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Sample records for relapsing favorable histology

  1. Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable Histology Wilms Tumors

    PubMed Central

    Walz, Amy L.; Ooms, Ariadne; Gadd, Samantha; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jamie M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Bowlby, Reanne; Brooks, Denise; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Schein, Jacqueline; Marra, Marco A.; Huff, Vicki; Dome, Jeffrey S.; Chi, Yueh-Yun; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Jafari, Nadereh; Ross, Nicole; Gastier-Foster, Julie M.; Perlman, Elizabeth J.

    2016-01-01

    SUMMARY We report the most common single nucleotide substitution/deletion mutations in Favorable Histology Wilms Tumors (FHWT) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPG) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG-mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death. PMID:25670082

  2. Considerations in the Diagnosis and Management of Pediatric Patients With Favorable Histology Wilms Tumor Who Present With Only Pulmonary Nodules.

    PubMed

    Green, Daniel M

    2016-04-01

    More than 70% of children with stage IV, favorable histology (FH) Wilms tumor will be relapse-free survivors 16 years after diagnosis. Successful treatment generally includes whole lung radiation therapy and doxorubicin. Such therapy is associated with adverse, long-term effects, including impaired pulmonary function, congestive heart failure, and second malignant neoplasms, especially breast cancer. Cooperative groups have adopted a risk-based approach to the treatment of these patients. It is important to recall the good overall prognosis for this group before recommendations for intensification are made based on preliminary data and in the absence of histological confirmation of persistent malignant disease.

  3. From cytology to histology: diagnosis of a relapsed mediastinal lymphoma by endobronchial ultrasound transbronchial histological needle

    PubMed Central

    Ariza-Prota, Miguel Angel; Bango Álvarez, Antonio; Pérez, Liliana; Pando-Sandoval, Ana; Fuentes, Nelson; Casan, Pere

    2015-01-01

    Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is highly accurate in diagnosing mediastinal lymphadenopathies of lung cancer and benign disorders, with the advantage that it is a minimally invasive technique, unlike open surgery and mediastinoscopy. However, the diagnostic accuracy of EBUS-TBNA for the diagnosis of lymphoma in patients with mediastinal lymphadenopathy is not well defined. The lack of tissue architecture obtained by cytological needles decreases the diagnostic accuracy for diagnosis and subtyping of de novo and relapsed mediastinal lymphomas. We present the first described case in the literature of an anaplastic large cell lymphoma relapsed, diagnosed on tissue fragments obtained by EBUS-TBNA with the particularity of using a histological needle. PMID:26090115

  4. Secondary Hemophagocytic Lymphohistiocytosis in a Patient With Favorable Histology Wilms Tumor.

    PubMed

    Murphy, Erin P; Mo, Jun; Yoon, Janet M

    2015-11-01

    Secondary hemophagocytic lymphohistiocytosis (HLH) is most commonly associated with malignancy, infection, or an underlying autoimmune disorder. Malignancy-associated hemophagocytic syndrome is responsible for most secondary HLH cases, but it has not been well described in children. We present a case of a 4-year-old female with favorable histology of Wilms tumor who developed secondary HLH after unsuccessful resection of the tumor and initiation of chemotherapy.

  5. The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation

    SciTech Connect

    Hoppe, R.T.; Kushlan, P.; Kaplan, H.S.; Rosenberg, S.A.; Brown, B.W.

    1981-09-01

    Between 1975 and 1978, 51 patients with favorable histology non-Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed.

  6. Intraoperative Spillage of Favorable Histology Wilms Tumor Cells: Influence of Irradiation and Chemotherapy Regimens on Abdominal Recurrence. A Report From the National Wilms Tumor Study Group

    SciTech Connect

    Kalapurakal, John A.; Li, Sierra M.; Breslow, Norman E.; Beckwith, J. Bruce; Ritchey, Michael L.; Shamberger, Robert C.; Haase, Gerald M.; Thomas, Patrick R.M.; Grundy, Paul; Green, Daniel M.; D'Angio, Giulio J.

    2010-01-15

    Purpose: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients. Methods and Materials: The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flank and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses. Results: The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). Conclusions: Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.

  7. Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission.

    PubMed

    Calafat, Margalida; Lobatón, Triana; Hernández-Gallego, Alba; Mañosa, Míriam; Torres, Paola; Cañete, Fiorella; Cabré, Eduard; Ojanguren, Isabel; Domènech, Eugeni

    2017-09-08

    It has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission. Patients with left-sided or extensive UC in clinical and endoscopic remission (Mayo endoscopic subscore ≤1) undergoing colonoscopy for dysplasia surveillance with random colonic biopsies between 2005-2015 were included. Basal plasmacytosis, acute (AHA), and the chronic (CHA) histological inflammatory activity of all biopsy sets were evaluated. One hundred and thirteen patients were included. Median time in clinical remission at inclusion was 27 months (IQR 15-56). Eight percent of patients relapsed within the first year and 33% during the whole follow-up period. In the univariate analysis, the presence of AHA, alone (P=0.048) or together with a past flare within the previous 12 months (P=0.01), was associated with CR within the first year of follow-up. In the multivariate analysis, AHA, together with a flare within the previous 12 months, remained the only risk factor for relapse (RR=7.5; IC95%; 1.8-29.9; P=0.005). In UC patients in clinical and endoscopic remission, the presence of AHA is a risk factor for clinical relapse. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors | Office of Cancer Genomics

    Cancer.gov

    We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations.

  9. Outcomes of Children With Favorable Histology Wilms Tumor and Peritoneal Implants Treated in National Wilms Tumor Studies-4 and -5

    SciTech Connect

    Kalapurakal, John A.; Green, Daniel M.; Haase, Gerald; Anderson, James R.; Dome, Jeffrey S.; Grundy, Paul E.

    2010-06-01

    Purpose: There are no published reports on the optimal management and survival rates of children with Wilms tumor (WT) and peritoneal implants (PIs). Methods and Materials: Among favorable histology WT patients enrolled in the National Wilms Tumor Study (NWTS)-4 and NWTS-5, 57 children had PIs at the time of nephrectomy. The median age was 3 years 5 months (range, 3 months to 14 years). The majority of children (42 of 57 [74%)] had Stage III tumors; 15 had Stage IV disease. All patients received multimodality therapy. Of 56 children who underwent primary surgery, 48 (84%) had gross total resection of all tumors. All patients received 3-drug chemotherapy with vincristine, dactinomycin, and doxorubicin. Whole-abdomen radiotherapy (RT) was used in 47 patients (82%), and in 50 patients (88%) the RT dose was 10.5 Gy. Results: After a median follow-up of 7.5 years, the overall abdominal and systemic tumor control rates were 97% and 93%, respectively. A comparative analysis between children with PIs and those without PIs showed no significant differences in the clinical characteristics between the two groups. The 5-year event-free survival rates with and without PIs were 90% (95% confidence interval, 78-96%) and 83% (95% confidence interval, 81-85%) respectively (p = 0.20). Conclusions: Multimodality therapy with surgery, whole-abdomen RT, and three-drug chemotherapy delivered according to the NWTS-4 and -5 protocols resulted in excellent abdominal and systemic tumor control rates. All children should be monitored in long-term surveillance programs for the early detection and management of therapy-related toxicities.

