, Taoufik

    2014-01-01

    Adult-onset Still’s disease (AOSD) is a multisystem inflammatory disease of unknown etiology. It is characterized by arthritis, hectic fever, transient rash and visceral lesions such as pleuropericarditis, lymphadenopathy and hepato splenomegaly. Although kidney involvement may appear in some cases of AOSD, minimal glomerular lesion (MGL) has not been described. We describe a female patient, who presented with multisystemic manifestations, including high spiking fever, arthralgias, striking hyperferritinemia, and proteinuria. Renal biopsy showed classic MGL. A diagnosis of AOSD was made on the basis of Yamaguchi’s criteria. The patient was treated with steroids, resulting in remission of the rheumatological condition closely paralleled by remission of proteinuria, thereby strongly suggesting a causative link between AOSD and MGL in this patient. Renal involvement in the AOSD was rarely reported in the literature. MGL may be a cause of unexplained proteinuria in AOSD. In this situation, renal biopsy is necessary to establish a definitive diagnosis.

  6. The paucity of minimal change disease in adolescents with primary nephrotic syndrome.

    PubMed

    Baqi, N; Singh, A; Balachandra, S; Ahmad, H; Nicastri, A; Kytinski, S; Homel, P; Tejani, A

    1998-02-01

    Data are sparse regarding the histological lesions associated with the primary nephrotic syndrome in adolescents. To our knowledge there are only two published articles that have specifically addressed the histopathological lesions that typify idiopathic nephrotic syndrome in the adolescent population. We reviewed our experience from the last 14 years of children between the ages of 12 and 18 years who were referred to our center for the evaluation of the nephrotic syndrome. A total of 29 adolescents met the inclusion criteria for this review. All patients were biopsied prior to the initiation of treatment. The sex ratio consisted of 52% males and 48% females and the racial breakdown was largely African-American, with 83% black adolescents, 7% Hispanic, and 10% Caucasian patients. Minimal change nephrotic syndrome (MCNS), the predominant lesion of children at an early age, was noted in only 20% of patients. The majority of patients (55.2%) had focal segmental glomerulosclerosis (FSGS); 7% had IgM nephropathy and 3.5% had diffuse mesangial hypercellularity. Only 7% of biopsied adolescents had membranoproliferative glomerulonephritis. Our results indicate that the most common lesion in this predominantly African-American patient population is FSGS, with only a small number showing MCNS. Thus, in our experience derived from a racially mixed population, adolescents with the nephrotic syndrome are less likely to have MCNS than younger children.

  7. Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry.

    PubMed

    Puig, N; Sarasquete, M E; Balanzategui, A; Martínez, J; Paiva, B; García, H; Fumero, S; Jiménez, C; Alcoceba, M; Chillón, M C; Sebastián, E; Marín, L; Montalbán, M A; Mateos, M V; Oriol, A; Palomera, L; de la Rubia, J; Vidriales, M B; Bladé, J; Lahuerta, J J; González, M; Miguel, J F S; García-Sanz, R

    2014-02-01

    We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (MM), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10(-4) residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in MM. PMID:23860448

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

    PubMed

    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. PMID:23750428

  9. Minimally invasive cell-seeded biomaterial systems for injectable/epicardial implantation in ischemic heart disease

    PubMed Central

    Ravichandran, Rajeswari; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Mukherjee, Shayanti; Ramakrishna, Seeram

    2012-01-01

    Myocardial infarction (MI) is characterized by heart-wall thinning, myocyte slippage, and ventricular dilation. The injury to the heart-wall muscle after MI is permanent, as after an abundant cell loss the myocardial tissue lacks the intrinsic capability to regenerate. New therapeutics are required for functional improvement and regeneration of the infarcted myocardium, to overcome harmful diagnosis of patients with heart failure, and to overcome the shortage of heart donors. In the past few years, myocardial tissue engineering has emerged as a new and ambitious approach for treating MI. Several left ventricular assist devices and epicardial patches have been developed for MI. These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit. An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery. Furthermore, intramyocardial injection of biomaterials and cells has opened new opportunities to explore and also to augment the potentials of this technique to ease morbidity and mortality rates owing to heart failure. This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI. Additionally, this review also provides a complete outlook on the tissue-engineering therapies presently being used for myocardial regeneration, as well as some perceptivity into the possible issues that may hinder its progress in the future. PMID:23271906

  10. Comparison between qualitative and real-time polymerase chain reaction to evaluate minimal residual disease in children with acute lymphoblastic leukemia

    PubMed Central

    Paula, Francisco Danilo Ferreira; Elói-Santos, Silvana Maria; Xavier, Sandra Guerra; Ganazza, Mônica Aparecida; Jotta, Patricia Yoshioka; Yunes, José Andrés; Viana, Marcos Borato; Assumpção, Juliana Godoy

    2015-01-01

    Introduction Minimal residual disease is an important independent prognostic factor that can identify poor responders among patients with acute lymphoblastic leukemia. Objective The aim of this study was to analyze minimal residual disease using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements by conventional polymerase chain reaction followed by homo-heteroduplex analysis and to compare this with real-time polymerase chain reaction at the end of the induction period in children with acute lymphoblastic leukemia. Methods Seventy-four patients diagnosed with acute lymphoblastic leukemia were enrolled. Minimal residual disease was evaluated by qualitative polymerase chain reaction in 57 and by both tests in 44. The Kaplan–Meier and multivariate Cox methods and the log-rank test were used for statistical analysis. Results Nine patients (15.8%) were positive for minimal residual disease by qualitative polymerase chain reaction and 11 (25%) by real-time polymerase chain reaction considering a cut-off point of 1 × 10−3 for precursor B-cell acute lymphoblastic leukemia and 1 × 10−2 for T-cell acute lymphoblastic leukemia. Using the qualitative method, the 3.5-year leukemia-free survival was significantly higher in children negative for minimal residual disease compared to those with positive results (84.1% ± 5.6% versus 41.7% ± 17.3%, respectively; p-value = 0.004). There was no significant association between leukemia-free survival and minimal residual disease by real-time polymerase chain reaction. Minimal residual disease by qualitative polymerase chain reaction was the only variable significantly correlated to leukemia-free survival. Conclusion Given the difficulties in the implementation of minimal residual disease monitoring by real-time polymerase chain reaction in most treatment centers in Brazil, the qualitative polymerase chain reaction strategy may be a cost-effective alternative. PMID:26670399

  11. Partial Sum Minimization of Singular Values in Robust PCA: Algorithm and Applications.

    PubMed

    Oh, Tae-Hyun; Tai, Yu-Wing; Bazin, Jean-Charles; Kim, Hyeongwoo; Kweon, In So

    2016-04-01

    Robust Principal Component Analysis (RPCA) via rank minimization is a powerful tool for recovering underlying low-rank structure of clean data corrupted with sparse noise/outliers. In many low-level vision problems, not only it is known that the underlying structure of clean data is low-rank, but the exact rank of clean data is also known. Yet, when applying conventional rank minimization for those problems, the objective function is formulated in a way that does not fully utilize a priori target rank information about the problems. This observation motivates us to investigate whether there is a better alternative solution when using rank minimization. In this paper, instead of minimizing the nuclear norm, we propose to minimize the partial sum of singular values, which implicitly encourages the target rank constraint. Our experimental analyses show that, when the number of samples is deficient, our approach leads to a higher success rate than conventional rank minimization, while the solutions obtained by the two approaches are almost identical when the number of samples is more than sufficient. We apply our approach to various low-level vision problems, e.g., high dynamic range imaging, motion edge detection, photometric stereo, image alignment and recovery, and show that our results outperform those obtained by the conventional nuclear norm rank minimization method. PMID:26353362

  12. The impact of concomitant diffuse idiopathic skeletal hyperostosis on the achievement of minimal disease activity in subjects with psoriatic arthritis.

    PubMed

    Pappone, Nicola; Di Minno, Matteo Nicola Dario; Iervolino, Salvatore; Lupoli, Roberta; Mader, Reuven; Zincarelli, Carmela; Peluso, Rosario

    2015-12-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheses. Psoriatic arthritis (PsA) is a seronegative spondyloarthritis associated with psoriasis. Given the possible overlap of the two diseases, we assessed whether DISH presence may affect PsA clinical outcomes. Also, predictors of DISH presence in the cohort were investigated. Consecutive PsA patients from two Italian Rheumatology Research Units were enrolled. Subjects were splitted into two groups, according to the current treatment (TNF-α blockers or traditional DMARDs). All patients underwent a rheumatologic examination, blood sample collections and spine radiographs. Information about traditional vascular risk factors was recorded. In each patient, the presence of minimal disease activity was evaluated and the presence of DISH was established according to the Resnick and Niwayama criteria. Among the 80 enrolled subjects (57.5 % men, mean age 56.5 ± 11.1 years), the overall prevalence of DISH was 30.0 %. Patients with DISH were older, with higher BMI and waist circumference. DISH subjects showed worsen BASMI, HAQ and ESR. In a multivariate regression model, BASMI was a significant predictor of DISH presence (OR 3.027, 95 % CI 1.449-6.325, p = 0.003). The prevalence of MDA was lower in DISH patients than in no-DISH (16.7 vs 41.1 %, p = 0.041), and the presence of DISH was a predictor of not achieving MDA (OR 3.485, 95 % CI 1.051-11.550, p = 0.041). PsA subjects with DISH showed worsen indices of spine mobility and articular function and lower prevalence of minimal disease activity than no-DISH patients.

  13. POLLUTION BALANCE METHOD AND THE DEMONSTRATION OF ITS APPLICATION TO MINIMIZING WASTE IN A BIOCHEMICAL PROCESS

    EPA Science Inventory

    In this study, we introduced several modifications to the WAR (waste reduction) algorithm developed earlier. These modifications were made for systematically handling sensitivity analysis and various tasks of waste minimization. A design hierarchy was formulated to promote appro...

  14. Detection of minimal residual disease in an AML patient with trisomy 8 using interphase fish.

    PubMed

    White, D L; Hutchins, C J; Turczynowicz, S; Suttle, J; Haylock, D N; Hughes, T P; Juttner, C A; To, L B

    1997-08-01

    Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) often exhibit clonal chromosomal abnormalities. Using a probe for the centromeric region of chromosome 8, fluorescence in situ hybridization (FISH) on interphase cells was used to detect trisomy 8 in an AML patient whose leukemia was characterised by the karyotype 47, XY, +8, del(9) (q21.1q32). We have demonstrated using FISH the presence of the trisomy at all stages of the patient's disease course (including remission, peripheral blood cell harvest and relapse), whereas conventional karyoptypic analysis was only able to detect the trisomy at diagnosis and clinical relapse. We have also shown using immunophenotyping, cell sorting and FISH, that the trisomic cells in this patient were restricted to the CD34+ subset of blood and bone marrow and could not be found in the CD 34-, T or B cell compartment. Overall we have shown FISH to be a rapid, quantitative method for the detection of cells with numerical chromosome abnormalities. FISH analysis of interphase cells provides valuable information on the status of the whole population, rather than just cycling cells, and can be applied successfully to monitor the level of leukemic cells.

  15. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

  16. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies. PMID:27012865

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

    PubMed

    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.

  18. A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma.

    PubMed

    Muz, Barbara; de la Puente, Pilar; Azab, Feda; Luderer, Micah John; King, Justin; Vij, Ravi; Azab, Abdel Kareem

    2016-04-01

    CD138 (also termed SDC1) has been the gold-standard surface marker to detect multiple myeloma (MM) cells for decades; however, drug-resistant residual and circulating MM cells were shown to have lower expression of this marker. In this study, we have shown that residual MM cells following bortezomib treatment are hypoxic. This combination of drug exposure and hypoxia down-regulates their CD138 expression, thereby making this marker unsuitable for detecting residual or other hypoxic MM cells, such as circulating tumour cells, in MM. Hence, we developed an alternative biomarker set which detects myeloma cells independent of their hypoxic and CD138 expression status in vitro, in vivo and in primary MM patients. The new markers were able to identify a clonal CD138-negative population as minimal residual disease in the bone marrow and peripheral blood of MM patients. Further investigation to characterize the role of this population as a prognostic marker in MM is warranted.

  19. Stochastic quasi-Newton method: application to minimal model for proteins.

    PubMed

    Chau, C D; Sevink, G J A; Fraaije, J G E M

    2011-01-01

    Knowledge of protein folding pathways and inherent structures is of utmost importance for our understanding of biological function, including the rational design of drugs and future treatments against protein misfolds. Computational approaches have now reached the stage where they can assess folding properties and provide data that is complementary to or even inaccessible by experimental imaging techniques. Minimal models of proteins, which make possible the simulation of protein folding dynamics by (systematic) coarse graining, have provided understanding in terms of descriptors for folding, folding kinetics, and folded states. Here we focus on the efficiency of equilibration on the coarse-grained level. In particular, we applied a new regularized stochastic quasi-Newton (S-QN) method, developed for accelerated configurational space sampling while maintaining thermodynamic consistency, to analyze the folding pathway and inherent structures of a selected protein, where regularization was introduced to improve stability. The adaptive compound mobility matrix B in S-QN, determined by a factorized secant update, gives rise to an automated scaling of all modes in the protein, in particular an acceleration of protein domain dynamics or principal modes and a slowing down of fast modes or "soft" bond constraints, similar to lincs/shake algorithms, when compared to conventional Langevin dynamics. We used and analyzed a two-step strategy. Owing to the enhanced sampling properties of S-QN and increased barrier crossing at high temperatures (in reduced units), a hierarchy of inherent protein structures is first efficiently determined by applying S-QN for a single initial structure and T=1>T(θ), where T(θ) is the collapse temperature. Second, S-QN simulations for several initial structures at very low temperature (T=0.01

  20. Application of the Flexible CO2 Laser in Minimally Invasive Laminectomies: Technical Note.

    PubMed

    Hussain, Namath S; Perez-Cruet, Mick

    2016-06-02

    Background Minimally invasive laminectomy is a very effective surgical method for treating lumbar stenosis. However, this technique can be technically difficult, especially in patients suffering from severe stenosis. The contralateral decompression from a unilateral approach can result in durotomy during removal of the hypertrophied ligamentum flavum. This complication can be difficult to treat through a small working channel. Objective To detail our group's operative experience with the CO2 laser and discuss our results and previous studies in the literature reporting results.  Methods The CO2 laser (Omniguide, Boston, MA) was investigated in the surgical ablation of the contralateral ligamentum flavum during minimally invasive laminectomies. Forty levels have been investigated thus far. The amount of voltage needed to adequately desiccate and remove the ligamentum flavum safely as well as the effectiveness of this technique were investigated. Results The contralateral ligamentum flavum could be removed effectively using the 9 to 11 watt continuous wavelength (10,600 nanometer) power setting on the CO2 laser. Shrinkage of the contralateral ligamentum flavum facilitated its removal using a number 2 Kerrison Punch. No durotomies occurred, and the use of the laser did not significantly lengthen operative times.  Conclusions The CO2 laser appears to be a useful tool in the armamentarium of instruments available to the minimally invasive spine surgeon and may help to reduce the incidence of durotomies when performing minimally invasive laminectomies.

  1. Multimodal function optimization using minimal representation size clustering and its application to planning multipaths.

    PubMed

    Hocaoğlu, C; Sanderson, A C

    1997-01-01

    A novel genetic algorithm (GA) using minimal representation size cluster (MRSC) analysis is designed and implemented for solving multimodal function optimization problems. The problem of multimodal function optimization is framed within a hypothesize-and-test paradigm using minimal representation size (minimal complexity) for species formation and a GA. A multiple-population GA is developed to identify different species. The number of populations, thus the number of different species, is determined by the minimal representation size criterion. Therefore, the proposed algorithm reveals the unknown structure of the multimodal function when a priori knowledge about the function is unknown. The effectiveness of the algorithm is demonstrated on a number of multimodal test functions. The proposed scheme results in a highly parallel algorithm for finding multiple local minima. In this paper, a path-planning algorithm is also developed based on the MRSC_GA algorithm. The algorithm utilizes MRSC_GA for planning paths for mobile robots, piano-mover problems, and N-link manipulators. The MRSC_GA is used for generating multipaths to provide alternative solutions to the path-planning problem. The generation of alternative solutions is especially important for planning paths in dynamic environments. A novel iterative multiresolution path representation is used as a basis for the GA coding. The effectiveness of the algorithm is demonstrated on a number of two-dimensional path-planning problems.

  2. Application of the Flexible CO2 Laser in Minimally Invasive Laminectomies: Technical Note

    PubMed Central

    Perez-Cruet, Mick

    2016-01-01

    Background Minimally invasive laminectomy is a very effective surgical method for treating lumbar stenosis. However, this technique can be technically difficult, especially in patients suffering from severe stenosis. The contralateral decompression from a unilateral approach can result in durotomy during removal of the hypertrophied ligamentum flavum. This complication can be difficult to treat through a small working channel. Objective To detail our group’s operative experience with the CO2 laser and discuss our results and previous studies in the literature reporting results.  Methods The CO2 laser (Omniguide, Boston, MA) was investigated in the surgical ablation of the contralateral ligamentum flavum during minimally invasive laminectomies. Forty levels have been investigated thus far. The amount of voltage needed to adequately desiccate and remove the ligamentum flavum safely as well as the effectiveness of this technique were investigated. Results The contralateral ligamentum flavum could be removed effectively using the 9 to 11 watt continuous wavelength (10,600 nanometer) power setting on the CO2 laser. Shrinkage of the contralateral ligamentum flavum facilitated its removal using a number 2 Kerrison Punch. No durotomies occurred, and the use of the laser did not significantly lengthen operative times.  Conclusions The CO2 laser appears to be a useful tool in the armamentarium of instruments available to the minimally invasive spine surgeon and may help to reduce the incidence of durotomies when performing minimally invasive laminectomies. PMID:27433407

  3. Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

    PubMed Central

    YAMAMOTO, NOBUYUKI; KOZAKI, AIKO; HARTOMO, TRI BUDI; YANAI, TOMOKO; HASEGAWA, DAIICHIRO; KAWASAKI, KEIICHIRO; KOSAKA, YOSHIYUKI; MATSUO, MASAFUMI; HIRASE, SATOSHI; MORI, TAKESHI; HAYAKAWA, AKIRA; IIJIMA, KAZUMOTO; NISHIO, HISAHIDE; NISHIMURA, NORIYUKI

    2015-01-01

    Neuroblastoma is an aggressive solid tumor that leads to tumor relapse in more than half of high-risk patients. Minimal residual disease (MRD) is primarily responsible for tumor relapses and may be detected in peripheral blood (PB) and bone marrow (BM) samples. To evaluate the disease status and treatment response, a number of MRD detection protocols based on either common or distinct markers for PB and BM samples have been reported. However, the correlation between the expression of MRD markers in PB and BM samples remains elusive in the clinical samples. In the present study, the expression of 11 previously validated MRD markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) was determined in 23 pairs of PB and BM samples collected from seven high-risk neuroblastoma patients at the same time point, and the sample was scored as MRD-positive if one of the MRD markers exceeded the normal range. Although the number of MRD-positive samples was not significantly different between PB and BM samples, the two most sensitive markers for PB samples (CRMP1 and KIF1A) were different from those for BM samples (PHOX2B and DBH). There was no statistically significant correlation between the expression of MRD markers in the PB and BM samples. These results suggest that MRD markers were differentially expressed in PB and BM samples from high-risk neuroblastoma patients. PMID:26722317

  4. Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Dal Bó, Suzane; Pezzi, Annelise; Amorin, Bruna; Valim, Vanessa; Isabel Bittencourt, Rosane; Silla, Lucia

    2013-01-01

    The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45−/dim, CD38+high, CD138+, CD19−, and  CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P = 0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population. PMID:23864957

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

    PubMed Central

    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

  6. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

    PubMed

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J; Strausberg, Robert L; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Gibbs, Peter

    2016-07-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

  7. Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia.

    PubMed

    Bibault, Jean-Emmanuel; Figeac, Martin; Hélevaut, Nathalie; Rodriguez, Céline; Quief, Sabine; Sebda, Shéhérazade; Renneville, Aline; Nibourel, Olivier; Rousselot, Philippe; Gruson, Bérengère; Dombret, Hervé; Castaigne, Sylvie; Preudhomme, Claude

    2015-09-01

    Minimal Residual Disease (MRD) detection can be used for early intervention in relapse, risk stratification, and treatment guidance. FLT3 ITD is the most common mutation found in AML patients with normal karyotype. We evaluated the feasibility of NGS with high coverage (up to 2.4.10(6) PE fragments) for MRD monitoring on FLT3 ITD. We sequenced 37 adult patients at diagnosis and various times of their disease (64 samples) and compared the results with FLT3 ITD ratios measured by fragment analysis. We found that NGS could detect variable insertion sites and lengths in a single test for several patients. We also showed mutational shifts between diagnosis and relapse, with the outgrowth of a clone at relapse different from that dominant at diagnosis. Since NGS is scalable, we were able to adapt sensitivity by increasing the number of reads obtained for follow-up samples, compared to diagnosis samples. This technique could be applied to detect biological relapse before its clinical consequences and to better tailor treatments through the use of FLT3 inhibitors. Larger cohorts should be assessed in order to validate this approach.

  8. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

    PubMed

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J; Strausberg, Robert L; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Gibbs, Peter

    2016-07-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence. PMID:27384348

  9. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol.

    PubMed

    Van der Velden, V H J; Corral, L; Valsecchi, M G; Jansen, M W J C; De Lorenzo, P; Cazzaniga, G; Panzer-Grümayer, E R; Schrappe, M; Schrauder, A; Meyer, C; Marschalek, R; Nigro, L L; Metzler, M; Basso, G; Mann, G; Den Boer, M L; Biondi, A; Pieters, R; Van Dongen, J J M

    2009-06-01

    Acute lymphoblastic leukemia (ALL) in infants younger than 1 year is a rare but relatively homogeneous disease ( approximately 80% MLL gene rearranged, approximately 70% CD10-negative) when compared with childhood and adult ALL. Several studies in children and adults with ALL have shown that minimal residual disease (MRD) status is a strong and independent prognostic factor. We therefore evaluated the prognostic significance of MRD in infant ALL. Ninety-nine infant patients treated according to the Interfant-99 protocol were included in this study. MRD was analyzed by real-time quantitative PCR analysis of rearranged immunoglobulin genes, T-cell receptor genes and MLL genes at various time points (TP) during therapy. Higher MRD levels at the end of induction (TP2) and consolidation (TP3) were significantly associated with lower disease-free survival. Combined MRD information at TP2 and TP3 allowed recognition of three patients groups that significantly differed in outcome. All MRD-high-risk patients (MRD levels > or =10(-4) at TP3; 26% of patients) relapsed. MRD-low-risk patients (MRD level <10(-4) at both TP2 and TP3) constituted 44% of patients and showed a relapse-rate of only 13%, whereas remaining patients (MRD-medium-risk patients; 30% of patients) had a relapse rate of 31%. Comparison between the current Interfant-06 stratification at diagnosis and the here presented MRD-based stratification showed that both stratifications recognized different subgroups of patients. These data indicate that MRD diagnostics has added value for recognition of risk groups in infant ALL and that MRD diagnostics can be used for treatment intervention in infant ALL as well.

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

    PubMed Central

    Ren, Hong; Liu, Jian; Zhang, Weijia; Wei, Chengguo; Xu, Jing; Zhang, Wen; Li, Xiao; Wang, Weiming; Lv, Danfeng; He, John Cijiang; Chen, Nan

    2015-01-01

    Objective To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Methods 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. Results 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. Conclusions 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. PMID:26536600

  11. Pollution balance method and the demonstration of its application to minimizing waste in a biochemical process

    SciTech Connect

    Hilaly, A.K.; Sikdar, S.K.

    1995-06-01

    In this study, the authors introduced several modifications to the WAR (waste reduction) algorithm developed earlier. These modifications were made for systematically handling sensitivity analysis and various tasks of waste minimization. A design hierarchy was formulated to promote appropriate waste reduction tasks at designated levels of the hierarchy. A sensitivity coefficient was used to measure the relative impacts of process variables on the pollution index of a process. The use of the WAR algorithm was demonstrated by a fermentation process for making penicillin.

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

    PubMed

    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 < 0.0001). In 3 out of 45 tests (6.7%) neoplastic cells were detected with only one method. In the first case, it was the method of four-color flow cytofluometry and in

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  16. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR.

  17. Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia.

    PubMed

    Sun, Hui; Li, Yi; Zhang, Zhi-fen; Ju, Ying; Li, Li; Zhang, Bing-chang; Liu, Bin

    2015-11-01

    Myeloid-derived suppressor cells (MDSCs) are thought to help provide a cellular microenvironments in many solid tumors, in which transformed cells proliferate, acquire new mutations, and evade host immunosurveillance. In the present study, we found that MDSCs (CD33 + CD11b + HLA-DR(low/neg)) in bone marrow were significantly increased in adult acute myeloid leukemia (AML) patients. MDSCs levels in newly diagnosed AML patients correlated well with extramedullary infiltration and plasma D-dimer levels. Remission rates in the MDSCs > 1500 group and MDSCs < 1500 group were 72.73 and 81.25 %, respectively. No significant differences were found between the two groups. MDSC levels in the complete remission group were significantly decreased after chemotherapy, while in the partial remission and non-remission groups, there were no significant differences. The level of MDSCs in the high minimal residual disease (MRD) group was significantly higher than that in the middle and low MRD groups. High levels of Wilms' Tumor-1 (WT-1) protein were strongly correlated with higher bone marrow MDSC levels. In conclusion, we report here a population of immunosuppressive monocytes in the bone marrow of patients with AML characterized by the CD33(high)CD11b + HLA-DR(low/neg) phenotype. These cells appear to impact the clinical course and prognosis of AML. This data may provide potentially important targets for novel therapies.

  18. Immaturity associated antigens are lost during induction for T cell lymphoblastic leukemia: implications for minimal residual disease detection

    PubMed Central

    Roshal, Mikhail; Fromm, Jonathan R; Winter, Stuart; Dunsmore, Kimberly; Wood, Brent

    2011-01-01

    Background Induction chemotherapy for acute leukemia often leads to antigenic shifts in residual abnormal blast populations. Studies in precursor B cell ALL (B-ALL) and AML have demonstrated that chemotherapy commonly results in the loss of antigens associated with immaturity, limiting their utility for minimal residual disease (MRD) detection. Little information is available about the stability of these antigens in precursor T cell ALL (T-ALL) though it is presumed that CD99 and TdT are highly informative based on limited studies. Methods In a longitudinal investigation, we explored patterns of lineage specific and immaturity associated antigens in T-ALL in a large cohort of patients treated under the multicenter Children's Oncology Group (COG) protocol. All samples were analyzed using multicolor flow cytometry in a standardized fashion at a single institution. Results We report that markers of immaturity particularly, TdT and CD99 dramatically decline on leukemic blasts during therapy. CD34 and CD10 expression is confined to a minority of pre-treatment samples and is also not stable. In contrast, lineage associated markers including CD2, CD3, CD4, CD5, CD7 and CD8 failed to show significant trends. Conclusions Our study strongly argues for expansion of immunophenotyping panels for T-ALL MRD to decrease reliance on immature antigens. This study represents the first demonstration of consistent immunophenotypic shifts in T-ALL. PMID:20155852

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

    PubMed

    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 <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). 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. PMID:26598032

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

    PubMed

    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 <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). 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.

  1. Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis

    PubMed Central

    Garin, Eduardo H.; Reiser, Jochen; Cara-Fuentes, Gabriel; Wei, Changli; Matar, Dany; Wang, Heiman; Alachkar, Nada; Johnson, Richard J.

    2014-01-01

    Background Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 were measured by ELISA. Glomeruli were stained for CD80. Results After abatacept, urinary CD80 became undetectable with concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in one patient with primary FSGS and in two recurrent FSGS subjects despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. One patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before abatacept. After Abatacept, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since urinary CD80 is only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria. PMID:25239302

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

    PubMed Central

    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. PMID:26351598

  3. Davidon-Broyden rank-one minimization methods in Hilbert space with application to optimal control problems

    NASA Technical Reports Server (NTRS)

    Straeter, T. A.

    1972-01-01

    The Davidon-Broyden class of rank one, quasi-Newton minimization methods is extended from Euclidean spaces to infinite-dimensional, real Hilbert spaces. For several techniques of choosing the step size, conditions are found which assure convergence of the associated iterates to the location of the minimum of a positive definite quadratic functional. For those techniques, convergence is achieved without the problem of the computation of a one-dimensional minimum at each iteration. The application of this class of minimization methods for the direct computation of the solution of an optimal control problem is outlined. The performance of various members of the class are compared by solving a sample optimal control problem. Finally, the sample problem is solved by other known gradient methods, and the results are compared with those obtained with the rank one quasi-Newton methods.

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

    PubMed

    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.

  5. Progress toward production of immunologic tolerance with no or minimal toxic immunosuppression for prevention of immunodeficiency and autoimmune diseases.

    PubMed

    Good, R A

    2000-07-01

    With donor and recipient matched at the major histocompatibility complex (MHC) locus, peripheral lymphoid tissue transplantation can be carried out without producing a graft-versus-host reaction or graft-versus-host disease (GVHD), thus correcting profound T cell immunodeficiencies of neonatally thymectomized mice. This analysis set the stage for clinical application of bone marrow transplantation (BMT) to provide for the first time cure of a human disease. With successful BMT, we cured immunologic deficiencies of a patient with XL severe combined immunodeficiency; thereafter we were the first to employ BMT to cure aplastic anemia. BMT regularly corrects immune and hematologic deficiencies caused by fatal irradiation without producing GVHD if the bone marrow (BM) used for the transplants has been purged of postthymic T cells. Over two decades in conjunction with Ikehara et al., we have shown that lethal total body irradiation (TBI) plus allogeneic BMT prevents or cures many organ-specific and systemic experimental autoimmune diseases. Animal models successfully treated by BMT include type I diabetes in nonobese diabetes (NOD) mice, type II diabetes in insulin-insensitive, glucose intolerant, diabetes mellitus (KK/Ay) mice, and autoimmune lupus erythematosus (LE) and glomerulonephritis in New Zealand Black x New Zealand White first generation hybrid (NZB x NZW)F1 females. El-Badri extended Ildstad's original research showing a high frequency of survival with a normal functioning immune system after stable mixed chimerism is produced by mixed BMT in C57BL/6 (normal long-lived black strain) mice transplanted with T cell-depleted marrow (TCDM) from BALB/c ("normal" long-lived strain) allogeneic donors and C57BL/6 syngeneic donors. We showed that osteoblasts act as facilitator cells for allogeneic BMT and promote engraftment of allogeneic hematopoietic stem cells. Wang et al. then showed that the autoimmunities and fulminating renal disease of BXSB (C57BL x SB cross and

  6. Minimal time change detection algorithm for reconfigurable control system and application to aerospace

    NASA Technical Reports Server (NTRS)

    Kim, Sungwan

    1994-01-01

    System parameters should be tracked on-line to build a reconfigurable control system even though there exists an abrupt change. For this purpose, a new performance index that we are studying is the speed of adaptation- how quickly does the system determine that a change has occurred? In this paper, a new, robust algorithm that is optimized to minimize the time delay in detecting a change for fixed false alarm probability is proposed. Simulation results for the aircraft lateral motion with a known or unknown change in control gain matrices, in the presence of doublet input, indicate that the algorithm works fairly well. One of its distinguishing properties is that detection delay of this algorithm is superior to that of Whiteness Test.

  7. Minimal diffusion formulation of Markov chain ensembles and its application to ion channel clusters

    NASA Astrophysics Data System (ADS)

    Güler, Marifi

    2015-06-01

    We study ensembles of continuous-time Markov chains evolving independently under a common transition rate matrix in some finite state space. A diffusion approximation, composed of two specifically coupled Ornstein-Uhlenbeck processes in stochastic differential equation representation, is formulated to deduce how the number of chains in a given particular state evolves in time. This particular form of the formulation builds upon a theoretical argument adduced here. The formulation is minimal in the sense that it is always a two-dimensional stochastic process regardless of the state space size or the transition matrix density, and that it requires no matrix square root operations. A set of criteria, put forward here as to be necessarily captured by any consistent approximation scheme, is used together with the master equation to determine uniquely the parameter values and noise variances in the formulation. The model is applied to the gating dynamics in ion channel clusters.

  8. Application of edible coating with starch and carvacrol in minimally processed pumpkin.

    PubMed

    Santos, Adriele R; da Silva, Alex F; Amaral, Viviane C S; Ribeiro, Alessandra B; de Abreu Filho, Benicio A; Mikcha, Jane M G

    2016-04-01

    The present study evaluated the effect of an edible coating of cassava starch and carvacrol in minimally processed pumpkin (MPP). The minimal inhibitory concentration (MIC) of carvacrol against Escherichia coli, Salmonella enterica serotype Typhimurium, Aeromonas hydrophila, and Staphylococcus aureus was determined. The edible coating that contained carvacrol at the MIC and 2 × MIC was applied to MPP, and effects were evaluated with regard to the survival of experimentally inoculated bacteria and autochthonous microflora in MPP. Total titratable acidity, pH, weight loss, and soluble solids over 7 days of storage under refrigeration was also analyzed. MIC of carvacrol was 312 μg/ml. Carvacrol at the MIC reduced the counts of E. coli and S. Typhimurium by approximately 5 log CFU/g. A. hydrophila was reduced by approximately 8 log CFU/g, and S. aureus was reduced by approximately 2 log CFU/g on the seventh day of storage. Carvacrol at the 2 × MIC completely inhibited all isolates on the first day of Storage. coliforms at 35 °C and 45 °C were not detected (< 3 MPN/g) with either treatment on all days of shelf life. The treatment groups exhibited a reduction of approximately 2 log CFU/g in psychrotrophic counts compared with controls on the last day of storage. Yeast and mold were not detected with either treatment over the same period. The addition of carvacrol did not affect total titratable acidity, pH, or soluble solids and improved weight loss. The edible coating of cassava starch with carvacrol may be an interesting approach to improve the safety and microbiological quality of MPP. PMID:27413224

  9. Application of edible coating with starch and carvacrol in minimally processed pumpkin.

    PubMed

    Santos, Adriele R; da Silva, Alex F; Amaral, Viviane C S; Ribeiro, Alessandra B; de Abreu Filho, Benicio A; Mikcha, Jane M G

    2016-04-01

    The present study evaluated the effect of an edible coating of cassava starch and carvacrol in minimally processed pumpkin (MPP). The minimal inhibitory concentration (MIC) of carvacrol against Escherichia coli, Salmonella enterica serotype Typhimurium, Aeromonas hydrophila, and Staphylococcus aureus was determined. The edible coating that contained carvacrol at the MIC and 2 × MIC was applied to MPP, and effects were evaluated with regard to the survival of experimentally inoculated bacteria and autochthonous microflora in MPP. Total titratable acidity, pH, weight loss, and soluble solids over 7 days of storage under refrigeration was also analyzed. MIC of carvacrol was 312 μg/ml. Carvacrol at the MIC reduced the counts of E. coli and S. Typhimurium by approximately 5 log CFU/g. A. hydrophila was reduced by approximately 8 log CFU/g, and S. aureus was reduced by approximately 2 log CFU/g on the seventh day of storage. Carvacrol at the 2 × MIC completely inhibited all isolates on the first day of Storage. coliforms at 35 °C and 45 °C were not detected (< 3 MPN/g) with either treatment on all days of shelf life. The treatment groups exhibited a reduction of approximately 2 log CFU/g in psychrotrophic counts compared with controls on the last day of storage. Yeast and mold were not detected with either treatment over the same period. The addition of carvacrol did not affect total titratable acidity, pH, or soluble solids and improved weight loss. The edible coating of cassava starch with carvacrol may be an interesting approach to improve the safety and microbiological quality of MPP.

  10. Application of Nanomedicine to the CNS Diseases.

    PubMed

    Carradori, D; Gaudin, A; Brambilla, D; Andrieux, K

    2016-01-01

    Drug delivery to the brain is a challenge because of the many mechanisms that protect the brain from the entry of foreign substances. Numerous molecules which could be active against brain disorders are not clinically useful due to the presence of the blood-brain barrier. Nanoparticles can be used to deliver these drugs to the brain. Encapsulation within colloidal systems can allow the passage of nontransportable drugs across this barrier by masking their physicochemical properties. It should be noted that the status of the blood-brain barrier is different depending on the brain disease. In fact, in some pathological situations such as tumors or inflammatory disorders, its permeability is increased allowing very easy translocation of carriers. This chapter gathers the promising results obtained by using nanoparticles as drug delivery systems with the aim to improve the therapy of some CNS diseases such as brain tumor, Alzheimer's disease, and stroke. The data show that several approaches can be investigated: (1) carrying drug through a permeabilized barrier, (2) crossing the barrier thanks to receptor-mediated transcytosis pathway in order to deliver drug into the brain parenchyma, and also (3) targeting and treating the endothelial cells themselves to preserve locally the brain tissue. The examples given in this chapter contribute to demonstrate that delivering drugs into the brain is one of the most promising applications of nanotechnology in clinical neuroscience. PMID:27678175

  11. 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?

    PubMed

    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.

  12. Application of the microbiological method DEFT/APC to detect minimally processed vegetables treated with gamma radiation

    NASA Astrophysics Data System (ADS)

    Araújo, M. M.; Duarte, R. C.; Silva, P. V.; Marchioni, E.; Villavicencio, A. L. C. H.

    2009-07-01

    Marketing of minimally processed vegetables (MPV) are gaining impetus due to its convenience, freshness and apparent health effect. However, minimal processing does not reduce pathogenic microorganisms to safe levels. Food irradiation is used to extend the shelf life and to inactivate food-borne pathogens. In combination with minimal processing it could improve safety and quality of MPV. A microbiological screening method based on the use of direct epifluorescent filter technique (DEFT) and aerobic plate count (APC) has been established for the detection of irradiated foodstuffs. The aim of this study was to evaluate the applicability of this technique in detecting MPV irradiation. Samples from retail markets were irradiated with 0.5 and 1.0 kGy using a 60Co facility. In general, with a dose increment, DEFT counts remained similar independent of the irradiation while APC counts decreased gradually. The difference of the two counts gradually increased with dose increment in all samples. It could be suggested that a DEFT/APC difference over 2.0 log would be a criteria to judge if a MPV was treated by irradiation. The DEFT/APC method could be used satisfactorily as a screening method for indicating irradiation processing.

  13. The minimal important difference of the King's Brief Interstitial Lung Disease Questionnaire (K-BILD) and forced vital capacity in interstitial lung disease.

    PubMed

    Patel, Amit S; Siegert, Richard J; Keir, Gregory J; Bajwah, Sabrina; Barker, Richard D; Maher, Toby M; Renzoni, Elisabetta A; Wells, Athol U; Higginson, Irene J; Birring, Surinder S

    2013-09-01

    Health status and forced vital capacity (FVC) are widely used outcome measures of interstitial lung disease (ILD) but there is a paucity of studies reporting the minimal clinically meaningful change in these parameters. A study was undertaken to assess the minimal important difference (MID) of an ILD specific health status questionnaire, the King's Brief ILD questionnaire (K-BILD) and that of FVC in a range of ILDs. 57 patients with ILD (17 idiopathic pulmonary fibrosis; IPF) completed the K-BILD (score range 0-100) at 2 separate clinic visits. Patients underwent spirometry at both visits. The MID was determined by a range of distribution methods (Standard error of mean: SEM and 0.3× Effect size: ES) and anchor based methods (objective: FVC and subjective: global rating of change questionnaires, GRCQ). The MID was derived by calculating an average of all methods. Health status was reduced at baseline in all patients, mean (SD) K-BILD total score 62(23). The average MID for K-BILD total score incorporating all methods was an 8 unit change (range 6-10). The average MID for FVC was a 6% change of baseline (range 4-7%). The K-BILD is a responsive patient reported outcome measure for patients with ILD. It can potentially be used to assess patients in the clinic and evaluate the response to therapy. The MID of the K-BILD total score is 8 units. The MID for FVC for a range of ILDs was 6%, similar to that reported recently for patients with IPF. Our findings will facilitate the clinical interpretation of health status and FVC data in ILD.

  14. Quantitative detection of the human cervical cancer oncogene for monitoring the minimal residual disease in acute leukemia

    PubMed Central

    Guo, Xiao-Nan; Ren, Jin-Hai; Zhang, Jing-Nan; Wang, Ying

    2015-01-01

    The human cervical cancer oncogene (HCCR) has been shown to be over-expressed in some solid tumors, and its function is involved in negative regulation of p53 tumor suppressor gene. However, the roles of HCCR in leukemia remain unclear. The present study is to investigate whether the expression levels of HCCR mRNA are associated with clinical prognosis in patients with acute leukemia (AL) and to explore the potential use as a biomarker for monitoring minimal residual disease (MRD) in AL. The mRNA levels of HCCR1 and HCCR2 were quantified by real-time reverse transcription polymerase chain reaction in bone marrow samples from 80 adult de novo AL patients and 20 normal healthy donors. The expressions of HCCR1 and HCCR2 were significantly higher in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) than those in healthy donors (P < 0.01), but there was no significant difference between AML and ALL (P > 0.05). Besides white blood cell count, we did not find any significant correlation between HCCR expression and clinical characteristics, such as age, sex, CD34 antigen expression, and response to chemotherapy. HCCR was monitored in 12 cases during remission and/or relapse. Significant reductions of both HCCR1 and HCCR2 mRNA levels were observed in patients who had achieved complete remission after chemotherapy but not in patients with non-responsive. However, an increased HCCR expression was detected in these patients who relapsed. Our findings suggest that HCCR gene is over-expressed in AL patients and may be as a useful biomarker for monitoring MRD in AL. PMID:25034723

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

    PubMed

    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.

  16. Improved minimal residual disease detection by targeted quantitative polymerase chain reaction in Nucleophosmin 1 type a mutated acute myeloid leukemia.

    PubMed

    Pettersson, Louise; Levéen, Per; Axler, Olof; Dvorakova, Dana; Juliusson, Gunnar; Ehinger, Mats

    2016-10-01

    Multicolor flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are important independent techniques to determine minimal residual disease (MRD) in acute myeloid leukemia (AML). MFC is the standard method, but may be unreliable. Therefore, MFC-based determination of MRD with an RQ-PCR-based approach targeting the nucleophosmin 1 (NPM1) type A mutation was set out to compare. Since most current NPM1 RQ-PCR MRD protocols suffer from clear definitions of quantifiability, we sought to define quantifiability in a reproducible and standardized manner. The limit of quantifiability of our RQ-PCR protocol for the NPM1 type A mutation varied between 0.002% and 0.04% residual leukemic cells depending on the features of the standard curve for each PCR experiment. The limit of detection was close to 0.001% leukemic cells. The limit of detection by MFC ranged from 0.01% to 1% depending on the phenotype of the leukemic cells as compared with non-leukemic bone marrow cells. Forty-five MRD samples from 15 patients using both NPM1 mutation specific RQ-PCR and MFC were analyzed. In 32 of the 45 samples (71%), an MRD-signal could be detected with RQ-PCR. A quantifiable NPM1 mutation signal was found in 15 samples (33%) (range 0.003%-2.6% leukemic cells). By contrast, only two follow-up samples (4%) showed residual leukemic cells (0.04% and 0.3%, respectively) by MFC. Thus, RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of MRD, which might have clinical implications. © 2016 Wiley Periodicals, Inc.

  17. Improved minimal residual disease detection by targeted quantitative polymerase chain reaction in Nucleophosmin 1 type a mutated acute myeloid leukemia.

    PubMed

    Pettersson, Louise; Levéen, Per; Axler, Olof; Dvorakova, Dana; Juliusson, Gunnar; Ehinger, Mats

    2016-10-01

    Multicolor flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are important independent techniques to determine minimal residual disease (MRD) in acute myeloid leukemia (AML). MFC is the standard method, but may be unreliable. Therefore, MFC-based determination of MRD with an RQ-PCR-based approach targeting the nucleophosmin 1 (NPM1) type A mutation was set out to compare. Since most current NPM1 RQ-PCR MRD protocols suffer from clear definitions of quantifiability, we sought to define quantifiability in a reproducible and standardized manner. The limit of quantifiability of our RQ-PCR protocol for the NPM1 type A mutation varied between 0.002% and 0.04% residual leukemic cells depending on the features of the standard curve for each PCR experiment. The limit of detection was close to 0.001% leukemic cells. The limit of detection by MFC ranged from 0.01% to 1% depending on the phenotype of the leukemic cells as compared with non-leukemic bone marrow cells. Forty-five MRD samples from 15 patients using both NPM1 mutation specific RQ-PCR and MFC were analyzed. In 32 of the 45 samples (71%), an MRD-signal could be detected with RQ-PCR. A quantifiable NPM1 mutation signal was found in 15 samples (33%) (range 0.003%-2.6% leukemic cells). By contrast, only two follow-up samples (4%) showed residual leukemic cells (0.04% and 0.3%, respectively) by MFC. Thus, RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of MRD, which might have clinical implications. © 2016 Wiley Periodicals, Inc. PMID:27191933

  18. Applicability of PM3 to transphosphorylation reaction path: Toward designing a minimal ribozyme

    NASA Technical Reports Server (NTRS)

    Manchester, John I.; Shibata, Masayuki; Setlik, Robert F.; Ornstein, Rick L.; Rein, Robert

    1993-01-01

    A growing body of evidence shows that RNA can catalyze many of the reactions necessary both for replication of genetic material and the possible transition into the modern protein-based world. However, contemporary ribozymes are too large to have self-assembled from a prebiotic oligonucleotide pool. Still, it is likely that the major features of the earliest ribozymes have been preserved as molecular fossils in the catalytic RNA of today. Therefore, the search for a minimal ribozyme has been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determine the effects of structural features of the ribozyme on the reaction it catalyzes. Using this model, quantum chemical calculations must be performed to determine quantitatively the effects of structural features on catalysis. Previous studies of the reaction path have been conducted at the ab initio level, but these methods are limited to small models due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on a simple model of the ribozyme-catalyzed reaction, or hydrolysis of phosphoric acid. We find that the results are qualitatively similar to ab initio results using large basis sets. Therefore, PM3 is suitable for studying the reaction path of the ribozyme-catalyzed reaction.

  19. Finite element based stability-constrained weight minimization of sandwich composite ducts for airship applications

    NASA Astrophysics Data System (ADS)

    Khode, Urmi B.

    High Altitude Long Endurance (HALE) airships are platform of interest due to their persistent observation and persistent communication capabilities. A novel HALE airship design configuration incorporates a composite sandwich propulsive hull duct between the front and the back of the hull for significant drag reduction via blown wake effects. The sandwich composite shell duct is subjected to hull pressure on its outer walls and flow suction on its inner walls which result in in-plane wall compressive stress, which may cause duct buckling. An approach based upon finite element stability analysis combined with a ply layup and foam thickness determination weight minimization search algorithm is utilized. Its goal is to achieve an optimized solution for the configuration of the sandwich composite as a solution to a constrained minimum weight design problem, for which the shell duct remains stable with a prescribed margin of safety under prescribed loading. The stability analysis methodology is first verified by comparing published analytical results for a number of simple cylindrical shell configurations with FEM counterpart solutions obtained using the commercially available code ABAQUS. Results show that the approach is effective in identifying minimum weight composite duct configurations for a number of representative combinations of duct geometry, composite material and foam properties, and propulsive duct applied pressure loading.

  20. Unconstrained and Constrained Minimization, Linear Scaling, and the Grassmann Manifold: Theory and Applications

    SciTech Connect

    RACZKOWSKI,DAVID; FONG,C.Y.; SCHULTZ,PETER A.; LIPPERT,ROSS A.; STECHEL,E.B.

    2000-07-19

    An unconstrained minimization algorithm for electronic structure calculations using density functional for systems with a gap is developed to solve for nonorthogonal Wannier-like orbitals in the spirit of E. B. Stechel, A. R. Williams, and P. J. Feibelman, Phys. Rev. B 49, 10,008 (1994). The search for the occupied sub-space is a Grassmann conjugate gradient algorithm generalized from the algorithm of A. Edelman, T.A. Arias, and S. T. Smith, SIAM J. on Matrix Anal. Appl. 20, 303 (1998). The gradient takes into account the nonorthogonality of a local atom-centered basis, gaussian in their implementation. With a localization constraint on the Wannier-like orbitals, well-constructed sparse matrix multiplies lead to O(N) scaling of the computationally intensive parts of the algorithm. Using silicon carbide as a test system, the accuracy, convergence, and implementation of this algorithm as a quantitative alternative to diagonalization are investigated. Results up to 1,458 atoms on a single processor are presented.

  1. Reduction of Minimal Residual Disease in Pediatric B-lineage Acute Lymphoblastic Leukemia by an Fc-optimized CD19 Antibody.

    PubMed

    Seidel, Ursula Jördis Eva; Schlegel, Patrick; Grosse-Hovest, Ludger; Hofmann, Martin; Aulwurm, Steffen; Pyz, Elwira; Schuster, Friedhelm R; Meisel, Roland; Ebinger, Martin; Feuchtinger, Tobias; Teltschik, Heiko-Manuel; Witte, Kai-Erik; Schwarze, Carl-Philipp; Rammensee, Hans-Georg; Handgretinger, Rupert; Jung, Gundram; Lang, Peter

    2016-09-01

    Prognosis of primary refractory and relapsed pediatric B-lineage acute lymphoblastic leukemia (ALL) is very poor. Relapse rates significantly correlate with persistent minimal residual disease (MRD). In MRD, favorable effector-target ratios prevail and thus this situation might be optimally suited for immunotherapy with antibodies recruiting immunological effector cells. We here report on the generation, preclinical characterization and first clinical application in B-lineage ALL of an Fc-optimized CD19 antibody. This third-generation antibody (4G7SDIE) mediated enhanced antibody-dependent cellular cytotoxicity (ADCC) against leukemic blasts with effector cells from healthy volunteers and B-lineage ALL patients. The antibody was produced in a university-owned production unit and was applied on a compassionate use basis to 14 pediatric patients with refractory and relapsed B-lineage ALL at the stage of MRD. In 10/14 patients, MRD was reduced by ≥ 1 log or below the patient-individual detection limit, and 5/14 patients have achieved ongoing complete molecular remission with a median leukemia-free survival of 428 days. Two additional patients died in complete molecular remission due to complications not related to antibody therapy. Besides profound in vivo B-cell depletion, side effects were negligible. A clinical phase 1/2 study to further assess the therapeutic activity of 4G7SDIE is in preparation.

  2. Teaching the Concept of Gibbs Energy Minimization through Its Application to Phase-Equilibrium Calculation

    ERIC Educational Resources Information Center

    Privat, Romain; Jaubert, Jean-Noe¨l; Berger, Etienne; Coniglio, Lucie; Lemaitre, Ce´cile; Meimaroglou, Dimitrios; Warth, Vale´rie

    2016-01-01

    Robust and fast methods for chemical or multiphase equilibrium calculation are routinely needed by chemical-process engineers working on sizing or simulation aspects. Yet, while industrial applications essentially require calculation tools capable of discriminating between stable and nonstable states and converging to nontrivial solutions,…

  3. Fast extraction of minimal paths in 3D images and applications to virtual endoscopy.

    PubMed

    Deschamps, T; Cohen, L D

    2001-12-01

    The aim of this article is to build trajectories for virtual endoscopy inside 3D medical images, using the most automatic way. Usually the construction of this trajectory is left to the clinician who must define some points on the path manually using three orthogonal views. But for a complex structure such as the colon, those views give little information on the shape of the object of interest. The path construction in 3D images becomes a very tedious task and precise a priori knowledge of the structure is needed to determine a suitable trajectory. We propose a more automatic path tracking method to overcome those drawbacks: we are able to build a path, given only one or two end points and the 3D image as inputs. This work is based on previous work by Cohen and Kimmel [Int. J. Comp. Vis. 24 (1) (1997) 57] for extracting paths in 2D images using Fast Marching algorithm. Our original contribution is twofold. On the first hand, we present a general technical contribution which extends minimal paths to 3D images and gives new improvements of the approach that are relevant in 2D as well as in 3D to extract linear structures in images. It includes techniques to make the path extraction scheme faster and easier, by reducing the user interaction. We also develop a new method to extract a centered path in tubular structures. Synthetic and real medical images are used to illustrate each contribution. On the other hand, we show that our method can be efficiently applied to the problem of finding a centered path in tubular anatomical structures with minimum interactivity, and that this path can be used for virtual endoscopy. Results are shown in various anatomical regions (colon, brain vessels, arteries) with different 3D imaging protocols (CT, MR). PMID:11731307

  4. Current applications of lasers in heart disease

    NASA Astrophysics Data System (ADS)

    Lee, Garrett; Chan, Ming C.; Mason, Dean T.

    1993-03-01

    Although the laser has been in existence for abut 30 years, its application in heart disease has only been examined in the past decade. Much attention has been given its exciting potential in treating coronary artery disease. Transmitted through a catheter comprised of one or more thin optical fibers which can be threaded nonsurgically into the coronary artery, the laser can ablate atherosclerotic plaque that obstructs the artery and diminishes blood flow to the myocardium. In clinical studies, the laser can treat some obstructive lesions that are not suitable for balloon angioplasty (i.e., long and diffuse lesions, very tight stenoses, ostial lesions, calcified lesions). In patients who failed balloon angioplasty due to severe dissection or abrupt closure, the laser may seal up the dissections and restore antegrade blood flow. In addition, the laser may have other applications and treatment modalities that are still under investigation. It may ablate ectopic ventricular foci, or terminate supraventricular tachyrhythmia by destroying the heart's abnormal conduction pathways. It can cut the hypertrophied septum that is associated with left ventricular outflow tract obstruction, or create a channel in the atrial septum as a palliative procedure in newborns with transposition of the great vessels. It may provide a wider orifice for blood flow within the heart in infants with pulmonary outflow obstruction and in adults with aortic valvular stenosis. It is also capable of fusing small thin-walled blood vessels together. Further, a more intriguing possibility is its use to bore several tiny channels in the myocardium to allow oxygenated blood from within the ventricular chamber to perfuse the ischemic heart tissue.

  5. Applications of supercritical fluid technology to pollution prevention and waste minimization

    SciTech Connect

    Turner, R.J.

    1995-10-01

    One approach to the prevention of pollution and the reduction of worker exposure from conventional solvents is the use of less hazardous substitutes. One of the more novel substitutes is carbon dioxide. Although carbon dioxide is a gas at ordinary conditions, it can be liquified by application of pressure. In its supercritical state, it exhibits good solvent properties. Separation of the carbon dioxide from the extracted materials can be accomplished by pressure reduction, adsorption onto activated carbon, or with a membrane process, e.g., decaffeination of coffee. This paper presents a brief overview of the university and federal laboratory collaborative efforts focusing on processes using supercritical carbon dioxide as a substitute for hazardous solvents. The SCCO2 technology applications under this program include extraction of natural pharmaceutical materials, phase-transfer catalysis, solvent replacement in chemical synthesis, temperature-solubility relationships, and separation of organic materials from soils and slurries. A paper on the extraction of heavy metals with SCCO2 was presented by Ataai et.al. at the 87th National Meeting, A&WMA. This work is also supported by the EPA.

  6. Management considerations to minimize environmental impacts of arsenic following monosodium methylarsenate (MSMA) applications to turfgrass.

    PubMed

    Mahoney, Denis J; Gannon, Travis W; Jeffries, Matthew D; Matteson, Audrey R; Polizzotto, Matthew L

    2015-03-01

    Monosodium methylarsenate (MSMA) is an organic arsenical herbicide currently utilized in turfgrass and cotton systems. In recent years, concerns over adverse impacts of arsenic (As) from MSMA applications have emerged; however, little research has been conducted in controlled field experiments using typical management practices. To address this knowledge gap, a field lysimeter experiment was conducted during 2012-2013 to determine the fate of As following MSMA applications to a bareground and an established turfgrass system. Arsenic concentrations in soil, porewater, and aboveground vegetation, were measured through one yr after treatment. Aboveground vegetation As concentration was increased compared to nontreated through 120 d after initial treatment (DAIT). In both systems, increased soil As concentrations were observed at 0-4 cm at 30 and 120 DAIT and 0-8 cm at 60 and 365 DAIT, suggesting that As was bound in shallow soil depths. Porewater As concentrations in MSMA-treated lysimeters from a 30-cm depth (22.0-83.8 μg L(-1)) were greater than those at 76-cm depth (0.4-5.1 μg L(-1)). These results were combined with previous research to devise management considerations in systems where MSMA is utilized. MSMA should not be applied if rainfall is forecasted within 7 DAIT and/or in areas with shallow water tables. Further, disposing of MSMA-treated turfgrass aboveground vegetation in a confined area - a common management practice for turfgrass clippings - may be of concern due to As release to surface water or groundwater as the vegetation decomposes. Finally, long-term MSMA use may cause soil As accumulation and thus downward migration of As over time; therefore, MSMA should be used in rotation with other herbicides.

  7. Management considerations to minimize environmental impacts of arsenic following monosodium methylarsenate (MSMA) applications to turfgrass.

    PubMed

    Mahoney, Denis J; Gannon, Travis W; Jeffries, Matthew D; Matteson, Audrey R; Polizzotto, Matthew L

    2015-03-01

    Monosodium methylarsenate (MSMA) is an organic arsenical herbicide currently utilized in turfgrass and cotton systems. In recent years, concerns over adverse impacts of arsenic (As) from MSMA applications have emerged; however, little research has been conducted in controlled field experiments using typical management practices. To address this knowledge gap, a field lysimeter experiment was conducted during 2012-2013 to determine the fate of As following MSMA applications to a bareground and an established turfgrass system. Arsenic concentrations in soil, porewater, and aboveground vegetation, were measured through one yr after treatment. Aboveground vegetation As concentration was increased compared to nontreated through 120 d after initial treatment (DAIT). In both systems, increased soil As concentrations were observed at 0-4 cm at 30 and 120 DAIT and 0-8 cm at 60 and 365 DAIT, suggesting that As was bound in shallow soil depths. Porewater As concentrations in MSMA-treated lysimeters from a 30-cm depth (22.0-83.8 μg L(-1)) were greater than those at 76-cm depth (0.4-5.1 μg L(-1)). These results were combined with previous research to devise management considerations in systems where MSMA is utilized. MSMA should not be applied if rainfall is forecasted within 7 DAIT and/or in areas with shallow water tables. Further, disposing of MSMA-treated turfgrass aboveground vegetation in a confined area - a common management practice for turfgrass clippings - may be of concern due to As release to surface water or groundwater as the vegetation decomposes. Finally, long-term MSMA use may cause soil As accumulation and thus downward migration of As over time; therefore, MSMA should be used in rotation with other herbicides. PMID:25556868

  8. Optimizing convergence rates of alternating minimization reconstruction algorithms for real-time explosive detection applications

    NASA Astrophysics Data System (ADS)

    Bosch, Carl; Degirmenci, Soysal; Barlow, Jason; Mesika, Assaf; Politte, David G.; O'Sullivan, Joseph A.

    2016-05-01

    X-ray computed tomography reconstruction for medical, security and industrial applications has evolved through 40 years of experience with rotating gantry scanners using analytic reconstruction techniques such as filtered back projection (FBP). In parallel, research into statistical iterative reconstruction algorithms has evolved to apply to sparse view scanners in nuclear medicine, low data rate scanners in Positron Emission Tomography (PET) [5, 7, 10] and more recently to reduce exposure to ionizing radiation in conventional X-ray CT scanners. Multiple approaches to statistical iterative reconstruction have been developed based primarily on variations of expectation maximization (EM) algorithms. The primary benefit of EM algorithms is the guarantee of convergence that is maintained when iterative corrections are made within the limits of convergent algorithms. The primary disadvantage, however is that strict adherence to correction limits of convergent algorithms extends the number of iterations and ultimate timeline to complete a 3D volumetric reconstruction. Researchers have studied methods to accelerate convergence through more aggressive corrections [1], ordered subsets [1, 3, 4, 9] and spatially variant image updates. In this paper we describe the development of an AM reconstruction algorithm with accelerated convergence for use in a real-time explosive detection application for aviation security. By judiciously applying multiple acceleration techniques and advanced GPU processing architectures, we are able to perform 3D reconstruction of scanned passenger baggage at a rate of 75 slices per second. Analysis of the results on stream of commerce passenger bags demonstrates accelerated convergence by factors of 8 to 15, when comparing images from accelerated and strictly convergent algorithms.

  9. Approach toward minimizing chemical interference in FAB mass spectra: the development and application of thermally - assisted FAB

    SciTech Connect

    Ackermann, B.L.

    1987-01-01

    Interferences with fast atom bombardment (FAB) mass spectrometry can be classified into two major categories. The first includes impurities which remain after analyte isolation/purification, and is especially problematic in samples of biological origin. The second type of chemical interference originates from the matrix used for FAB. An example of the first type, also known as sample-related interference, is presented in the context of the analysis of the urinary metabolites of the analgesic acetaminophen by means of the off-line combination of reverse phase HPLC and FAB. Recommendations are made for efficient use of these two methods with specific regard to minimizing chemical interferences. In addition, a method for calculating analyte signal to background (S/B) values is introduced as a means of evaluating the quality of the FAB mass spectrum. A method known as thermally-assisted FAB (TA-FAB) is introduced as a means of minimizing matrix-related background. Success to date has been achieved using aqueous saccharide solutions as TA-FAB matrices. Several important improvements to FAB result from thermal control of the matrix including a selection against matrix background, and the possibility of valid background subtraction. The development of TA-FAB is described in the context of applications of the technique to the analysis of several representative nonvolatile biomolecules including a series of cyclic tetrapeptide mycotoxins. In the final section, the hypothesis of ternary perculation (TP) is submitted to account for behavior observed during TA-FAB.

  10. Analysis of the application of decontamination technologies to radioactive metal waste minimization using expert systems

    SciTech Connect

    Bayrakal, S.

    1993-09-30

    Radioactive metal waste makes up a significant portion of the waste currently being sent for disposal. Recovery of this metal as a valuable resource is possible through the use of decontamination technologies. Through the development and use of expert systems a comparison can be made of laser decontamination, a technology currently under development at Ames Laboratory, with currently available decontamination technologies for applicability to the types of metal waste being generated and the effectiveness of these versus simply disposing of the waste. These technologies can be technically and economically evaluated by the use of expert systems techniques to provide a waste management decision making tool that generates, given an identified metal waste, waste management recommendations. The user enters waste characteristic information as input and the system then recommends decontamination technologies, determines residual contamination levels and possible waste management strategies, carries out a cost analysis and then ranks, according to cost, the possibilities for management of the waste. The expert system was developed using information from literature and personnel experienced in the use of decontamination technologies and requires validation by human experts and assignment of confidence factors to the knowledge represented within.

  11. Identification of integrated airframe: Propulsion effects on an F-15 aircraft for application to drag minimization

    NASA Technical Reports Server (NTRS)

    Schkolnik, Gerard S.

    1993-01-01

    The application of an adaptive real-time measurement-based performance optimization technique is being explored for a future flight research program. The key technical challenge of the approach is parameter identification, which uses a perturbation-search technique to identify changes in performance caused by forced oscillations of the controls. The controls on the NASA F-15 highly integrated digital electronic control (HIDEC) aircraft were perturbed using inlet cowl rotation steps at various subsonic and supersonic flight conditions to determine the effect on aircraft performance. The feasibility of the perturbation-search technique for identifying integrated airframe-propulsion system performance effects was successfully shown through flight experiments and postflight data analysis. Aircraft response and control data were analyzed postflight to identify gradients and to determine the minimum drag point. Changes in longitudinal acceleration as small as 0.004 g were measured, and absolute resolution was estimated to be 0.002 g or approximately 50 lbf of drag. Two techniques for identifying performance gradients were compared: a least-squares estimation algorithm and a modified maximum likelihood estimator algorithm. A complementary filter algorithm was used with the least squares estimator.

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

    PubMed

    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. A DNA real-time quantitative PCR method suitable for routine monitoring of low levels of minimal residual disease in chronic myeloid leukemia.

    PubMed

    Bartley, Paul A; Latham, Susan; Budgen, Bradley; Ross, David M; Hughes, Elizabeth; Branford, Susan; White, Deborah; Hughes, Timothy P; Morley, Alexander A

    2015-03-01

    The BCR-ABL1 sequence has advantages over the BCR-ABL1 transcript as a molecular marker in chronic myeloid leukemia and has been used in research studies. We developed a DNA real-time quantitative PCR (qPCR) method for quantification of BCR-ABL1 sequences, which is also potentially suitable for routine use. The BCR-ABL1 breakpoint was sequenced after isolation by nested short-range PCR of DNA from blood, marrow, and cells on slides, obtained either at diagnosis or during treatment, or from artificial mixtures. PCR primers were chosen from a library of presynthesized and pretested BCR (n = 19) and ABL1 (n = 568) primers. BCR-ABL1 sequences were quantified relative to BCR sequences in 521 assays on 266 samples from 92 patients. For minimal residual disease detectable by DNA qPCR and RT-qPCR, DNA qPCR gave similar minimal residual disease results as RT-qPCR but had better precision at low minimal residual disease levels. The limit of detection of DNA qPCR depended on the amount of DNA assayed, being 10(-5.8) when 5 μg was assayed and 10(-7.0) when 80 μg was assayed. DNA qPCR may be useful and practical for monitoring the increasing number of patients with minimal residual disease around or below the limit of detection of RT-qPCR as the assay itself is simple and the up-front costs will be amortized if sequential assays are performed.

  14. Minimization of thermal impact by application of electrode cooling in a co-linear PEF treatment chamber.

    PubMed

    Meneses, Nicolas; Jaeger, Henry; Knorr, Dietrich

    2011-10-01

    A co-linear pulsed electric field (PEF) treatment chamber was analyzed and optimized considering electrical process conditions, temperature, and retention of heat-sensitive compounds during a continuous PEF treatment of peach juice. The applicability of a jacket heat-exchanger device surrounding the ground electrode was studied in order to provide active cooling and to avoid temperature peaks within the treatment chamber thus reducing the total thermal load to which the product is exposed. Simulation of the PEF process was performed using a finite element method prior to experimental verification. Inactivation of polyphenoloxydase (PPO) and peroxidase (POD) as well as the degradation of ascorbic acid (AA) in peach juice was quantified and used as indirect indicators for the temperature distribution. Peaks of product temperature within the treatment chamber were reduced, that is, from 98 to 75 °C and retention of the indicators PPO, POD, and AA increased by more than 10% after application of the active electrode cooling device. Practical Application:  The co-linear PEF treatment chamber is widely used for continuous PEF treatment of liquid products and also suitable for industrial scale application; however, Joule heating in combination with nonuniform electric field distribution may lead to unwanted thermal effects. The proposed design showed potential to reduce the thermal load, to which the food is exposed, allowing the retention of heat-sensitive components. The design is applicable at laboratory or industrial scale to perform PEF trials avoiding temperature peaks, which is also the basis for obtaining inactivation kinetic models with minimized thermal impact on the kinetic variables.

  15. What is minimally invasive dentistry?

    PubMed

    Ericson, Dan

    2004-01-01

    Minimally Invasive Dentistry is the application of "a systematic respect for the original tissue." This implies that the dental profession recognizes that an artifact is of less biological value than the original healthy tissue. Minimally invasive dentistry is a concept that can embrace all aspects of the profession. The common delineator is tissue preservation, preferably by preventing disease from occurring and intercepting its progress, but also removing and replacing with as little tissue loss as possible. It does not suggest that we make small fillings to restore incipient lesions or surgically remove impacted third molars without symptoms as routine procedures. The introduction of predictable adhesive technologies has led to a giant leap in interest in minimally invasive dentistry. The concept bridges the traditional gap between prevention and surgical procedures, which is just what dentistry needs today. The evidence-base for survival of restorations clearly indicates that restoring teeth is a temporary palliative measure that is doomed to fail if the disease that caused the condition is not addressed properly. Today, the means, motives and opportunities for minimally invasive dentistry are at hand, but incentives are definitely lacking. Patients and third parties seem to be convinced that the only things that count are replacements. Namely, they are prepared to pay for a filling but not for a procedure that can help avoid having one.

  16. [Minimal Change Esophagitis].

    PubMed

    Ryu, Han Seung; Choi, Suck Chei

    2016-01-25

    Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms and long-term complications. GERD can be divided into erosive reflux disease and non-erosive reflux disease based on endoscopic findings defined by the presence of mucosal break. The Los Angeles classification excludes minimal changes as an evidence of reflux esophagitis because of poor interobserver agreement. In the Asian literature, minimal changes are considered as one of the endoscopic findings of reflux esophagitis, but the clinical significance is still controversial. Minimal change esophagitis is recognized quite frequently among patients with GERD and many endoscopists recognize such findings in their clinical practice. This review is intended to clarify the definition of minimal change esophagitis and their histology, interobserver agreement, and symptom association with GERD.

  17. [Application of precision medicine in obesity and metabolic disease surgery].

    PubMed

    Wang, Cunchuan; Gao, Zhiguang

    2016-01-01

    The U. S. A. president Obama called for a new initiative to fund precision medicine during his State of Union Address on January 20th, 2015, which meant that the human medicine enters a new era. The meaning of "precision medicine" is significantly similar to the concept of precision obesity and metabolic disease surgery, which was proposed by the author in early August 2011. Nowadays, obesity and metabolic disease surgery has been transformed from open surgery to laparoscopic surgery, the extensive mode to the precision mode. The key value concept is to minimize postoperative complication, minimize postoperative hospital stay and obtain the best effect of weight loss by accurate preoperative assessment, delicate operation, excellent postoperative management and scientific follow-up. The precision obesity and metabolic disease surgery has more development space in the future. PMID:26797833

  18. Disease resistance: Molecular mechanisms and biotechnological applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This special issue “Disease resistance: molecular mechanisms and biotechnological applications” contains 11 review articles and four original research papers. Research in the area of engineering for disease resistance continues to progress although only 10% of the transgenic plants registered for ...

  19. Evolutionary perspectives on wildlife disease: concepts and applications

    PubMed Central

    Vander Wal, Eric; Garant, Dany; Pelletier, Fanie

    2014-01-01

    Wildlife disease has the potential to cause significant ecological, socioeconomic, and health impacts. As a result, all tools available need to be employed when host–pathogen dynamics merit conservation or management interventions. Evolutionary principles, such as evolutionary history, phenotypic and genetic variation, and selection, have the potential to unravel many of the complex ecological realities of infectious disease in the wild. Despite this, their application to wildlife disease ecology and management remains in its infancy. In this article, we outline the impetus behind applying evolutionary principles to disease ecology and management issues in the wild. We then introduce articles from this special issue on Evolutionary Perspectives on Wildlife Disease: Concepts and Applications, outlining how each is exemplar of a practical wildlife disease challenge that can be enlightened by applied evolution. Ultimately, we aim to bring new insights to wildlife disease ecology and its management using tools and techniques commonly employed in evolutionary ecology. PMID:25469154

  20. Shifting Paradigms in Minimally Invasive Surgery: Applications of Transanal Natural Orifice Transluminal Endoscopic Surgery in Colorectal Surgery

    PubMed Central

    Lee, Grace Clara; Sylla, Patricia

    2015-01-01

    Since the advent of laparoscopy, minimally invasive techniques such as single port laparoscopy, robotics, endoscopically assisted laparoscopy, and transanal endoscopic surgery continue to revolutionize the field of colorectal surgery. Transanal natural orifice transluminal endoscopic surgery (NOTES) represents a further paradigm shift by combining the advantages of these earlier techniques to reduce the size and number of abdominal incisions and potentially optimize rectal dissection, especially with respect to performance of an oncologically adequate total mesorectal excision (TME) for rectal cancer. Since the first experimental report of transanal rectosigmoid resection in 2007, the potential impact of transanal NOTES in colorectal surgery has been extensively investigated in experimental models and recently transitioned to clinical application. There have been 14 clinical trials of transanal TME (taTME) for rectal cancer that have demonstrated the feasibility and preliminary oncologic safety of this approach in carefully selected patients, with results comparable to outcomes after laparoscopic and open TME, including cumulative intraoperative and postoperative complication rates of 5.5 and 35.5%, respectively, 97.3% rate of complete or near-complete specimens, and 93.6% rate of negative margins. Transanal NOTES has also been safely applied to proctectomy and colectomy for benign indications. The consensus among published series suggests that taTME is most safely performed with transabdominal assistance by surgeons experienced with laparoscopic TME, transanal endoscopic surgery, and sphincter-preserving techniques including intersphincteric resection. Future applications of transanal NOTES may include evolution to a pure endoscopic transanal approach for TME, colectomy, and sentinel lymph node biopsy for rectal cancer, with a potential role for robotic assistance. PMID:26491411

  1. Lipidomics applications for discovering biomarkers of diseases in clinical chemistry.

    PubMed

    Zhao, Ying-Yong; Cheng, Xian-long; Lin, Rui-Chao

    2014-01-01

    Lipids are the fundamental components of biological membranes as well as the metabolites of organisms. Lipids play diverse and important roles in biologicals. The lipid imbalance is closely associated with numerous human lifestyle-related diseases, such as atherosclerosis, obesity, diabetes, and Alzheimer's disease. Lipidomics or lipid profiling is a system-based study of all lipids aiming at comprehensive analysis of lipids in the biological system. Lipidomics has been accepted as a lipid-related research tool in lipid biochemistry, clinical biomarker discovery, disease diagnosis, and in understanding disease pathology. Lipidomics will not only provide insights into the specific functions of lipid species in health and disease, but will also identify potential biomarkers for establishing preventive or therapeutic programs for human diseases. This review presents an overview of lipidomics followed by in-depth discussion of its application to the study of human diseases, including extraction methods of lipids, analytical technologies, data analysis, and clinical research in cancer, neuropsychiatric disease, cardiovascular disease, kidney disease, and respiratory disease. We describe the current status of the identification of metabolic biomarkers in different diseases. We also discuss the lipidomics for the future perspectives and their potential problems. The application of lipidomics in clinical studies may provide new insights into lipid profiling and pathophysiological mechanisms.