  10. Salvage high-dose-rate brachytherapy for histologically confirmed macroscopic local relapsed prostate cancer after radical prostatectomy

    PubMed Central

    Buchser, David; Melcon, J. Ignacio Rodriguez; Casquero, Francisco; Llarena, Roberto; Cacicedo, Jon; Bilbao, Pedro

    2016-01-01

    Purpose To evaluate the feasibility of the use of real-time magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion guided high-dose-rate brachytherapy (HDR-BT) +/– external beam radiation therapy (EBRT) in patients with histologically-proven local relapse after radical prostatectomy. Material and methods We retrospectively reviewed 13 patients treated with real-time MRI-TRUS fusion HDR-BT for a local relapse of prostate cancer after radical surgery. All patients underwent multiparametric magnetic resonance imaging (mpMRI) to confirm the presence of macroscopic lesions in prostate bed, and choline positron emission tomography/computed tomography (PET/CT) to rule out nodal or distant metastases. Local failure was confirmed by transrectal biopsy. Patients without previous EBRT received 1 fraction of 15 Gy with HDR-BT plus hypofractionated EBRT (37.5 Gy in 15 fractions). Two patients received 2 fractions of 12 Gy with HDR-BT without EBRT. Follow-up visits were at 1, 3, 6 months, and every 6 months thereafter. Results After a median follow-up of 7 months, all patients showed an appropriate biochemical response. Median prostate-specific antigen (PSA) levels before treatment, 1 month, and 6 months after HDR-BT were 2.62 ng/ml (range: 1.55-9.61), 0.97 ng/ml (range: 0.12-3.14), 0.23 ng/ml (range: 0.1-0.74), respectively. Five patients (42%) experienced acute grade 1 GU toxicity and 1 patient (8%) suffered from grade 2 GU toxicity. Regarding gastrointestinal (GI) toxicity, 5 patients referred grade 1 acute toxicity and 1 grade 2 (proctitis). No late toxicity has been observed so far. Conclusions MRI-TRUS fusion guided salvage HDR-BT +/– EBRT is a feasible procedure for patients with local macroscopic relapse in tumor bed after radical prostatectomy. Exquisite selection of patients through mpMRI and choline PET/CT is crucial to avoid overtreatment. A larger number of patients and longer follow-up are required in order to draw more solid conclusions

  11. TARGET Researchers Identify Mutations in SIX1/2 and microRNA Processing Genes in Favorable Histology Wilms Tumor | Office of Cancer Genomics

    Cancer.gov

    TARGET researchers molecularly characterized favorable histology Wilms tumor (FHWT), a pediatric renal cancer. Comprehensive genome and transcript analyses revealed single-nucleotide substitution/deletion mutations in microRNA processing genes (15% of FHWT patients) and Sine Oculis Homeobox Homolog 1/2 (SIX1/2) genes (7% of FHWT patients). SIX1/2 genes play a critical role in renal development and were not previously associated with FHWT, thus presenting a novel role for SIX1/2 pathway aberrations in this disease.

  12. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    SciTech Connect

    Breslow, Norman E. . E-mail: norm@u.washington.edu; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-05-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes.

  13. Correlation of pre-operative CT findings with surgical & histological tumor dissemination patterns at cytoreduction for primary advanced and relapsed epithelial ovarian cancer: A retrospective evaluation.

    PubMed

    Nasser, S; Lazaridis, A; Evangelou, M; Jones, B; Nixon, K; Kyrgiou, M; Gabra, H; Rockall, A; Fotopoulou, C

    2016-11-01

    Computed tomography (CT) is an essential part of preoperative planning prior to cytoreductive surgery for primary and relapsed epithelial ovarian cancer (EOC). Our aim is to correlate pre-operative CT results with intraoperative surgical and histopathological findings at debulking surgery. We performed a systematic comparison of intraoperative tumor dissemination patterns and surgical resections with preoperative CT assessments of infiltrative disease at key resection sites, in women who underwent multivisceral debulking surgery due to EOC between January 2013 and December 2014 at a tertiary referral center. The key sites were defined as follows: diaphragmatic involvement(DI), splenic disease (SI), large (LBI) and small (SBI) bowel involvement, rectal involvement (RI), porta hepatis involvement (PHI), mesenteric disease (MI) and lymph node involvement (LNI). A total of 155 patients, mostly with FIGO stage IIIC disease (65%) were evaluated (primary=105, relapsed=50). Total macroscopic cytoreduction rates were: 89%. Pre-operative CT findings displayed high specificity across all tumor sites apart from the retroperitoneal lymph node status, with a specificity of 65%. The ability however of the CT to accurately identify sites affected by invasive disease was relatively low with the following sensitivities as relating to final histology: 32% (DI), 26% (SI), 46% (LBI), 44% (SBI), 39% (RI), 57% (PHI), 31% (MI), 63% (LNI). Pre-operative CT imaging shows high specificity but low sensitivity in detecting tumor involvement at key sites in ovarian cancer surgery. CT findings alone should not be used for surgical decision making. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  14. Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.

    PubMed

    Mangiacavalli, Silvia; Pochintesta, Lara; Pascutto, Cristiana; Cocito, Federica; Pompa, Alessandra; Cazzola, Mario; Corso, Alessandro

    2013-02-01

    Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase.

  15. Relapse and relapse prevention.

    PubMed

    Brandon, Thomas H; Vidrine, Jennifer Irvin; Litvin, Erika B

    2007-01-01

    Most psychological disorders and problem behaviors are characterized by very high rates of postremittance relapse. Thus, advances in the long-term efficacy of psychological interventions require understanding the causes and processes of relapse, with the ultimate goal of developing strategies that reduce the probability of relapse. Existing psychological theory and interventions relevant to relapse and relapse prevention (RP) are reviewed, with a focus on addictive behaviors. The past two decades have produced increased attention toward the relapse problem and important advances in the conceptualization of relapse (i.e., as a process rather than a discrete event). Further progress will require the translation of basic theory into applied theory, the development of integrative theories of relapse, and the design and testing of theory-based, multimodal RP interventions.

  16. The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen.

    PubMed

    Urbano-Ispizua, Alvaro; Pavletic, Steven Z; Flowers, Mary E; Klein, John P; Zhang, Mei-Jie; Carreras, Jeanette; Montoto, Silvia; Perales, Miguel-Angel; Aljurf, Mahmoud D; Akpek, Görgün; Bredeson, Christopher N; Costa, Luciano J; Dandoy, Christopher; Freytes, César O; Fung, Henry C; Gale, Robert Peter; Gibson, John; Hamadani, Mehdi; Hayashi, Robert J; Inamoto, Yoshihiro; Inwards, David J; Lazarus, Hillard M; Maloney, David G; Martino, Rodrigo; Munker, Reinhold; Nishihori, Taiga; Olsson, Richard F; Rizzieri, David A; Reshef, Ran; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Smith, Sonali M; Socié, Gérard; Wirk, Baldeep; Yu, Lolie C; Saber, Wael

    2015-10-01

    The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.

  17. THE IMPACT OF GRAFT VERSUS HOST DISEASE ON RELAPSE RATE IN PATIENTS WITH LYMPHOMA DEPENDS ON THE HISTOLOGICAL SUB-TYPE AND THE INTENSITY OF THE CONDITIONING REGIMEN

    PubMed Central

    Urbano-Ispizua, Alvaro; Pavletic, Steven Z.; Flowers, Mary E.; Klein, John P.; Zhang, Mei-Jie; Carreras, Jeanette; Montoto, Silvia; Perales, Miguel-Angel; Aljurf, Mahmoud D.; Akpek, Görgün; Bredeson, Christopher N.; Costa, Luciano J.; Dandoy, Christopher; Freytes, César O.; Fung, Henry C.; Gale, Robert Peter; Gibson, John; Hamadani, Mehdi; Hayashi, Robert J.; Inamoto, Yoshihiro; Inwards, David J.; Lazarus, Hillard M.; Maloney, David G.; Martino, Rodrigo; Munker, Reinhold; Nishihori, Taiga; Olsson, Richard F.; Rizzieri, David A.; Reshef, Ran; Saad, Ayman; Savani, Bipin N.; Schouten, Harry C.; Smith, Sonali M.; Socié, Gérard; Wirk, Baldeep; Yu, Lolie C.; Saber, Wael

    2015-01-01

    Purpose To analyze the impact of graft versus host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Patients and Methods Adult patients with a diagnosis of Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL), or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor HCT between 1997 and 2009 were included. Results Two thousand six hundred and eleven cases were included. Reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplants. In a multivariate analysis of myeloablative cases (n=970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n=1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (RR 0.51, p=0.049) and in MCL (RR 0.41, p=0.019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR 0.14, p=0.007; and RR 0.15, p=0.0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment related mortality (TRM) and overall survival (OS) in FL cases, and did not impact TRM, OS or PFS in MCL. Conclusion This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in follicular and mantle cell lymphoma patients. PMID:25981509

  18. Patterns of intra-abdominal relapse (IAR) in patients with Wilms' tumor who received radiation: analysis by histopathology. A report of National Wilms' tumor studies 1 and 2 (NWTS-1 and 2)

    SciTech Connect

    Tefft, M.; D'Angio, G.J.; Beckwith, B.; Farewell, V.; Meyer, J.A.

    1980-06-01

    336 non-metastatic patients who received radiation in national Wilms' Tumor Study-1 and 2 have been reviewed. Follow-up was minimum of two years. 15/273 (6%) of the favorable history patients had intra-abdominal relapse as compared to 8/44 unfavorable histology (18%) (P = 0.003). Developing intra-abdominal relapse does not seem related to low radiation therapy doses or small volumes. However, a delay of greater than ten days to start radiation therapy from nephrectomy was related to the occurrence of intra-abdominal relapse in unfavorable histology patients (P < 0.001).

  19. Extinction, relapse, and behavioral momentum.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2010-05-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior.

  20. Extinction, Relapse, and Behavioral Momentum

    PubMed Central

    Podlesnik, Christopher A.; Shahan, Timothy A.

    2010-01-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral-momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior. PMID:20152889

  1. Menstrual phase effects on smoking relapse

    PubMed Central

    Allen, Sharon S.; Bade, Tracy; Center, Bruce; Finstad, Deborah; Hatsukami, Dorothy

    2015-01-01

    Aims To examine if menstrual phase affects relapse in women attempting to quit smoking. Design An intent-to-treat randomized smoking cessation trial where women were assigned to quit smoking in either the follicular (F) or luteal (L) menstrual phase and were followed for up to 26 weeks. They were assessed for relapse by days to relapse and relapse phase to determine if those who begin a quit attempt during the F phase were more successful than those who begin during the L phase. Setting Tobacco Use Research Center, University of Minnesota, Minneapolis, Minnesota. Participants A total of 202 women. Measurements Latency to relapse from continuous and prolonged abstinence, point prevalence, phase of relapse, first slip within the first 3 and 5 days post-quit date, subject completion rates and symptomatology (i.e. withdrawal and craving). Findings The mean days to relapse from continuous abstinence and relapse from prolonged abstinence for the F group were 13.9 and 20.6 days, respectively, and 21.5 and 39.2 days, respectively, for the L group. Using point prevalence analysis at 14 days, 84% of the F group had relapsed compared with 65% of the L group [χ2 = 10.024, P = 0.002; odds ratio (OR) = 2.871, 95% confidence interval (CI), 1.474– 5.590]. At 30 days, 86% of the F group relapsed, compared with 66% of the L group (χ2 = 11.076, P = 0.001; OR = 3.178, 95% CI, 1.594–6.334). Conclusion Women attempting to quit smoking in the F phase had less favorable outcomes than those attempting to quit in the L phase. This could relate to ovarian hormones, which may play a role in smoking cessation for women. PMID:18412759

  2. ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

    PubMed Central

    Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.

    2016-01-01

    Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575

  3. Phase II Study of Sunitinib Malate, a Multi-Targeted Tyrosine Kinase Inhibitor in Patients with Relapsed or Refractory Soft Tissue Sarcomas. Focus on 3 Prevalent Histologies: Leiomyosarcoma, Liposarcoma, and Malignant Fibrous Histiocytoma

    PubMed Central

    Mahmood, S. Tariq; Agresta, Samuel; Vigil, Carlos; Zhao, Xiuhua; Han, Gang; D’Amato, Gina; Calitri, Ciara E.; Dean, Michelle; Garrett, Christopher; Schell, Michael J.; Antonia, Scott; Chiappori, Alberto

    2013-01-01

    SUMMARY Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate-refractory gastrointestinal stromal tumors). This single-institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma, and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty-eight patients were enrolled, and 35% were heavily pretreated (≥2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression-free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1, and 2.5 and 13.6 months, respectively. The 3-month progression-free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma, and MFH were 75% and 69.2%, 60%, and 62.5%, and and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low-grade disease could have been included and the small numbers, a 3-month progression-free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted. PMID:21154746

  4. Risk of Ovarian Cancer Relapse Score

    PubMed Central

    Rizzuto, Ivana; Stavraka, Chara; Chatterjee, Jayanta; Borley, Jane; Hopkins, Thomas Glass; Gabra, Hani; Ghaem-Maghami, Sadaf; Huson, Les; Blagden, Sarah P.

    2015-01-01

    Objective The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (<0.33), intermediate (0.34–0.67), and high (>0.67) probability of relapse. Conclusions The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support. PMID:25647256

  5. Brain histology.

    PubMed

    Jeans, Alexander; Esiri, Margaret

    2008-10-01

    In this article we summarise nervous system histology in health and disease and acquaint the reader with developments in the staining techniques that are in current use, particularly immunostains. Although clinicians do not need to know the details of stain appearances, some familiarity with these aspects of neuropathology is invaluable in interpreting the reports they receive from the laboratory, as well as reminding them of the amazing beauty of the central nervous system's microscopic structure.

  6. Favor referential representations.

    PubMed

    Frazier, L; McNamara, P

    1995-06-01

    Avrutin and Hickok (1993) argue that agrammatic patients have the ability to represent nonreferential or "government" chains ("who ... e") but not referential or "binding" chains ("which girl ... e"). By contrast, we propose the "referential representation hypothesis," which suggests that agrammatics attempt to cope with their well-known capacity limitations by favoring referential or content-based representations. This predicts that agrammatic patients' performance should degrade noticeably as task demands increase, and referential demands should take priority over computational ones. In a semantic task, referential phrases should lead to better or more accurate performances. In syntactic tasks, the availability of a referential or content-based representation will interfere with the development of a syntactic representation, resulting in worse syntactic performance on the referential phrases than on nonreferential ones. This predicts that agrammatic patients should incorrectly accept (resumptive) pronoun sentences with a referential wh-phrase because the pronouns will find the semantic or discourse referent of the referential wh-phrase and take it as an antecedent for the pronoun. However, they should reject a (resumptive) pronoun in a sentence with the nonreferential question constituent "who" or "what." "Who" and "what" will remain in syntactic form, since they have only grammatical content and therefore will have only a "nonreferential" syntactic representation. Consequently, they cannot serve as the antecedent of the pronoun. These predictions were largely confirmed by the results of a grammaticality judgement study. Agrammatics performed well on questions with pragmatic biases but failed to distinguish reliably between grammatical and ungrammatical questions where pragmatic biases were neutralized. They assigned especially low ratings to object gap sentences with referential wh-constituents, as predicted. They assigned relatively high ratings to

  7. [Relapse: causes and consequences].

    PubMed

    Thomas, P

    2013-09-01

    Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

  8. Relapsing pityriasis rosea.

    PubMed

    Drago, Francesco; Ciccarese, Giulia; Rebora, Alfredo; Parodi, Aurora

    2014-01-01

    To assess the prevalence of relapses of pityriasis rosea (PR), a retrospective cohort study investigated all PR cases diagnosed in Genoa between 2000 and 2013 and followed them up to today. Of 570 cases, 21 (3.7%) relapsed. Most of them had a single episode, but 4 had two episodes and 2 had three episodes. The herald patch was always absent, size and number of the lesions were reduced, and duration was shorter than that of the primary episodes. Constitutional symptoms were present, though less severe than in the primary eruption. Most recurrences occurred within 1 year (16/21, 76.2%). Men outnumbered women and the mean age of the relapsing patients (20.3 years) was higher than that for the primary episode. A pathogenetic hypothesis is provided: since PR is associated with reactivation of human herpesvirus 6/7, a parallelism with other typical reactivating human herpesviruses (varicella zoster virus and Epstein-Barr virus) has been established.