  2. Minimal Disseminated Disease in Childhood T-Cell Lymphoblastic Lymphoma: A Report From the Children's Oncology Group

    PubMed Central

    Coustan-Smith, Elaine; Sandlund, John T.; Perkins, Sherrie L.; Chen, Helen; Chang, Myron; Abromowitch, Minnie; Campana, Dario

    2009-01-01

    Purpose Disease dissemination to the bone marrow is detected at diagnosis in approximately 15% of children with T-cell lymphoblastic lymphoma (T-LL). It is unclear whether the remaining patients have submicroscopic systemic disease and, if so, what is the clinical significance of this finding. Patients and Methods Using a flow cytometric method that can detect one T-LL cell among 10,000 normal cells, we examined bone marrow and peripheral-blood samples collected from 99 children with T-LL at diagnosis, as well as blood samples collected from 42 patients during treatment. Results In 71 (71.7%) of the 99 marrow samples obtained at diagnosis, T-LL cells represented 0.01% to 31.6% (median, 0.22%) of mononuclear cells; 57 of the 71 T-LL–positive samples were from patients with stage II/III disease. Results of studies in bilateral marrow aspirates were highly concordant. Two-year event-free survival (EFS) was 68.1% ± 11.1% (SE) for patients with ≥ 1% T-LL cells in bone marrow versus 90.7% ± 4.4% for those with lower levels of marrow involvement (P = .031); EFS for patients with ≥ 5% lymphoblasts was 51.9% ± 18.0% (P = .009). T-LL cells were as prevalent in blood as in marrow; monitoring residual T-LL cells in blood during remission induction therapy identified patients with slower disease clearance. Conclusion More than two thirds of children with T-LL have disseminated disease at diagnosis, a proportion much higher than previously demonstrated. Measurements of disease dissemination at diagnosis might provide useful prognostic information, which can be further refined by monitoring response to therapy through blood testing. PMID:19546402

  3. End of induction minimal residual disease alone is not a useful determinant for risk stratified therapy in pediatric T-cell acute lymphoblastic leukemia.

    PubMed

    Parekh, Chintan; Gaynon, Paul S; Abdel-Azim, Hisham

    2015-11-01

    The role of end of induction minimal residual disease (MRD) as determined by flow cytometry for treatment assignment in pediatric T-cell acute lymphoblastic leukemia (T-ALL) is not well defined. We studied 33 children with newly diagnosed T-ALL. Thirty-two of 33 patients remain in continuous complete remission at a median of 4 years. Nineteen patients were MRD positive at the end of induction and all remain in remission with augmented Berlin Frankfurt Münster-based therapy. One patient underwent hematopoietic stem cell transplant for rising MRD. Persistent end of induction MRD alone is not an indication to alter therapy in pediatric T-ALL.

  4. RESEARCH NOTE FROM COLLABORATION: NNLC: non-negative least chi-square minimization and application to HPGe detectors

    NASA Astrophysics Data System (ADS)

    Désesquelles, P.; Ha, T. M. H.; Korichi, A.; LeBlanc, F.; Petrache, C. M.; AGATA Collaboration

    2009-03-01

    A new method is proposed for the problem of solving chi-square minimization with a positive solution. This method is embodied in an evolution of the popular NNLS algorithm. Its efficiency with respect to residue minimization is illustrated by the improvement it permits on the location of gamma-interactions inside an AGATA HPGe detector.

  5. Minimal Reduplication

    ERIC Educational Resources Information Center

    Kirchner, Jesse Saba

    2010-01-01

    This dissertation introduces Minimal Reduplication, a new theory and framework within generative grammar for analyzing reduplication in human language. I argue that reduplication is an emergent property in multiple components of the grammar. In particular, reduplication occurs independently in the phonology and syntax components, and in both cases…

  6. Optimized oral cholera vaccine distribution strategies to minimize disease incidence: A mixed integer programming model and analysis of a Bangladesh scenario.

    PubMed

    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.

  7. Metabolomics: Applications and Promise in Mycobacterial Disease

    PubMed Central

    Banoei, Mohammad Mehdi; Winston, Brent W.; Schraufnagel, Dean E.

    2015-01-01

    Until recently, the study of mycobacterial diseases was trapped in culture-based technology that is more than a century old. The use of nucleic acid amplification is changing this, and powerful new technologies are on the horizon. Metabolomics, which is the study of sets of metabolites of both the bacteria and host, is being used to clarify mechanisms of disease, and can identify changes leading to better diagnosis, treatment, and prognostication of mycobacterial diseases. Metabolomic profiles are arrays of biochemical products of genes in their environment. These complex patterns are biomarkers that can allow a more complete understanding of cell function, dysfunction, and perturbation than genomics or proteomics. Metabolomics could herald sweeping advances in personalized medicine and clinical trial design, but the challenges in metabolomics are also great. Measured metabolite concentrations vary with the timing within a condition, the intrinsic biology, the instruments, and the sample preparation. Metabolism profoundly changes with age, sex, variations in gut microbial flora, and lifestyle. Validation of biomarkers is complicated by measurement accuracy, selectivity, linearity, reproducibility, robustness, and limits of detection. The statistical challenges include analysis, interpretation, and description of the vast amount of data generated. Despite these drawbacks, metabolomics provides great opportunity and the potential to understand and manage mycobacterial diseases. PMID:26196272

  8. Applications of Doppler ultrasound in clinical vascular disease

    NASA Technical Reports Server (NTRS)

    Barnes, R. W.; Hokanson, D. E.; Sumner, D. S.; Strandness, D. E., Jr.

    1975-01-01

    Doppler ultrasound has become the most useful and versatile noninvasive technique for objective evaluation of clinical vascular disease. Commercially available continuous-wave instruments provide qualitative and quantitative assessment of venous and arterial disease. Pulsed Doppler ultrasound was developed to provide longitudinal and transverse cross-sectional images of the arterial lumen with a resolution approaching that of conventional X-ray techniques. Application of Doppler ultrasound in venous, peripheral arterial, and cerebrovascular diseases is reviewed.

  9. Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize childhood allergic disease.

    PubMed

    Makrides, Maria; Gunaratne, Anoja W; Collins, Carmel T

    2013-01-01

    There has been growing interest in the role of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the modulation of the immune response during early childhood and whether this may translate to a reduction in childhood allergic disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have been reported, largely involving children who are at high hereditary risk of developing allergies. These studies relatively consistently indicate that supplementation during pregnancy results in fewer children with atopic eczema in early childhood. On the other hand, supplementation studies confined exclusively to the postnatal period have demonstrated mixed results with one trial showing no effect and the other suggesting a transient effect on symptoms of respiratory disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period and before allergic response is established may be a useful strategy to prevent early childhood allergic disease in children at high hereditary risk. Further work is needed to establish the optimal period of supplementation and whether longer term benefits exist. PMID:24107505

  10. Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize childhood allergic disease.

    PubMed

    Makrides, Maria; Gunaratne, Anoja W; Collins, Carmel T

    2013-01-01

    There has been growing interest in the role of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in the modulation of the immune response during early childhood and whether this may translate to a reduction in childhood allergic disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have been reported, largely involving children who are at high hereditary risk of developing allergies. These studies relatively consistently indicate that supplementation during pregnancy results in fewer children with atopic eczema in early childhood. On the other hand, supplementation studies confined exclusively to the postnatal period have demonstrated mixed results with one trial showing no effect and the other suggesting a transient effect on symptoms of respiratory disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period and before allergic response is established may be a useful strategy to prevent early childhood allergic disease in children at high hereditary risk. Further work is needed to establish the optimal period of supplementation and whether longer term benefits exist.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26889476

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

    PubMed

    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. PMID:26889476

  14. Vibration attenuation of rotating machines by application of magnetorheological dampers to minimize energy losses in the rotor support

    NASA Astrophysics Data System (ADS)

    Zapoměl, J.; Ferfecki, P.

    2016-09-01

    A frequently used technological solution for minimization of undesirable effects caused by vibration of rotating machines consists in placing damping devices in the rotor supports. The application of magnetorheological squeeze film dampers enables their optimum performance to be achieved in a wide range of rotating speeds by adapting their damping effect to the current operating conditions. The damping force, which is produced by squeezing the layer of magnetorheological oil, can be controlled by changing magnetic flux passing through the lubricant. The force acting between the rotor and its frame is transmitted through the rolling element bearing, the lubricating layer and the squirrel spring. The loading of the bearing produces a time variable friction moment, energy losses, uneven rotor running, and has an influence on the rotor service life and the current fluctuation in electric circuits. The carried out research consisted in the development of a mathematical model of a magnetorheological squeeze film damper, its implementation into the computational models of rotor systems, and in performing the study on the dependence of the energy losses and variation of the friction moment on the damping force and its control. The new and computationally stable mathematical model of a magnetorheological squeeze film damper, its implementation in the computational models of rigid rotors and learning more on the energy losses generated in the rotor supports in dependence on the damping effect are the principal contributions of this paper. The results of the computational simulations prove that a suitable control of the damping force enables the energy losses to be reduced in a wide velocity range.

  15. Optimal Effect of Phenol Block in the Sciatic Nerve of Rats: Standardization of Minimized Dosage and Duration of Application.

    PubMed

    Lin, Chuan-Chao; Chang, Chein-Wei; Tsai, Su-Ju

    2015-08-31

    The phenol nerve block has been widely used in clinical practice for spasticity reduction, but the correlation between the dosage of phenol and its effectiveness has seldom been discussed. The objective was to determine the optimal duration of phenol in contact with the nervous tissue and to investigate the dose-response relationship of 5% aqueous phenol solution by percutaneous nerve block in rats. Group I (n = 8) received sciatic nerve block by bathing the nerves in phenol solution, and group II (n = 40) by injecting phenol percutaneously. Group IIa to IId received different volumes (0.80, 0.16, 0.08 and 0.04 ml) and group IIe received normal saline. Compound muscle action potential (CMAP) was measured pre-injection and at 90 and 270 sec after injection and after surgical exposure of the nerves. The duration of CMAP reduced by 10%, 25%, 50%, 75% and 100% after phenol injection was also recorded. The mean latency for the evoked response to subside in direct phenol application (group I) and percutaneous nerve block (group IIa) were 73.5 ± 5.9 and 62.4 ± 7.6 sec, respectively. There was no statistical difference for the time periods in the blocking effect elicited by phenol solution between these two methods. Ninety sec was set as the optimal duration for phenol to produce complete conduction blockage. Higher volume of phenol produced more significant blocking effect at 90 and 270 sec after injection. Percutaneous injection with 0.16 ml of phenol solution had the same blocking effect as 0.8 ml. The continuous injection model for percutaneous phenol block indeed used significantly more phenol than actually needed. Clinically, the progressive injection model can be used to minimize injection volume.

  16. Optimal Effect of Phenol Block in the Sciatic Nerve of Rats: Standardization of Minimized Dosage and Duration of Application.

    PubMed

    Lin, Chuan-Chao; Chang, Chein-Wei; Tsai, Su-Ju

    2015-08-31

    The phenol nerve block has been widely used in clinical practice for spasticity reduction, but the correlation between the dosage of phenol and its effectiveness has seldom been discussed. The objective was to determine the optimal duration of phenol in contact with the nervous tissue and to investigate the dose-response relationship of 5% aqueous phenol solution by percutaneous nerve block in rats. Group I (n = 8) received sciatic nerve block by bathing the nerves in phenol solution, and group II (n = 40) by injecting phenol percutaneously. Group IIa to IId received different volumes (0.80, 0.16, 0.08 and 0.04 ml) and group IIe received normal saline. Compound muscle action potential (CMAP) was measured pre-injection and at 90 and 270 sec after injection and after surgical exposure of the nerves. The duration of CMAP reduced by 10%, 25%, 50%, 75% and 100% after phenol injection was also recorded. The mean latency for the evoked response to subside in direct phenol application (group I) and percutaneous nerve block (group IIa) were 73.5 ± 5.9 and 62.4 ± 7.6 sec, respectively. There was no statistical difference for the time periods in the blocking effect elicited by phenol solution between these two methods. Ninety sec was set as the optimal duration for phenol to produce complete conduction blockage. Higher volume of phenol produced more significant blocking effect at 90 and 270 sec after injection. Percutaneous injection with 0.16 ml of phenol solution had the same blocking effect as 0.8 ml. The continuous injection model for percutaneous phenol block indeed used significantly more phenol than actually needed. Clinically, the progressive injection model can be used to minimize injection volume. PMID:26211647

  17. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma.

    PubMed

    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 < .001). Five-year survival of MDD-negative and MDD-positive/MRD-negative patients was 91% ± 3% and 92% ± 5%, respectively, compared with 65% ± 9% of MDD-positive/MRD-positive patients (P < .001). Early evaluation of MRD in NPM-ALK-positive ALCL identifies patients with a very high relapse risk and inferior survival.

  18. Human Pluripotent Stem Cells: Applications and Challenges in Neurological Diseases

    PubMed Central

    Hibaoui, Youssef; Feki, Anis

    2012-01-01

    The ability to generate human pluripotent stem cells (hPSCs) holds great promise for the understanding and the treatment of human neurological diseases in modern medicine. The hPSCs are considered for their in vitro use as research tools to provide relevant cellular model for human diseases, drug discovery, and toxicity assays and for their in vivo use in regenerative medicine applications. In this review, we highlight recent progress, promises, and challenges of hPSC applications in human neurological disease modeling and therapies. PMID:22934023

  19. Quantification of TEL-AML1 transcript for minimal residual disease assessment in childhood acute lymphoblastic leukaemia.

    PubMed

    Drunat, S; Olivi, M; Brunie, G; Grandchamp, B; Vilmer, E; Bièche, I; Cavé, H

    2001-08-01

    Strategies currently used for residual disease detection in acute lymphoblastic leukaemia (ALL) rely on polymerase chain reaction (PCR) detection of immunoglobulin and T-cell receptor rearrangements. The TEL-AML1 fusion transcript, which is associated with t(12;21) (p13;q22), is found in 25% of childhood B-cell precursor ALL, and represents an interesting alternative target. We compared two methods for quantitating TEL-AML1 fusion transcripts: competitive PCR and real-time PCR. These techniques showed similar sensitivity (5 x 10(-5)) and reproducibility. Giving highly correlated results, both techniques can be conveniently used for TEL-AML1 transcript quantification. The constancy of TEL-AML1 expression was evaluated by measuring TEL-AML1 transcripts at different steps of the cell cycle, and in 21 cases of ALL at diagnosis. No major variation in TEL-AML1 expression was observed during the cell cycle or in 20/21 of the ALL patients. Residual disease was then determined after completion of induction therapy in 20 patients with a TEL-AML1-positive ALL. Seven patients out of 20 (35%) were still positive, including two patients with high level of residual blasts (close to or beyond 10(-2)). When comparison was possible, results obtained using TEL-AML1 quantification were in accordance with those obtained using T-cell receptor rearrangements analysis.

  20. Application of ozone in the treatment of periodontal disease

    PubMed Central

    Srikanth, Adusumilli; Sathish, Manthena; Sri Harsha, Anumolu Venkatanaga

    2013-01-01

    Gingivitis and periodontitis are most common inflammatory diseases of supporting tissues of teeth. Role of microbial etiology and host response in progression of gingival and periodontal diseases has been well established. Because of the beneficial biological effects of ozone, due to its antimicrobial and immunostimulating effect, it is well indicated in the treatment of gingival and periodontal diseases. The objective of this article is to provide a general review about clinical applications of ozone in treatment of periodontal diseases and to summarize the available in vitro and in vivo studies in Periodontics in which ozone has been used. PMID:23946585

  1. Analysis of a waste-minimization program for nonhazardous solid wastes utilizing source-reduction and recycling techniques and its application to Air Force installations. Master's thesis

    SciTech Connect

    McDermott, B.G.

    1991-09-01

    This nation has fallen victim to its own excessive behavior and has created an overabundance of trash, referred to in this thesis as Nonhazardous Solid Waste (NSW). This situation has created environmental and health problems that can no longer be ignored. All types of communities are affected including Air Force installations. Unfortunately, the AF does not currently have a long term waste management policy or program regarding NHSW minimization. This research concentrates on the application of a NHSW minimization program for AF installations using the two most preferred methods, source reduction and recycling. The development of a comprehensive waste minimization program using the techniques described is the most effective and efficient way to decrease the solid waste burden. The construction and implementation of these programs is not easy, especially for an organization as complex and diverse as the AF. However, the payoffs from a well planned and executed program far outweigh any costs.

  2. Development and Feasibility Testing of Image-Guided Minimally Invasive Tissue for Diagnosis Treatment of Benign and Malignant Breast Disease

    NASA Technical Reports Server (NTRS)

    Jeffrey, Stefanie S.

    1999-01-01

    Dr. Robert Mah and Dr. Stefanie Jeffrey worked on the development of the NASA Smart Probe in its application as a device to measure and interpret physiologic and image-based parameters of breast tissue. To date the following has been achieved: 1 . Choice of candidate sensors to be tested in breast tissue. 2. Preliminary designs for probe tip, specifically use of different tip shapes, cutting edges, and sensor configuration. 3. Design of sonographic guidance system. 4. Design of data extraction and analysis tool using scanned information of images of the breast tissue to provide a higher dimension of information for breast tissue characterization and interpretation. 5. Initial ex-vivo (fruit and tofu) and in-vivo (rodent) testing to confirm unique substance and tissue characterization by the Smart Probe software.

  3. Chimerism testing and detection of minimal residual disease after allogeneic hematopoietic transplantation using the bioView (Duet) combined morphological and cytogenetical analysis.

    PubMed

    Shimoni, A; Nagler, A; Kaplinsky, C; Reichart, M; Avigdor, A; Hardan, I; Yeshurun, M; Daniely, M; Zilberstein, Y; Amariglio, N; Brok-Simoni, F; Rechavi, G; Trakhtenbrot, L

    2002-08-01

    Recurrent disease remains a major obstacle to cure after allogeneic transplantation. Various methods have been developed to detect minimal residual disease (MRD) after transplantation to identify patients at risk for relapse. Chimerism tests differentiate recipient and donor cells and are used to identify MRD when there are no other disease-specific markers. The detection of MRD does not always correlate with relapse risk. Chimerism testing may also identify normal hematopoietic cells or other cells not contributing to relapse. In this study we report our initial experience with a novel system that provides combined morphological and cytogenetical analysis on the same cells. This system allows rapid automatic scanning of a large number of cells, thus increasing the sensitivity of detection of small recipient population. The clinical significance of MRD detection is improved by identifying the morphology of recipient cells. Identification of recipient characteristics within blasts predicts overt relapse in leukemia patients and precedes it by a few weeks to months. Identification within mature hematopoietic cells may not be closely associated with relapse. The system also allows chimerism testing after sex-mismatched transplants, within cellular subsets, with no need for sorting of cells. The system merits further study in larger scale trials.

  4. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

    PubMed

    Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

    2015-08-01

    The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10(-3). Conventional intensive consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs. PMID:25748682

  5. Self-reported adherence to a home-based exercise program among patients affected by psoriatic arthritis with minimal disease activity.

    PubMed

    Chimenti, Maria Sole; Triggianese, Paola; Conigliaro, Paola; Santoro, Matteo; Lucchetti, Ramona; Perricone, Roberto

    2014-11-01

    More than half of all patients with psoriatic arthritis (PsA) exhibit progressive erosive arthritis, associated with severe functional impairment and psychosocial disability. Biologics have been suggested to be more effective in inducing minimal disease activity" (MDA) than disease-modifying antirheumatic drugs (DMARDs). Behavioral patient education appears to be more effective in encouraging patients to increase their physical activity (PA) levels. The aim of the study was to evaluate the benefits of home-based exercises program on disease activity and quality of life in MDA-PsA patients treated with an anti-tumor necrosis factor (TNF) and DMARD therapy. We observed a self-reported adherence rate to home-based exercise of 76.6% and data showed the impact of the exercise program on self-reported health and mental assessment. A positive relationship between patient and therapist is crucial, influencing the quality of the performance, the emotional support, and increasing motivation in PsA patients.

  6. Evaluation of the performance during hard turning of OHNS steel with minimal cutting fluid application and its comparison with minimum quantity lubrication

    NASA Astrophysics Data System (ADS)

    Raj, Anil; Wins, K. Leo Dev; Varadarajan, A. S.

    2016-09-01

    Cutting fluid application plays a significant role in the manufacturing industries that acts as a coolant as well as a lubricant. The conventional flood cooling application of cutting fluids not only increases the production cost on account of the expenses involved in procurement, storage and disposal but also creates serious environmental and health hazards. In order to overcome these negative effects, techniques like Minimum quantity lubrication (MQL) and Minimal Cutting fluid application (MCFA) have increasingly found their way into the area of metal cutting and have already been established as an alternative to conventional wet machining. This paper investigates the effect of minimal Cutting fluid application (MCFA) which involves application of high velocity pulsing jet of proprietary cutting fluids at the contact zones using a special fluid application system. During hard turning of oil hardened non shrinkable steel (OHNS) on cutting temperature and tool wear and to compare the performance with Minimum quantity lubrication (MQL) assisted hard turning in which cutting fluid is carried in a high velocity stream of air. An attempt was also made to compare the performance during Turning with MCFA and MQL application with conventional wet and dry turning by analysing the tool wear pattern using SEM images.

  7. Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications.

    PubMed

    Kuo, Tom K; Ho, Jennifer H; Lee, Oscar K

    2009-01-01

    Mesenchymal stem cells are stem/progenitor cells originated from the mesoderm and can different into multiple cell types of the musculoskeletal system. The vast differentiation potential and the relative ease for culture expansion have established mesenchymal stem cells as the building blocks in cell therapy and tissue engineering applications for a variety of musculoskeletal diseases, including repair of fractures and bone defects, cartilage regeneration, treatment of osteonecrosis of the femoral head, and correction of genetic diseases such as osteogenesis imperfect. However, research in the past decade has revealed differentiation potentials of mesenchymal stem cells beyond lineages of the mesoderm, suggesting broader applications than originally perceived. In this article, we review the recent developments in mesenchymal stem cell research with respect to their emerging properties and applications in nonmusculoskeletal diseases. PMID:19523328

  8. Urinary messenger RNA of the receptor activator of NF-kappaB could be used to differentiate between minimal change disease and membranous nephropathy.

    PubMed

    Liu, Shuangxin; Mei, Ping; Shi, Wei; Zhang, Bin; Li, Sijia; Liang, Xinling; Ye, Zhiming; Xu, Lixia; Ma, Jianchao; Li, Zhilian; Zhang, Li; Wang, Wenjian; Wang, Liping; Li, Rizhao; Feng, Zhonglin; Dong, Wei; Tao, Yiming

    2014-11-01

    Podocyte damage and loss together have an important role in the pathogenesis and progression of glomerulonephritis. Glomerulonephritis patients and healthy controls were enrolled in this study. Biochemical, clinical and experimental procedures included measurement of total urinary protein, renal biopsy and gene expression analysis of the receptor activator of NF-kappaB (RANK). The urinary mRNA levels of RANK were significantly higher in the glomerulonephritis group compared to the controls. The urinary RANK level of glomerular subtypes was correlated significantly with proteinuria. The calculated area of RANK mRNA levels under the curve was 0.61 for minimal change disease (MCD), 0.97 for membranous nephropathy (MN), 0.65 for IgA nephropathy (IgAN), 0.70 for lupus nephritis (LN) and 0.70 for focal segmental glomerulosclerosis (FSGS). The urinary mRNA of RANK might be used to differentiate histologic subtypes of glomerulonephritis, particularly between MCD and MN.

  9. Theory of protein misfolding and applications to misfolding diseases

    NASA Astrophysics Data System (ADS)

    Plotkin, Steven S.

    2009-03-01

    Physics-based algorithms can predict the misfolding mechanisms of proteins involved in aggregation-related diseases, including ALS and the Prion diseases. Predictions based on such an algorithm that we have developed, which employs both atomistic interactions and surface-area based coarse-graining, have been recently verified by immunological assays and point to diagnostic and therapeutic applications. I will describe the results of our misfolding theory, and discuss future directions towards drug research.

  10. Application of regenerative medicine for kidney diseases.

    PubMed

    Yokoo, Takashi; Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application. PMID:19279698

  11. Application of Regenerative Medicine for Kidney Diseases

    PubMed Central

    Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF). The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application. PMID:19279698

  12. A review of disease progression models of Parkinson's disease and applications in clinical trials.

    PubMed

    Venuto, Charles S; Potter, Nicholas B; Ray Dorsey, E; Kieburtz, Karl

    2016-07-01

    Quantitative disease progression models for neurodegenerative disorders are gaining recognition as important tools for drug development and evaluation. In Parkinson's disease (PD), several models have described longitudinal changes in the Unified Parkinson's Disease Rating Scale (UPDRS), one of the most utilized outcome measures for PD trials assessing disease progression. We conducted a literature review to examine the methods and applications of quantitative disease progression modeling for PD using a combination of key words including "Parkinson disease," "progression," and "model." For this review, we focused on models of PD progression quantifying changes in the total UPDRS scores against time. Four different models reporting equations and parameters have been published using linear and nonlinear functions. The reasons for constructing disease progression models of PD thus far have been to quantify disease trajectories of PD patients in active and inactive treatment arms of clinical trials, to quantify and discern symptomatic and disease-modifying treatment effects, and to demonstrate how model-based methods may be used to design clinical trials. The historical lack of efficiency of PD clinical trials begs for model-based simulations in planning for studies that result in more informative conclusions, particularly around disease modification. © 2016 International Parkinson and Movement Disorder Society.

  13. Minimal cosmography

    NASA Astrophysics Data System (ADS)

    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.

  14. Minimization of the root of a quadratic functional under a system of affine equality constraints with application to portfolio management

    NASA Astrophysics Data System (ADS)

    Landsman, Zinoviy

    2008-10-01

    We present an explicit closed form solution of the problem of minimizing the root of a quadratic functional subject to a system of affine constraints. The result generalizes Z. Landsman, Minimization of the root of a quadratic functional under an affine equality constraint, J. Comput. Appl. Math. 2007, to appear, see , articles in press, where the optimization problem was solved under only one linear constraint. This is of interest for solving significant problems pertaining to financial economics as well as some classes of feasibility and optimization problems which frequently occur in tomography and other fields. The results are illustrated in the problem of optimal portfolio selection and the particular case when the expected return of finance portfolio is certain is discussed.

  15. 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.

    PubMed

    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.

  16. 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

    PubMed Central

    Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P

    2016-01-01

    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. PMID:26639181

  17. 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.

    PubMed

    Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P

    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. PMID:26639181

  18. The impact of pre-transplant minimal residual disease on outcome of intensified myeloablative cord blood transplant for acute myeloid leukemia in first or second complete remission.

    PubMed

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Zhang, Lei; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2016-01-01

    The impact of pretransplant minimal residual disease (MRD) on outcome of myeloablative cord blood transplant (CBT) for acute myeloid leukemia (AML) in complete remission (CR) has not been reported. Seventy-two AML patients were assessed for MRD before CBT, and the majority (84.7%) of these patients received single-unit CBT. All patients received intensified myeloablative conditioning with BUCY2 or TBICY plus high-dose cytarabine, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic GVHD were comparable between MRD-negative and MRD-positive groups. The cumulative incidence of transplant-related mortality (TRM) and relapse did not differ significantly between the two cohorts (25.6% vs. 32.5%, 16.1% vs. 19.2%; p = 0.52, 0.61). There were no apparent differences in 3-year overall survival (OS) (68.9% in MRD-negative group and 57.9% in MRD-positive group, p = 0.31) and 3-year leukemia-free survival (LFS) (62.5% in MRD-negative group and 52.7% in MRD-positive group, p = 0.42) between both groups. The current study suggests that AML patients in morphological CR1 or CR2 who have detectable MRD might benefit from unrelated CBT with intensified myeloablative conditioning. PMID:26690538

  19. 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.

    PubMed

    Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P

    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.

  20. The impact of pre-transplant minimal residual disease on outcome of intensified myeloablative cord blood transplant for acute myeloid leukemia in first or second complete remission.

    PubMed

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Zhang, Lei; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2016-01-01

    The impact of pretransplant minimal residual disease (MRD) on outcome of myeloablative cord blood transplant (CBT) for acute myeloid leukemia (AML) in complete remission (CR) has not been reported. Seventy-two AML patients were assessed for MRD before CBT, and the majority (84.7%) of these patients received single-unit CBT. All patients received intensified myeloablative conditioning with BUCY2 or TBICY plus high-dose cytarabine, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic GVHD were comparable between MRD-negative and MRD-positive groups. The cumulative incidence of transplant-related mortality (TRM) and relapse did not differ significantly between the two cohorts (25.6% vs. 32.5%, 16.1% vs. 19.2%; p = 0.52, 0.61). There were no apparent differences in 3-year overall survival (OS) (68.9% in MRD-negative group and 57.9% in MRD-positive group, p = 0.31) and 3-year leukemia-free survival (LFS) (62.5% in MRD-negative group and 52.7% in MRD-positive group, p = 0.42) between both groups. The current study suggests that AML patients in morphological CR1 or CR2 who have detectable MRD might benefit from unrelated CBT with intensified myeloablative conditioning.

  1. Principles and application of antibody libraries for infectious diseases.

    PubMed

    Lim, Bee Nar; Tye, Gee Jun; Choong, Yee Siew; Ong, Eugene Boon Beng; Ismail, Asma; Lim, Theam Soon

    2014-12-01

    Antibodies have been used efficiently for the treatment and diagnosis of many diseases. Recombinant antibody technology allows the generation of fully human antibodies. Phage display is the gold standard for the production of human antibodies in vitro. To generate monoclonal antibodies by phage display, the generation of antibody libraries is crucial. Antibody libraries are classified according to the source where the antibody gene sequences were obtained. The most useful library for infectious diseases is the immunized library. Immunized libraries would allow better and selective enrichment of antibodies against disease antigens. The antibodies generated from these libraries can be translated for both diagnostic and therapeutic applications. This review focuses on the generation of immunized antibody libraries and the potential applications of the antibodies derived from these libraries.

  2. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy.

    PubMed

    Rawstron, A C; Kennedy, B; Evans, P A; Davies, F E; Richards, S J; Haynes, A P; Russell, N H; Hale, G; Morgan, G J; Jack, A S; Hillmen, P

    2001-07-01

    Previous studies have suggested that the level of residual disease at the end of therapy predicts outcome in chronic lymphocytic leukemia (CLL). However, available methods for detecting CLL cells are either insensitive or not routinely applicable. A flow cytometric assay was developed that can differentiate CLL cells from normal B cells on the basis of their CD19/CD5/CD20/CD79b expression. The assay is rapid and can detect one CLL cell in 10(4) to 10(5) leukocytes in all patients. We have compared this assay to conventional assessment in 104 patients treated with CAMPATH-1H and/or autologous transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly depleted in responding patients, but remained detectable in nonresponders. Patients with more than 0.01 x 10(9)/L circulating CLL cells always had significant (> 5%) marrow disease, and blood monitoring could be used to time marrow assessments. In 25 out of 104 patients achieving complete remission by National Cancer Institute (NCI) criteria, the detection of residual bone marrow disease at more than 0.05% of leukocytes in 6 out of 25 patients predicted significantly poorer event-free (P =.0001) and overall survival (P =.007). CLL cells are detectable at a median of 15.8 months (range, 5.5-41.8) posttreatment in 9 out of 18 evaluable patients with less than 0.05% CLL cells at end of treatment. All patients with detectable disease have progressively increasing disease levels on follow-up. The use of sensitive techniques, such as the flow assay described here, allow accurate quantitation of disease levels and provide an accurate method for guiding therapy and predicting outcome. These results suggest that the eradication of detectable disease may lead to improved survival and should be tested in future studies.

  3. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    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.

  4. Bone Marrow Minimal Residual Disease Was an Early Response Marker and a Consistent Independent Predictor of Survival After Anti-GD2 Immunotherapy

    PubMed Central

    Cheung, Nai-Kong V.; Ostrovnaya, Irina; Kuk, Deborah; Cheung, Irene Y.

    2015-01-01

    Purpose Immunotherapy is a standard of care for children with high-risk neuroblastoma, where bone marrow (BM) is the predominant metastatic site. Early response markers of minimal residual disease (MRD) in the BM that are also predictive of survival could help individualize patient therapies. Patients and Methods After achieving first remission (n = 163), primary refractory disease (n = 102), or second remission (n = 95), children with stage 4 neuroblastoma received anti-GD2 3F8 antibody immunotherapy. BM MRD before 3F8 treatment and after cycle 2 (postMRD) was measured using a four-marker panel (B4GALNT1, PHOX2B, CCND1, and ISL1) by quantitative reverse transcription polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic variables were tested in both univariable and multivariable analyses, and MRD markers were further assessed individually and in combination as binary composite (postMRD: 0 and 1) and as equal sum (postMRDSum: 0 to 4) using the Cox regression models, and their predictive accuracy was determined by the concordance index. Results When BM was evaluated after cycle 2, individual markers were highly predictive of PFS and OS. The prediction accuracy improved when they were combined in postMRDSum. A multivariable model taking into account all the variables significant in the univariable analyses identified postMRDSum to be independently predictive of PFS and OS. When the model for OS also included missing killer immunoglobulin-like receptor ligand, human antimouse antibody response, and the enrollment disease status, the concordance index was 0.704. Conclusion BM MRD after two cycles of immunotherapy was confirmed as an early response marker and a consistent independent predictor of survival. PMID:25559819

  5. Interferon-α: A Potentially Effective Treatment for Minimal Residual Disease in Acute Leukemia/Myelodysplastic Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2015-11-01

    In this prospective clinical study, the safety and efficacy of preemptive interferon-α (IFN-α) treatment were investigated and compared with preemptive donor lymphocyte infusion (DLI) in patients who were minimal residual disease (MRD)-positive after allogeneic hematopoietic stem cell transplantation (HSCT). Patients undergoing allogeneic HSCT were eligible if they had acute leukemia or myelodysplastic syndrome and were MRD-positive after HSCT. Patients who were able to receive DLI were assigned to a preemptive DLI group (n = 45); patients who could not or did not agree to receive DLI after HSCT received preemptive IFN-α. A total of 22 patients received preemptive IFN-α; the median treatment duration was 35 days (range, 4 to 180 days). Seven patients relapsed, and 1 patient died from severe pneumonia. The 1-year cumulative incidence of chronic graft-versus-host disease (cGVHD) after intervention was 90.9% for the IFN-α group and 62.9% for the DLI group (P < .001). MRD status after preemptive intervention was comparable in the 2 groups, and the 1-year cumulative incidence of relapse after intervention was 27.3% for the IFN-α group and 35.6% for the DLI group (P = .514). The 1-year cumulative incidence of nonrelapse mortality after intervention was 4.5% for the IFN-α group and 4.4% for the DLI group (P = .985). The 1-year probability of disease-free survival after intervention was 68.2% for the IFN-α group and 60.0% for the DLI group (P = .517). In multivariate analysis, early-onset MRD, persistent MRD after intervention, and absence of cGVHD after intervention were significantly associated with poorer clinical outcomes. Thus, preemptive IFN-α may be a potential alternative for MRD-positive patients who cannot receive preemptive DLI after HSCT.

  6. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics.

    PubMed

    Mahla, Ranjeet Singh

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.

  7. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    PubMed Central

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

  8. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics.

    PubMed

    Mahla, Ranjeet Singh

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

  9. Comparison between Three Promising ß-emitting Radionuclides, 67Cu, 47Sc and 161Tb, with Emphasis on Doses Delivered to Minimal Residual Disease

    PubMed Central

    Champion, Christophe; Quinto, Michele A.; Morgat, Clément; Zanotti-Fregonara, Paolo; Hindié, Elif

    2016-01-01

    PURPOSE: Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy β- emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of 67Cu, 47Sc and 161Tb to irradiate small tumors. METHODS: The absorbed dose deriving from a homogeneous distribution of 67Cu, 47Sc or 161Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including β- spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm3, which would result in a dose of 160 Gy if totally absorbed. RESULTS: The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, 161Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with 67Cu, 14.8 Gy with 47Sc and 44.5 Gy with 161Tb. Auger and conversion electrons accounted for 71% of 161Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by 161Tb was 4.1 times higher than that from 67Cu and 8.1 times that from 47Sc. CONCLUSION: 161Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy β- emission and low-energy conversion and Auger electrons. Therefore 161Tb might be a better candidate than 67Cu and 47Sc for treating minimal residual disease in a clinical setting. PMID:27446495

  10. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

  11. Biotechnologically engineered protein binders for applications in amyloid diseases.

    PubMed

    Haupt, Christian; Fändrich, Marcus

    2014-10-01

    The aberrant self-assembly of polypeptide chains into amyloid structures is a common phenomenon in several neurodegenerative diseases, systemic amyloidosis, and 'normal' aging. Improvements in laboratory-scale detection of these structures, their clinical diagnosis, and the treatment of disease likely depend on the advent of new molecules that recognize particular states or induce their clearance in vivo. This review will describe what biotechnology can do to generate proteinaceous amyloid-binders, explain their molecular recognition mechanisms, and summarize possibilities to functionalize further these ligands for specific applications.

  12. Marine Bioactives: Pharmacological Properties and Potential Applications against Inflammatory Diseases

    PubMed Central

    D’Orazio, Nicolantonio; Gammone, Maria Alessandra; Gemello, Eugenio; De Girolamo, Massimo; Cusenza, Salvatore; Riccioni, Graziano

    2012-01-01

    application of many marine bioactives against inflammatory diseases. PMID:22690145

  13. 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

    PubMed Central

    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 < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of 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

  14. [Atypical BCR-ABL transcripts in patients with chronic myeloid leukemia--the scheme for the diagnosis and monitoring of minimal residual disease].

    PubMed

    Link-Lenczowska, Dorota; Sacha, Tomasz; Zawada, Magdalena; Czekalska, Sylwia; Florek, Izabela; Skotnicki, Aleksander B

    2014-01-01

    More than 95% of patients with detected translocation t(9;22), is characterized by the fusion between exons e13 or e14 of BCR gene, which are located in major breakpoint cluster region (M-bcr) and exon a2 of ABL gene. These fusions are described as b2a2 (e13a2) and b3a2 (e14a2). Other fusions of exons e1, e6, e8, e12, e19, e20 of BCR gene with exons a2 or a3 of ABL gene occur very rarely and lead to formation of so called unusual fusion BCR-ABL genes. The aim of this study is to describe long-term observations of the occurrence and routine procedure in the diagnosis of atypical variants of the fusion gene BCR-ABL in a population of patients with chronic myeloid leukemia (CML). It was found that the vast majority of patients with detected BCR-ABL transcripts were b3a2 and b2a2. Other detected variants, which are described as rare were: e1a2, b2a3, b3a3, c3a2, e6a2, e6a3. At the stage of diagnosis as well as during monitoring of the effects of treatment, molecular methods which are based on polymerase chain reaction were used (multiplex RT-PCR, nested RT-PCR, RQ-PCR). Multiplex RT-PCR reaction gave possibility to detect variants of the fusion BCR-ABL gene in one reaction and was crucial in the selection of appropriate test used for further monitoring of the disease and the effectiveness of treatment. This paper proposes a scheme for dealing with the diagnosis and monitoring of minimal residual disease (MRD) in patients with CML treated with tyrosine kinase inhibitors (TKIs) in the presence of rare fusion of the BCR and ABL genes. PMID:25248240

  15. 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).

    PubMed

    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.

  16. Parkinson's disease hand tremor detection system for mobile application.

    PubMed

    Fraiwan, Luay; Khnouf, Ruba; Mashagbeh, Abdel Razaq

    2016-01-01

    Parkinson's disease currently affects millions of people worldwide and is steadily increasing. Many symptoms are associated with this disease, including rest tremor, bradykinesia, stiffness or rigidity of the extremities and postural instability. No cure is currently available for Parkinson's disease patients; instead most medications are for treatment of symptoms. This treatment depends on the quantification of these symptoms such as hand tremor. This work proposes a new system for mobile phone applications. The system is based on measuring the acceleration from the Parkinson's disease patient's hand using a mobile cell phone accelerometer. Recordings from 21 Parkinson's disease patients and 21 healthy subjects were used. These recordings were analysed using a two level wavelet packet analysis and features were extracted forming a feature vector of 12 elements. The features extracted from the 42 subjects were classified using a neural networks classifier. The results obtained showed an accuracy of 95% and a Kappa coefficient of 90%. These results indicate that a cell phone accelerometer can accurately detect and record rest tremor in Parkinson's disease patients. PMID:26977823

  17. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma.

    PubMed

    Paiva, Bruno; Gutiérrez, Norma C; Rosiñol, Laura; Vídriales, María-Belén; Montalbán, María-Ángeles; Martínez-López, Joaquín; Mateos, María-Victoria; Cibeira, María-Teresa; Cordón, Lourdes; Oriol, Albert; Terol, María-José; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Palomera, Luis; de la Rubia, Javier; Díaz-Mediavilla, Joaquín; Sureda, Anna; Gorosquieta, Ana; Alegre, Adrian; Martin, Alejandro; Hernández, Miguel T; Lahuerta, Juan-José; Bladé, Joan; San Miguel, Jesús F

    2012-01-19

    The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated. PMID:22128143

  18. Minimally invasive percutaneous endovascular therapies in the management of complications of non-alcoholic fatty liver disease (NAFLD): A case report

    PubMed Central

    Salsamendi, Jason; Pereira, Keith; Kang, Kyungmin; Fan, Ji

    2015-01-01

    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. PMID:26629307

  19. Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia.

    PubMed

    Cassaday, Ryan D; Alan Potts, D; Stevenson, Philip A; Bar, Merav; Georges, George E; Shustov, Andrei R; Sorror, Mohamed L; Wood, Brent L; Delaney, Colleen; Doney, Kristine C; Storb, Rainer F; Sandmaier, Brenda M

    2016-09-01

    Comparisons without hematopoietic cell transplantation (HCT) to myeloablative (MAC) or reduced-intensity HCT (RIC) for adults with acute lymphoblastic leukemia (ALL) in first minimal-residual-disease negative remission (MRD(Neg) CR1) are limited. Further, the importance of MRD(Neg) following salvage therapy (MRD(Neg) CR2+) is unknown. We evaluated 89 patients in MRD(Neg) CR1 after adult-inspired treatment: 33 received MAC (12 Philadelphia chromosome [Ph]+), 17 received RIC (13 Ph+), and 39 Deferred HCT (3 Ph+). Three-year overall survival (OS) estimates for MAC, RIC, and Deferred HCT were 71%, 69%, and 68%, while 3-year event-free survival (EFS) estimates were 65%, 54%, and 28%, respectively. Further, HCT in MRD(Neg) CR1 performed similarly to MRD(Neg) CR2+: 3-year OS estimates were 70% and 69%, and 3-year EFS estimates were 62% and 62%, respectively. In conclusion, adults with ALL in MRD(Neg) CR1 following adult-inspired therapy had similar OS with or without HCT, and HCT in MRD(Neg) CR2 + can yield long-term survival. PMID:27002921

  20. Flow cytometry with anti HLA-antibodies: a simple but highly sensitive method for monitoring chimerism and minimal residual disease after HLA-mismatched stem cell transplantation.

    PubMed

    Schumm, M; Feuchtinger, T; Pfeiffer, M; Hoelle, W; Bethge, W; Ebinger, M; Kuci, S; Handgretinger, R; Lang, P

    2007-06-01

    Transplantation of HLA-mismatched stem cells may allow determination of chimerism status of single cells by differential expression of HLA molecules. Monoclonal antibodies against HLA antigens can be used to determine the HLA type of sub-populations by standard flow cytometry. Blood samples from 23 patients transplanted from HLA-mismatched family donors were monitored using HLA-specific antibodies. Suitable antibodies could be found for all donor recipient pairs by using differences in HLA Bw4 and Bw6 groups or other serological antigens. Pretransplant controls of donor and recipient were used to correct for variable fluorescence intensities of the antibodies and sub-populations. Owing to the high sensitivity, cell populations with a minimum frequency of 0.1% were detectable. Flow-cytometric analysis was confirmed by chimerism analysis of immunomagnetically isolated T cells by standard PCR technique. In addition to chimerism evaluation, HLA antibodies improved the detection of leukemic cells after transplantation with aberrant phenotype. In conclusion, flow cytometry using antibodies against HLA antigens is an interesting tool for determination of chimerism and minimal residual disease after HLA-mismatched transplantation. Information about the chimerism status is given on a single-cell level and allows fast and convenient analysis of sub-populations.

  1. Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT-PCR.

    PubMed

    Cassinat, B; Zassadowski, F; Balitrand, N; Barbey, C; Rain, J D; Fenaux, P; Degos, L; Vidaud, M; Chomienne, C

    2000-02-01

    We took advantage of a recently developed system allowing performance of real-time quantitation of polymerase chain reaction to develop a quantitative method of measurement of PML-RARalpha transcripts which are hallmarks of acute promyelocytic leukemia (APL) with t(15;17) translocation. Indeed, although quantitation of minimal residual disease has proved to be useful in predicting clinical outcome in other leukemias such as chronic myeloid leukemia or acute lymphoblastic leukemia, no quantitative data have been provided in the case of APL. We present here a method for quantitation of the most frequent subtypes of t(15;17) transcripts (namely bcr1 and bcr3). One specific forward primer is used for each subtype in order to keep amplicon length under 200 bp. The expression of PML-RARalpha transcripts is normalized using the housekeeping porphobilinogen deaminase (PBGD) gene. This technique allows detection of 10 copies of PML-RARalpha or PBGD plasmids, and quantitation was efficient up to 100 copies. One t(15;17)-positive NB4 cell could be detected among 106 HL60 cells, although quantitation was efficient up to one cell among 105. Repeatability and reproducibility of the method were satisfying as intra- and inter-assay variation coefficients were not higher than 15%. The efficiency of the method was finally tested in patient samples, showing a decrease of the PML-RARalpha copy number during therapy, and an increase at the time of relapse.

  2. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)

    PubMed Central

    2012-01-01

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available. PMID:23210797

  3. Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia.

    PubMed

    Terwey, Theis Helge; Hemmati, Philipp Georg; Nagy, Marion; Pfeifer, Heike; Gökbuget, Nicola; Brüggemann, Monika; Le Duc, Tanja Melinh; le Coutre, Philipp; Dörken, Bernd; Arnold, Renate

    2014-10-01

    Little data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions.

  4. Minimizing Nitrate Reduction during Kjeldahl Digestion of Plant Tissue Extracts and Stem Exudates : APPLICATION TO N STUDIES.

    PubMed

    Pace, G M; Mackown, C T; Volk, R J

    1982-01-01

    From 10 to 60% of the nitrate present in plant tissue extracts and stem exudates of corn (Zea mays L.) was found to be reduced during Kjeldahl digestion, even in the absence of added reducing agents. This reduction is of particular concern in [(15)N]nitrate assimilation studies, because it results in an overestimate of nitrate reduction. To overcome this problem, a method was developed for removing nitrate prior to Kjeldahl digestion, thereby preventing nitrate reduction. The procedure utilizes hydrogen peroxide for partial oxidation of organic matter in order to minimize the nitration of organic compounds. The free nitrates are then volatilized as nitric acid from concentrated sulfuric acid at 95 degrees C. When the proposed method was used as a pretreatment to Kjeldahl digestion, less than 0.5% of the applied nitrate was recovered in the reduced nitrogen fraction of plant tissue extracts and stem exudates.

  5. RNAi and small interfering RNAs in human disease therapeutic applications

    PubMed Central

    Lares, Monica R.; Rossi, John J.; Ouellet, Dominique L.

    2010-01-01

    Small interfering RNAs (siRNAs) have shown to effectively down-regulate gene expression in human cells, giving them potential to eradicate disease. Prospects for clinical applications are discussed in this review, along with an overview of recent history and our current understanding of siRNAs used for therapeutic application in human diseases, such as cancer and viral infections. Over recent years, progress has been made in lipids, ligands, nanoparticles, polymers and viral vectors as delivery agents and for gene-based expression of siRNA to enhance the efficacy and specificity of these methods while at the same time reducing toxicity. It has become apparent that given the recent advances in chemistry and delivery, RNAi will soon prove to be an important and widely used therapeutic modality. PMID:20833440

  6. Is demography destiny? Application of machine learning techniques to accurately predict population health outcomes from a minimal demographic dataset.

    PubMed

    Luo, Wei; Nguyen, Thin; Nichols, Melanie; Tran, Truyen; Rana, Santu; Gupta, Sunil; Phung, Dinh; Venkatesh, Svetha; Allender, Steve

    2015-01-01

    For years, we have relied on population surveys to keep track of regional public health statistics, including the prevalence of non-communicable diseases. Because of the cost and limitations of such surveys, we often do not have the up-to-date data on health outcomes of a region. In this paper, we examined the feasibility of inferring regional health outcomes from socio-demographic data that are widely available and timely updated through national censuses and community surveys. Using data for 50 American states (excluding Washington DC) from 2007 to 2012, we constructed a machine-learning model to predict the prevalence of six non-communicable disease (NCD) outcomes (four NCDs and two major clinical risk factors), based on population socio-demographic characteristics from the American Community Survey. We found that regional prevalence estimates for non-communicable diseases can be reasonably predicted. The predictions were highly correlated with the observed data, in both the states included in the derivation model (median correlation 0.88) and those excluded from the development for use as a completely separated validation sample (median correlation 0.85), demonstrating that the model had sufficient external validity to make good predictions, based on demographics alone, for areas not included in the model development. This highlights both the utility of this sophisticated approach to model development, and the vital importance of simple socio-demographic characteristics as both indicators and determinants of chronic disease.

  7. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children’s Oncology Group study AALL0232

    PubMed Central

    Wood, Brent L.; Devidas, Meenakshi; Loh, Mignon L.; Raetz, Elizabeth A.; Salzer, Wanda L.; Nachman, James B.; Carroll, Andrew J.; Heerema, Nyla A.; Gastier-Foster, Julie M.; Willman, Cheryl L.; Dai, Yunfeng; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.; Larsen, Eric

    2015-01-01

    Minimal residual disease (MRD) is highly prognostic in pediatric B-precursor acute lymphoblastic leukemia (B-ALL). In Children’s Oncology Group high-risk B-ALL study AALL0232, we investigated MRD in subjects randomized in a 2 × 2 factorial design to receive either high-dose methotrexate (HD-MTX) or Capizzi methotrexate (C-MTX) during interim maintenance (IM) or prednisone or dexamethasone during induction. Subjects with end-induction MRD ≥0.1% or those with morphologic slow early response were nonrandomly assigned to receive a second IM and delayed intensification phase. MRD was measured by 6-color flow cytometry in 1 of 2 reference labs, with excellent agreement between the two. Subjects with end-induction MRD <0.01% had a 5-year event-free survival (EFS) of 87% ± 1% vs 74% ± 4% for those with MRD 0.01% to 0.1%; increasing MRD amounts was associated with progressively worse outcome. Subjects converting from MRD positive to negative by end consolidation had a relatively favorable 79% ± 5% 5-year disease-free survival vs 39% ± 7% for those with MRD ≥0.01%. Although HD-MTX was superior to C-MTX, MRD retained prognostic significance in both groups (86% ± 2% vs 58% ± 4% for MRD-negative vs positive C-MTX subjects; 88% ± 2% vs 68% ± 4% for HD-MTX subjects). Intensified therapy given to subjects with MRD >0.1% did not improve either 5-year EFS or overall survival (OS). However, these subjects showed an early relapse rate similar to that seen in MRD-negative ones, with EFS/OS curves for patients with 0.1% to 1% MRD crossing those with 0.01% to 0.1% MRD at 3 and 4 years, thus suggesting that the intensified therapy altered the disease course of MRD-positive subjects. Additional interventions targeted at the MRD-positive group may further improve outcome. This trial was registered at www.clinicaltrials.gov as #NCT00075725. PMID:26124497

  8. Application of Induced Pluripotent Stem Cells in Liver Diseases

    PubMed Central

    Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

    2014-01-01

    Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

  9. Minimization of the Vibration Energy of Thin-Plate Structures and the Application to the Reduction of Gearbox Vibration

    NASA Technical Reports Server (NTRS)

    Inoue, Katsumi; Krantz, Timothy L.

    1995-01-01

    While the vibration analysis of gear systems has been developed, a systematic approach to the reduction of gearbox vibration has been lacking. The technique of reducing vibration by shifting natural frequencies is proposed here for gearboxes and other thin-plate structures using the theories of finite elements, modal analysis, and optimization. A triangular shell element with 18 degrees of freedom is developed for structural and dynamic analysis. To optimize, the overall vibration energy is adopted as the objective function to be minimized at the excitation frequency by varying the design variable (element thickness) under the constraint of overall constant weight. Modal analysis is used to determine the sensitivity of the vibration energy as a function of the eigenvalues and eigenvectors. The optimum design is found by the gradient projection method and a unidimensional search procedure. By applying the computer code to design problems for beams and plates, it was verified that the proposed method is effective in reducing vibration energy. The computer code is also applied to redesign the NASA Lewis gear noise rig test gearbox housing. As one example, only the shape of the top plate is varied, and the vibration energy levels of all the surfaces are reduced, yielding an overall reduction of 1/5 compared to the initial design. As a second example, the shapes of the top and two side plates are varied to yield an overall reduction in vibration energy of 1/30.

  10. Application of Raman microscopy and band-target entropy minimization to identify minor components in model pharmaceutical tablets.

    PubMed

    Widjaja, Effendi; Seah, Regina Kim Hong

    2008-01-22

    The aim of the current study is to establish a useful analytical technique to detect and identify minor components of pharmaceutical drug tablets using Raman microscopy and advanced multivariate data analysis method, namely band-target entropy minimization (BTEM). Model pharmaceutical tablets comprising four components with varying proportions were prepared with a custom press tooling after blending. One of the components, magnesium stearate, was made as a minor component, with weight percentages of 2%, 1%, 0.5%, and 0.2% in four model tablets. Raman point-by-point mapping was performed on an area of 200 microm x 200 microm using a near infrared laser source and a 50x objective lens with a step size of 5 microm in both the x and y directions. Advanced multivariate analysis, BTEM, was then performed on the Raman mapping data to recover all observable pure component spectra. BTEM was successfully applied to recover the pure component spectrum of magnesium stearate, which was present as a minor component (as low as 0.2 wt%) in the prepared tablet. The success of BTEM in identifying minor chemical species offers a new analytical technology for detecting impurities or any other minor components in pharmaceutical tablets.

  11. Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.

    PubMed

    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.

  12. Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis.

    PubMed

    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.

  13. 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.

    PubMed

    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.

  14. Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

    PubMed Central

    Lai, Xiaoyu; Tan, Yamin; Zheng, Weiyan; Shi, Jimin; Zhao, Yanmin; Lin, Maofang; He, Jingsong; Cai, Zhen; Luo, Yi; Huang, He

    2016-01-01

    We evaluated the prognostic effect of minimal residual disease at first achievement of complete remission (MRD at CR1) in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of 97 patients received treatment in our center between 2007 and 2012 were retrospectively reviewed in this study. Patients were divided into two arms according to the post-remission therapy (chemotherapy alone or allogeneic hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was detected by four-color flow cytometry. We chose 0.02% and 0.2% as the cut-off points of MRD at CR1 for risk stratification using receiver operating characteristic analysis. The 3-year overall survival (OS) and leukemia free survival (LFS) rates for the whole cohort were 46.2% and 40.5%. MRD at CR1 had a significantly negative correlation with survival in both arms. Three-year OS rates in the chemotherapy arm were 70.0%, 25.2%, 0% (P = 0.003) for low, intermediate, and high levels of MRD at CR1, respectively. Three-year OS rates in the transplant arm were 81.8%, 64.3%, 27.3% (P = 0.005) for low, intermediate, and high levels of MRD at CR1, respectively. Multivariate analysis confirmed that higher level of MRD at CR1 was a significant adverse factor for OS and LFS. Compared with chemotherapy alone, allo-HSCT significantly improved LFS rates in patients with intermediate (P = 0.005) and high (P = 0.022) levels of MRD at CR1, but not patients with low level of MRD at CR1 (P = 0.851). These results suggested that MRD at CR1 could strongly predict the outcome of adult ALL. Patients with intermediate and high levels of MRD at CR1 would benefit from allo-HSCT. PMID:27695097

  15. Minimal hepatic glucose-6-phosphatase-α activity required to sustain survival and prevent hepatocellular adenoma formation in murine glycogen storage disease type Ia.

    PubMed

    Lee, Young Mok; Kim, Goo-Young; Pan, Chi-Jiunn; Mansfield, Brian C; Chou, Janice Y

    2015-06-01

    Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. In a previous 70-90 week-study, we showed that a recombinant adeno-associated virus (rAAV) vector-mediated gene transfer that restores more than 3% of wild-type hepatic G6Pase-α activity in G6pc (-/-) mice corrects hepatic G6Pase-α deficiency with no evidence of HCA. We now examine the minimal hepatic G6Pase-α activity required to confer therapeutic efficacy. We show that rAAV-treated G6pc (-/-) mice expressing 0.2% of wild-type hepatic G6Pase-α activity suffered from frequent hypoglycemic seizures at age 63-65 weeks but mice expressing 0.5-1.3% of wild-type hepatic G6Pase-α activity (AAV-LL mice) sustain 4-6 h of fast and grow normally to age 75-90 weeks. Despite marked increases in hepatic glycogen accumulation, the AAV-LL mice display no evidence of hepatic abnormalities, hepatic steatosis, or HCA. Interprandial glucose homeostasis is maintained by the G6Pase-α/glucose-6-phosphate transporter (G6PT) complex, and G6PT-mediated microsomal G6P uptake is the rate-limiting step in endogenous glucose production. We show that hepatic G6PT activity is increased in AAV-LL mice. These findings are encouraging for clinical studies of G6Pase-α gene-based therapy for GSD-Ia.

  16. Minimizing the Risk of Disease Transmission in Emergency Settings: Novel In Situ Physico-Chemical Disinfection of Pathogen-Laden Hospital Wastewaters.

    PubMed

    Sozzi, Emanuele; Fabre, Kerline; Fesselet, Jean-François; Ebdon, James E; Taylor, Huw

    2015-01-01

    'Coalition for Cholera Prevention and Control' recently highlighted the research as meriting serious consideration and further study. Further applications of the method to other emergency settings are being actively explored by the authors through discussion with the World Health Organization with regards to the ongoing Ebola outbreak in West Africa, and with the UK-based NGO Oxfam with regards to excreta-borne disease management in the Philippines and Myanmar, as a component of post-disaster incremental improvements to local sanitation chains.

  17. Minimizing the Risk of Disease Transmission in Emergency Settings: Novel In Situ Physico-Chemical Disinfection of Pathogen-Laden Hospital Wastewaters.

    PubMed

    Sozzi, Emanuele; Fabre, Kerline; Fesselet, Jean-François; Ebdon, James E; Taylor, Huw

    2015-01-01

    'Coalition for Cholera Prevention and Control' recently highlighted the research as meriting serious consideration and further study. Further applications of the method to other emergency settings are being actively explored by the authors through discussion with the World Health Organization with regards to the ongoing Ebola outbreak in West Africa, and with the UK-based NGO Oxfam with regards to excreta-borne disease management in the Philippines and Myanmar, as a component of post-disaster incremental improvements to local sanitation chains. PMID:26110821

  18. Minimizing the Risk of Disease Transmission in Emergency Settings: Novel In Situ Physico-Chemical Disinfection of Pathogen-Laden Hospital Wastewaters

    PubMed Central

    Sozzi, Emanuele; Fabre, Kerline; Fesselet, Jean-François; Ebdon, James E.; Taylor, Huw

    2015-01-01

    ‘Coalition for Cholera Prevention and Control’ recently highlighted the research as meriting serious consideration and further study. Further applications of the method to other emergency settings are being actively explored by the authors through discussion with the World Health Organization with regards to the ongoing Ebola outbreak in West Africa, and with the UK-based NGO Oxfam with regards to excreta-borne disease management in the Philippines and Myanmar, as a component of post-disaster incremental improvements to local sanitation chains. PMID:26110821

  19. Application of satellite imagery to monitoring human rights abuse of vulnerable communities, with minimal risk to relief staff

    NASA Astrophysics Data System (ADS)

    Lavers, C.; Bishop, C.; Hawkins, O.; Grealey, E.; Cox, C.; Thomas, D.; Trimel, S.

    2009-07-01

    Space imagery offers remote surveillance of ethnic people groups at risk of human rights abuse. We highlight work in alleged violations in Burma and Sudan, using satellite imagery for verification with Amnesty International. We consider how imaging may effectively support small to medium-sized Non Governmental Organisations and charities, e.g. HART, working in dangerous zones on the ground. Satellite based sensing applications are now at a sufficiently mature stage for moderate Governmental funding levels to help prevent human rights abuse, rather than the greater cost of rebuilding communities and healing sectarian divisions after abuse has taken place.

  20. Diagnostic Applications of Cone-Beam CT for Periodontal Diseases

    PubMed Central

    AlJehani, Yousef A.

    2014-01-01

    Objectives. This paper aims to review the diagnostic application of cone beam computed tomography (CBCT) in the field of periodontology. Data. Original articles that reported on the use of CBCT for periodontal disease diagnosis were included. Sources. MEDLINE (1990 to January 2014), PubMed (using medical subject headings), and Google Scholar were searched using the following terms in different combinations: “CBCT,” “volumetric CT,” “periodontal disease ,” and “periodontitis.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Conclusions. Bony defects, caters, and furcation involvements seem to be better depicted on CBCT, whereas bone quality and periodontal ligament space scored better on conventional intraoral radiography. CBCT does not offer a significant advantage over conventional radiography for assessing the periodontal bone levels. PMID:24803932

  1. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    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. PMID:27630988

  2. Influenza SIRS with Minimal Pneumonitis.

    PubMed

    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. PMID:27630988

  3. Clinical applications of lightguide diffuse reflectance spectrophotometry in vascular disease

    NASA Astrophysics Data System (ADS)

    Harrison, David K.; Delaney, Colin; Brown, Linda; Newton, David J.; McCollum, Peter T.

    1994-02-01

    There is enormous potential for application of lightguide tissue reflectance spectrophotometry in the diagnosis and treatment of peripheral vascular disease. In the present study, measurements were carried out in 10 such pre-amputation patients to compare the use of micro-lightguide spectrophotometry with the macro-lightguide technique. These preliminary results show excellent agreement between the new, non-invasive micro-lightguide technique and the `gold standard' skin blood flow measurements. This technique could thus provide a more functional, non-invasive assessment of healing potential than skin blood flow measurement.

  4. New imaging applications in the evaluation of pediatric renal disease.

    PubMed

    Norton, Karen I

    2003-04-01

    Continued improvements in imaging technology have changed many of the traditional diagnostic algorithms for evaluating pediatric renal disease. Newer imaging modalities offer more accurate, specific, and early diagnoses, but can be time consuming and costly. Less invasive modalities, such as ultrasound, computed tomography, and magnetic resonance imaging have widespread applications in pediatric practice. The risks of radiation exposure, contrast toxicity, and sedation or anesthesia versus the potential benefits of obtaining precise diagnostic information should always be considerations before electing any imaging procedure in children.

  5. Progress on conformal microwave array applicators for heating chestwall disease

    NASA Astrophysics Data System (ADS)

    Stauffer, P. R.; Maccarini, P. F.; Juang, T.; Jacobsen, S. K.; Gaeta, C. J.; Schlorff, J. L.; Milligan, A. J.

    2007-02-01

    Previous studies have reported the computer modeling, CAD design, and theoretical performance of single and multiple antenna arrays of Dual Concentric Conductor (DCC) square slot radiators driven at 915 and 433 MHz. Subsequently, practical CAD designs of microstrip antenna arrays constructed on thin and flexible printed circuit board (PCB) material were reported which evolved into large Conformal Microwave Array (CMA) sheets that could wrap around the surface of the human torso for delivering microwave energy to large areas of superficial tissue. Although uniform and adjustable radiation patterns have been demonstrated from multiple element applicators radiating into simple homogeneous phantom loads, the contoured and heterogeneous tissue loads typical of chestwall recurrent breast cancer have required additional design efforts to achieve good coupling and efficient heating from the increasingly larger conformal array applicators used to treat large area contoured patient anatomy. Thus recent work has extended the theoretical optimization of DCC antennas to improve radiation efficiency of each individual aperture and reduce mismatch reflections, radiation losses, noise, and cross coupling of the feedline distribution network of large array configurations. Design improvements have also been incorporated into the supporting bolus structure to maintain effective coupling of DCC antennas into contoured anatomy and to monitor and control surface temperatures under the entire array. New approaches for non-invasive monitoring of surface and sub-surface tissue temperatures under each independent heat source are described that make use of microwave radiometry and flexible sheet grid arrays of thermal sensors. Efforts to optimize the clinical patient interface and move from planar rectangular shapes to contoured vest applicators that accommodate entire disease in a larger number of patients are summarized. By applying heat more uniformly to large areas of contoured anatomy

  6. Minimally invasive mediastinal surgery

    PubMed Central

    Melfi, Franca M. A.; Mussi, Alfredo

    2016-01-01

    In the past, mediastinal surgery was associated with the necessity of a maximum exposure, which was accomplished through various approaches. In the early 1990s, many surgical fields, including thoracic surgery, observed the development of minimally invasive techniques. These included video-assisted thoracic surgery (VATS), which confers clear advantages over an open approach, such as less trauma, short hospital stay, increased cosmetic results and preservation of lung function. However, VATS is associated with several disadvantages. For this reason, it is not routinely performed for resection of mediastinal mass lesions, especially those located in the anterior mediastinum, a tiny and remote space that contains vital structures at risk of injury. Robotic systems can overcome the limits of VATS, offering three-dimensional (3D) vision and wristed instrumentations, and are being increasingly used. With regards to thymectomy for myasthenia gravis (MG), unilateral and bilateral VATS approaches have demonstrated good long-term neurologic results with low complication rates. Nevertheless, some authors still advocate the necessity of maximum exposure, especially when considering the distribution of normal and ectopic thymic tissue. In recent studies, the robotic approach has shown to provide similar neurological outcomes when compared to transsternal and VATS approaches, and is associated with a low morbidity. Importantly, through a unilateral robotic technique, it is possible to dissect and remove at least the same amount of mediastinal fat tissue. Preliminary results on early-stage thymomatous disease indicated that minimally invasive approaches are safe and feasible, with a low rate of pleural recurrence, underlining the necessity of a “no-touch” technique. However, especially for thymomatous disease characterized by an indolent nature, further studies with long follow-up period are necessary in order to assess oncologic and neurologic results through minimally

  7. Application of sliding-window discretization and minimization of stochastic complexity for the analysis of fAFLP genotyping fingerprint patterns of Vibrionaceae.

    PubMed

    Dawyndt, Peter; Thompson, Fabiano L; Austin, Brian; Swings, Jean; Koski, Timo; Gyllenberg, Mats

    2005-01-01

    Minimization of stochastic complexity (SC) was used as a method for classification of genotypic fingerprints. The method was applied to fluorescent amplified fragment length polymorphism (fAFLP) fingerprint patterns of 507 Vibrionaceae representatives. As the current BinClass implementation of the optimization algorithm for classification only works on binary vectors, the original fingerprints were discretized in a preliminary step using the sliding-window band-matching method, in order to maximally preserve the information content of the original band patterns. The novel classification generated using the BinClass software package was subjected to an in-depth comparison with a hierarchical classification of the same dataset, in order to acknowledge the applicability of the new classification method as a more objective algorithm for the classification of genotyping fingerprint patterns. Recent DNA-DNA hybridization and 16S rRNA gene sequence experiments proved that the classification based on SC-minimization forms separate clusters that contain the fAFLP patterns for all representatives of the species Enterovibrio norvegicus, Vibrio fortis, Vibrio diazotrophicus or Vibrio campbellii, while previous hierarchical cluster analysis had suggested more heterogeneity within the fAFLP patterns by splitting the representatives of the above-mentioned species into multiple distant clusters. As a result, the new classification methodology has highlighted some previously unseen relationships within the biodiversity of the family Vibrionaceae.

  8. Minimization and Mitigation of Wire EDM Cutting Errors in the Application of the Contour Method of Residual Stress Measurement

    NASA Astrophysics Data System (ADS)

    Ahmad, Bilal; Fitzpatrick, Michael E.

    2016-01-01

    The contour method of residual stress measurement relies on the careful application of wire electro-discharge machining (WEDM) for the cutting stage. Changes in material removal rates during the cut lead to errors in the final calculated values of residual stress. In this study, WEDM cutting parameters have been explored to identify the optimum conditions for contour method residual stress measurements. The influence of machine parameters on the surface roughness and cutting artifacts in the contour cut is discussed. It has been identified that the critical parameter in improving the surface finish is the spark pulse duration. A typical cutting artifact and its impact on measured stress values have been identified and demonstrated for a contour cut in a welded marine steel. A procedure is presented to correct contour displacement data from the influence of WEDM cutting artifacts, and is demonstrated on the correction of a measured weld residual stress. The corrected contour method improved the residual stress magnitude up to 150 MPa. The corrected contour method results were validated by X-ray diffraction, incremental center hole drilling, and neutron diffraction.

  9. Minimal Residual Disease-Based Risk Stratification in Chinese Childhood Acute Lymphoblastic Leukemia by Flow Cytometry and Plasma DNA Quantitative Polymerase Chain Reaction

    PubMed Central

    Cheng, Suk Hang; Lau, Kin Mang; Li, Chi Kong; Chan, Natalie P. H.; Ip, Rosalina K. L.; Cheng, Chi Keung; Lee, Vincent; Shing, Matthew M. K.; Leung, Alex W. K.; Ha, Shau Yin; Cheuk, Daniel K. L.; Lee, Anselm C. W.; Li, Chak Ho; Luk, Chung Wing; Ling, Siu Cheung; Hrusak, Ondrej; Mejstrikova, Ester; Leung, Yonna; Ng, Margaret H. L.