  9. Relapsing fever in Jordan

    PubMed Central

    Babudieri, B.

    1957-01-01

    The author reports on a survey carried out by him in 1954 on relapsing fever in Jordan. In that country the disease is largely tick-borne, the main vector being Ornithodoros tholozani. Some of the frequent cases in the town of Nablus and the village of Marda in West Jordan may, however, be caused by O. coniceps. The centres of infection are some of the numerous caves scattered throughout the hilly areas and certain houses in which chickens are kept. It is believed that the vector ticks could be successfully exterminated by the use of insecticides and by the adoption of certain procedures outlined by the author. Arsenobenzol compounds and penicillin have been shown not to be very effective for the treatment of relapsing fever, but good results have been obtained with Aureomycin and Terramycin. ImagesFIG. 1FIG. 4 PMID:13472437

  10. Lymphoma Heterogeneity: Three Different Histological Pictures and One Unique Clone

    PubMed Central

    Alonso-Alvarez, Sara; Blanco, Óscar; Alcoceba, Miguel; Balanzategui, Ana; Caballero, Juan C.; Dávila, Julio; González, Marcos; Caballero, María D.; Martín, Alejandro; García-Sanz, Ramón

    2016-01-01

    We report a patient who developed up to three different lymphomas with the same clonal IGH rearrangement. She was first diagnosed of splenic zone marginal lymphoma and relapsed for the first time with Hodgkin lymphoma histology and later with diffuse large B-cell lymphoma histology. Subsequent biopsies and analysis of clonally rearranged IGH genes helped to elucidate the clonal relationship between the three histologies and to confirm a common origin from the three tissue histologies. An integrated diagnosis should always be performed in order to achieve the most accurate diagnosis and be able to choose the best therapeutic options for our patients. PMID:27867670

  11. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children’s Research Hospital experience

    PubMed Central

    Leary, Sarah E. S.; Wozniak, Amy W.; Billups, Catherine A.; Wu, Jianrong; McPherson, Valerie; Neel, Michael D.; Rao, Bhaskar N.; Daw, Najat C.

    2013-01-01

    Background Chemotherapy has improved the outcome of patients with newly diagnosed osteosarcoma, but its role in relapsed disease is unclear. Methods We reviewed the records of all patients who were treated for relapsed high-grade osteosarcoma at our institution between 1970 and 2004. Post-relapse event-free survival (PREFS) and post-relapse survival (PRS) were estimated, and outcome comparisons were made using the exact log-rank test. Results The 10-year PREFS and PRS of the 110 patients were 11.8% ± 3.5% and 17.0% ± 4.3%, respectively. Metastasis at initial diagnosis (14%), and relapse in lung only (75%) were not significantly associated with PREFS or PRS. Time from initial diagnosis to first relapse (RL1) ≥18 months (43%), surgery at RL1 (76%), and ability to achieve second complete remission (CR2, 56%) were favorably associated with PREFS and PRS (p≤0.0002). In patients without CR2, chemotherapy at RL1 was favorably associated with PREFS (p=0.01) but not with PRS. In patients with lung relapse only, unilateral relapse and number of nodules (≤3) were associated with better PREFS and PRS (p≤0.0005); no patients with bilateral relapse survived 10 years. The median PREFS after treatment with cisplatin, doxorubicin, methotrexate, and ifosfamide was 3.5 months (95% CI, 2.1-5.2) and median PRS 8.2 months (95% CI, 5.2-15.1). Conclusions Late relapse, surgical resection, and unilateral involvement (in lung relapse only) favorably impact outcome after relapse. Surgery is essential for survival; chemotherapy may slow disease progression in patients without CR2. These data are useful for designing clinical trials that evaluate novel agents. PMID:23625626

  12. Natalizumab for relapsing-remitting multiple sclerosis.

    PubMed

    Horga, A; Tintoré, M

    2011-01-01

    Natalizumab is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier and has been approved for the treatment of relapsing-remitting multiple sclerosis. To provide a review and update of the pharmacological and therapeutic characteristics of natalizumab, with special emphasis on the most recently published data on the efficacy, effectiveness and safety of this drug. Several randomized clinical trials in patients with relapsing forms of multiple sclerosis have demonstrated that natalizumab substantially reduces clinical and radiological disease activity. Post hoc analysis of phase III clinical trials and the results of post-approval observational studies indicate that natalizumab significantly increases the proportion of patients with complete clinical and radiological response and is effective in patients with highly active forms of multiple sclerosis and suboptimal response to other treatments. Like other monoclonal antibodies, natalizumab can cause hypersensitivity reactions, which are severe in 1% of patients. Other adverse effects are generally mild or infrequent. Nevertheless, several cases of progressive multifocal leukoencephalopathy have been detected in patients treated with natalizumab monotherapy. The risk of this severe complication seems to increase with the number of doses administered. Natalizumab has a favorable risk-benefit ratio in the treatment of relapsing -remitting multiple sclerosis. However, because of the potential risk of progressive multifocal leukoencephalopathy, patients must be carefully selected and specific protocols must be followed during the drug's administration. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  13. Relapsing polychondritis with meningoencephalitis.

    PubMed

    Tsai, Monica; Hu, Mengjun; Zussman, Jamie; Worswick, Scott

    2017-01-01

    Relapsing polychondritis (RP) is a rare autoimmune disease of the cartilaginous structures of the body with many systemic manifestations including meningoencephalitis (ME). We present a case of a man with RP-associated ME that was responsive to steroid treatment. An updated literature review of 7 cases of RP-associated ME also is provided. Early diagnosis of this condition may be of benefit to this select population of patients, and further research regarding the prognosis, mechanisms, and treatment of RP may be necessary in the future.

  14. Clinico-histologic conferences: histology and disease.

    PubMed

    Shaw, Phyllis A; Friedman, Erica S

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical context, promote integration and application of science knowledge, and to foster peer teaching and learning: the Clinico-Histologic Conference (CHC) for the Mount Sinai School of Medicine Histology course. Teams of six students were each assigned specific disease processes and were charged with creating oral presentations and handouts that taught their classmates about the clinical manifestations, etiopathogeneses, diagnoses, and treatments of the assigned processes, along with comparisons of normal histology to the pathology of the disease. Each team also created four questions, some of which were used on Histology written examinations. The physician facilitator evaluated the presentation and handouts. About two-thirds of students agreed the CHC enhanced appreciation of the importance of histology, provided a context for integration and application of basic science to patient care and enhanced their ability to teach their peers. Student feedback demonstrated that the CHCs were successful in promoting teamwork, peer teaching, and the application of histology to diagnose diseases. The authors believe that teaching basic science content in this new format enhanced student learning and application of medical knowledge, and that this new teaching format can be adopted by other medical school courses.

  15. Possibilities for Relapsing Fever Reemergence

    PubMed Central

    2006-01-01

    Relapsing fever Borrelia infections have attracted little attention in recent years; however, where endemic, these infections still result in considerable illness and death. Despite the marked antimicrobial drug susceptibility of these organisms, therapy is often delayed through lack of clinical suspicion. With increasing travel, infections may be imported, through exotic relapsing fever infection or through resurgence of infected disease vectors. Although louseborne relapsing fever is now geographically limited, it was once of global importance. The possibility for reemergence was recently highlighted by the probable reemergence of louseborne relapsing fever in homeless persons from France. Host limitations enforced through louseborne transmission are less applicable for the tickborne forms of relapsing fever. Although the latter have reduced potential for epidemic spread, they have the ability to infect diverse hosts, thus establishing reservoirs of infection and presenting greater challenges for their control. PMID:16704771

  16. Clinicopathologic features associated with relapse in cryptogenic organizing pneumonia.

    PubMed

    Nishino, Michiya; Mathai, Susan K; Schoenfeld, David; Digumarthy, Subba R; Kradin, Richard L

    2014-02-01

    Organizing pneumonia (OP) is a histopathologic pattern of response to lung injury. Fibrin is a marker of acute microvascular injury, and variable amounts of intraalveolar fibrin are seen in OP; however, its relevance to clinical outcomes is unclear. We examined lung wedge biopsies of 26 patients with cryptogenic organizing pneumonia (COP), assessed the amount of fibrin associated with airspace organization, and correlated fibrin levels with other histologic, clinical, and radiographic findings. Seven patients with COP had disease relapse. Patients with multifocal fibrin deposits or acute fibrinous and organizing pneumonia (collectively, "high fibrin") showed a higher rate of OP relapse compared to those with no or focal fibrin (60% versus 6%, P < .05). Patients with radiographic evidence of disease involving all three lung zones (upper, middle, and lower) also showed higher rates of relapse compared to those in whom disease was limited to one or two zones (41% versus 0%, P = .055). In patients with both pathologic evidence of high fibrin and radiographic evidence of three-zone disease, OP relapse could be predicted with a sensitivity of 86% and specificity of 84% (positive predictive value of 67% and negative predictive value of 94%). The presence of high levels of intraalveolar fibrin in lung biopsies and radiographic evidence of disease involving all three lung zones is associated with increased risk of relapse in patients with COP, and these features may help identify patients who may benefit from more intensive steroid therapy. © 2014.

  17. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience.

    PubMed

    Leary, Sarah E S; Wozniak, Amy W; Billups, Catherine A; Wu, Jianrong; McPherson, Valerie; Neel, Michael D; Rao, Bhaskar N; Daw, Najat C

    2013-07-15

    Chemotherapy has improved the outcome of patients with newly diagnosed osteosarcoma, but its role in relapsed disease is unclear. We reviewed the records of all patients who were treated for relapsed high-grade osteosarcoma at our institution between 1970 and 2004. Postrelapse event-free survival (PREFS) and postrelapse survival (PRS) were estimated, and outcome comparisons were made using an exact log-rank test. The 10-year PREFS and PRS of the 110 patients were 11.8% ± 3.5% and 17.0% ± 4.3%, respectively. Metastasis at initial diagnosis (14%), and relapse in lung only (75%) were not significantly associated with PREFS or PRS. Time from initial diagnosis to first relapse (RL1) ≥18 months (43%), surgery at RL1 (76%), and ability to achieve second complete remission (CR2, 56%) were favorably associated with PREFS and PRS (P  ≤  0.0002). In patients without CR2, chemotherapy at RL1 was favorably associated with PREFS (P = 0.01) but not with PRS. In patients with lung relapse only, unilateral relapse and number of nodules ( ≤ 3) were associated with better PREFS and PRS (P  ≤  0.0005); no patients with bilateral relapse survived 10 years. The median PREFS after treatment with cisplatin, doxorubicin, methotrexate, and ifosfamide was 3.5 months (95% confidence interval, 2.1-5.2), and the median PRS was 8.2 months (95% confidence interval, 5.2-15.1). Late relapse, surgical resection, and unilateral involvement (in lung relapse only) favorably impact outcome after relapse. Surgery is essential for survival; chemotherapy may slow disease progression in patients without CR2. These data are useful for designing clinical trials that evaluate novel agents. © 2013 American Cancer Society.

  18. Relapsing-Remitting MS (RRMS)

    MedlinePlus Videos and Cool Tools

    ... and Wellness Diet & Nutrition Exercise Emotional Health Smoking Sleep Alcohol Heat & Temperature Sensitivity Travel and Recreation Managing ... well as worsening (a confirmed increase in disability over a specified period of time following a relapse) ...

  19. Active aortitis in relapsing polychondritis

    PubMed Central

    Selim, A; Fulford, L; Mohiaddin, R; Sheppard, M

    2001-01-01

    Relapsing polychondritis (RP) is a rare inflammatory multiorgan disorder affecting cartilaginous structures and other connective tissues. Serious cardiovascular complications have been reported in patients with RP, the most frequent being aortic or mitral regurgitation and aortic aneurysms. Aortitis is a very rare complication. An unusual case of active aortitis in a patient with RP, despite intensive immunosupressive treatment, is described with a special emphasis on the pathological findings. Key Words: relapsing polychondritis • aortitis • aortic regurgitation PMID:11684729

  20. Relapse revisited--again.

    PubMed

    Dyer, Kenneth C; Vaden, James L; Harris, Edward F

    2012-08-01

    Long-term changes in the dentitions of orthodontic patients have been studied. However, most studies in the literature report findings after only a few years posttreatment. In this study, we examined records an average of 24 years after active treatment. The purpose was to answer 2 questions: (1) does irregularity increase with time after treatment, and (2) how much relapse can be expected if a conservatively treated sample is recalled 2.5 decades after active treatment? The sample consisted of dental casts of 52 women who were treated in the mid-1970s to the early 1980s with 0.022 × 0.028-in standard edgewise appliances. Each was given a maxillary Hawley retainer and either a mandibular Hawley or a banded canine-to-canine retainer at debanding. Retention lasted 24 to 32 months. The same practitioner treated all the patients. The sample is one of convenience; specifically, inclusion depended only on each patient's willingness to return for a recall examination. Records were collected at 3 examinations for each patient: start of treatment, end of the active phase of treatment, and long-term retention recall. The long-term maxillary and mandibular casts were measured and occluded in maximum intercuspation. Variables were measured, including incisor overjet and overbite, buccal segment relationship of the first molars and canines, and incisor irregularity in each arch. Variables were measured on the casts with digital readout sliding calipers precise to 0.001 mm. Mandibular incisor irregularity at recall was less than 3.5 mm in 77% of the patients examined. Correction of the maxillary incisor irregularity remained relatively stable over the time interval studied. Buccal segment Class II correction remained stable at the recall examination. Orthodontic treatment can yield reasonably good long-term stability in both occlusal correction and tooth alignment. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  1. Use of a Relapse Monitoring Board

    PubMed Central

    MacFadden, Wayne; Anand, Ravi; Khanna, Sumant; Rapaport, Mark H.; Haskins, J. Thomas; Turkoz, Ibrahim; Alphs, Larry

    2011-01-01

    Objective: Independent review boards can provide an objective appraisal of investigators' decisions and may be useful for determining complex primary outcomes, such as bipolar disorder relapse, in crossnational studies. This article describes the use of an independent, blinded relapse monitoring board to assess the primary outcome (relapse) in an international clinical trial of risperidone long-acting therapy adjunctive to standard-care pharmacotherapy for patients with bipolar disorder. Design: The fully autonomous relapse monitoring board was composed of a chair and two additional members—all psychiatrists and experts in the diagnostic, clinical, and therapeutic management of bipolar disorder. The relapse monitoring board met six times during the study to review patient relapse data and was charged with the responsibility of determining if the events described by investigators qualified as relapses. Additionally, the relapse monitoring board reviewed data for all randomized patients to identify any relapse events not recognized by investigators. Results: Primary efficacy results were similar and significant for investigator- and relapse monitoring board-determined relapses. Ten discrepancies were noted: two of the 42 investigator-determined relapses did not meet the intended clinical relapse threshold as determined by the relapse monitoring board; conversely, the relapse monitoring board confirmed eight relapse events not identified by investigators. The relapse monitoring board had no direct interactions with patients and had to rely on the accuracy of investigator assessments. Also, once an investigator determined a relapse and the patients discontinued the study, less information was available to the relapse monitoring board for relapse assessment. Conclusions: Use of the relapse monitoring board supported the validity of the study by incorporating a level of standardization to mitigate the risk that local practice in different cultures and medical systems

  2. Clinico-Histologic Conferences: Histology and Disease

    ERIC Educational Resources Information Center

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

  3. Clinico-Histologic Conferences: Histology and Disease

    ERIC Educational Resources Information Center

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

    Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

  4. Novel therapies for relapsed myeloma.

    PubMed

    Stewart, A Keith

    2009-01-01

    Treatment of myeloma relapse needs to be individualized to reflect the effectiveness and toxicities of prior therapies, with consideration given to pragmatic issues such as the tempo of relapse, age of the patient, access to drugs and patient preference. In general, combination therapies have been associated with higher response rates and improved progression-free survival and may be preferable when a rapid response is required. Nevertheless, in a slower-tempo relapse it is unclear at this juncture whether sequencing of drugs or multi-agent combinations offer superior overall survival results. Fortunately, active novel agents that offer further possibilities for some myeloma patients have become available in clinical trials. In this review we will describe the various classes of novel drugs being tested and the pros and cons of preclinical testing, and will particularly focus on two agents with single-agent activity in myeloma: carfilzomib, a proteasome inhibitor, and pomalidomide, a member of the immunomodulatory class of drugs.