    2013-01-01

    Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1–10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15≥10% or day-33≥0.01% but not both, II-C: day-15≥10% and day-33≥0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD≥10−4 were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients’ prognosis, with 20–35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥10−4. We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring. PMID:23936021

  10. Outcomes of Children With BCR-ABL1–Like Acute Lymphoblastic Leukemia Treated With Risk-Directed Therapy Based on the Levels of Minimal Residual Disease

    PubMed Central

    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

  11. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL

    PubMed Central

    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

    2016-01-01

    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 < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02–5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both 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. PMID:27427275

  12. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

    PubMed

    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

    2016-01-01

    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 < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02-5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both 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. PMID:27427275

  13. Minimally invasive pancreatic surgery – a review

    PubMed Central

    Damoli, Isacco; Ramera, Marco; Paiella, Salvatore; Marchegiani, Giovanni; Bassi, Claudio

    2015-01-01

    During the past 20 years the application of a minimally invasive approach to pancreatic surgery has progressively increased. Distal pancreatectomy is the most frequently performed procedure, because of the absence of a reconstructive phase. However, middle pancreatectomy and pancreatoduodenectomy have been demonstrated to be safe and feasible as well. Laparoscopic distal pancreatectomy is recognized as the gold standard treatment for small tumors of the pancreatic body-tail, with several advantages over the traditional open approach in terms of patient recovery. The surgical treatment of lesions of the pancreatic head via a minimally invasive approach is still limited to a few highly experienced surgeons, due to the very challenging resection and complex anastomoses. Middle pancreatectomy and enucleation are indicated for small and benign tumors and offer the maximum preservation of the parenchyma. The introduction of a robotic platform more than ten years ago increased the interest of many surgeons in minimally invasive treatment of pancreatic diseases. This new technology overcomes all the limitations of laparoscopic surgery, but actual benefits for the patients are still under investigation. The increased costs associated with robotic surgery are under debate too. This article presents the state of the art of minimally invasive pancreatic surgery. PMID:26240612

  14. The ZOOM minimization package

    SciTech Connect

    Fischler, Mark S.; Sachs, D.; /Fermilab

    2004-11-01

    A new object-oriented Minimization package is available for distribution in the same manner as CLHEP. This package, designed for use in HEP applications, has all the capabilities of Minuit, but is a re-write from scratch, adhering to modern C++ design principles. A primary goal of this package is extensibility in several directions, so that its capabilities can be kept fresh with as little maintenance effort as possible. This package is distinguished by the priority that was assigned to C++ design issues, and the focus on producing an extensible system that will resist becoming obsolete.

  15. Aqueous cationic, anionic and non-ionic multi-walled carbon nanotubes, functionalised with minimal framework damage, for biomedical application.

    PubMed

    Chen, Shu; Hu, Sheng; Smith, Elizabeth F; Ruenraroengsak, Pakatip; Thorley, Andrew J; Menzel, Robert; Goode, Angela E; Ryan, Mary P; Tetley, Teresa D; Porter, Alexandra E; Shaffer, Milo S P

    2014-06-01

    The use of a thermochemical grafting approach provides a versatile means to functionalise as-synthesised, bulk multi-walled carbon nanotubes (MWNTs) without altering their inherent structure. The associated retention of properties is desirable for a wide range of commercial applications, including for drug delivery and medical purposes; it is also pertinent to studies of intrinsic toxicology. A systematic series of water-compatible MWNTs, with diameter around 12 nm have been prepared, to provide structurally-equivalent samples predominantly stabilised by anionic, cationic, or non-ionic groups. The surface charge of MWNTs was controlled by varying the grafting reagents and subsequent post-functionalisation modifications. The degree of grafting was established by thermal analysis (TGA). High resolution transmission electron microscope (HRTEM) and Raman measurements confirmed that the structural framework of the MWNTs was unaffected by the thermochemical treatment, in contrast to a conventional acid-oxidised control which was severely damaged. The effectiveness of the surface modification was demonstrated by significantly improved solubility and stability in both water and cell culture medium, and further quantified by zeta-potential analysis. The grafted MWNTs exhibited relatively low bioreactivity on transformed human alveolar epithelial type 1-like cells (TT1) following 24 h exposure as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase release (LDH) assays. The exposure of TT1 cells to MWNTs suppressed the release of the inflammatory mediators, interleukin 6 (IL-6) and interleukin 8 (IL-8). TEM cell uptake studies indicated efficient cellular entry of MWNTs into TT1 cells, via a range of mechanisms. Cationic MWNTs showed a more substantial interaction with TT1 cell membranes than anionic MWNTs, demonstrating a surface charge effect on cell uptake.

  16. Aqueous cationic, anionic and non-ionic multi-walled carbon nanotubes, functionalised with minimal framework damage, for biomedical application

    PubMed Central

    Chen, Shu; Hu, Sheng; Smith, Elizabeth F.; Ruenraroengsak, Pakatip; Thorley, Andrew J.; Menzel, Robert; Goode, Angela E.; Ryan, Mary P.; Tetley, Teresa D.; Porter, Alexandra E.; Shaffer, Milo S. P.

    2014-01-01

    The use of a thermochemical grafting approach provides a versatile means to functionalise as-synthesised, bulk multi-walled carbon nanotubes (MWNTs) without altering their inherent structure. The associated retention of properties is desirable for a wide range of commercial applications, including for drug delivery and medical purposes; it is also pertinent to studies of intrinsic toxicology. A systematic series of water-compatible MWNTs, with diameter around 12 nm have been prepared, to provide structurally-equivalent samples predominantly stabilised by anionic, cationic, or non-ionic groups. The surface charge of MWNTs was controlled by varying the grafting reagents and subsequent post-functionalisation modifications. The degree of grafting was established by thermal analysis (TGA). High resolution transmission electron microscope (HRTEM) and Raman measurements confirmed that the structural framework of the MWNTs was unaffected by the thermochemical treatment, in contrast to a conventional acid-oxidised control which was severely damaged. The effectiveness of the surface modification was demonstrated by significantly improved solubility and stability in both water and cell culture medium, and further quantified by zeta-potential analysis. The grafted MWNTs exhibited relatively low bioreactivity on human immortal alveolar epithelial type 1-like cells (TT1) following 24h exposure as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase release (LDH) assays. The exposure of TT1 cells to MWNTs suppressed the release of the inflammatory mediators, interleukin 6 (IL-6) and interleukin 8 (IL-8). TEM cell uptake studies indicated efficient cellular entry of MWNTs into TT1 cells, via a range of mechanisms. Cationic MWNTs showed a more substantial interaction with TT1 cell membranes than anionic MWNTs, demonstrating a surface charge effect on cell uptake. PMID:24631251

  17. Waste minimization handbook, Volume 1

    SciTech Connect

    Boing, L.E.; Coffey, M.J.

    1995-12-01

    This technical guide presents various methods used by industry to minimize low-level radioactive waste (LLW) generated during decommissioning and decontamination (D and D) activities. Such activities generate significant amounts of LLW during their operations. Waste minimization refers to any measure, procedure, or technique that reduces the amount of waste generated during a specific operation or project. Preventive waste minimization techniques implemented when a project is initiated can significantly reduce waste. Techniques implemented during decontamination activities reduce the cost of decommissioning. The application of waste minimization techniques is not limited to D and D activities; it is also useful during any phase of a facility`s life cycle. This compendium will be supplemented with a second volume of abstracts of hundreds of papers related to minimizing low-level nuclear waste. This second volume is expected to be released in late 1996.

  18. Maximizing Accuracy in Half Life Measurements, by Minimizing Error, with Application to BISMUTH-212 and POLONIUM-218

    NASA Astrophysics Data System (ADS)

    Poupaki, Irene

    1990-01-01

    Radon and short-lived progeny existing in all three primordial series, namely uranium, thorium and actinium, are of most significance for human exposure, since their inhalation is implicated in bronchogenic carcinoma. Because the dosimetric calculations utilize half-life, it is important to know this parameter with the maximum possible accuracy. The half-lives of Po-218 and Bi-212, radon-222 and radon-220 progeny, were measured as 3.078 +/- 0.01 min and 59.81 +/- 0.23 min respectively. Experimental data collected by alpha-counting included background from both the counter and the intrinsic radioactivity. A comparison of all mathematical methods presently employed in the analysis of experimental radioactivity decay is presented. The most commonly used methods are, the least squares, the weighted least squares with different weighting factors and the maximum likelihood (Peierls) method. Artificial data corresponding to three different nuclides, different total experimental duration, and different counting time intervals were generated. Testing these data showed that the WLSQ with the correct weighting factor gives the higher accuracy and precision. Without spectrometry, it is impossible to measure the quantity or half-life of Po-218 unless correction is made for the Po-214 daughter. For the measurement of Po-218, samples containing the short-lived radon-222 daughters were collected electrostatically. A method used to estimate the initial radon daughters concentration in air based on regression analysis is proposed. The comparison of this with the well known Thomas method using artificial data showed that the regression analysis method leads to more accurate results. The Bi-212 samples were prepared from a Th-228 solution by spontaneous electrodeposition on platinum and nickel disks. Corrections for the curve stripping have been applied. The methods developed here have general application to the measurement of any radioactive nuclides. A review of the measured half

  19. Application of optical spectroscopic techniques for disease diagnosis

    NASA Astrophysics Data System (ADS)

    Saha, Anushree

    Optical spectroscopy, a truly non-invasive tool for remote diagnostics, is capable of providing valuable information on the structure and function of molecules. However, most spectroscopic techniques suffer from drawbacks, which limit their application. As a part of my dissertation work, I have developed theoretical and experimental methods to address the above mentioned issues. I have successfully applied these methods for monitoring the physical, chemical and biochemical parameters of biomolecules involved in some specific life threatening diseases like lead poisoning and age-related macular degeneration (AMD). I presented optical studies of melanosomes, which are one of the vital organelles in the human eye, also known to be responsible for a disease called age-related macular degeneration (AMD), a condition of advanced degeneration which causes progressive blindness. I used Raman spectroscopy, to first chemically identify the composition of melanosome, and then monitor the changes in its functional and chemical behavior due to long term exposure to visible light. The above study, apart from explaining the role of melanosomes in AMD, also sets the threshold power for lasers used in surgeries and other clinical applications. In the second part of my dissertation, a battery of spectroscopic techniques was successfully applied to explore the different binding sites of lead ions with the most abundant carrier protein molecule in our circulatory system, human serum albumin. I applied optical spectroscopic tools for ultrasensitive detection of heavy metal ions in solution which can also be used for lead detection at a very early stage of lead poisoning. Apart from this, I used Raman microspectroscopy to study the chemical alteration occurring inside a prostate cancer cell as a result of a treatment with a low concentrated aqueous extract of a prospective drug, Nerium Oleander. The experimental methods used in this study has tremendous potential for clinical

  20. Esophagectomy - minimally invasive

    MedlinePlus

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  1. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial.

    PubMed

    Willekens, Christophe; Blanchet, Odile; Renneville, Aline; Cornillet-Lefebvre, Pascale; Pautas, Cécile; Guieze, Romain; Ifrah, Norbert; Dombret, Hervé; Jourdan, Eric; Preudhomme, Claude; Boissel, Nicolas

    2016-03-01

    In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558).

  2. Clinical Utility of Sequential Minimal Residual Disease Measurements in the Context of Risk-based Therapy in Childhood Acute Lymphoblastic Leukemia: a Prospective Study

    PubMed Central

    Pui, Ching-Hon; Pei, Deqing; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Bowman, W Paul; Sandlund, John T; Ribeiro, Raul C; Rubnitz, Jeffrey E; Inaba, Hiroto; Bhojwani, Deepa; Gruber, Tanja A; Leung, Wing H; Downing, James R; Evans, William E; Relling, Mary V; Campana, Dario

    2015-01-01

    Summary Background The level of minimal residual disease (MRD) during remission induction is the most important prognostic indicator in acute lymphoblastic leukemia (ALL). We determined the clinical significance of MRD in the context of a prospective clinical study in which sequential MRD measurements were used to guide treatment decisions. Methods Between 2000 and 2007, 498 evaluable patients with newly diagnosed ALL were enrolled in St. Jude Study XV. Risk of relapse was provisionally classified as low, standard or high according to presenting clinical and laboratory features. Final risk assignment to determine treatment intensity was based mainly on MRD levels measured on days 19 and 46 of remission induction, and on week 7 of continuation treatment. Additional MRD determinations were made on weeks 17, 48 and 120 (end of therapy). Findings Regardless of the provisional risk classification, 10-year event-free survival was significantly inferior for patients with MRD ≥1% on day 19 compared with that of patients having lower MRD levels: 69.2% (95% CI 49.6–82.4, n=36) versus 95.5% (91.7–97.5, n=244) (p<0.001) for the provisional low-risk group and 65.1% (50.7–76.2, n=56) versus 82.9% (75.6–88.2, n=142) (p=0.008) for the provisional standard-risk group. Twelve patients with provisional low-risk ALL and MRD ≥1% on day 19 but negative MRD (<0.01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88.9% (43.3–98.4). For the 244 provisional low-risk patients, an MRD level of <1% on day 19 predicted a superior outcome, regardless of the MRD level on day 46. Among provisional standard-risk patients with MRD <1% on day 19, the 15 with persistent MRD on day 46 tended to have an inferior 10-year event-free survival compared with the 126 lacking detectable MRD (72.7% [42.5–88.8] versus 84.0% [76.3–89.4], p=0.06) after receiving the same post-remission treatment for standard-risk ALL. Among patients attaining MRD

  3. Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease

    PubMed Central

    Del Prete, Anna; Scalera, Antonella; Iadevaia, Maddalena Diana; Miranda, Agnese; Zulli, Claudio; Gaeta, Laura; Tuccillo, Concetta; Federico, Alessandro; Loguercio, Carmelina

    2012-01-01

    Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population. PMID:22991573

  4. Breath Analysis in Disease Diagnosis: Methodological Considerations and Applications

    PubMed Central

    Lourenço, Célia; Turner, Claire

    2014-01-01

    Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles. PMID:24957037

  5. Neurostimulation in Alzheimer's disease: from basic research to clinical applications.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Tezzon, Frediano; Christova, Monica; Schwenker, Kerstin; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2015-05-01

    The development of different methods of brain stimulation provides a promising therapeutic tool with potentially beneficial effects on subjects with impaired cognitive functions. We performed a systematic review of the studies published in the field of neurostimulation in Alzheimer's disease (AD), from basic research to clinical applications. The main methods of non-invasive brain stimulation are repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Preliminary findings have suggested that both techniques can enhance performances on several cognitive functions impaired in AD. Another non-invasive emerging neuromodulatory approach, the transcranial electromagnetic treatment, was found to reverse cognitive impairment in AD transgenic mice and even improves cognitive performance in normal mice. Experimental studies suggest that high-frequency electromagnetic fields may be critically important in AD prevention and treatment through their action at mitochondrial level. Finally, the application of a widely known invasive technique, the deep brain stimulation (DBS), has increasingly been considered as a therapeutic option also for patients with AD; it has been demonstrated that DBS of fornix/hypothalamus and nucleus basalis of Meynert might improve or at least stabilize cognitive functioning in AD. Initial encouraging results provide support for continuing to investigate non-invasive and invasive brain stimulation approaches as an adjuvant treatment for AD patients. PMID:25721941

  6. Current and future applications of dried blood spots in viral disease management.

    PubMed

    Snijdewind, Ingrid J M; van Kampen, Jeroen J A; Fraaij, Pieter L A; van der Ende, Marchina E; Osterhaus, Albert D M E; Gruters, Rob A

    2012-03-01

    Almost five decades after their first application in diagnostics, dried blood spot (DBS) cards remain to be of key interest in many research areas and clinical applications. The advantages of sample stability during transport and storage, can now be combined with the high sensitivity of novel diagnostic techniques for the measurement and analysis of nucleic acids, proteins and small molecules which may overcome the limitations of the small samples sizes in DBS cards. Here we present a survey of the literature on the use of DBS cards for diagnosis, monitoring and epidemiological studies of virus infections other than HIV, including CMV, HBV, HCV, HAV, HEV, HTLV, EBV, HSV, measles-, rubella- and dengue-virus. The minimal invasiveness of sampling and the relative ease of handling and storing DBS cards is expected to offer additional opportunities to measure and analyze biomarkers of viral disease in resource poor settings or when limited amount of blood can be obtained. Large retrospective studies of virus infections in newborns using stored DBS cards have already been undertaken for screening of congenital infections. In addition, DBS cards have been used prospectively for prevalence studies, outbreak surveillance, mass screening for viral infections, follow-up of chronic infection and its treatment in resource-limited areas. We do not expect that current wet sampling techniques of plasma or serum will be replaced by DBS sampling but it allows extension of sampling in persons and settings that are currently difficult to access or that lack suitable storage facilities. In conclusion, DBS card sampling and storage will aid adequate outbreak management of existing and emerging viral diseases. PMID:22244848

  7. Application of the reuseable, KanMX selectable marker to industrial yeast: construction and evaluation of heterothallic wine strains of Saccharomyces cerevisiae, possessing minimal foreign DNA sequences.

    PubMed

    Walker, Michelle E; Gardner, Jennie M; Vystavelova, Andrea; McBryde, Colin; de Barros Lopes, Miguel; Jiranek, Vladimir

    2003-12-01

    The characterisation of wine yeasts and the complex metabolic processes influencing wine fermentation and the quality of wine might best be achieved by exploiting the standard classical and recombinant genetic techniques which have been successfully used with laboratory strains. However, application of these techniques to industrial strains has been restricted because such strains are typically prototrophic and often polyploid. To overcome this problem, we have identified commercial wine strains with good mating and sporulation properties from which heterothallic derivatives were constructed by disruption of the HO gene. Consequently, these haploids are amenable to genetic analysis, whilst retaining desirable wine-making properties. The approach used was an adaptation of a previously published gene disruption procedure for laboratory yeast and is based on the acquisition of geneticin resistance from a removable KanMX marker. The present work is the first report of the application of a construct of this type to the disruption of the HO gene in wine yeasts that are in common commercial use. Most of the 4.9-kb disruption construct was successfully removed from the genome of the haploid derivative strains by loop-out of the KanMX marker through meiotic recombination. Sequencing of the HO region confirmed the reduction of foreign sequences to a 582-bp fragment comprised largely of a single direct repeat at the target gene. The removal of the active foreign gene (conferring antibiotic resistance) allows the application of other constructs based on the KanMX module without the need to resort to other selectable marker systems. Laboratory-scale fermentation trials typically showed minimal differences between the HO disruptants and the parental wine strains in terms of fermentation kinetics and formation of key metabolites.

  8. 40 CFR 257.3-6 - Disease.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Disease. 257.3-6 Section 257.3-6... and Practices § 257.3-6 Disease. (a) Disease Vectors. The facility or practice shall not exist or occur unless the on-site population of disease vectors is minimized through the periodic application...

  9. 40 CFR 257.3-6 - Disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Disease. 257.3-6 Section 257.3-6... and Practices § 257.3-6 Disease. (a) Disease Vectors. The facility or practice shall not exist or occur unless the on-site population of disease vectors is minimized through the periodic application...

  10. 40 CFR 257.3-6 - Disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Disease. 257.3-6 Section 257.3-6... and Practices § 257.3-6 Disease. (a) Disease Vectors. The facility or practice shall not exist or occur unless the on-site population of disease vectors is minimized through the periodic application...

  11. 40 CFR 257.3-6 - Disease.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Disease. 257.3-6 Section 257.3-6... and Practices § 257.3-6 Disease. (a) Disease Vectors. The facility or practice shall not exist or occur unless the on-site population of disease vectors is minimized through the periodic application...

  12. 40 CFR 257.3-6 - Disease.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Disease. 257.3-6 Section 257.3-6... and Practices § 257.3-6 Disease. (a) Disease Vectors. The facility or practice shall not exist or occur unless the on-site population of disease vectors is minimized through the periodic application...

  13. Transanal Minimally Invasive Surgery

    PubMed Central

    deBeche-Adams, Teresa; Nassif, George

    2015-01-01

    Transanal minimally invasive surgery (TAMIS) was first described in 2010 as a crossover between single-incision laparoscopic surgery and transanal endoscopic microsurgery (TEM) to allow access to the proximal and mid-rectum for resection of benign and early-stage malignant rectal lesions. The TAMIS technique can also be used for noncurative intent surgery of more advanced lesions in patients who are not candidates for radical surgery. Proper workup and staging should be done before surgical decision-making. In addition to the TAMIS port, instrumentation and set up include readily available equipment found in most operating suites. TAMIS has proven its usefulness in a wide range of applications outside of local excision, including repair of rectourethral fistula, removal of rectal foreign body, control of rectal hemorrhage, and as an adjunct in total mesorectal excision for rectal cancer. TAMIS is an easily accessible, technically feasible, and cost-effective alternative to TEM. PMID:26491410

  14. Preparation and characterization of semi-refined kappa carrageenan-based edible film for nano coating application on minimally processed food

    NASA Astrophysics Data System (ADS)

    Manuhara, Godras Jati; Praseptiangga, Danar; Muhammad, Dimas Rahadian Aji; Maimuni, Bawani Hindami

    2016-02-01

    Shorter and easier processing of semi-refined kappa carrageenan extracted from Euchema cottonii red seaweed result in cheaper price of the polysaccharide. In this study, edible film was prepared from the semi-refined carrageenan without any salt addition. The effect of the carrageenan concentration (1.0, 1.5, and 2.0% w/v) on physical and mechanical properties of the edible film was studied. Edible film thickness and tensile strength increased but elongation at break and water vapor transmission rate (WVTR) decreased as the concentration increased. Based on the characteristic of the edible film, formulation using 2% carrageenan was recommended. The edible film demonstrated the characteristic as follow: 0.054 mm thickness, 21.14 MPa tensile strength, 12.36% elongation at break, and 9.56 g/m2.hour WVTR. It was also noted the carrageenan-based edible film indicated potential physical and mechanical characteristics for nano coating applications on minimally processed food.

  15. Applications of laser in ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Chen, Mingzhe; Zhang, Yongzhen

    1999-09-01

    Current data demonstrate that laser coronary angioplasty is most useful in complex lesions not well suited for percutaneous transluminal coronary angioplasty (PTCA). It is not `stand-alone' procedure, and should be considered an adjunct to PTCA or stenting. To date, there are not data supporting reduction of restenosis. Direct myocardial revascularization (DMR), either transmyocardial revascularization (TMR) or percutaneous (catheter-based) myocardial revascularization (PMR), uses laser to create channels between ischemic myocardium and left ventricular cavity. Candidates include patients with chronic, severe, refractory angina and those unable to undergo angioplasty or bypass surgery because conduits or acceptable target vessels are lacking. Although the mechanisms of action of DMR have not yet been clearly elucidated, but several theories have been proposed, including channel patency, angiogenesis, and denervation. TMR, typically requiring open thoracotomy, is effective for improving myocardial perfusion and reducing angina. Pilot studies demonstrate that clinical application of PMR is feasible and safe and effective for decreasing angina. Late sequelae also remain to be determined. An ongoing randomized clinical trial is comparing PMR with conventional medical therapy in patients with severe, refractory angina and disease unamenable to angioplasty or bypass surgery.

  16. [Minimally invasive breast surgery].

    PubMed

    Mátrai, Zoltán; Gulyás, Gusztáv; Kunos, Csaba; Sávolt, Akos; Farkas, Emil; Szollár, András; Kásler, Miklós

    2014-02-01

    Due to the development in medical science and industrial technology, minimally invasive procedures have appeared in the surgery of benign and malignant breast diseases. In general , such interventions result in significantly reduced breast and chest wall scars, shorter hospitalization and less pain, but they require specific, expensive devices, longer surgical time compared to open surgery. Furthermore, indications or oncological safety have not been established yet. It is quite likely, that minimally invasive surgical procedures with high-tech devices - similar to other surgical subspecialties -, will gradually become popular and it may form part of routine breast surgery even. Vacuum-assisted core biopsy with a therapeutic indication is suitable for the removal of benign fibroadenomas leaving behind an almost invisible scar, while endoscopically assisted skin-sparing and nipple-sparing mastectomy, axillary staging and reconstruction with latissimus dorsi muscle flap are all feasible through the same short axillary incision. Endoscopic techniques are also suitable for the diagnostics and treatment of intracapsular complications of implant-based breast reconstructions (intracapsular fluid, implant rupture, capsular contracture) and for the biopsy of intracapsular lesions with uncertain pathology. Perception of the role of radiofrequency ablation of breast tumors requires further hands-on experience, but it is likely that it can serve as a replacement of surgical removal in a portion of primary tumors in the future due to the development in functional imaging and anticancer drugs. With the reduction of the price of ductoscopes routine examination of the ductal branch system, guided microdochectomy and targeted surgical removal of terminal ducto-lobular units or a "sick lobe" as an anatomical unit may become feasible. The paper presents the experience of the authors and provides a literature review, for the first time in Hungarian language on the subject. Orv. Hetil

  17. Application of metagenomics in understanding oral health and disease

    PubMed Central

    Xu, Ping; Gunsolley, John

    2014-01-01

    Oral diseases including periodontal disease and caries are some of the most prevalent infectious diseases in humans. Different microbial species cohabitate and form a polymicrobial biofilm called dental plaque in the oral cavity. Metagenomics using next generation sequencing technologies has produced bacterial profiles and genomic profiles to study the relationships between microbial diversity, genetic variation, and oral diseases. Several oral metagenomic studies have examined the oral microbiome of periodontal disease and caries. Gene annotations in these studies support the association of specific genes or metabolic pathways with oral health and with specific diseases. The roles of pathogenic species and functions of specific genes in oral disease development have been recognized by metagenomic analysis. A model is proposed in which three levels of interactions occur in the oral microbiome that determines oral health or disease. PMID:24642489

  18. Application of metagenomics in understanding oral health and disease.

    PubMed

    Xu, Ping; Gunsolley, John

    2014-04-01

    Oral diseases including periodontal disease and caries are some of the most prevalent infectious diseases in humans. Different microbial species cohabitate and form a polymicrobial biofilm called dental plaque in the oral cavity. Metagenomics using next generation sequencing technologies has produced bacterial profiles and genomic profiles to study the relationships between microbial diversity, genetic variation, and oral diseases. Several oral metagenomic studies have examined the oral microbiome of periodontal disease and caries. Gene annotations in these studies support the association of specific genes or metabolic pathways with oral health and with specific diseases. The roles of pathogenic species and functions of specific genes in oral disease development have been recognized by metagenomic analysis. A model is proposed in which three levels of interactions occur in the oral microbiome that determines oral health or disease.

  19. Development and application of chronic disease risk prediction models.

    PubMed

    Oh, Sun Min; Stefani, Katherine M; Kim, Hyeon Chang

    2014-07-01

    Currently, non-communicable chronic diseases are a major cause of morbidity and mortality worldwide, and a large proportion of chronic diseases are preventable through risk factor management. However, the prevention efficacy at the individual level is not yet satisfactory. Chronic disease prediction models have been developed to assist physicians and individuals in clinical decision-making. A chronic disease prediction model assesses multiple risk factors together and estimates an absolute disease risk for the individual. Accurate prediction of an individual's future risk for a certain disease enables the comparison of benefits and risks of treatment, the costs of alternative prevention strategies, and selection of the most efficient strategy for the individual. A large number of chronic disease prediction models, especially targeting cardiovascular diseases and cancers, have been suggested, and some of them have been adopted in the clinical practice guidelines and recommendations of many countries. Although few chronic disease prediction tools have been suggested in the Korean population, their clinical utility is not as high as expected. This article reviews methodologies that are commonly used for developing and evaluating a chronic disease prediction model and discusses the current status of chronic disease prediction in Korea.

  20. iPS cell technologies: significance and applications to CNS regeneration and disease

    PubMed Central

    2014-01-01

    In 2006, we demonstrated that mature somatic cells can be reprogrammed to a pluripotent state by gene transfer, generating induced pluripotent stem (iPS) cells. Since that time, there has been an enormous increase in interest regarding the application of iPS cell technologies to medical science, in particular for regenerative medicine and human disease modeling. In this review article, we outline the current status of applications of iPS technology to cell therapies (particularly for spinal cord injury), as well as neurological disease-specific iPS cell research (particularly for Parkinson’s disease and Alzheimer’s disease). Finally, future directions of iPS cell research are discussed including a) development of an accurate assay system for disease-associated phenotypes, b) demonstration of causative relationships between genotypes and phenotypes by genome editing, c) application to sporadic and common diseases, and d) application to preemptive medicine. PMID:24685317

  1. IRIS: A database application system for diseases identification using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Arshad, Ahmad Zulhilmi; Munajat, Yusof; Ibrahim, Raja Kamarulzaman Raja; Mahmood, Nasrul Humaimi

    2015-05-01

    Infrared information on diseases identification system (IRIS) is an application for diseases identification and analysis by using Fourier transform infrared (FTIR) spectroscopy. This is the preliminary step to gather information from the secondary data which was extracted from recognized various research and scientific paper, which are combined into a single database as in IRIS for our purpose of study. The importance of this database is to examine the fingerprint differences between normal and diseases cell or tissue. With the implementation of this application is it hopes that the diseases identification using FTIR spectroscopy would be more reliable and may assist either physicians, pathologists, or researchers to diagnose the certain type of disease efficiently.

  2. Minimally invasive aortic valve surgery

    PubMed Central

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-01-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  3. Minimally invasive aortic valve surgery.

    PubMed

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-09-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  4. Application of personalized medicine to chronic disease: a feasibility assessment

    PubMed Central

    2013-01-01

    Personalized Medicine has the potential to improve health outcomes and reduce the cost of care; however its adoption has been slow in Canada. Bridgepoint Health is a complex continuous care provider striving to reduce the burden of polypharmacy in chronic patients. The main goal of the study was to explore the feasibility of utilizing personalized medicine in the treatment of chronic complex patients as a preliminary institutional health technology assessment. We analyzed stroke treatment optimization as a clinical indication that could serve as a “proof of concept” for the widespread implementation of pharmacogenetics. The objectives of the study were three-fold: 1. Review current practice in medication administration for stroke treatment at Bridgepoint Health 2. Critically analyze evidence that pharmacogenetic testing could (or could not) enhance drug selection and treatment efficacy for stroke patients; 3. Assess the cost-benefit potential of a pharmacogenetic intervention for stroke. Review current practice in medication administration for stroke treatment at Bridgepoint Health Critically analyze evidence that pharmacogenetic testing could (or could not) enhance drug selection and treatment efficacy for stroke patients; Assess the cost-benefit potential of a pharmacogenetic intervention for stroke. We conducted a review of stroke treatment practices at Bridgepoint Health, scanned the literature for drug-gene and drug-outcome interactions, and evaluated the potential consequences of pharmacogenetic testing using the ACCE model. There is a substantial body of evidence suggesting that pharmacogenetic stratification of stroke treatment can improve patient outcomes in the long-term, and provide substantial efficiencies for the healthcare system in the short-term. Specifically, pharmacogenetic stratification of antiplatelet and anticoagulant therapies for stroke patients may have a major impact on the risk of disease recurrence, and thus should be explored

  5. Metabonomic applications in toxicity screening and disease diagnosis.

    PubMed

    Shockcor, John P; Holmes, Elaine

    2002-01-01

    Biofluid NMR spectroscopy is a powerful tool providing a comprehensive metabolic profile of the low molecular weight components in biofluids that reflect concentrations and fluxes of endogenous metabolites involved in key intermediary cellular pathways, thereby giving an indication of an organisms physiological or pathophysiological status [1]. The interaction of pharmacological agents with cells and tissues can also be monitored using recently developed high resolution magic-angle spinning (HRMAS) NMR spectroscopic technology for biological matrices [1]. However, recent developments in both spectrometer and software technology has resulted in improved capacity for sample handling, leading to a rapid growth in the size of toxicological spectral databases, and increased the complexity of the biological spectral data generated. Thus more emphasis has been placed on the need to develop improved automated procedures for data processing and interpretation. By harnessing chemometric tools for analysis of complex spectral data, the toxicological consequences of xenobiotic exposure can be evaluated efficiently on line. Automation of spectral processing procedures and the construction of mathematically based 'expert systems' for the prediction of drug-induced toxicity founded on IH NMR spectral profiles have now been achieved. Chemometric analysis of biological NMR spectra has provided the main analytical platform for metabonomic analysis, providing a systems approach to evaluating pathophysiological or genetic influences on the metabolic status of an organism [1]. This technology is currently being given high-priority in the pharmaceutical industry with respect to development of efficient high throughput toxicity screening systems for lead candidate selection. In this article, we review the recent developments in metabonomics and consider their application in toxicological screening, disease diagnosis and functional genomics.

  6. MicroRNAs in common diseases and potential therapeutic applications.

    PubMed

    Tsai, Louis M; Yu, Di

    2010-01-01

    1. Evidence gathered in recent years has revealed microRNAs (miRNAs) fine-tune gene expression and play an important role in various cellular processes, including cell growth, differentiation, proliferation and apoptosis. 2. The present review summarizes current knowledge of miRNA pathways in the pathogenesis of cancer, cardiac diseases, neurodegenerative diseases, diabetes, autoimmune/inflammatory diseases and infection. 3. There is considerable potential to target miRNAs as a novel approach in the treatment of human diseases. Currently, miRNA-based therapies are being examined in both animal models and human clinical trials.

  7. [Application of traditional Chinese medicine in the prevention and treatment of new sudden infectious disease].

    PubMed

    Zhang, Ning; Guo, Yu-ming; Wang, Li-fu; Gong, Man; Du, Ning; Xiao, Xiao-he

    2015-12-01

    There has been thousands of years' history that traditional Chinese medicines were used in the prevention and treatment of infectious disease. In recent years, traditional Chinese medicine plays a unique role in the control of variety of new infectious diseases. This article provides a summary on our knowledge of the traditional Chinese medicine theory in the explanation of infectious disease, application of Chinese medicines and the pharmacological mechanism in the successful management on the Ebola virus disease.

  8. Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases

    PubMed Central

    Ishida, Kentaro; Gee, Peter; Hotta, Akitsu

    2015-01-01

    Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9. PMID:26501275

  9. [Application for Lifestyle disease by iPS cells technologies].

    PubMed

    Takashima, Yasuhiro

    2016-03-01

    Currently it is less advanced to understand the pathology of lifestyle disease by using iPS cells because there is partly less direct connection between life style disease and iPS cells. So much more scientists focus on regenerative medicine such as beta cells therapy using iPS cells technologies. It will be indeed a powerful tool to generate beta cells from iPS cells as even in type2 diabetes patients, hyposecretion of insulin from beta cells in pancreas is one of causes. Another reason is complexity of the pathology of life style disease. There are a lot of reasons to cause lifestyle disease. Lifestyle diseases include cancer, chronic liver disease, Type 2 diabetes, heart disease, metabolic syndrome, chronic renal failure, stroke, and obesity. Since obesity is one of major causes of lifestyle diseases, we want to focus on adipogenesis from iPS cells in this review. We analysed and established the differentiation protocol into adipocytes from mouse ES cells and human iPS cells. The other point in this review is the starting pluripotent cells for differentiation. Quality of pluripotent stem cells are one of most critical factors to succeed in getting well-differentiated cells. Recently, we have developed new naive human pluripotent stem cells (PSC),"Reset cells". Naive PSC have more similar to human epibast cells than conventional human PSC. They will be more ideal cells for differentiation because of their hypomethylated status and earlier stage of development. PMID:26923982

  10. [Application for Lifestyle disease by iPS cells technologies].

    PubMed

    Takashima, Yasuhiro

    2016-03-01

    Currently it is less advanced to understand the pathology of lifestyle disease by using iPS cells because there is partly less direct connection between life style disease and iPS cells. So much more scientists focus on regenerative medicine such as beta cells therapy using iPS cells technologies. It will be indeed a powerful tool to generate beta cells from iPS cells as even in type2 diabetes patients, hyposecretion of insulin from beta cells in pancreas is one of causes. Another reason is complexity of the pathology of life style disease. There are a lot of reasons to cause lifestyle disease. Lifestyle diseases include cancer, chronic liver disease, Type 2 diabetes, heart disease, metabolic syndrome, chronic renal failure, stroke, and obesity. Since obesity is one of major causes of lifestyle diseases, we want to focus on adipogenesis from iPS cells in this review. We analysed and established the differentiation protocol into adipocytes from mouse ES cells and human iPS cells. The other point in this review is the starting pluripotent cells for differentiation. Quality of pluripotent stem cells are one of most critical factors to succeed in getting well-differentiated cells. Recently, we have developed new naive human pluripotent stem cells (PSC),"Reset cells". Naive PSC have more similar to human epibast cells than conventional human PSC. They will be more ideal cells for differentiation because of their hypomethylated status and earlier stage of development.

  11. [Application of iodine metabolism analysis methods in thyroid diseases].

    PubMed

    Han, Jian-hua; Qiu, Ling

    2013-08-01

    The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases.