  5. Relapsing Fever Borreliae in Africa

    PubMed Central

    Elbir, Haitham; Raoult, Didier; Drancourt, Michel

    2013-01-01

    The study of relapsing fever borreliae in Africa has long suffered from the use of non-specific laboratory tools for the direct detection of these spirochetes in clinical and vector specimens. Accordingly, Borrelia hispanica, Borrelia crocidurae, Borrelia duttonii, and Borrelia recurrentis have traditionally been distinguished on the basis of geography and vector and the unproven hypothesis that each species was exclusive to one vector. The recent sequencing of three relapsing fever Borrelia genomes in our laboratory prompted the development of more specific tools and a reappraisal of the epidemiology in Africa. Five additional potential species still need to be cultured from clinical and vector sources in East Africa to further assess their uniqueness. Here, we review the molecular evidence of relapsing fever borreliae in hosts and ectoparasites in Africa and explore the diversity, geographical distribution, and vector association of these pathogens for Africans and travelers to Africa. PMID:23926141

  6. Relapsed Hodgkin Lymphoma: Management Strategies

    PubMed Central

    Montanari, Francesca; Diefenbach, Catherine

    2016-01-01

    Although Hodgkin lymphoma (HL) is largely curable with first-line therapy, approximately one-third of patients will not have a complete response to frontline treatment or will subsequently relapse. Only 50 % of these patients will be effectively salvaged with conventional therapies. The prognosis is particularly poor for those patients with chemotherapy refractory disease, who are unable to obtain even transient disease control, and for patients who relapse following high dose chemotherapy and autologous stem cell transplant. In this review, we summarize the most recent updates on the management of patients with relapsed HL, the role of novel therapies such as brentuximab vedotin, and an overview of promising new agents currently under investigation. We also discuss the role of consolidation strategies such as high-dose chemotherapy and autologous stem cell transplant, and reduced-intensity allogeneic hematopoietic stem cell transplant, and the need for new strategies in the elderly patient population. PMID:24942298

  7. Interactive Atlas of Histology

    PubMed Central

    Goubran, Emile Z.; Vinjamury, Sivarama P.

    2007-01-01

    Purpose: An interactive atlas of histology was developed for online use by chiropractic students to enable them to practice and self-assess their ability to identify various histological structures. This article discusses the steps in the development, implementation, and usefulness of an interactive atlas of histology for students who take histology examinations. Methods: The atlas was developed by digitizing images imported through a video-microscope using actual microscope slides. Leica EWS 2100 and PowerPoint software were used to construct the atlas. The usefulness of the atlas was assessed through a comparison of histology exam scores between four classes before and four classes after the use of the atlas. Analysis of admissions data, including overall grade point average (GPA), science and nonscience GPA, and a number of course units, was done initially to avoid any identifiable differences in the academic competency between the two being compared. A survey of the students was also done to assess atlas usefulness and students' satisfaction with the atlas. Results: Analysis of histology exam scores showed that the average scores in the lab exam were significantly higher for the classes that used the atlas. Survey results showed a high level of student satisfaction with the atlas. Conclusion: The development and use of an online interactive atlas of histology for chiropractic students helped to improve lab exams scores. In addition, students were satisfied with the features and usefulness of this atlas. PMID:18483638

  8. Modeling relapse in infectious diseases.

    PubMed

    van den Driessche, P; Zou, Xingfu

    2007-05-01

    An integro-differential equation is proposed to model a general relapse phenomenon in infectious diseases including herpes. The basic reproduction number R(0) for the model is identified and the threshold property of R(0) established. For the case of a constant relapse period (giving a delay differential equation), this is achieved by conducting a linear stability analysis of the model, and employing the Lyapunov-Razumikhin technique and monotone dynamical systems theory for global results. Numerical simulations, with parameters relevant for herpes, are presented to complement the theoretical results, and no evidence of sustained oscillatory solutions is found.

  9. Early relapse after rituximab chemoimmunotherapy.

    PubMed

    Kiss, Flora; Buslig, Julia; Szegedi, Istvan; Scholtz, Beata; Kappelmayer, Janos; Kiss, Csongor

    2008-02-01

    In relapsed/refractory childhood acute lymphoblastic leukemia (ALL) of the B-cell lineage rituximab, a monoclonal anti-CD20 antibody was used successfully in some cases. We report on a 15-year-old female with relapsed CD20-positive B-cell progenitor ALL treated with rituximab because of positive minimal residual disease signals after chemotherapy, as checked by flow cytometry and real time quantitative-PCR. Rituximab eliminated the CD20-positive subpopulation, but not the more immature leukemic cells. The patient died with fulminant aspergillosis before hematopoietic stem cell transplantation could be performed.

  10. Breast cancer in women using digoxin: tumor characteristics and relapse risk

    PubMed Central

    2013-01-01

    Introduction Digoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer. Methods Incident breast cancer cases in Danish women (n = 49,312; 1995 to 2008) were identified. Analyses were conducted in women 20 to 74 years old. Relapse hazard ratios (HR) were compared in women using and not using digoxin, adjusting for age, calendar period, protocol, tumor size, nodal involvement, histology grade, estrogen-receptor (ER) status, and anti-estrogen therapy in Cox regression models. Results At diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person-years); 24 relapses occurred in women later starting digoxin (384 person-years). Overall relapse risk HR in digoxin users was 1.13 (95% confidence interval: 0.88, 1.46) compared to non-users. Relapse risk in digoxin users was significantly increased in the first year (2.19; 1.26, 3.78) but not thereafter (0.99; 0.74, 1.32) (P = 0.02 for difference in HRs). First-year relapse hazard was high in digoxin-using women with ER+ tumors (2.51; 1.39, 4.55) but not ER- tumors (0.72; 0.10, 5.27). Recurrence hazard was not significantly changed among digoxin-using women also using tamoxifen. Conclusions Breast cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis. PMID:23421975

  11. GRIZZLY/FAVOR Interface Project Report

    SciTech Connect

    Dickson, Terry L; Williams, Paul T; Yin, Shengjun; Klasky, Hilda B; Tadinada, Sashi; Bass, Bennett Richard

    2013-06-01

    As part of the Light Water Reactor Sustainability (LWRS) Program, the objective of the GRIZZLY/FAVOR Interface project is to create the capability to apply GRIZZLY 3-D finite element (thermal and stress) analysis results as input to FAVOR probabilistic fracture mechanics (PFM) analyses. The one benefit of FAVOR to Grizzly is the PROBABILISTIC capability. This document describes the implementation of the GRIZZLY/FAVOR Interface, the preliminary verification and tests results and a user guide that provides detailed step-by-step instructions to run the program.

  12. Treatment of relapsed Wilms tumour (WT) patients: experience with topotecan. A report from the SIOP Renal Tumour Study Group (RTSG).