  12. [Application of iodine metabolism analysis methods in thyroid diseases].

    PubMed

    Han, Jian-hua; Qiu, Ling

    2013-08-01

    The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases. PMID:23987480

  13. Diagnostic Performance of Intravascular Ultrasound-Derived Minimal Lumen Area to Predict Functionally Significant Non-Left Main Coronary Artery Disease: a Meta-Analysis

    PubMed Central

    Shin, Ho-Cheol; Bae, Jong Seok; Jin, Han-Young; Seo, Jeong-Sook; Yang, Tae-Hyun; Kim, Dae-Kyeong; Cho, Kyoung-Im; Kim, Bo-Hyun; Park, Yong Hyun; Je, Hyung-Gon; Kim, Dong-Soo

    2016-01-01

    Background and Objectives Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention frequently results in unnecessary stenting due to the low positive predictive value of IVUS-derived minimal lumen area (MLA) for identification of functionally significant coronary stenosis. We appraised the diagnostic accuracy of IVUS-derived MLA compared with the fractional flow reserve (FFR) to assess intermediate coronary stenosis. Subjects and Methods We searched MEDLINE and Cochrane databases for studies using IVUS and FFR methods to establish the best MLA cut-off values to predict significant non-left main coronary artery stenosis. Summary estimates were obtained using a random-effects model. Results The 17 studies used in our analysis enrolled 3920 patients with 4267 lesions. The weighted overall mean MLA cut-off value was 2.58 mm2. The pooled MLA sensitivity that predicted functionally significant coronary stenosis was 0.75 (confidence interval [CI]: 0.72 to 0.77) and the specificity was 0.66 (CI: 0.64 to 0.68). The positive likelihood ratio (LR) was 2.33 (CI: 2.06 to 2.63) and LR (-) was 0.33 (CI: 0.26 to 0.42). The pooled diagnostic odds ratio (DOR) was 7.53 (CI: 5.26 to 10.76) and the area under the summary receiver operating characteristic curve for all the trials was 0.782 with a Q point of 0.720. Meta-regression analysis demonstrated that an FFR cut-off point of 0.75 was associated with a four times higher diagnostic accuracy compared to that of 0.80 (relative DOR: 3.92; 95% CI: 1.25 to 12.34). Conclusion IVUS-derived MLA has limited diagnostic accuracy and needs careful interpretation to correlate with functionally significant non-left main coronary artery stenosis. PMID:27721852

  14. IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

    PubMed Central

    Roumier, Christophe; Cheok, Meyling; Marceau-Renaut, Alice; Nibourel, Olivier; Geffroy, Sandrine; Helevaut, Nathalie; Rousselot, Philippe; Gruson, Bérengère; Gardin, Claude; Chretien, Marie-Lorraine; Sebda, Shéhérazade; Figeac, Martin; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Castaigne, Sylvie; Dombret, Hervé; Renneville, Aline; Preudhomme, Claude

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis. PMID:26486081

  15. IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association.

    PubMed

    Debarri, Houria; Lebon, Delphine; Roumier, Christophe; Cheok, Meyling; Marceau-Renaut, Alice; Nibourel, Olivier; Geffroy, Sandrine; Helevaut, Nathalie; Rousselot, Philippe; Gruson, Bérengère; Gardin, Claude; Chretien, Marie-Lorraine; Sebda, Shéhérazade; Figeac, Martin; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Castaigne, Sylvie; Dombret, Hervé; Renneville, Aline; Preudhomme, Claude

    2015-12-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis.

  16. Application of 5-ALA for differential diagnostics of stomach diseases

    NASA Astrophysics Data System (ADS)

    Okhotnikova, Natalja L.; Dadvany, Sergey A.; Kuszin, Michail I.; Kharnas, Sergey S.; Zavodnov, Victor Y.; Sklyanskaya, Olga A.; Loschenov, Victor B.; Volkova, Anna I.; Agafonov, Valery V.

    2001-01-01

    59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

  17. Osteopathic manipulative treatment: novel application to dermatological disease.

    PubMed

    Campbell, Shannon M; Winkelmann, Richard R; Walkowski, Stevan

    2012-10-01

    Dermatological diseases, such as dysesthesia syndromes, stasis dermatoses, and hyperhidrosis are difficult to treat due to their complex etiologies. Current theories suggest these diseases are caused by physiological imbalances, such as nerve impingement, localized tissue congestion, and impaired autonomic regulation. Osteopathic manipulative therapy targets these physiological dysfunctions and may serve as a beneficial therapeutic option. Osteopathic manipulative therapy techniques include high velocity low amplitude, muscle energy, counterstrain, myofascial release, craniosacral, and lymphatic drainage. An osteopathic manipulative therapy technique is chosen based on its physiological target for a particular disease. Osteopathic manipulative therapy may be useful alone or in combination with standard therapeutic options. However, due to the lack of standardized trials supporting the efficacy of osteopathic manipulative therapy treatment for dermatological disease, randomized, well-controlled studies are necessary to confirm its therapeutic value. PMID:23125887

  18. Osteopathic manipulative treatment: novel application to dermatological disease.

    PubMed

    Campbell, Shannon M; Winkelmann, Richard R; Walkowski, Stevan

    2012-10-01

    Dermatological diseases, such as dysesthesia syndromes, stasis dermatoses, and hyperhidrosis are difficult to treat due to their complex etiologies. Current theories suggest these diseases are caused by physiological imbalances, such as nerve impingement, localized tissue congestion, and impaired autonomic regulation. Osteopathic manipulative therapy targets these physiological dysfunctions and may serve as a beneficial therapeutic option. Osteopathic manipulative therapy techniques include high velocity low amplitude, muscle energy, counterstrain, myofascial release, craniosacral, and lymphatic drainage. An osteopathic manipulative therapy technique is chosen based on its physiological target for a particular disease. Osteopathic manipulative therapy may be useful alone or in combination with standard therapeutic options. However, due to the lack of standardized trials supporting the efficacy of osteopathic manipulative therapy treatment for dermatological disease, randomized, well-controlled studies are necessary to confirm its therapeutic value.

  19. Cell biomechanics and its applications in human disease diagnosis

    NASA Astrophysics Data System (ADS)

    Nematbakhsh, Yasaman; Lim, Chwee Teck

    2015-04-01

    Certain diseases are known to cause changes in the physical and biomechanical properties of cells. These include cancer, malaria, and sickle cell anemia among others. Typically, such physical property changes can result in several fold increases or decreases in cell stiffness, which are significant and can result in severe pathology and eventual catastrophic breakdown of the bodily functions. While there are developed biochemical and biological assays to detect the onset or presence of diseases, there is always a need to develop more rapid, precise, and sensitive methods to detect and diagnose diseases. Biomechanical property changes can play a significant role in this regard. As such, research into disease biomechanics can not only give us an in-depth knowledge of the mechanisms underlying disease progression, but can also serve as a powerful tool for detection and diagnosis. This article provides some insights into opportunities for how significant changes in cellular mechanical properties during onset or progression of a disease can be utilized as useful means for detection and diagnosis. We will also showcase several technologies that have already been developed to perform such detection and diagnosis.

  20. Efficacy of a minimal home-based psychoeducative intervention versus usual care for managing anxiety and dyspnoea in patients with severe chronic obstructive pulmonary disease: a randomised controlled trial protocol

    PubMed Central

    Bove, Dorthe Gaby; Overgaard, Dorthe; Lomborg, Kirsten; Lindhardt, Bjarne Ørskov; Midtgaard, Julie

    2015-01-01

    Introduction In its final stages, chronic obstructive pulmonary disease is a severely disabling condition that is characterised by dyspnoea, which causes substantial anxiety. Anxiety is associated with an impaired quality of life and increased hospital admissions. Untreated comorbid anxiety can have devastating consequences for both patients and their relatives. Non-pharmacological interventions, including cognitive–behavioural therapy, have been effective in managing anxiety and dyspnoea in patients with chronic obstructive pulmonary disease. However, the majority of existing interventions have tested the efficacy of relatively intensive comprehensive programmes and primarily targeted patients who have moderate pulmonary disease. We present the rationale and design for a trial that focused on addressing the challenges experienced by severe pulmonary disease populations. The trial investigates the efficacy of a minimal home-based psychoeducative intervention versus usual care for patients with severe chronic obstructive pulmonary disease. Methods and analysis The trial is a randomised controlled trial with a 4-week and 3-month follow-up. 66 patients with severe chronic obstructive pulmonary disease and associated anxiety will be randomised 1:1 to either an intervention or control group. The intervention consists of a single psychoeducative session in the patient's home in combination with a telephone booster session. The intervention is based on a manual, with a theoretical foundation in cognitive–behavioural therapy and psychoeducation. The primary outcome is patient-reported anxiety as assessed by the Hospital and Anxiety and Depression Scale (HADS). Ethics and dissemination This trial complies with the latest Declaration of Helsinki, and The Ethics Committee of the Capital Region of Denmark (number H-1-2013-092) was queried for ethical approval. Trial results will be disseminated in peer-reviewed publications and presented at scientific conferences. Trial

  1. Prototype early warning system for heart disease detection using Android Application.

    PubMed

    Zennifa, Fadilla; Fitrilina; Kamil, Husnil; Iramina, Keiji

    2014-01-01

    Heart Disease affects approximately 70 million people worldwide where most people do not even know the symptoms. This research examines the prototype of early warning system for heart disease by android application. It aims to facilitate users to early detect heart disease which can be used independently. To build the application in android phone, variable centered intelligence rule system (VCIRS) as decision makers and pulse sensor - Arduino as heart rate detector were applied in this study. Moreover, in Arduino, the heart rate will become an input for symptoms in Android Application. The output of this system is the conclusion statement of users diagnosed with either coronary heart disease, hypertension heart disease, rheumatic heart disease or do not get any kind of heart disease. The result of diagnosis followed by analysis of the value of usage variable rate (VUR) rule usage rate (RUR) and node usage rate (NUR) that shows the value of the rule that will increase when the symptoms frequently appear. This application was compared with the medical analysis from 35 cases of heart disease and it showed concordance between diagnosis from android application and expert diagnosis of the doctors.

  2. Sequential monitoring of chimerism and detection of minimal residual disease after allogeneic blood stem cell transplantation (BSCT) using multiplex PCR amplification of short tandem repeat-markers.

    PubMed

    Thiede, C; Bornhäuser, M; Oelschlägel, U; Brendel, C; Leo, R; Daxberger, H; Mohr, B; Florek, M; Kroschinsky, F; Geissler, G; Naumann, R; Ritter, M; Prange-Krex, G; Lion, T; Neubauer, A; Ehninger, G

    2001-02-01

    Sequential analysis of chimerism after allogeneic blood stem cell transplantation (BSCT) has been shown to be predictive for graft failure and relapse. We have explored the impact of a novel approach for the quantitative determination of chimerism using a commercial PCR assay with multiplex amplification of nine STR-loci and fluorescence detection. The feasibility was studied in 121 patients transplanted from related or unrelated donors. Follow-up investigation was performed in 88 patients. Twenty-eight of these patients had received a transplantation after dose-reduced conditioning therapy. Results were compared to data obtained by FISH analysis in a subgroup of patients receiving grafts from sex-mismatched donors. The analysis was possible in all patients, the median number of informative alleles was 4 (range 1-8) compared to 7 (range 1-9) in the related and unrelated situation, respectively. A good correlation was seen in 84 samples from 14 patients analyzed in parallel with STR-PCR and FISH. Decreasing values of donor chimerism were detected prior to or concomitantly with the occurrence of graft failure and relapse of disease in all patients investigated prospectively. Using FACS-sorted material, eg peripheral blood CD34+ cells, the assay permitted the detection of residual recipient cells with high sensitivity (down to one CD34+ Kasumi cell in 40,000 normal WBC). Evaluation of the inter-laboratory reproducibility revealed that in 20 samples analyzed in three different centers, the median coefficient of variation was 2.1% (range 0.7-9.6%). Taken together, the results support the use of the test as a valuable tool in the follow-up of patients undergoing allogeneic BSCT. In cases lacking PCR-detectable disease-specific gene products, this assay may represent an alternative to recently established real-time PCR methods. PMID:11236950

  3. Preclinical testing of radiopharmaceuticals for novel applications in HIV, bacterial and fungal infectious diseases.

    PubMed

    Shah, M; Garg, G; Dadachova, E

    2015-09-01

    Antibiotics, antifungal and antiviral medications have traditionally been used in the management of infections. Due to widespread emergence of resistance to antimicrobial medications, and their side effects, there is a growing need for alternative approaches for management of such conditions. Antibiotic resistant bacterial pathogens are on the rise. A cure has not been achieved for viral infections like AIDS, while fungal and parasitic infections are constant threats to the health of general public. The incidence of opportunistic infections in immunocompromised individuals like HIV patients, patients receiving high dose steroids, chemotherapy patients, and organ transplant recipients is on the rise. Radioimmunotherapy (RIT) has the potential to be a suitable and viable therapeutic modality in the arena of infection management. Provided the target-associated antigen is expressed by the target cells and minimally or not expressed by other tissues, selective targeting of radiation to target sites can be theoretically accomplished with relative sparing normal tissues from radiation exposure. In our laboratory we successfully demonstrated the effectiveness of RIT for treating infectious diseases. We targeted murine cryptococcosis with a mAb to the Cryptococcus neoformans capsular glucuronoxylomannan labeled with Bismuth-213 ((213)Bi) or Rhenium-188 ((188)Re). We subsequently extended the applicability of RIT for treating bacterial and viral infections. One of the advantages of using RIT to treat infections as opposed to cancer is that, in contrast to tumor cells, cells expressing microbial antigens are antigenically very different from host tissues and thus provide the potential for exquisite specificity and low cross-reactivity. Ever increasing incidence of infectious pathologies, exhaustion of antimicrobial possibilities and rising drug resistance calls for use of alternative and novel therapeutic options and we believe RIT is the need of the hour to combat these

  4. Potential application of lithium in Parkinson's and other neurodegenerative diseases.

    PubMed

    Lazzara, Carol A; Kim, Yong-Hwan

    2015-01-01

    Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

  5. Potential application of lithium in Parkinson's and other neurodegenerative diseases

    PubMed Central

    Lazzara, Carol A.; Kim, Yong-Hwan

    2015-01-01

    Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases. PMID:26578864

  6. Modeling seasonal behavior changes and disease transmission with application to chronic wasting disease.

    PubMed

    Oraby, Tamer; Vasilyeva, Olga; Krewski, Daniel; Lutscher, Frithjof

    2014-01-01

    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

  7. Modeling seasonal behavior changes and disease transmission with application to chronic wasting disease.

    PubMed

    Oraby, Tamer; Vasilyeva, Olga; Krewski, Daniel; Lutscher, Frithjof

    2014-01-01

    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

  8. Prebiotic Supplementation has Only Minimal Effects on Growth Efficiency, Intestinal Health and Disease Resistance of Westslope Cutthroat Trout Oncorhynchus clarkii lewisi Fed 30% Soybean Meal.

    PubMed

    Sealey, Wendy M; Conley, Zachariah B; Bensley, Molly

    2015-01-01

    Prebiotics have successfully been used to prevent infectious diseases in aquaculture and there is an increasing amount of literature that suggests that these products can also improve alternative protein utilization and digestion. Therefore, the objective of this study was to examine whether prebiotic supplementation increased the growth efficiency, intestinal health, and disease resistance of cutthroat trout fed a high level of dietary soybean meal. To achieve this objective, juvenile Westslope cutthroat trout (Oncorhynchus clarkii lewisi) were fed a practical type formulation with 0 or 30% dietary soybean meal with or without the commercial prebiotic (Grobiotic-A) prior to experimental exposure to Flavobacterium psychrophilum. Juvenile Westslope cutthroat trout (initial weight 7.8 g/fish ±SD of 0.5 g) were stocked at 30 fish/tank in 75 L tanks with six replicate tanks per diet and fed their respective diets for 20 weeks. Final weights of Westslope cutthroat trout were affected by neither dietary soybean meal inclusion level (P = 0.9582) nor prebiotic inclusion (P = 0.9348) and no interaction was observed (P = 0.1242). Feed conversion ratios were similarly not affected by soybean meal level (P = 0.4895), prebiotic inclusion (P = 0.3258) or their interaction (P = 0.1478). Histological examination of the distal intestine of Westslope cutthroat trout demonstrated increases in inflammation due to both increased soybean meal inclusion level (P = 0.0038) and prebiotic inclusion (P = 0.0327) without significant interaction (P = 0.3370). Feeding dietary soybean meal level at 30% increased mortality of F. psychrophilum cohabitation challenged Westslope cutthroat trout (P = 0.0345) while prebiotic inclusion tended to decrease mortality (P = 0.0671). These results indicate that subclinical alterations in intestinal inflammation levels due to high dietary inclusion levels of soybean meal could predispose Westslope cutthroat

  9. Prebiotic Supplementation has Only Minimal Effects on Growth Efficiency, Intestinal Health and Disease Resistance of Westslope Cutthroat Trout Oncorhynchus clarkii lewisi Fed 30% Soybean Meal

    PubMed Central

    Sealey, Wendy M.; Conley, Zachariah B.; Bensley, Molly

    2015-01-01

    Prebiotics have successfully been used to prevent infectious diseases in aquaculture and there is an increasing amount of literature that suggests that these products can also improve alternative protein utilization and digestion. Therefore, the objective of this study was to examine whether prebiotic supplementation increased the growth efficiency, intestinal health, and disease resistance of cutthroat trout fed a high level of dietary soybean meal. To achieve this objective, juvenile Westslope cutthroat trout (Oncorhynchus clarkii lewisi) were fed a practical type formulation with 0 or 30% dietary soybean meal with or without the commercial prebiotic (Grobiotic-A) prior to experimental exposure to Flavobacterium psychrophilum. Juvenile Westslope cutthroat trout (initial weight 7.8 g/fish ±SD of 0.5 g) were stocked at 30 fish/tank in 75 L tanks with six replicate tanks per diet and fed their respective diets for 20 weeks. Final weights of Westslope cutthroat trout were affected by neither dietary soybean meal inclusion level (P = 0.9582) nor prebiotic inclusion (P = 0.9348) and no interaction was observed (P = 0.1242). Feed conversion ratios were similarly not affected by soybean meal level (P = 0.4895), prebiotic inclusion (P = 0.3258) or their interaction (P = 0.1478). Histological examination of the distal intestine of Westslope cutthroat trout demonstrated increases in inflammation due to both increased soybean meal inclusion level (P = 0.0038) and prebiotic inclusion (P = 0.0327) without significant interaction (P = 0.3370). Feeding dietary soybean meal level at 30% increased mortality of F. psychrophilum cohabitation challenged Westslope cutthroat trout (P = 0.0345) while prebiotic inclusion tended to decrease mortality (P = 0.0671). These results indicate that subclinical alterations in intestinal inflammation levels due to high dietary inclusion levels of soybean meal could predispose Westslope cutthroat

  10. Application of Functional Genomics for Bovine Respiratory Disease Diagnostics

    PubMed Central

    Rai, Aswathy N.; Epperson, William B.; Nanduri, Bindu

    2015-01-01

    Bovine respiratory disease (BRD) is the most common economically important disease affecting cattle. For developing accurate diagnostics that can predict disease susceptibility/resistance and stratification, it is necessary to identify the molecular mechanisms that underlie BRD. To study the complex interactions among the bovine host and the multitude of viral and bacterial pathogens, as well as the environmental factors associated with BRD etiology, genome-scale high-throughput functional genomics methods such as microarrays, RNA-seq, and proteomics are helpful. In this review, we summarize the progress made in our understanding of BRD using functional genomics approaches. We also discuss some of the available bioinformatics resources for analyzing high-throughput data, in the context of biological pathways and molecular interactions. Although resources for studying host response to infection are avail-able, the corresponding information is lacking for majority of BRD pathogens, impeding progress in identifying diagnostic signatures for BRD using functional genomics approaches. PMID:26526746

  11. Momentum-based morphometric analysis with application to Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Chen, Jingyun; Khan, Ali R.; McKeown, Martin J.; Beg, Mirza F.

    2011-03-01

    We apply the initial momentum shape representation of diffeomorphic metric mapping from a template region of interest (ROI) to a given ROI as a morphometic marker in Parkinson's disease. We used a three-step segmentation-registrationmomentum process to derive feature vectors from ROIs in a group of 42 subjects consisting of 19 Parkinson's Disease (PD) subjects and 23 normal control (NC) subjects. Significant group differences between PD and NC subjects were detected in four basal ganglia structures including the caudate, putamen, thalamus and globus pallidus. The magnitude of regionally significant between-group differences detected ranged between 34-75%. Visualization of the different structural deformation pattern between-groups revealed that some parts of basal ganglia structure actually hypertrophy, presumably as a compensatory response to more widespread atrophy. Our results of both hypertrophy and atrophy in the same structures further demonstrate the importance of morphological measures as opposed to overall volume in the assessment of neurodegenerative disease.

  12. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    PubMed

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium. PMID:26726947

  13. Anaesthesia for minimally invasive surgery

    PubMed Central

    Dec, Marta

    2015-01-01

    Minimally invasive surgery (MIS) is rising in popularity. It offers well-known benefits to the patient. However, restricted access to the surgical site and gas insufflation into the body cavities may result in severe complications. From the anaesthetic point of view MIS poses unique challenges associated with creation of pneumoperitoneum, carbon dioxide absorption, specific positioning and monitoring a patient to whom the anaesthetist has often restricted access, in a poorly lit environment. Moreover, with refinement of surgical procedures and growing experience the anaesthetist is presented with patients from high-risk groups (obese, elderly, with advanced cardiac and respiratory disease) who once were deemed unsuitable for the laparoscopic technique. Anaesthetic management is aimed at getting the patient safely through the procedure, minimizing the specific risks arising from laparoscopy and the patient's coexisting medical problems, ensuring quick recovery and a relatively pain-free postoperative course with early return to normal function. PMID:26865885

  14. Minimally Invasive Valve Surgery

    PubMed Central

    Pope, Nicolas H.; Ailawadi, Gorav

    2014-01-01

    Cardiac valve surgery is life saving for many patients. The advent of minimally invasive surgical techniques has historically allowed for improvement in both post-operative convalescence and important clinical outcomes. The development of minimally invasive cardiac valve repair and replacement surgery over the past decade is poised to revolutionize the care of cardiac valve patients. Here, we present a review of the history and current trends in minimally invasive aortic and mitral valve repair and replacement, including the development of sutureless bioprosthetic valves. PMID:24797148

  15. Lasers in minimally invasive periodontal and peri-implant therapy.

    PubMed

    Mizutani, Koji; Aoki, Akira; Coluzzi, Donald; Yukna, Raymond; Wang, Chen-Ying; Pavlic, Verica; Izumi, Yuichi

    2016-06-01

    Laser therapy has the potential to be an effective, minimally invasive procedure in periodontal therapy. The aim of the present review was to survey the relevant literature on the clinical application of lasers as a minimally invasive treatment for periodontitis and peri-implant disease. Currently, there are a large number of published clinical studies and case reports that evaluate the adjunctive use of diode, carbon dioxide, neodymium-doped yttrium aluminium garnet (Nd:YAG), erbium-doped yttrium aluminium garnet (Er:YAG) and erbium, chromium-doped: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) lasers or antimicrobial photodynamic therapy for nonsurgical and minimally invasive surgical treatment of periodontal pockets. These procedures are expected not only to control inflammation but also to provide biostimulation effects with photonic energy. Recent meta-analyses did not show statistically significant differences in pocket reduction and clinical attachment gain compared with mechanical debridement alone, although limited positive effects of adjunctive laser therapy were reported. At present, systematic literature approaches suggest that more evidence-based studies need to be performed to support the integration of various laser therapies into the treatment of periodontal and peri-implant diseases. The disparity between previous statistical analyses and individual successful clinical outcomes of laser applications might reveal the necessity of developing optimal laser-treatment modalities of different wavelengths and better-defined indications for each protocol. PMID:27045437

  16. Developments in renal pharmacogenomics and applications in chronic kidney disease

    PubMed Central

    Padullés, Ariadna; Rama, Inés; Llaudó, Inés; Lloberas, Núria

    2014-01-01

    Chronic kidney disease (CKD) has shown an increasing prevalence in the last century. CKD encompasses a poor prognosis related to a remarkable number of comorbidities, and many patients suffer from this disease progression. Once the factors linked with CKD evolution are distinguished, it will be possible to provide and enhance a more intensive treatment to high-risk patients. In this review, we focus on the emerging markers that might be predictive or related to CKD progression physiopathology as well as those related to a different pattern of response to treatment, such as inhibitors of the renin–angiotensin system (including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers; the vitamin D receptor agonist; salt sensitivity hypertension; and progressive kidney-disease markers with identified genetic polymorphisms). Candidate-gene association studies and genome-wide association studies have analyzed the genetic basis for common renal diseases, including CKD and related factors such as diabetes and hypertension. This review will, in brief, consider genotype-based pharmacotherapy, risk prediction, drug target recognition, and personalized treatments, and will mainly focus on findings in CKD patients. An improved understanding will smooth the progress of switching from classical clinical medicine to gene-based medicine. PMID:25206311

  17. MicroRNAs and Their Applications in Kidney Diseases

    PubMed Central

    Badal, Shawn S.; Danesh, Farhad R.

    2014-01-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that employ classic Watson-Crick base-pairing to identify their target genes, ultimately resulting in destabilizing their target mRNAs and/or inhibiting their translation. The role of miRNAs in a wide-range of human diseases, including those afflicting the kidney, has been intensely investigated. However there is still a vast dearth of knowledge regarding their specific mode of action and therapeutic effects in various kidney diseases. This review discusses the latest efforts to further our understanding of the basic biology of miRNAs, their impact on various kidney diseases and their potential as novel biomarkers and therapeutic agents. We initially provide an overview of miRNA biology and the canonical pathway implicated in their biogenesis. We will then discuss commonly employed experimental strategies for miRNA research and highlight some of the newly described state-of-the-art technologies to identify miRNAs and their target genes. Finally, we will carefully examine the emerging role of miRNAs in the pathogenesis of various kidney diseases. PMID:24928414

  18. Early negative minimal residual disease in bone marrow after immunotherapy is less predictive of late or non-marrow relapse among patients with high-risk stage 4 neuroblastoma.

    PubMed

    Cheung, Irene Y; Feng, Yi; Cheung, Nai-Kong V

    2013-07-01

    Molecular detection of minimal residual disease (MRD) measured by quantitative reverse transcription-polymerase chain reaction using a four-marker panel in the bone marrow (BM) after only two treatment cycles of anti-GD2 immunotherapy was a strong independent outcome predictor among high-risk patients with stage 4 neuroblastoma in first remission. While 32 of 46 MRD-negative patients relapsed within 2 years from immunotherapy, only four had marrow relapse; in three of these four patients, MRD turned positive in the subsequent BM. We conclude that negative MRD in the post-cycle two BM was rarely associated with BM relapse, but it did not exclude recurrences at other sites.

  19. 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.

    PubMed

    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. PMID:18465242

  20. A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

    Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment

  1. A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

    Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment

  2. Minimizing Shortness of Breath

    MedlinePlus

    ... Top Doctors in the Nation Departments & Divisions Home Health Insights Stress & Relaxation Breathing and Relaxation Minimizing Shortness of Breath ... Management Assess Your Stress Coping Strategies Identifying ... & Programs Health Insights Doctors & Departments Research & Science Education & Training Make ...

  3. An application of PIXE in medicine: Legionnaires' disease

    NASA Astrophysics Data System (ADS)

    Chen, James R.

    1981-03-01

    The name "Legionnaires' disease" refers to an acute respiratory illness that was first recognized at an American Legion Convention in Philadelphia in July, 1976. 221 people became ill and 34 died. During the ensuing months before the etiologic agent, a previously unknown species of bacterium, was isolated, many investigators suspected that a toxic agent, in particular nickel carbonyl, might have caused the outbreak of illness. We describe the use of proton-induced X-ray emission (PIXE) to analyse the nickel concentrations of the autopsy specimens. We show that the high nickel concentrations in the lung specimens were due to contamination during the autopsies. Recently we have used PIXE to show that the selenium concentrations in the serums of the acutely ill Legionnaires' patients are significantly lower than in their matching convalescent-phase serums. This finding may be related to the patient's response to the disease or to the specific characteristics of the Legionnaires' bacterium itself.

  4. Eleventh annual Department of Energy low-level waste management conference. Volume 3: Waste characterization, waste reduction and minimization, prototype licensing application

    SciTech Connect

    1989-11-01

    Thirteen papers are presented in volume 3. The seven papers on waste characterization discuss sampling, analysis, and certification techniques for low-level radioactive wastes. Three papers discuss US DOE waste minimization policies and regulations, Y-12 Plant`s reduction of chlorinated solvents, and C-14 removal from spent resins. The last three papers discuss the licensing studies for earth-mounded concrete bunkers for LLW disposal. Papers have been processed separately for inclusion on the data base.

  5. A Screening Test for Wilson's Disease and its Application to Psychiatric Patients

    PubMed Central

    Cox, Diane Wilson

    1967-01-01

    Varied modes of onset make the early diagnosis of Wilson's disease difficult. A deficiency of serum ceruloplasmin, usually characteristic of the disease, was used as the basis for a screening test. Simple test materials and provision for handling about 50 plasma samples simultaneously made this test feasible for large-scale screening. The screening test was applied to 336 persons hospitalized for psychiatric disorders, to detect patients with Wilson's disease before the classical symptoms appeared. Two patients with ceruloplasmin levels below the normal limits were detected but did not have Wilson's disease. Further application of the screening test to relatives of patients known to have Wilson's disease and to individuals with any symptoms of the disease (hepatic disease, extrapyramidal dysfunction, psychiatric disorders, behaviour problems in children) would aid in early diagnosis and more effective treatment. ImagesFig. 1 PMID:6017170

  6. Principles of disease prevention from discovery to application.

    PubMed

    Wynder, E L

    1994-01-01

    This paper reviews the well-known evidence that many of our diseases today relate to lifestyle practices that have their beginning in childhood. While mechanistic understanding of a disease is of obvious value, the history of medicine has shown that preventive measures can be applied long before the pathogenesis of a disease is understood. The greatest obstacle to preventive medicine for the average person is the illusion of immortality and that each of us does not readily make a sacrifice of something pleasurable for a potential benefit in the future, and that for health professionals preventive medicine is not as economically rewarding as therapeutic practice. Hospitals, physicians, parents, and schools can all contribute to enhancing healthy lifestyle practices. We place here particular emphasis on early comprehensive school health education and strongly suggest that such educational efforts must be on par with the teaching of other subjects since good healthy habits strongly affect both children's physical and mental development and thus contribute to a more productive future society.

  7. Integration of apple rootstock genotype with reduced Brassica seed meal application rates for replant disease control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pre-plant soil application of Brassica seed meal (SM) formulations can provide fumigant level control of apple replant disease. However, due to high cost of the SM treatment relative to non-tarped soil fumigation, reduced application rates would likely accelerate commercial adoption of this technolo...

  8. Iowa Commercial Pesticide Applicator Manual, Category 1C: Agricultural Crop Disease Control. CS-11.

    ERIC Educational Resources Information Center

    Nyvall, Robert F.; Ryan, Stephen O.

    This manual provides information needed to meet specific standards for certification as a pesticide applicator. It summarizes the economically important diseases of field and forage crops such as corn, soybeans and alfalfa. Special attention is given to pesticide application methods and safety. (CS)

  9. Tuberculosis Diagnosis: Relevancy of Veterinary Applications to Human Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Veterinary applications of tuberculosis (TB) tests may provide insight into the diagnostic potential and technical development of emerging tests for human TB. Interferon (IFN)-gamma release assays (IGRA) were developed initially for bovine TB eradication programs. As the test relies on functional le...

  10. Autoimmune disease and vaccination: impact on infectious disease prevention and a look at future applications.

    PubMed

    McKinnon, John E; Maksimowicz-McKinnon, Kathleen

    2016-01-01

    Vaccines hold promise both for the prevention of infections and as potential immunologic therapy for patients with autoimmune disease (AD). These patients are at high risk for both common and opportunistic infections, but this risk can be significantly reduced and even obviated with the use of recommended available vaccines. Unfortunately, patients with ADs are not routinely offered or provided indicated vaccinations and have higher rates of complications from vaccine-preventable illnesses than patients without ADs. In addition, vaccine therapy is currently under study for the treatment of autoimmune disorders, with early studies demonstrating immunomodulatory effects that may counter undesired immune activation and alleviate disease activity.

  11. Current Progress in Nanotechnology Applications for Diagnosis and Treatment of Kidney Diseases

    PubMed Central

    Lee, Sue Hyun; Lee, Jung Bok; Bae, Min Soo; Balikov, Daniel A.; Hwang, Amy; Boire, Timothy C.; Kwon, Il Keun; Sung, Hak-Joon

    2016-01-01

    Significant progress has been made in nanomedicine, primarily in the form of nanoparticles, for theranostic applications to various diseases. A variety of materials, both organic and inorganic, have been used to develop nanoparticles with promise to achieve improved efficacy in medical applications as well as reduced systemic side effects compared to current standard of care medical practices. In particular, this article highlights the recent development and application of nanoparticles for diagnosing and treating nephropathologies. PMID:26121684

  12. Applications of luminescent systems to infectious disease methodology

    NASA Technical Reports Server (NTRS)

    Picciolo, G. L.; Chappelle, E. W.; Deming, J. W.; Mcgarry, M. A.; Nibley, D. A.; Okrend, H.; Thomas, R. R.

    1976-01-01

    The characterization of a clinical sample by a simple, fast, accurate, automatable analytical measurement is important in the management of infectious disease. Luminescence assays offer methods rich with options for these measurements. The instrumentation is common to each assay, and the investment is reasonable. Three general procedures were developed to varying degrees of completeness which measure bacterial levels by measuring their ATP, FMN and iron porphyrins. Bacteriuria detection and antibiograms can be determined within half a day. The characterization of the sample for its soluble ATP, FMN or prophyrins was also performed.

  13. Application of multiplex immunoassay technology to investigations of ocular disease.

    PubMed

    Jones, Valerie Sloane; Wu, Jian; Zhu, Si-Wei; Huang, Ruo-Pan

    2016-01-01

    Eye-derived fluids, including tears, aqueous humour and vitreous humour often contain molecular signatures of ocular disease states. These signatures can be composed of cytokines, chemokines, growth factors, proteases and soluble receptors. However, the small quantities (<10 µl) of these fluids severely limit the detection of these proteins by traditional enzyme-linked immunosorbent assay or Western blot. To maximise the amount of information generated from the analysis of these specimens, many researchers have employed multiplex immunoassay technologies for profiling the expression or modification of multiple proteins from minute sample volumes. PMID:27577534

  14. Proteomics in veterinary medicine: applications and trends in disease pathogenesis and diagnostics.

    PubMed

    Ceciliani, F; Eckersall, D; Burchmore, R; Lecchi, C

    2014-03-01

    Advancement in electrophoresis and mass spectrometry techniques along with the recent progresses in genomics, culminating in bovine and pig genome sequencing, widened the potential application of proteomics in the field of veterinary medicine. The aim of the present review is to provide an in-depth perspective about the application of proteomics to animal disease pathogenesis, as well as its utilization in veterinary diagnostics. After an overview on the various proteomic techniques that are currently applied to veterinary sciences, the article focuses on proteomic approaches to animal disease pathogenesis. Included as well are recent achievements in immunoproteomics (ie, the identifications through proteomic techniques of antigen involved in immune response) and histoproteomics (ie, the application of proteomics in tissue processed for immunohistochemistry). Finally, the article focuses on clinical proteomics (ie, the application of proteomics to the identification of new biomarkers of animal diseases).

  15. Minimally Invasive Forefoot Surgery in France.

    PubMed

    Meusnier, Tristan; Mukish, Prikesht

    2016-06-01

    Study groups have been formed in France to advance the use of minimally invasive surgery. These techniques are becoming more frequently used and the technique nuances are continuing to evolve. The objective of this article was to advance the awareness of the current trends in minimally invasive surgery for common diseases of the forefoot. The percutaneous surgery at the forefoot is less developed at this time, but also will be discussed.

  16. Future of Minimally Invasive Colorectal Surgery.

    PubMed

    Whealon, Matthew; Vinci, Alessio; Pigazzi, Alessio

    2016-09-01

    Minimally invasive surgery is slowly taking over as the preferred operative approach for colorectal diseases. However, many of the procedures remain technically difficult. This article will give an overview of the state of minimally invasive surgery and the many advances that have been made over the last two decades. Specifically, we discuss the introduction of the robotic platform and some of its benefits and limitations. We also describe some newer techniques related to robotics. PMID:27582647

  17. Application of multispectral systems for the diagnosis of plant diseases

    NASA Astrophysics Data System (ADS)

    Feng, Jie; Liao, Ningfang; Wang, Guolong; Luo, Yongdao; Liang, Minyong

    2008-03-01

    Multispectral imaging technique combines space imaging and spectral detecting. It can obtain the spectral information and image information of object at the same time. Base on this concept, A new method proposed multispectral camera system to demonstrated plant diseases. In this paper, multispectral camera was used as image capturing device. It consists of a monochrome CCD camera and 16 narrow-band filters. The multispectral images of Macbeth 24 color patches are captured under the illumination of incandescent lamp in this experiment The 64 spectral reflectances of each color patches are calculated using Spline interpolation from 400 to 700nm in the process. And the color of the object is reproduced from the estimated spectral reflectance. The result for reproduction is contrast with the color signal using X-rite PULSE spectrophotometer. The average and maximum ΔΕ * ab are 9.23 and 12.81. It is confirmed that the multispectral system realizes the color reproduction of plant diseases from narrow-band multispectral image.

  18. Minimally invasive procedures

    PubMed Central

    Baltayiannis, Nikolaos; Michail, Chandrinos; Lazaridis, George; Anagnostopoulos, Dimitrios; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Kioumis, Ioannis; Pitsiou, Georgia; Katsikogiannis, Nikolaos; Tsakiridis, Kosmas; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos

    2015-01-01

    Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small “ports” from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry—meaning only one small incision, like the “uniport” video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional “open” surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery. PMID:25861610

  19. [The application of genetic risk score in genetic studies of complex human diseases].

    PubMed

    Dayan, Niu; Weili, Yan

    2015-12-01

    Complex diseases such as cardiovascular disease, type 2 diabetes, essential hypertension, asthma, obesity and cancer have spread across the globe and become the predominant cause of death. There are growing concerns over the role of genetic susceptibility in pathogenesis of complex diseases. However, the related susceptibility genes and sequence variations are still unknown. To elucidate the genetic basis of complex diseases, researchers have identified a large number of genetic variants associated with complex diseases through genome-wide association studies (GWAS) and candidate gene studies recently. The identification of these causal and/or associated variants promotes the development of approaches for complex diseases prediction and prevention. Genetic risk score (GRS), an emerging method for exploring correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes of complex diseases, integrates weak effects of multiple SNPs and dramatically enhances predictability of complex diseases by gene polymorphisms. This method has been applied successfully in genetic studies of many complex diseases. Here we focus on the introduction of the computational methods and evaluation criteria of GRS, enumerate a series of achievements through GRS application, discuss some limitations during application, and finally prospect the future of GRS.

  20. 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.

    PubMed

    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.

  1. Pre-transplant achievement of negativity in minimal residual disease and French-American-British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an analysis of Southeast Asian patients.

    PubMed

    Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

    2015-05-01

    To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome.

  2. Clinical innovations in minimally invasive surgery in Korea

    PubMed Central

    Han, Kook Nam; Choi, Young Ho

    2016-01-01

    Over the past decade, the surgical approach to treating thoracic disease has shifted to minimally invasive surgery. Without compromising the outcomes, this approach may lead to fewer resections and fewer incisions for those resections. Video-assisted thoracoscopic surgery (VATS) is a recent but major advancement that has become an established approach for major thoracic surgery. More recently, robotic surgery has been gaining recognition because it can overcome the limitations of VATS and encourage a minimally invasive approach. Indications and applications of many other innovative surgical techniques and strategies to improve overall survival have expanded rapidly. In this article, we do not represent all thoracic surgeries occurring in Korea and do not reflect the large active centers in the country. However, as one of the most innovative and active Korean centers for thoracic surgery and research, we reviewed our procedures and programs for thoracic surgery.

  3. Clinical innovations in minimally invasive surgery in Korea

    PubMed Central

    Han, Kook Nam; Choi, Young Ho

    2016-01-01

    Over the past decade, the surgical approach to treating thoracic disease has shifted to minimally invasive surgery. Without compromising the outcomes, this approach may lead to fewer resections and fewer incisions for those resections. Video-assisted thoracoscopic surgery (VATS) is a recent but major advancement that has become an established approach for major thoracic surgery. More recently, robotic surgery has been gaining recognition because it can overcome the limitations of VATS and encourage a minimally invasive approach. Indications and applications of many other innovative surgical techniques and strategies to improve overall survival have expanded rapidly. In this article, we do not represent all thoracic surgeries occurring in Korea and do not reflect the large active centers in the country. However, as one of the most innovative and active Korean centers for thoracic surgery and research, we reviewed our procedures and programs for thoracic surgery. PMID:27651938

  4. [AM and its application in plant disease prevention of Chinese medicinal herbs cultivation].

    PubMed

    Xiao, Wenjuan; Yang, Guang; Chen, Meilan; Guo, Lanpin; Wang, Min

    2011-02-01

    To study the beneficial effect of AMF from the utilization achievement in the agroforestry research, we discuss the application of AM in medicinal plant disease prevention and control. This paper summarized the type of medicinal plant disease, the influence of plant disease and the commonly used prevention method in production. As for the adverse consequences caused by plant's non-infectious and infectious diseases, AM has some improvement function. Something will affect the function of AM in the prevention of medicinal plant disease, for example, the relationship between AMF and the plants, the quantity, the time and the environmental factors about AMF inoculation and so on. In order to achieve the useful effect of AM in the prevention of medicinal plant disease, we should choose the suitable condition during production in practice to carry on the vaccination. PMID:21585020

  5. Application of Infrared and Raman Spectroscopy for the Identification of Disease Resistant Trees

    PubMed Central

    Conrad, Anna O.; Bonello, Pierluigi

    2016-01-01

    New approaches for identifying disease resistant trees are needed as the incidence of diseases caused by non-native and invasive pathogens increases. These approaches must be rapid, reliable, cost-effective, and should have the potential to be adapted for high-throughput screening or phenotyping. Within the context of trees and tree diseases, we summarize vibrational spectroscopic and chemometric methods that have been used to distinguish between groups of trees which vary in disease susceptibility or other important characteristics based on chemical fingerprint data. We also provide specific examples from the literature of where these approaches have been used successfully. Finally, we discuss future application of these approaches for wide-scale screening and phenotyping efforts aimed at identifying disease resistant trees and managing forest diseases. PMID:26779211

  6. Gene editing and its application for hematological diseases.

    PubMed

    Osborn, Mark J; Belanto, Joseph J; Tolar, Jakub; Voytas, Daniel F

    2016-07-01

    The use of precise, rationally designed gene-editing nucleases allows for targeted genome and transcriptome modification, and at present, four major classes of nucleases are being employed: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (MNs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. Each reagent shares the ability to recognize and bind a target sequence of DNA. Depending on the properties of the reagent, the DNA can be cleaved on one or both strands, or epigenetic changes can be mediated. These novel properties can impact hematological disease by allowing for: (1) direct modification of hematopoietic stem/progenitor cells (HSPCs), (2) gene alteration of hematopoietic lineage committed terminal effectors, (3) genome engineering in non-hematopoietic cells with reprogramming to a hematopoietic phenotype, and (4) transcriptome modulation for gene regulation, modeling, and discovery.

  7. Genetic studies in chronic kidney disease: interpretation and clinical applicability.

    PubMed

    Witasp, Anna; Nordfors, Louise; Carrero, Juan Jesus; Luttropp, Karin; Lindholm, Bengt; Schalling, Martin; Stenvinkel, Peter

    2012-01-01

    The tools of modern molecular biology are evolving rapidly, resulting in vastly more efficient approaches to illuminating human genetic variations and their effects on common multifactorial disorders such as chronic kidney disease (CKD). Indeed, candidate gene association studies and genome-wide association studies (GWASs) have generated novel genetic variants in previously unrecognized biological pathways, highlighting disease mechanisms with a potential role in CKD etiology, morbidity and mortality. Nephrologists now need to find ways to make use of these advancements and meet the increasingly stringent requirements for valid study design, data handling and interpretation of genetic studies. Adding to our prior article in this journal, which introduced the basics of genotype-phenotype association studies in CKD, this second article focuses on how to ascertain robust and reproducible findings by applying adequate methodological and statistical approaches to genotype-phenotype studies in CKD populations. Moreover, this review will briefly discuss genotype-based risk prediction, pharmacotherapy, drug target identification and individualized treatment solutions, specifically highlighting potentially important findings in CKD patients. This increased knowledge will hopefully facilitate the exciting transition from conventional clinical medicine to gene-based medicine. However, before this can be accomplished, unsolved issues regarding the complex human genetic architecture as well technical and clinically oriented obstacles will have to be overcome. Additionally, new policies and standardized risk evaluations for genetic testing in the clinical setting will have to be established to guarantee that CKD patients are provided with high-quality genotype-guided counseling that will help to improve their poor outcomes.

  8. Application of RNA silencing to plant disease resistance

    PubMed Central

    2012-01-01

    To reduce the losses caused by plant pathogens, plant biologists have adopted numerous methods to engineer resistant plants. Among them, RNA silencing-based resistance has been a powerful tool that has been used to engineer resistant crops during the last two decades. Based on this mechanism, diverse approaches were developed. In this review, we focus on the application of RNA silencing to produce plants that are resistant to plant viruses such as RNA and DNA viruses, viroids, insects, and the recent expansion to fungal pathogens. PMID:22650989

  9. Minimally invasive procedures on the lumbar spine

    PubMed Central

    Skovrlj, Branko; Gilligan, Jeffrey; Cutler, Holt S; Qureshi, Sheeraz A

    2015-01-01

    Degenerative disease of the lumbar spine is a common and increasingly prevalent condition that is often implicated as the primary reason for chronic low back pain and the leading cause of disability in the western world. Surgical management of lumbar degenerative disease has historically been approached by way of open surgical procedures aimed at decompressing and/or stabilizing the lumbar spine. Advances in technology and surgical instrumentation have led to minimally invasive surgical techniques being developed and increasingly used in the treatment of lumbar degenerative disease. Compared to the traditional open spine surgery, minimally invasive techniques require smaller incisions and decrease approach-related morbidity by avoiding muscle crush injury by self-retaining retractors, preventing the disruption of tendon attachment sites of important muscles at the spinous processes, using known anatomic neurovascular and muscle planes, and minimizing collateral soft-tissue injury by limiting the width of the surgical corridor. The theoretical benefits of minimally invasive surgery over traditional open surgery include reduced blood loss, decreased postoperative pain and narcotics use, shorter hospital length of stay, faster recover and quicker return to work and normal activity. This paper describes the different minimally invasive techniques that are currently available for the treatment of degenerative disease of the lumbar spine. PMID:25610845

  10. Conventional and Pretargeted Radioimmunotherapy Using Bismuth-213 to Target and Treat Non-Hodgkin Lymphomas Expressing CD20: A Preclinical Model toward Optimal Consolidation Therapy to Eradicate Minimal Residual Disease.

    SciTech Connect

    Park, Steven I.; Shenoi, Jaideep; Pagel, John M.; Hamlin, Donald K.; Wilbur, D. Scott; Orgun, Nural; Kenoyer, Aimee L.; Frayo, Shani; Axtman, Amanda; Back, Tom; Lin, Yukang; Fisher, Darrell R.; Gopal, Ajay K.; Green, Damian J.; Press, Oliver W.

    2010-11-18

    Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease (MRD) because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 min, tumor uptake for 1F5(scFv)4SA was 16.5 ± 7.0 % injected dose per gram (ID/g) compared with 2.3 ± 0.9 % ID/g for the control FP. Mice treated with anti-CD20 PRIT and 600 µCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared to controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared to 23 days for the control FP (p<0.0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.

  11. Minimally invasive surgery. Future developments.

    PubMed

    Wickham, J E

    1994-01-15

    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 introduced into body cavities to perform operations that are currently impossible. New materials will allow changes in instrument construction, such as use of memory metals to make heat activated scissors or forceps. With the reduced trauma associated with minimally invasive surgery, fewer operations will require long hospital stays. Traditional surgical wards will become largely redundant, and hospitals will need to cope with increased through-put of patients. Operating theatres will have to be equipped with complex high technology equipment, and hospital staff will need to be trained to manage it. Conventional nursing care will be carried out more in the community. Many traditional specialties will be merged, and surgical training will need fundamental revision to ensure that surgeons are competent to carry out the new procedures. PMID:8312776

  12. Ways To Minimize Bullying.

    ERIC Educational Resources Information Center

    Mueller, Mary Ellen; Parisi, Mary Joy

    This report delineates a series of interventions aimed at minimizing incidences of bullying in a suburban elementary school. The social services staff was scheduled to initiate an anti-bullying incentive in fall 2001 due to the increased occurrences of bullying during the prior year. The target population consisted of third- and fourth-grade…

  13. Minimally invasive periodontal therapy.

    PubMed

    Dannan, Aous

    2011-10-01

    Minimally invasive dentistry is a concept that preserves dentition and supporting structures. However, minimally invasive procedures in periodontal treatment are supposed to be limited within periodontal surgery, the aim of which is to represent alternative approaches developed to allow less extensive manipulation of surrounding tissues than conventional procedures, while accomplishing the same objectives. In this review, the concept of minimally invasive periodontal surgery (MIPS) is firstly explained. An electronic search for all studies regarding efficacy and effectiveness of MIPS between 2001 and 2009 was conducted. For this purpose, suitable key words from Medical Subject Headings on PubMed were used to extract the required studies. All studies are demonstrated and important results are concluded. Preliminary data from case cohorts and from many studies reveal that the microsurgical access flap, in terms of MIPS, has a high potential to seal the healing wound from the contaminated oral environment by achieving and maintaining primary closure. Soft tissues are mostly preserved and minimal gingival recession is observed, an important feature to meet the demands of the patient and the clinician in the esthetic zone. However, although the potential efficacy of MIPS in the treatment of deep intrabony defects has been proved, larger studies are required to confirm and extend the reported positive preliminary outcomes.

  14. Minimizing Promotion Trauma.

    ERIC Educational Resources Information Center

    Darling, LuAnn W.; McGrath, Loraine

    1983-01-01

    Nursing administrators can minimize promotion trauma and its unnecessary cost by building awareness of the transition process, clarifying roles and expectations, and attending to the promoted employee's needs. This article will help nursing administrators develop a concept of manager care combined with programs for orientation of new managers,…

  15. Periodic minimal surfaces

    NASA Astrophysics Data System (ADS)

    Mackay, Alan L.

    1985-04-01

    A minimal surface is one for which, like a soap film with the same pressure on each side, the mean curvature is zero and, thus, is one where the two principal curvatures are equal and opposite at every point. For every closed circuit in the surface, the area is a minimum. Schwarz1 and Neovius2 showed that elements of such surfaces could be put together to give surfaces periodic in three dimensions. These periodic minimal surfaces are geometrical invariants, as are the regular polyhedra, but the former are curved. Minimal surfaces are appropriate for the description of various structures where internal surfaces are prominent and seek to adopt a minimum area or a zero mean curvature subject to their topology; thus they merit more complete numerical characterization. There seem to be at least 18 such surfaces3, with various symmetries and topologies, related to the crystallographic space groups. Recently, glyceryl mono-oleate (GMO) was shown by Longley and McIntosh4 to take the shape of the F-surface. The structure postulated is shown here to be in good agreement with an analysis of the fundamental geometry of periodic minimal surfaces.

  16. Minimally invasive pancreatic surgery.

    PubMed

    Yiannakopoulou, E

    2015-12-01

    Minimally invasive pancreatic surgery is feasible and safe. Laparoscopic distal pancreatectomy should be widely adopted for benign lesions of the pancreas. Laparoscopic pancreaticoduodenectomy, although technically demanding, in the setting of pancreatic ductal adenocarcinoma has a number of advantages including shorter hospital stay, faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. Furthermore, it seems that progression-free survival is longer in patients undergoing laparoscopic pancreaticoduodenectomy in comparison with those undergoing open pancreaticoduodenectomy. Minimally invasive middle pancreatectomy seems appropriate for benign or borderline tumors of the neck of the pancreas. Technological advances including intraoperative ultrasound and intraoperative fluorescence imaging systems are expected to facilitate the wide adoption of minimally invasive pancreatic surgery. Although, the oncological outcome seems similar with that of open surgery, there are still concerns, as the majority of relevant evidence comes from retrospective studies. Large multicenter randomized studies comparing laparoscopic with open pancreatectomy as well as robotic assisted with both open and laparoscopic approaches are needed. Robotic approach could be possibly shown to be less invasive than conventional laparoscopic approach through the less traumatic intra-abdominal handling of tissues. In addition, robotic approach could enable the wide adoption of the technique by surgeon who is not that trained in advanced laparoscopic surgery. A putative clinical benefit of minimally invasive pancreatic surgery could be the attenuated surgical stress response leading to reduced morbidity and mortality as well as lack of the detrimental immunosuppressive effect especially for the oncological patients. PMID:26530291

  17. Lyme disease and conservation

    USGS Publications Warehouse

    Ginsberg, H.

    1994-01-01

    Lyme disease is a tick-borne illness that is wide-spread in North America, especially in the northeastern and northcentral United States. This disease could negatively influence efforts to conserve natural populations in two ways: (1) the disease could directly affect wild animal health; and (2) tick control efforts could adversely affect natural populations and communities. Lyme disease affects several domestic animals, but symptoms have been reported in only a few wild species. Direct effects of Lyme disease on wild animal populations have not been reported, but the disease should be considered as a possible cause in cases of unexplained population declines in endemic areas. Methods available to manage ticks and Lyme disease include human self-protection techniques, manipulation of habitats and hosts species populations, biological control, and pesticide applications. The diversity of available techniques allows selection of approaches to minimize environmental effects by (1) emphasizing personal protection techniques, (2) carefully targeting management efforts to maximize efficiency, and (3) integrating environmentally benign techniques to improve management while avoiding broad-scale environmentally destructive approaches. The environmental effects of Lyme disease depend, to a large extent, on the methods chosen to minimize human exposure to infected ticks. Conservation biologists can help design tick management programs that effectively lower the incidence of human Lyme disease while simultaneously minimizing negative effects on natural populations.

  18. Clinical Applications of Molecular Biology for Infectious Diseases

    PubMed Central

    Speers, David J

    2006-01-01

    Molecular biological methods for the detection and characterisation of microorganisms have revolutionised diagnostic microbiology and are now part of routine specimen processing. Polymerase chain reaction (PCR) techniques have led the way into this new era by allowing rapid detection of microorganisms that were previously difficult or impossible to detect by traditional microbiological methods. In addition to detection of fastidious microorganisms, more rapid detection by molecular methods is now possible for pathogens of public health importance. Molecular methods have now progressed beyond identification to detect antimicrobial resistance genes and provide public health information such as strain characterisation by genotyping. Treatment of certain microorganisms has been improved by viral resistance detection and viral load testing for the monitoring of responses to antiviral therapies. With the advent of multiplex PCR, real-time PCR and improvements in efficiency through automation, the costs of molecular methods are decreasing such that the role of molecular methods will further increase. This review will focus on the clinical utility of molecular methods performed in the clinical microbiology laboratory, illustrated with the many examples of how they have changed laboratory diagnosis and therefore the management of infectious diseases. PMID:16886046

  19. Beyond Oncology – Application of HPMA Copolymers in Non-cancerous Diseases

    PubMed Central

    Liu, Xin-Ming; Miller, Scott C.; Wang, Dong

    2009-01-01

    Macromolecular drug conjugates have been developed to improve the efficacy and safety profile of various therapeutic agents for many years. Among them, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates are the most extensively studied delivery platforms for the effective treatment of cancer. In recent years, the applications of HPMA copolymers for the treatment of a broader range of non-cancerous diseases have also been explored. This review highlights the recent developments in the rational design, synthesis, and evaluation of novel HPMA copolymer-drug conjugates for non-cancerous diseases, such as musculoskeletal diseases, infectious diseases and spinal cord injury. The translation potential of these applications are also briefly discussed. PMID:19909776

  20. Polyphenol oxidase activity from three sicilian artichoke [ Cynara cardunculus L. Var. scolymus L. (Fiori)] cultivars: studies and technological application on minimally processed production.

    PubMed

    Todaro, Aldo; Peluso, Orazio; Catalano, Anna Eghle; Mauromicale, Giovanni; Spagna, Giovanni

    2010-02-10

    Several papers helped with the development of more methods to control browning, or study thermal polyphenol oxidase (PPO) inactivation, but did not provide any solutions to technological process problems and food process improvement. Artichokes [ Cynara cardunculus L. var. scolymus L. (Fiori)] are susceptible to browning; this alteration could affect and reduce the suitability for its use, fresh or processed. Within this study, the catecholase and cresolase activities of PPO from three different Sicilian artichokes cultivar were characterized with regard to substrate specificity and enzyme kinetics, optimum pH and temperature, temperature and pH stability, and inhibitor test; all of the results were used for technological purposes, particularly to optimize minimally processed productions (ready-to-eat and cook-chilled artichokes).

  1. A model for developing job rotation schedules that eliminate sequential high workloads and minimize between-worker variability in cumulative daily workloads: Application to automotive assembly lines.

    PubMed

    Yoon, Sang-Young; Ko, Jeonghan; Jung, Myung-Chul

    2016-07-01

    The aim of study is to suggest a job rotation schedule by developing a mathematical model in order to reduce cumulative workload from the successive use of the same body region. Workload assessment using rapid entire body assessment (REBA) was performed for the model in three automotive assembly lines of chassis, trim, and finishing to identify which body part exposed to relatively high workloads at workstations. The workloads were incorporated to the model to develop a job rotation schedule. The proposed schedules prevent the exposure to high workloads successively on the same body region and minimized between-worker variance in cumulative daily workload. Whereas some of workers were successively assigned to high workload workstation under no job rotation and serial job rotation. This model would help to reduce the potential for work-related musculoskeletal disorders (WMSDs) without additional cost for engineering work, although it may need more computational time and relative complex job rotation sequences.

  2. A model for developing job rotation schedules that eliminate sequential high workloads and minimize between-worker variability in cumulative daily workloads: Application to automotive assembly lines.

    PubMed

    Yoon, Sang-Young; Ko, Jeonghan; Jung, Myung-Chul

    2016-07-01

    The aim of study is to suggest a job rotation schedule by developing a mathematical model in order to reduce cumulative workload from the successive use of the same body region. Workload assessment using rapid entire body assessment (REBA) was performed for the model in three automotive assembly lines of chassis, trim, and finishing to identify which body part exposed to relatively high workloads at workstations. The workloads were incorporated to the model to develop a job rotation schedule. The proposed schedules prevent the exposure to high workloads successively on the same body region and minimized between-worker variance in cumulative daily workload. Whereas some of workers were successively assigned to high workload workstation under no job rotation and serial job rotation. This model would help to reduce the potential for work-related musculoskeletal disorders (WMSDs) without additional cost for engineering work, although it may need more computational time and relative complex job rotation sequences. PMID:26995031

  3. Obtaining Soluble Folded Proteins from Inclusion Bodies Using Sarkosyl, Triton X-100, and CHAPS: Application to LB and M9 Minimal Media.

    PubMed

    Massiah, Michael A; Wright, Katharine M; Du, Haijuan

    2016-04-01

    This unit describes a straightforward and efficient method of using sarkosyl to solubilize and recover difficult recombinant proteins, such as GST- and His6 -tagged fusion proteins, that are overexpressed in E. coli. This protocol is especially useful for rescuing recombinant proteins overexpressed in M9 minimal medium. Sarkosyl added to lysis buffers helps with both protein solubility and cell lysis. Higher percentage sarkosyl (up to 10%) can extract >95% of soluble protein from inclusion bodies. In the case of sarkosyl-solubilized GST-fusion proteins, batch-mode affinity purification requires addition of a specific ratio of Triton X-100 and CHAPS, while sarkosyl-solubilized His6 -tagged fusion proteins can be directly purified on Ni(2+) resin columns. Proteins purified by this method could be widely used in biological assays, structure analysis and mass spectrum assay.

  4. Amaranth oil application for coronary heart disease and hypertension

    PubMed Central

    Martirosyan, Danik M; Miroshnichenko, Lidia A; Kulakova, Svetlana N; Pogojeva, Ala V; Zoloedov, Vladimir I

    2007-01-01

    Cardiovascular disease (CVD) is the Nation's leading killer for both men and women among all racial and ethnic groups. Development and progression of CVD is linked to the presence of risk factors such as hyperlipidemia, hypertension, obesity, and diabetes mellitus. It is known that cholesterol is an indicator of increased risk of heart attack and stroke. Low-density cholesterol (LDL) above 130 mg/dl high-density cholesterol (HDL) cholesterol below 35 mg/dl and total blood cholesterol above 200 mg/dl are indicators of problematic cholesterol. Proper ranges of cholesterol are important in the prevention of CVD. It has been suggested that a reduction in the consumption of saturated and an increase in unsaturated fatty acids is beneficial and prevents CVD. Amaranth grain contains tocotrienols and squalene compounds, which are known to affect cholesterol biosynthesis. The cholesterol precursors squalene, lanosterol and other methyl sterols, reflect cholesterol synthesis [1-3], whereas plant sterols and cholestanol, a metabolite of cholesterol, reflect the efficiency of cholesterol absorption in normal and hyperlipidemic populations [4-6]. Qureshi with co-authors [7] showed that feeding of chickens with amaranth oil decreases blood cholesterol levels, which are supported by the work of others [8]. Previously, we have shown that Amaranth oil modulates the cell membrane fluidity [9] and stabilized membranes that could be one reason as to why it is beneficial to those who consume it. It is known that in hypertension, the cell membrane is defective and hence, the movement of the Na and K ions across the cell membranes could defective that could contribute to the development of increase in blood pressure. Based on these properties of amaranth oil we hypothesize that it could be of significant benefit for patients with CVD. PMID:17207282

  5. Optimal control on hybrid ode systems with application to a tick disease model.

    PubMed

    Ding, Wandi

    2007-10-01

    We are considering an optimal control problem for a type of hybrid system involving ordinary differential equations and a discrete time feature. One state variable has dynamics in only one season of the year and has a jump condition to obtain the initial condition for that corresponding season in the next year. The other state variable has continuous dynamics. Given a general objective functional, existence, necessary conditions and uniqueness for an optimal control are established. We apply our approach to a tick-transmitted disease model with age structure in which the tick dynamics changes seasonally while hosts have continuous dynamics. The goal is to maximize disease-free ticks and minimize infected ticks through an optimal control strategy of treatment with acaricide. Numerical examples are given to illustrate the results.

  6. Study of Mobile GIS Application on the Field of GPR in the Road Disease Detection

    NASA Astrophysics Data System (ADS)

    Liao, Q.; Yang, F.

    2013-12-01

    With the reflection principle of pulsed electromagnetic waves, ground penetrating radar (GPR) is available to measure depth of the pavement layer, reflecting different hidden danger underground. Currently, GPR has been widely used in road engineering with the constantly improved ability of detection and diagnosis to road diseases. The sum of road disease data of a region, a city, and even a wider range will be a very informative database, so we need a more convenient way to achieve data query intuitively. As mobile internet develops continuously, application of mobile terminal device plays a more important role in information platform. Mobile GIS, with smartphone as its terminal, is supported by the mobile Internet, GPS or base station as its positioning method. In this article, based on Android Platform and using C/S pattern, the LBS application of road diseases information which integrates Baidu Map API and database technology was discussed. After testing, it can display and query the real-time and historical road diseases data, the classification of data on a phone intuitively and easily. Because of the location technique and high portability of smart phone, the spot investigations of road diseases become easier. Though, the system needs further improvement, especially with the improving of the mobile phone performance, the system can also add the function of analysis to the disease data, thus forming a set of service system with more applicable.

  7. Diagnostic imaging in head and neck disease: current applications of ultrasound.

    PubMed

    Scheible, F W; Leopold, G R

    1978-01-01

    Diagnostic ultrasound has become firmly established as a key imaging modality in obstetrics and gynecology. Its role in abdominal and retroperitoneal disease is also well known and continues to expand. Although usage of ultrasound in the head and neck had its beginnings many years ago, the advent of newer high-resolution transducers has allowed for further investigation of diseases in this area. Of particular interest are the thyroid gland and the extracranial carotid arteries. This review summarizes the current utility of gray-scale and real-time ultrasound in evaluating head and neck disease, and discusses potential future applications of the modality.

  8. Application of human induced pluripotent stem cells for modeling and treating neurodegenerative diseases.

    PubMed

    Payne, Natalie L; Sylvain, Aude; O'Brien, Carmel; Herszfeld, Daniella; Sun, Guizhi; Bernard, Claude C A

    2015-01-25

    The advent of human induced pluripotent stem cells (hiPSCs), reprogrammed in vitro from both healthy and disease-state human somatic cells, has triggered an enormous global research effort to realize personalized regenerative medicine for numerous degenerative conditions. hiPSCs have been generated from cells of many tissue types and can be differentiated in vitro to most somatic lineages, not only for the establishment of disease models that can be utilized as novel drug screening platforms and to study the molecular and cellular processes leading to degeneration, but also for the in vivo cell-based repair or modulation of a patient's disease profile. hiPSCs derived from patients with the neurodegenerative diseases amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and multiple sclerosis have been successfully differentiated in vitro into disease-relevant cell types, including motor neurons, dopaminergic neurons and oligodendrocytes. However, the generation of functional iPSC-derived neural cells that are capable of engraftment in humans and the identification of robust disease phenotypes for modeling neurodegeneration still require several key challenges to be addressed. Here, we discuss these challenges and summarize recent progress toward the application of iPSC technology for these four common neurodegenerative diseases.

  9. Applications of metabolomics for kidney disease research: from biomarkers to therapeutic targets.

    PubMed

    Wettersten, Hiromi I; Weiss, Robert H

    2013-01-01

    Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research. PMID:23538740

  10. Genomic risk prediction of complex human disease and its clinical application.

    PubMed

    Abraham, Gad; Inouye, Michael

    2015-08-01

    Recent advances in genome-wide association studies have stimulated interest in the genomic prediction of disease risk, potentially enabling individual-level risk estimates for early intervention and improved diagnostic procedures. Here, we review recent findings and approaches to genomic prediction model construction and performance, then contrast the potential benefits of such models in two complex human diseases, aiding diagnosis in celiac disease and prospective risk prediction for cardiovascular disease. Early indications are that optimal application of genomic risk scores will differ substantially for each disease depending on underlying genetic architecture as well as current clinical and public health practice. As costs decline, genomic profiles become common, and popular understanding of risk and its communication improves, genomic risk will become increasingly useful for the individual and the clinician.

  11. [Application of spatial relative risk estimation in communicable disease risk evaluation].

    PubMed

    Zhang, Yewu; Guo, Qing; Wang, Xiaofeng; Yu, Meng; Su, Xuemei; Dong, Yan; Zhang, Chunxi

    2015-05-01

    This paper summaries the application of adaptive kernel density algorithm in the spatial relative risk estimation of communicable diseases by using the reported data of infectious diarrhea (other than cholera, dysentery, typhoid and paratyphoid) in Ludian county and surrounding area in Yunnan province in 2013. Statistically significant fluctuations in an estimated risk function were identified through the use of asymptotic tolerance contours, and finally these data were visualized though disease mapping. The results of spatial relative risk estimation and disease mapping showed that high risk areas were in southeastern Shaoyang next to Ludian. Therefore, the spatial relative risk estimation of disease by using adaptive kernel density algorithm and disease mapping technique is a powerful method in identifying high risk population and areas.

  12. [Application of spatial relative risk estimation in communicable disease risk evaluation].

    PubMed

    Zhang, Yewu; Guo, Qing; Wang, Xiaofeng; Yu, Meng; Su, Xuemei; Dong, Yan; Zhang, Chunxi

    2015-05-01

    This paper summaries the application of adaptive kernel density algorithm in the spatial relative risk estimation of communicable diseases by using the reported data of infectious diarrhea (other than cholera, dysentery, typhoid and paratyphoid) in Ludian county and surrounding area in Yunnan province in 2013. Statistically significant fluctuations in an estimated risk function were identified through the use of asymptotic tolerance contours, and finally these data were visualized though disease mapping. The results of spatial relative risk estimation and disease mapping showed that high risk areas were in southeastern Shaoyang next to Ludian. Therefore, the spatial relative risk estimation of disease by using adaptive kernel density algorithm and disease mapping technique is a powerful method in identifying high risk population and areas. PMID:26080648

  13. Applications of metabolomics for kidney disease research: from biomarkers to therapeutic targets.

    PubMed

    Wettersten, Hiromi I; Weiss, Robert H

    2013-01-01

    Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research.

  14. Discrete Minimal Surface Algebras

    NASA Astrophysics Data System (ADS)

    Arnlind, Joakim; Hoppe, Jens

    2010-05-01

    We consider discrete minimal surface algebras (DMSA) as generalized noncommutative analogues of minimal surfaces in higher dimensional spheres. These algebras appear naturally in membrane theory, where sequences of their representations are used as a regularization. After showing that the defining relations of the algebra are consistent, and that one can compute a basis of the enveloping algebra, we give several explicit examples of DMSAs in terms of subsets of sln (any semi-simple Lie algebra providing a trivial example by itself). A special class of DMSAs are Yang-Mills algebras. The representation graph is introduced to study representations of DMSAs of dimension d ≤ 4, and properties of representations are related to properties of graphs. The representation graph of a tensor product is (generically) the Cartesian product of the corresponding graphs. We provide explicit examples of irreducible representations and, for coinciding eigenvalues, classify all the unitary representations of the corresponding algebras.

  15. Magnetic resonance cholangiography: applications in patients with calculus disease of the biliary tract.

    PubMed

    Liu, Terrence H; Organ, Claude H

    2004-04-01

    Magnetic resonance cholangiography (MRC) is a non-invasive imaging modality that has become widely available. In the short time since its introduction, MRC has been shown to possess excellent accuracy for the diagnosis of various biliary pathologies, including choledocholithiasis. Investigations of the clinical applications of MRC are ongoing. This review summarizes the diagnostic capabilities of MRC and discusses its application in the management of patients with gallstone diseases.

  16. Minimal Disease Assessment in the Treatment of Children and Adolescents with Intermediate-Risk (Stage III/IV) B-Cell Non-Hodgkin Lymphoma: A Children’s Oncology Group Report

    PubMed Central

    Shiramizu, Bruce; Goldman, Stanton; Kusao, Ian; Agsalda, Melissa; Lynch, James; Smith, Lynette; Harrison, Lauren; Morris, Erin; Gross, Thomas G.; Sanger, Warren; Perkins, Sherrie; Cairo, Mitchell S.

    2011-01-01

    Summary Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (p=0.40). At EOT, only 13/32 patients had MRD data available with 1 relapse in the MRD-positive group and no recurrences in the MRD-negative group (p=0.077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL. PMID:21496005

  17. Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report.

    PubMed

    Shiramizu, Bruce; Goldman, Stanton; Kusao, Ian; Agsalda, Melissa; Lynch, James; Smith, Lynette; Harrison, Lauren; Morris, Erin; Gross, Thomas G; Sanger, Warren; Perkins, Sherrie; Cairo, Mitchell S

    2011-06-01

    Children/adolescents with mature B-cell non-Hodgkin lymphoma (B-NHL) have an excellent prognosis but relapses still occur. While chromosomal aberrations and/or clonal immunoglobulin (Ig) gene rearrangements may indicate risk of failure, a more universal approach was developed to detect minimal disease (MD). Children/adolescents with intermediate-risk B-NHL were treated with French-British-American/Lymphome Malins de Burkitt 96 (FAB/LMB96) B4 modified chemotherapy and rituximab. Specimens from diagnosis, end of induction (EOI), and end of therapy (EOT) were assayed for MD. Initial specimens were screened for IGHV family usage with primer pools followed by individual primers to identify MD. Thirty-two diagnostic/staging specimens screened positive with primer pools and unique IGHV family primers were identified. Two patients relapsed; first relapse (4 months from diagnosis) was MD-positive at EOI, the second (36 months from diagnosis) was MD-positive at EOT. At EOI, recurrent rates were similar between the MRD-positive and MRD-negative patients (P = 0·40). At EOT, only 13/32 patients had MRD data available with one relapse in the MRD-positive group and no recurrences in the MRD-negative group (P = 0·077). The study demonstrated molecular-disseminated disease in which IgIGHV primer pools could be used to assess MD. This feasibility study supports future investigations to assess the validity and significance of MD screening in a larger cohort of patients with intermediate-risk mature B-NHL. PMID:21496005

  18. Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Consensus statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI).