    PubMed

    Mavinkurve-Groothuis, A M C; van den Heuvel-Eibrink, M M; Tytgat, G A; van Tinteren, H; Vujanic, G; Pritchard-Jones, K L P; Howell, L; Graf, N; Bergeron, C; Acha, T; Catania, S; Spreafico, F

    2015-04-01

    Topotecan has been variably incorporated in the treatment of patients with relapsed Wilms tumour (WT) who failed initial treatment with three or more effective drugs. Our objective was to describe outcome and to retrospectively investigate the potential role of topotecan in relapsed WT patients. Children who were treated with topotecan as part of their chemotherapeutic regimens for relapsed WT were identified and included in our retrospective study. Patient charts were reviewed for general patient characteristics, histology and stage at initial diagnosis, number and type of relapse, salvage treatment schedules, toxicity, response to treatment and outcome. From 2000 to 2012, 30 children (median age at relapse 5.5 years, range 1.6-14.5 years) were identified to have received topotecan as part of their salvage regimens (primary progressive disease n = 3, first, second and third relapse n = 13, 9 and 2 respectively, partial response n = 3). Topotecan was administered as a single agent (12 patients) or in combination with other drugs (18 patients). Sixteen patients had high-risk histology according to the SIOP classification, 15 died within 12 months because of progressive disease. Fourteen patients had SIOP intermediate-risk histology of which four patients displayed objective responses to topotecan. Overall, 6 out of 14 intermediate-risk patients survived (median follow up of 6 years), however, three of whom (stage V) had bilateral nephrectomy after topotecan treatment. Topotecan does not seem to show effectiveness in the treatment of relapsed WT patients with initial high-risk histology. In patients with intermediate-risk histology, the role of topotecan might deserve further attention, to prove its efficacy. © 2014 Wiley Periodicals, Inc.

  13. Determinants of Relapse Following Smoking Cessation.

    ERIC Educational Resources Information Center

    Shiffman, Saul M.

    Although research has been conducted on who will relapse after having quit smoking in clinics, little has been done to determine the immediate precipitants of recidivism. A telephone hotline, manned by four experienced interviewers, was set up to receive calls from ex-smokers who had relapsed or who felt at high risk for relapse. A structured…

  14. Natalizumab reduces relapse clinical severity and improves relapse recovery in MS.

    PubMed

    Lublin, Fred D; Cutter, Gary; Giovannoni, Gavin; Pace, Amy; Campbell, Nolan R; Belachew, Shibeshih

    2014-11-01

    Compare relapse clinical severity, post-relapse residual disability, and the probability of confirmed complete recovery from relapse between patients who relapsed during natalizumab (n=183/627 [29%]) and placebo (n=176/315 [56%]) treatments in the AFFIRM trial. In this post-hoc analysis, relapse clinical severity and residual disability were defined by change in Expanded Disability Status Scale (EDSS) score occurring between pre-relapse and at-relapse assessment and between pre-relapse and post-relapse assessment, respectively. Patients were considered completely recovered from relapse when their post-relapse EDSS score was less than or equal to their pre-relapse EDSS score, and this was maintained for 12 or 24 weeks. At relapse, an increase in EDSS score of ≥0.5 points occurred in 71% of natalizumab and 84% of placebo patients (P=0.0088); an increase of ≥1.0 point occurred in 49% of natalizumab and 61% of placebo patients (P=0.0349) (mean increase in EDSS at relapse: natalizumab=0.77; placebo=1.09; P=0.0044). After relapse, residual disability of ≥0.5 EDSS points remained in 31% of natalizumab and 45% of placebo patients (P=0.0136) (mean post-relapse residual EDSS increase: natalizumab=0.06; placebo=0.28; P=0.0170). In patients with an increase in EDSS of ≥0.5 or ≥1.0 during relapse, natalizumab increased the probability of 12-week confirmed complete recovery from relapse by 55% (hazard ratio [HR]=1.554; P=0.0161) and 67% (HR=1.673; P=0.0319) compared to placebo, respectively. In AFFIRM, natalizumab treatment decreased the clinical severity of relapses and improved recovery from disability induced by relapses. These beneficial effects would limit the step-wise accumulation of disability. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Animal models of fear relapse.

    PubMed

    Goode, Travis D; Maren, Stephen

    2014-01-01

    Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Animal Models of Fear Relapse

    PubMed Central

    Goode, Travis D.; Maren, Stephen

    2014-01-01

    Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. PMID:25225304

  17. Respiratory complications of relapsing polychondritis

    PubMed Central

    Gibson, G. J.; Davis, P.

    1974-01-01

    Gibson, G. J. and Davis, P. (1974).Thorax, 29, 726-731. Respiratory complications of relapsing polychondritis. The respiratory function of a patient with relapsing polychondritis is described. He had severe airflow obstruction due to disease of both the extra and intrathoracic large airways. Evidence of small airways disease was lacking. The airflow obstruction was probably due to a combination of structural narrowing and an enhanced dynamic effect. Despite the severity of his disease the patient's exercise capacity was only slightly reduced but he developed carbon dioxide retention on exercise. Involvement of the airways is a common feature of this rare disease and demands full physiological and radiographic assessment if tracheostomy or other surgical procedure is contemplated. Images PMID:4450183

  18. Salaries in histology.

    PubMed

    Buesa, René J

    2008-04-01

    An analysis of histology salaries from the last 4 national surveys conducted by the American Society of Clinical Pathologists is presented. The regional variations within and between years for histology salaries presented in the last 4 national surveys of medical laboratory specialties are not statistically significant. Local variations greater than the national variations reflect the preponderant effect of local supply and demand over regional characteristics. Salaries by hospitals are significantly different only between 2 size categories and the supervisors' salary. There is no correlation between the salary increase for any histology position in any one year and the vacancy level in the previous year. On the other hand, the correlation between histotechnicians' salaries and both the cost of living and the median income are significant, as well as between the latter and the supervisors' salary. The histotechnologists' salaries are significantly correlated with the consumer price index but not with the inflation rate. A survey of histology salaries in foreign countries was also undertaken and compared with salaries in the United States. National salaries rank close to the general average for 10 foreign countries when expressed as ratios with the personal gross domestic product or with the countries' minimum wage. For the midpoint salary ranges, the United States ranks fourth after Canada, the United Kingdom, and Australia, the latter 3 countries with structured pay rates adjusted to local costs of living in contrast with United States' salary characteristics. Histology salaries rest on negotiations within each employer's salary structure and fluctuate according to license level, documented studies, special training(s), years of experience, references, and the ability to negotiate, where each side tries to take advantage of the other. The result is a heterogeneous and chaotic salary situation driven by personal and local needs, where the histology worker usually

  19. Relapse of HHV8-positive multicentric Castleman disease following rituximab-based therapy in HIV-positive patients.

    PubMed

    Pria, Alessia Dalla; Pinato, David; Roe, Jennifer; Naresh, Kikeri; Nelson, Mark; Bower, Mark

    2017-04-13

    Successful treatment of HIV-associated multicentric Castleman disease (HIV+MCD) with rituximab-based approaches has dramatically improved survival and reduced the risk of human herpesvirus 8 (HHV8)-associated lymphoma. Longer term outcomes including relapse rates have not been described and are important to establish the potential role of maintenance therapy. A prospective cohort of 84 patients with biopsy-proven HIV+MCD were treated with risk-stratified rituximab-based therapy. Four patients (5%) died of refractory HIV+MCD and 80 achieved clinical remission. The median follow-up for the 80 patients was 6.9 years and their 5-year overall survival was 92% (95% confidence interval [CI], 85 to 99). Eighteen have relapsed (all histologically confirmed), including 5 with concomitant HHV8-associated lymphoma and MCD at relapse. The 5-year relapse-free survival is 82% (95% CI, 72 to 92). No clinical or laboratory findings that were present at MCD diagnosis predicted subsequent relapse, and the median time to first relapse was 30 months (maximum, 10 years). There were no significant differences in clinicopathological features at initial diagnosis and at relapse. All patients were successfully retreated at relapse with rituximab-based therapy. Only 1 patient died of relapsed MCD (at fifth relapse 9.4 years after initial diagnosis). Despite the use of rituximab, the risk of developing HHV8-associated lymphoma was significantly elevated in this cohort, with an incidence of 11.4/1000 person-years. The relatively low relapse rate and high salvage rates at relapse reduce the potential benefit of maintenance therapy; this should only be advocated in the context of a clinical trial. © 2017 by The American Society of Hematology.