    PubMed

    Lopes, Antonio Augusto; Barst, Robyn J; Haworth, Sheila Glennis; Rabinovitch, Marlene; Al Dabbagh, Maha; Del Cerro, Maria Jesus; Ivy, Dunbar; Kashour, Tarek; Kumar, Krishna; Harikrishnan, S; D'Alto, Michele; Thomaz, Ana Maria; Zorzanelli, Leína; Aiello, Vera D; Mocumbi, Ana Olga; Santana, Maria Virginia T; Galal, Ahmed Nasser; Banjar, Hanaa; Tamimi, Omar; Heath, Alexandra; Flores, Patricia C; Diaz, Gabriel; Sandoval, Julio; Kothari, Shyam; Moledina, Shahin; Gonçalves, Rilvani C; Barreto, Alessandra C; Binotto, Maria Angélica; Maia, Margarida; Al Habshan, Fahad; Adatia, Ian

    2014-06-01

    Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation.

  19. Minimal residual disease after allogeneic stem cell transplant: a comparison among multiparametric flow cytometry, Wilms tumor 1 expression and chimerism status (Complete chimerism versus Low Level Mixed Chimerism) in acute leukemia.

    PubMed

    Rossi, Giovanni; Carella, Angelo Michele; Minervini, Maria Marta; Savino, Lucia; Fontana, Andrea; Pellegrini, Fabio; Greco, Michele Mario; Merla, Emanuela; Quarta, Gianni; Loseto, Giacomo; Capalbo, Silvana; Palumbo, Gaetano; Cascavilla, Nicola

    2013-12-01

    Relapse represents the main cause of treatment failure after allogeneic stem cell transplant (allo-SCT). The detection of minimal residual disease (MRD) by multiparametric flow cytometry (MFC), chimerism, cytogenetics and molecular analysis may be critical to prevent relapse. Therefore, we assessed the overall agreement among chimerism (low level mixed chimerism [LL-MC] vs. complete chimerism [CC]), MFC and Wilms tumor 1 (WT1) mRNA to detect MRD and investigated the impact of MRD obtained from the three methods on patient outcome. Sixty-seven fresh bone marrow (BM) samples from 24 patients (17 acute myeloid leukemia [AML], seven acute lymphoblastic leukemia [ALL]) in complete remission (CR) after allo-SCT were investigated at different time points. A moderate agreement was found among the three techniques investigated. A higher concordance between positive results from MFC (75.0% vs. 32.7%, p = 0.010) and WT1 (58.3% vs. 29.1%, p = 0.090) was detected among LL-MC rather than CC samples. Relapse-free survival (RFS) and overall survival (OS) were found to be higher in MRD negative patients than in MRD positive patients analyzed with MFC and WT1. Our results discourage the use of low autologous signals as the only marker of MRD, and suggest the usefulness of MFC and WT1 real-time quantitative polymerase chain reaction (RQ-PCR) in stratifying patients with respect to risk of relapse.

  20. Off-pump occlusion of trans-thoracic minimal invasive surgery (OPOTTMIS) on simple congenital heart diseases (ASD, VSD and PDA) attached consecutive 210 cases report: A single institute experience

    PubMed Central

    2011-01-01

    Objective This paper intends to report our experiences by using an operation of off-pump occlusion of trans-thoracic minimal invasive surgery (OPOTTMIS) on the treatment of consecutive 210 patients with simple congenital heart diseases (CHD) including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Methods The retrospective clinical data of OPOTTMIS in our institute were collected and compared to other therapeutic measures adopted in the relevant literatures. After operation, all the patients received electrocardiography (ECG) and echocardiography (echo) once a month within the initial 3 months, and no less than once every 3 ~ 6 months later. Results The successful rate of the performed OPOTTMIS operation was 99.5%, the mortality and complication incidence within 72 hours were 0.5% and 4.8%, respectively. There were no major complications during peri-operation such as cardiac rupture, infective endocarditis, strokes, haemolysis and thrombosis. The post-operation follow-up outcomes by ECG and echo checks of 3 months to 5 years showed that there were no III° AVB, no obvious Occluder migration and device broken and no moderate cardiac valve regurgitation, except 1 VSD and 1 PDA with mild residual shunts, and 2 PDA with heart expansion after operation. However, all the patients' heart functions were in class I~II according to NYH standard. Conclusion The OPOTTMIS is a safe, less complex, feasible and effective choice to selected simple CHD patients with some good advantages and favorable short term efficacies. PMID:21486486

  1. Minimal residual disease in early phase of chemotherapy reflects poor outcome in children with acute lymphoblastic leukemia--a retrospective study by the Children's Cancer and Leukemia Study Group in Japan.

    PubMed

    Okamoto, Tomomi; Yokota, Shouhei; Katano, Naoyuki; Seriu, Taku; Nakao, Makoto; Taniwaki, Masafumi; Watanabe, Arata; Asami, Keiko; Kikuta, Atsushi; Koizumi, Shoichi; Kawakami, Tetsuo; Ohta, Shigeru; Miyake, Munenori; Watanabe, Tsutomu; Iwai, Asayuki; Kamitamari, Akira; Ijichi, Osamu; Hyakuna, Nobuyuki; Mimaya, Junichi; Fujimoto, Takeo; Tsurusawa, Masahito

    2002-05-01

    We analyzed the minimal residual disease (MRD) in 50 children with acute lymphoblastic leukemia (ALL) by amplifying the clonally rearranged T-cell receptor (TCR) gamma/delta chain and/or immunoglobulin (Ig) kappa chain gene using the allele-specific-PCR method. All children were treated according to the protocols of the Children's Cancer and Leukemia Study Group of Japan (CCLSG). The patients were stratified into four risk-groups according to the leukocyte count and age at diagnosis. We prospectively sampled the patients' bone marrow at 1 month (point 1) and 3 months (point 2) after the initiation of chemotherapy and quantitated the MRD retrospectively. The results of MRD were closely related with the clinical outcome. The relapse rate of the patients MRD-positive at points 1 and 2 was 46% (6/13) and 86% (6/7), respectively, whereas those MRD-negative results at point 1 and 2 were 13% (3/13) and 3% (3/30), respectively. We found significant differences in the event-free survival between MRD-positive children and MRD-negative children like the reports, which have been made by BFM and EORTC groups. We conclude that MRD in an early phase of chemotherapy can be a good predictor of the prognosis of childhood ALL regardless of the protocol of chemotherapy or race.

  2. Application of remote thermal imaging and night vision technology to improve endangered wildlife resource management with minimal animal distress and hazard to humans

    NASA Astrophysics Data System (ADS)

    Lavers, C.; Franks, K.; Floyd, M.; Plowman, A.

    2005-01-01

    Advanced electromagnetic sensor systems more commonly associated with the hightech military battlefield may be applied to remote surveillance of wildlife. The first comprehensive study of a wide global variety of Near Infra Red (NIR) and thermal wildlife portraits are presented with this technology: for mammals, birds and other animals. The paper illustrates the safety aspects afforded to zoo staff and personnel in the wild during the day and night from potentially lethal and aggressive animals, and those difficult to approach normally. Such remote sensing systems are non-invasive and provide minimal disruption and distress to animals both in captivity and in the wild. We present some of the veterinarian advantages of such all weather day and night systems to identify sickness and injuries at an early diagnostic stage, as well as age related effects and mammalian cancer. Animals have very different textured surfaces, reflective and emissive properties in the NIR and thermal bands than when compared with the visible spectrum. Some surface features may offer biomimetic materials design advantages.

  3. An Experimental Approach to Controllably Vary Protein Oxidation While Minimizing Electrode Adsorption for Boron-Doped Diamond Electrochemical Surface Mapping Applications

    PubMed Central

    McClintock, Carlee S; Hettich, Robert L.

    2012-01-01

    Oxidative protein surface mapping has become a powerful approach for measuring the solvent accessibility of folded protein structures. A variety of techniques exist for generating the key reagent – hydroxyl radicals – for these measurements; however, these approaches range significantly in their complexity and expense of operation. This research expands upon earlier work to enhance the controllability of boron-doped diamond (BDD) electrochemistry as an easily accessible tool for producing hydroxyl radicals in order to oxidize a range of intact proteins. Efforts to modulate oxidation level while minimizing the adsorption of protein to the electrode involved the use of relatively high flow rates to reduce protein residence time inside the electrochemical flow chamber. Additionally, a different cell activation approach using variable voltage to supply a controlled current allowed us to precisely tune the extent of oxidation in a protein-dependent manner. In order to gain perspective on the level of protein adsorption onto the electrode surface, studies were conducted to monitor protein concentration during electrolysis and gauge changes in the electrode surface between cell activation events. This report demonstrates the successful use of BDD electrochemistry for greater precision in generating a target number of oxidation events upon intact proteins. PMID:23210708

  4. Development of 2D band-target entropy minimization and application to the deconvolution of multicomponent 2D nuclear magnetic resonance spectra.

    PubMed

    Guo, Liangfeng; Wiesmath, Anette; Sprenger, Peter; Garland, Marc

    2005-03-15

    Spectral reconstruction from multicomponent spectroscopic data is the frequent primary goal in chemical system identification and exploratory chemometric studies. Various methods and techniques have been reported in the literature. However, few algorithms/methods have been devised for spectral recovery without the use of any a priori information. In the present studies, a higher dimensional entropy minimization method based on the BTEM algorithm (Widjaja, E.; Li, C.; Garland, M. Organometallics 2002, 21, 1991-1997.) and related techniques were extended to large-scale arrays, namely, 2D NMR spectroscopy. The performance of this novel method had been successfully verified on various real experimental mixture spectra from a series of randomized 2D NMR mixtures (COSY NMR and HSQC NMR). With the new algorithm and raw multicomponent NMR alone, it was possible to reconstruct the pure spectroscopic patterns and calculate the relative concentration of each species without recourse to any libraries or any other a priori information. The potential advantages of this novel algorithm and its implications for general chemical system identification of unknown mixtures are discussed. PMID:15762569

  5. 10 CFR 20.1406 - Minimization of contamination.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Minimization of contamination. 20.1406 Section 20.1406... License Termination § 20.1406 Minimization of contamination. (a) Applicants for licenses, other than early... procedures for operation will minimize, to the extent practicable, contamination of the facility and...

  6. 10 CFR 20.1406 - Minimization of contamination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Minimization of contamination. 20.1406 Section 20.1406... License Termination § 20.1406 Minimization of contamination. (a) Applicants for licenses, other than early... procedures for operation will minimize, to the extent practicable, contamination of the facility and...

  7. Extracorporeal shockwave therapy for peyronie disease.

    PubMed

    Groth, T; Monga, M

    2003-01-01

    While surgery is the mainstay of therapy for Peyronie disease requiring correction of angulation, interest has grown in the application of extracorporeal shockwave therapy (ESWT) as a minimally invasive approach. This article reviews the current literature reporting the use of ESWT for Peyronie disease.

  8. The simultaneous application of positive-end expiratory pressure with the Trendelenburg position minimizes respiratory fluctuations in internal jugular vein size

    PubMed Central

    Han, Sun Sook; Han, Woong Ki; Ko, Dong Chan

    2014-01-01

    Background The respiratory cycle alters the size of the right internal jugular vein (RIJV). We assessed the changes in RIJV size during the respiratory cycle in patients under positive pressure ventilation. Moreover, we examined the effects of positive-end expiratory pressure (PEEP) and the Trendelenburg position on respiratory fluctuations. Methods A prospective study of 24 patients undergoing general endotracheal anesthesia was performed. Images of the RIJV were obtained in the supine position with no PEEP (baseline, S0) and after applying three different maneuvers in random order: (1) a PEEP of 10 cmH2O (S10), (2) a 10° Trendelenburg tilt position (T0), and (3) a 10° Trendelenburg tilt position combined with a PEEP of 10 cmH2O (T10). Using the images when the area was smallest and largest, cross-sectional area (CSA), anteroposterior diameter, and transverse diameter were measured. Results All maneuvers minimized the fluctuation in RIJV size (all P = 0.0004). During the respiratory cycle, the smallest CSA compared to the largest CSA at S0, S10, T0, and T10 decreased by 28.3 8.5, 8.0, and 4.4%, respectively. Furthermore, compared to S0, a 10° Trendelenburg tilt position with a PEEP of 10 cmH2O significantly increased the CSA in the largest areas by 83.8% and in the smallest areas by 169.4%. Conclusions A 10° Trendelenburg tilt position combined with a PEEP of 10 cmH2O not only increases the size of the RIJV but also reduces fluctuation by the respiratory cycle. PMID:24910725

  9. An adaptive algorithm for detection of multiple-type, positively stained nuclei in IHC images with minimal prior information: application to OLIG2 staining gliomas

    NASA Astrophysics Data System (ADS)

    Akakin, Hatice C.; Gokozan, Hamza; Otero, Jose; Gurcan, Metin N.

    2015-03-01

    We propose a method to detect and segment the oligodendrocytes and gliomas in OLIG2 immunoperoxidase stained tissue sections. Segmentation of cell nuclei is essential for automatic, fast, accurate and consistent analysis of pathology images. In general, glioma cells and oligodendrocytes mostly differ in shape and size within the tissue slide. In OLIG2 stained tissue images, gliomas are represented with irregularly shaped nuclei with varying sizes and brown shades. On the other hand, oligodendrocytes have more regular round nuclei shapes and are smaller in size when compared to glioma cells found in oligodendroglioma, astrocytomas, or oligoastrocytomas. The first task is to detect the OLIG2 positive cell regions within a region of interest image selected from a whole slide. The second task is to segment each cell nucleus and count the number of cell nuclei. However, the cell nuclei belonging to glioma cases have particularly irregular nuclei shapes and form cell clusters by touching or overlapping with each other. In addition to this clustered structure, the shading of the brown stain and the texture of the nuclei differ slightly within a tissue image. The final step of the algorithm is to classify glioma cells versus oligodendrocytes. Our method starts with color segmentation to detect positively stained cells followed by the classification of single individual cells and cell clusters by K-means clustering. Detected cell clusters are segmented with the H-minima based watershed algorithm. The novel aspects of our work are: 1) the detection and segmentation of multiple-type, positively-stained nuclei by incorporating only minimal prior information; and 2) adaptively determining clustering parameters to adjust to the natural variation in staining as well as the underlying cellular structure while accommodating multiple cell types in the image. Performance of the algorithm to detect individual cells is evaluated by sensitivity and precision metrics. Promising

  10. A phosphorescent rhenium emitter with minimal fluorescent component induced by heavy atom: synthetic procedure, molecular structure, photophysical feature and optoelectronic application.

    PubMed

    Cui, Xiao; Zhang, He Ming

    2014-01-24

    In this paper, a Br-containing diamine ligand of 2-(4-bromophenyl)-5-(pyridin-2-yl)-1,3,4-oxadiazole (referred to as BrPO) and its corresponding Re(I) complex of Re(CO)3(BrPO)Br are synthesized and studied in detail, including molecular structure, photophysical feature, thermal stability and electrochemical property. Experimental data suggest that Re(CO)3(BrPO)Br takes a octahedral coordination environment, and the π-π attraction between BrPO ligands makes complex molecules take a highly-ordered arrangement. Re(CO)3(BrPO)Br is found to be a yellow emitter peaking at 565 nm with emission yield of 0.11 and excited state lifetime of 4.21 μs. The emission comes from triplet excited state of ML&LLCT, where ML&LLCT means metal-to-ligand-charge-transfer and ligand-to-ligand-charge-transfer as suggested by theoretical calculation. The fluorescent component in the emissive center is minimized by the heavy-atom turbulence effect. Re(CO)3(BrPO)Br owns a high thermal decomposition of 280°C, with HOMO of -5.45eV and LUMO of -3.12 eV. The optimal electroluminescent device using Re(CO)3(BrPO)Br as the emitting dopant gives a maximum brightness of 5906 cd/m(2) and a maximum current efficiency of 5.6 cd/A.

  11. Minimally refined biomass fuel

    DOEpatents

    Pearson, Richard K.; Hirschfeld, Tomas B.

    1984-01-01

    A minimally refined fluid composition, suitable as a fuel mixture and derived from biomass material, is comprised of one or more water-soluble carbohydrates such as sucrose, one or more alcohols having less than four carbons, and water. The carbohydrate provides the fuel source; water solubilizes the carbohydrates; and the alcohol aids in the combustion of the carbohydrate and reduces the vicosity of the carbohydrate/water solution. Because less energy is required to obtain the carbohydrate from the raw biomass than alcohol, an overall energy savings is realized compared to fuels employing alcohol as the primary fuel.

  12. Minimal E6 unification

    NASA Astrophysics Data System (ADS)

    Susič, Vasja

    2016-06-01

    A realistic model in the class of renormalizable supersymmetric E6 Grand Unified Theories is constructed. Its matter sector consists of 3 × 27 representations, while the Higgs sector is 27 +27 ¯+35 1'+35 1' ¯+78 . An analytic solution for a Standard Model vacuum is found and the Yukawa sector analyzed. It is argued that if one considers the increased predictability due to only two symmetric Yukawa matrices in this model, it can be considered a minimal SUSY E6 model with this type of matter sector. This contribution is based on Ref. [1].

  13. Minimizing travel claims cost with minimal-spanning tree model

    NASA Astrophysics Data System (ADS)

    Jamalluddin, Mohd Helmi; Jaafar, Mohd Azrul; Amran, Mohd Iskandar; Ainul, Mohd Sharizal; Hamid, Aqmar; Mansor, Zafirah Mohd; Nopiah, Zulkifli Mohd

    2014-06-01

    Travel demand necessitates a big expenditure in spending, as has been proven by the National Audit Department (NAD). Every year the auditing process is carried out throughout the country involving official travel claims. This study focuses on the use of the Spanning Tree model to determine the shortest path to minimize the cost of the NAD's official travel claims. The objective is to study the possibility of running a network based in the Kluang District Health Office to eight Rural Clinics in Johor state using the Spanning Tree model applications for optimizing travelling distances and make recommendations to the senior management of the Audit Department to analyze travelling details before an audit is conducted. Result of this study reveals that there were claims of savings of up to 47.4% of the original claims, over the course of the travel distance.

  14. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

    PubMed Central

    Chen, Hui; Jiang, Wen

    2014-01-01

    The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing, high-throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterization of oral microbiota and analyzing the changes of the microbiome in the states of health or disease. Deep understanding the knowledge of microbiota will pave the way for more effective prevent dentistry and contribute to the development of personalized dental medicine. PMID:25352835

  15. Future perspectives of Smartphone applications for rheumatic diseases self-management.

    PubMed

    Azevedo, Ana Rita Pereira; de Sousa, Hugo Manuel Lopes; Monteiro, Joaquim António Faria; Lima, Aurea Rosa Nunes Pereira

    2015-03-01

    Rheumatic diseases (RD) self-management interventions are designed to improve health-related quality of life, health care utilization, and perceived self-efficacy. Despite these demonstrated good results, there are several issues that hinder or render less appealing these interventions. One economically and socially viable solution is exploiting the potential of Smartphone technology. This potential comes from Smartphones pervasive presence in actual society, combined with the advantages of being personal, intuitive, and computationally powerful, with capability to support applications and assist its user throughout different activities of daily living and environments persistently. With their global acceptance increasing quickly, there is a great opportunity for mobile health in using Smartphone applications for RD self-management. Besides the potential of such applications, research on the development and evaluation of such applications is in the early stages. Therefore, it is important to foresee its future applicability in order to meet the needs of the twenty-first century.

  16. Short Message Service (SMS) Applications for Disease Prevention in Developing Countries

    PubMed Central

    Suggs, L. Suzanne; Odermatt, Peter

    2012-01-01

    Background The last decade has witnessed unprecedented growth in the number of mobile phones in the developing world, thus linking millions of previously unconnected people. The ubiquity of mobile phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention efforts. Objective The aim of this review was to describe the characteristics and outcomes of SMS interventions for disease prevention in developing countries and provide recommendations for future work. Methods A systematic search of peer-reviewed and gray literature was performed for papers published in English, French, and German before May 2011 that describe SMS applications for disease prevention in developing countries. Results A total of 34 SMS applications were described, among which 5 had findings of an evaluation reported. The majority of SMS applications were pilot projects in various levels of sophistication; nearly all came from gray literature sources. Many applications were initiated by the project with modes of intervention varying between one-way or two-way communication, with or without incentives, and with educative games. Evaluated interventions were well accepted by the beneficiaries. The primary barriers identified were language, timing of messages, mobile network fluctuations, lack of financial incentives, data privacy, and mobile phone turnover. Conclusion This review illustrates that while many SMS applications for disease prevention exist, few have been evaluated. The dearth of peer-reviewed studies and the limited evidence found in this systematic review highlight the need for high-quality efficacy studies examining behavioral, social, and economic outcomes of SMS applications and mobile phone interventions aimed to promote health in developing country contexts. PMID:22262730

  17. MIARMA: A minimal-loss information method for filling gaps in time series. Application to CoRoT light curves

    NASA Astrophysics Data System (ADS)

    Pascual-Granado, J.; Garrido, R.; Suárez, J. C.

    2015-03-01

    Context. Gaps in time series cause spurious frequencies in the power spectra. In light curves of pulsating stars, this hampers identifying the theoretical oscillation modes. When these gaps are smaller than the total time span, the commonly used approach to overcome these difficulties involves linear interpolation. The original frequency content of the pulsating stars is not preserved in the resulting time series. Aims: The method presented here intends to minimize the effect of the gaps in the power spectra by gap-filling that preserves at best the original information, that is, the stellar oscillation frequency content for asteroseismology. Methods: We used a forward-backward predictor based on autoregressive moving-average modelling (ARMA) in the time domain. The algorithm MIARMA is particularly suitable for replacing invalid data such as those present in the light curves of the CoRoT satellite due to the pass through the South Atlantic Anomaly, and eventually for the data gathered by the NASA planet hunter Kepler. We selected a sample of stars from the ultra-precise photometry collected by the asteroseismic camera on board the CoRoT satellite: the δ Scuti star HD 174966, showing periodic variations of the same order as the CoRoT observational window, the Be star HD 51193, showing longer time variations, and the solar-like HD 49933, with rapid time variations. Results: We show that in some cases linear interpolations are less reliable than previously believed. The ARMA interpolation method provides a cleaner power spectrum, that is, less contaminated by spurious frequencies. In summary, MIARMA appears to be a suitable method for filling gaps in the light curves of pulsating stars observed by CoRoT since the method aims to preserve their frequency content, which is a necessary condition for asteroseismic studies. The CoRoT space mission, launched on December 27th 2006, has been developed and is operated by CNES, with the contribution of Austria, Belgium, Brazil

  18. DiME: A Scalable Disease Module Identification Algorithm with Application to Glioma Progression

    PubMed Central

    Liu, Yunpeng; Tennant, Daniel A.; Zhu, Zexuan; Heath, John K.; Yao, Xin; He, Shan

    2014-01-01

    Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction), to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II) - and high (GBM) - grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression) between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME. PMID:24523864

  19. Minimizing the impact of the mosquito adulticide naled on honey bees, Apis mellifera (Hymenoptera: Apidae): aerial ultra-low-volume application using a high-pressure nozzle system.

    PubMed

    Zhong, He; Latham, Mark; Payne, Steve; Brock, Cate

    2004-02-01

    The impact of the mosquito adulticide naled on honey bees, Apis mellifera L., was evaluated by exposing test beehives to nighttime aerial ultra-low-volume (ULV) applications using a high-pressure nozzle system. The tests were conducted during routine mosquito control missions at Manatee County, Florida, in summer 2000. Two treatment sites were sprayed a total of four times over a 10-wk period. Honey bees, which clustered outside of the hive entrances, were subjected to naled exposure during these mosquito control sprays. The highest average naled ground deposition was 2,688 microg/m2 at the Port Manatee site, which resulted in statistically significant bee mortality (118) compared with the controls. At the Terra Ceia Road site, an intermediate level of naled deposition was found (1,435 microg/m2). For this spray mission, the range of dead bees per hive at Terra Ceia was 2 to 9 before spraying and 5 to 36 after naled application. Means of all other naled ground depositions were < 850 microl/m2. We concluded that substantial bee mortality (> 100 dead bees) resulted when naled residue levels were > 2,000 kg/m2 and honey bees were clustered outside of the hive entrances during mosquito adulticide applications. Compared with the flat-fan nozzle systems currently used by most of Florida's mosquito control programs, the high-pressure nozzle system used in this experiment substantially reduced environmental insecticide contamination and lead to decreased bee mortality. Statistical analysis also showed that average honey yield at the end of the season was not significantly reduced for those hives that were exposed to the insecticide. PMID:14998120

  20. Genetic algorithms for minimal source reconstructions

    SciTech Connect

    Lewis, P.S.; Mosher, J.C.

    1993-12-01

    Under-determined linear inverse problems arise in applications in which signals must be estimated from insufficient data. In these problems the number of potentially active sources is greater than the number of observations. In many situations, it is desirable to find a minimal source solution. This can be accomplished by minimizing a cost function that accounts from both the compatibility of the solution with the observations and for its ``sparseness``. Minimizing functions of this form can be a difficult optimization problem. Genetic algorithms are a relatively new and robust approach to the solution of difficult optimization problems, providing a global framework that is not dependent on local continuity or on explicit starting values. In this paper, the authors describe the use of genetic algorithms to find minimal source solutions, using as an example a simulation inspired by the reconstruction of neural currents in the human brain from magnetoencephalographic (MEG) measurements.

  1. Controlling molecular transport in minimal emulsions

    PubMed Central

    Gruner, Philipp; Riechers, Birte; Semin, Benoît; Lim, Jiseok; Johnston, Abigail; Short, Kathleen; Baret, Jean-Christophe

    2016-01-01

    Emulsions are metastable dispersions in which molecular transport is a major mechanism driving the system towards its state of minimal energy. Determining the underlying mechanisms of molecular transport between droplets is challenging due to the complexity of a typical emulsion system. Here we introduce the concept of ‘minimal emulsions', which are controlled emulsions produced using microfluidic tools, simplifying an emulsion down to its minimal set of relevant parameters. We use these minimal emulsions to unravel the fundamentals of transport of small organic molecules in water-in-fluorinated-oil emulsions, a system of great interest for biotechnological applications. Our results are of practical relevance to guarantee a sustainable compartmentalization of compounds in droplet microreactors and to design new strategies for the dynamic control of droplet compositions. PMID:26797564

  2. Controlling molecular transport in minimal emulsions

    NASA Astrophysics Data System (ADS)

    Gruner, Philipp; Riechers, Birte; Semin, Benoît; Lim, Jiseok; Johnston, Abigail; Short, Kathleen; Baret, Jean-Christophe

    2016-01-01

    Emulsions are metastable dispersions in which molecular transport is a major mechanism driving the system towards its state of minimal energy. Determining the underlying mechanisms of molecular transport between droplets is challenging due to the complexity of a typical emulsion system. Here we introduce the concept of `minimal emulsions', which are controlled emulsions produced using microfluidic tools, simplifying an emulsion down to its minimal set of relevant parameters. We use these minimal emulsions to unravel the fundamentals of transport of small organic molecules in water-in-fluorinated-oil emulsions, a system of great interest for biotechnological applications. Our results are of practical relevance to guarantee a sustainable compartmentalization of compounds in droplet microreactors and to design new strategies for the dynamic control of droplet compositions.

  3. Rodent models of cardiopulmonary disease: their potential applicability in studies of air pollutant susceptibility.

    PubMed Central

    Kodavanti, U P; Costa, D L; Bromberg, P A

    1998-01-01

    The mechanisms by which increased mortality and morbidity occur in individuals with preexistent cardiopulmonary disease following acute episodes of air pollution are unknown. Studies involving air pollution effects on animal models of human cardiopulmonary diseases are both infrequent and difficult to interpret. Such models are, however, extensively used in studies of disease pathogenesis. Primarily they comprise those developed by genetic, pharmacologic, or surgical manipulations of the cardiopulmonary system. This review attempts a comprehensive description of rodent cardiopulmonary disease models in the context of their potential application to susceptibility studies of air pollutants regardless of whether the models have been previously used for such studies. The pulmonary disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive pulmonary disease, interstitial fibrosis, and infection. The models of systemic hypertension and congestive heart failure include: those derived by genetics (spontaneously hypertensive, Dahl S. renin transgenic, and other rodent models); congestive heart failure models derived by surgical manipulations; viral myocarditis; and cardiomyopathy induced by adriamycin. The characteristic pathogenic features critical to understanding the susceptibility to inhaled toxicants are described. It is anticipated that this review will provide a ready reference for the selection of appropriate rodent models of cardiopulmonary diseases and identify not only their pathobiologic similarities and/or differences to humans but also their potential usefulness in susceptibility studies. Images Figure 2 PMID:9539009

  4. Various MRS application tools for Alzheimer disease and mild cognitive impairment.

    PubMed

    Gao, F; Barker, P B

    2014-06-01

    MR spectroscopy is a noninvasive technique that allows the detection of several naturally occurring compounds (metabolites) from well-defined regions of interest within the human brain. Alzheimer disease, a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. During the past 20 years, multiple studies have been performed on MR spectroscopy in patients with both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy studies have found decreased N-acetylaspartate and increased myo-inositol in both patients with mild cognitive impairment and Alzheimer disease, with greater changes in Alzheimer disease than in mild cognitive impairment. This review summarizes the information content of proton brain MR spectroscopy and its related technical aspects, as well as applications of MR spectroscopy to mild cognitive impairment and Alzheimer disease. While MR spectroscopy may have some value in the differential diagnosis of dementias and assessing prognosis, more likely its role in the near future will be predominantly as a tool for monitoring disease response or progression in treatment trials. More work is needed to evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its relationship to other imaging modalities.

  5. Logarithmic superconformal minimal models

    NASA Astrophysics Data System (ADS)

    Pearce, Paul A.; Rasmussen, Jørgen; Tartaglia, Elena

    2014-05-01

    The higher fusion level logarithmic minimal models {\\cal LM}(P,P';n) have recently been constructed as the diagonal GKO cosets {(A_1^{(1)})_k\\oplus (A_1^ {(1)})_n}/ {(A_1^{(1)})_{k+n}} where n ≥ 1 is an integer fusion level and k = nP/(P‧- P) - 2 is a fractional level. For n = 1, these are the well-studied logarithmic minimal models {\\cal LM}(P,P')\\equiv {\\cal LM}(P,P';1). For n ≥ 2, we argue that these critical theories are realized on the lattice by n × n fusion of the n = 1 models. We study the critical fused lattice models {\\cal LM}(p,p')_{n\\times n} within a lattice approach and focus our study on the n = 2 models. We call these logarithmic superconformal minimal models {\\cal LSM}(p,p')\\equiv {\\cal LM}(P,P';2) where P = |2p - p‧|, P‧ = p‧ and p, p‧ are coprime. These models share the central charges c=c^{P,P';2}=\\frac {3}{2}\\big (1-{2(P'-P)^2}/{P P'}\\big ) of the rational superconformal minimal models {\\cal SM}(P,P'). Lattice realizations of these theories are constructed by fusing 2 × 2 blocks of the elementary face operators of the n = 1 logarithmic minimal models {\\cal LM}(p,p'). Algebraically, this entails the fused planar Temperley-Lieb algebra which is a spin-1 Birman-Murakami-Wenzl tangle algebra with loop fugacity β2 = [x]3 = x2 + 1 + x-2 and twist ω = x4 where x = eiλ and λ = (p‧- p)π/p‧. The first two members of this n = 2 series are superconformal dense polymers {\\cal LSM}(2,3) with c=-\\frac {5}{2}, β2 = 0 and superconformal percolation {\\cal LSM}(3,4) with c = 0, β2 = 1. We calculate the bulk and boundary free energies analytically. By numerically studying finite-size conformal spectra on the strip with appropriate boundary conditions, we argue that, in the continuum scaling limit, these lattice models are associated with the logarithmic superconformal models {\\cal LM}(P,P';2). For system size N, we propose finitized Kac character formulae of the form q^{-{c^{P,P';2}}/{24}+\\Delta ^{P,P';2} _{r

  6. Esophageal surgery in minimally invasive era

    PubMed Central

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-01

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  7. The clinical impact of IKZF1 deletions in paediatric B-cell precursor acute lymphoblastic leukaemia is independent of minimal residual disease stratification in Nordic Society for Paediatric Haematology and Oncology treatment protocols used between 1992 and 2013.

    PubMed

    Olsson, Linda; Ivanov Öfverholm, Ingegerd; Norén-Nyström, Ulrika; Zachariadis, Vasilios; Nordlund, Jessica; Sjögren, Helene; Golovleva, Irina; Nordgren, Ann; Paulsson, Kajsa; Heyman, Mats; Barbany, Gisela; Johansson, Bertil

    2015-09-01

    Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (∆IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether ∆IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N = 218) or multiplex ligation-dependent probe amplification (N = 116) analyses. ∆IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P < 0·001) and overall survival (pOS; 73% vs. 89%; P = 0·001). Adjusting for known risk factors, including white blood cell (WBC) count and MRD, ∆IKZF1 was the strongest independent factor for relapse and death. ∆IKZF1 was present in 27% of cases with non-informative cytogenetics ('BCP-other') and a poor 10-year pOS was particularly pronounced in this group (58% vs. 90%; P < 0·001). Importantly, neither MRD nor WBC count predicted events in the ∆IKZF1-positive cases. Co-occurrence of pseudoautosomal region 1 (PAR1) deletions in Xp22.33/Yp11.32 (P2RY8-CRLF2) and ∆IKZF1 increased the risk of relapse (75% vs. 30% for cases with only ∆IKZF1; P = 0·045), indicating that BCP-other ALL with both P2RY8-CRLF2 and ∆IKZF1 constitutes a particularly high-risk group.

  8. Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients.

    PubMed

    Malagola, Michele; Skert, Cristina; Borlenghi, Erika; Chiarini, Marco; Cattaneo, Chiara; Morello, Enrico; Cancelli, Valeria; Cattina, Federica; Cerqui, Elisa; Pagani, Chiara; Passi, Angela; Ribolla, Rossella; Bernardi, Simona; Giustini, Viviana; Lamorgese, Cinzia; Ruggeri, Giuseppina; Imberti, Luisa; Caimi, Luigi; Russo, Domenico; Rossi, Giuseppe

    2016-02-01

    Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB-WT1 ≥ 16/10(4) ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q-PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk-adapted, postinduction therapy of AML.

  9. Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications

    PubMed Central

    Samir, Mohamed; Pessler, Frank

    2016-01-01

    MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic. PMID:27092305

  10. Land application of mine water causes minimal uranium loss offsite in the wet-dry tropics: Ranger Uranium Mine, Northern Territory, Australia.

    PubMed

    Mumtaz, Saqib; Streten, Claire; Parry, David L; McGuinness, Keith A; Lu, Ping; Gibb, Karen S

    2015-11-01

    Ranger Uranium Mine (RUM) is situated in the wet-dry tropics of Northern Australia. Land application (irrigation) of stockpile (ore and waste) runoff water to natural woodland on the mine lease is a key part of water management at the mine. Consequently, the soil in these Land Application Areas (LAAs) presents a range of uranium (U) and other metals concentrations. Knowledge of seasonal and temporal changes in soil U and physicochemical parameters at RUM LAAs is important to develop suitable management and rehabilitation strategies. Therefore, soil samples were collected from low, medium, high and very high U sites at RUM LAAs for two consecutive years and the effect of time and season on soil physicochemical parameters particularly U and other major solutes applied in irrigation water was measured. Concentrations of some of the solutes applied in the irrigation water such as sulphur (S), iron (Fe) and calcium (Ca) showed significant seasonal and temporal changes. Soil S, Fe and Ca concentration decreased