  20. Very late relapse of medulloblastoma.

    PubMed

    Cieślak, Ewa; Kepka, Lucyna; Fijuth, Jacek; Marchel, Andrzej; Kroh, Halina

    2004-01-01

    A case of 47-year-old woman with a local relapse of medulloblastoma 23 years after initial presentation is reported. At the age of 24, the patient underwent resection of medulloblastoma of the right cerebellar lobe, followed by the craniospinal orthovoltage irradiation (3600 R to the brain, and 3000 R to the spinal cord). At the 21st year of follow-up, a second cancer originating in the thyroid gland was diagnosed. Thyroidectomy followed by 131-iodotherapy for the papillary cancer was performed. Two years later she was operated for the recurrence of medulloblastoma at the former site. The patient was unfit for chemotherapy due to poor bone marrow reserve following the previous treatment. The reirradiation of the posterior cranial fossa was performed postoperatively. The patient was given 45 Gy in 25 fractions to the recurred tumour volume with 2 cm margin within 41 days. The treatment was performed by 6 MV photons with conformal technique and noncoplanar beams arrangement. The patient is disease free 15 months after relapse of medulloblastoma. The following problems are discussed: late relapse of medulloblastoma, secondary cancers after craniospinal irradiation, and retreatment of CNS tumours.

  1. Leptomeningeal carcinomatosis as the primary presentation of relapse in breast cancer

    PubMed Central

    Sacco, Keith; Muhammad, Aun; Saleem, Waqar; Alshaker, Heba; Monzon, Leonardo; Islam, Mohammad Rafiqul; Pchejetski, Dmitri

    2016-01-01

    Leptomeningeal metastasis (LM) is an uncommon presentation of relapse in breast cancer, which is associated with poor clinical outcomes and poor prognosis. Notably, LM most commonly occurs in breast cancer. The aim of the present review was to investigate the occurrence of LM as the primary presentation of relapse following remission in breast cancer patients and to determine whether specific histological subtypes are predisposed to meningeal metastases. In addition, the present review evaluated whether patients presenting with LM as the primary site of relapse exhibit differences in survival when compared with patients exhibiting metastasis to other sites. Cross-sectional studies have demonstrated that LM is commonly associated with other sites of distant metastasis including lung, liver and bone metastases. The histological breast cancer subtype most commonly associated with LM was invasive lobular carcinoma, while triple-negative breast cancer patients appear to be predisposed to the development of LM when considering the overall prevalence of histological breast cancer subtypes. At present, data regarding LM as the primary site of relapse are limited due to its rarity as the first site of metastasis in breast cancer. Case-controlled studies are required to investigate the incidence of LM as the primary site of recurrence in breast cancer patients as this would enable treatment standardization and identification of prognostic factors for improved survival. PMID:27446350

  2. The effect of low-frequency mechanical vibration on retention in an orthodontic relapse model.

    PubMed

    Yadav, Sumit; Assefnia, Amir; Gupta, Himank; Vishwanath, Meenakshi; Kalajzic, Zana; Allareddy, Veerasathpurush; Nanda, Ravindra

    2016-02-01

    To investigate the effect of low-frequency mechanical vibration (LFMV) on the prevention of relapse after active orthodontic tooth movement, bone volume fraction (BVF), tissue density, and the integrity of periodontal ligament. Thirty male CD1, 12-week-old mice were used for the study. Mice were randomly divided into three groups: 1. control group, 2. relapse group, and 3. relapse + 30 Hz vibration group. In the control group, first molar was moved mesially for 7 days using nickel-titanium coil spring delivering 10g of force, whereas in relapse and relapse + 30 Hz groups, first molar was moved mesially for 7 days and then orthodontic force was removed and molar was allowed to relapse for 7 days. In relapse + 30 Hz group, LFMVs were applied at 30 Hz. Micro-focus computed tomography (micro-CT) was used for tooth movement measurements (relapse), BVF, and tissue density. Additionally, immunostaining for sclerostin, tartrate-resistant acid phosphatase staining, and picro-sirius red staining were performed on histological sections. LFMV at 30 Hz showed a tendency to decrease relapse but was not statistically significant. Micro-CT analysis showed a trend towards increase in BVF and tissue density with application of LFMV. Sclerostin expression was decreased with 30 Hz vibration. Additionally, the picro-sirius staining showed that LFMV at 30 Hz helped in maintaining the thickness and integrity of collagen fibres in periodontal ligament. This is an animal study and extrapolation of the current findings to the clinical situation must be done with caution, as there is no osteonal remodelling (secondary remodelling) in mice when compared to humans. There was no statistically significant difference in the amount of relapse between the relapse-only and relapse + 30 Hz groups. However, there was a trend of decrease in relapse with 30 Hz mechanical vibration. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved

  3. Gastritis: the histology report.

    PubMed

    Rugge, Massimo; Pennelli, Gianmaria; Pilozzi, Emanuela; Fassan, Matteo; Ingravallo, Giuseppe; Russo, Valentina M; Di Mario, Francesco

    2011-03-01

    Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice.

  4. Histologic classification of gliomas.

    PubMed

    Perry, Arie; Wesseling, Pieter

    2016-01-01

    Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation.

  5. β2-Adrenergic receptor gene polymorphisms in the relapse of myasthenia gravis with thymus abnormality.

    PubMed

    Wang, Lili; Zhang, Yun; He, Maolin

    2017-04-01

    The role of β2-adrenergic receptor (β2-AR) in the relapse of myasthenia gravis (MG) associated with thymus abnormality has not been fully identified. Using polymerase chain reaction and gene sequencing method, we investigated the relationship of β2-AR gene polymorphisms with different thymus pathology in MG patients. The role of β2-AR gene polymorphisms in the relapse of MG was further investigated. Age of onset (p = 0.034), the onset symptom of ocular MG (OMG; p = 0.023), the first symptom of OMG second generalization (p = 0.040) were different in MG with thymoma from those in MG with normal thymus or thymus hyperplasia. Gene polymorphisms of β2-AR on positions 16 and 27 showed no significant difference between relapsed and non-relapsed MG patients with thymus abnormality (thymus hyperplasia: position 16, p = 0.792; position 27, p = 0.664; thymoma: position 16, p = 0.226; position 27, p = 0.615). However, genotypes distribution on position 27 among MG patients with three thymus histology was significantly different (χ² = 8.153, p = 0.041). Furthermore, glucocorticoid can decrease relapse of MG with thymus hyperplasia (p = 0.021). MG patients with thymus abnormality differ from MG patients with normal thymus in age of onset, the onset symptom of OMG and the first symptom of OMG second generalization. β2-AR gene polymorphisms had no relationship with the relapse of MG with thymus abnormality. Gene polymorphism of β2-AR on position 27 was associated with different thymus histology of MG. Glucocorticoid was able to reduce the risk of relapse of MG with thymus hyperplasia.

  6. Vascular involvement in relapsing polychondritis.

    PubMed Central

    Esdaile, J.; Hawkins, D.; Gold, P.; Freedman, S. O.; Duguid, W. P.

    1977-01-01

    Review of four cases of relapsing polychondritis (RP) seen at one hospital in the 12-year period 1963 to 1974 revealed that one patient had aortic insufficiency with large artery involvement, two others had involvement of medium and large arteries and the fourth may have had mucocutaneous vasculitis. Valvular disease has occurred in 9% of all cases of RP reported in the literature and, if vasculitis beyong the aortic root is included, 25% of cases of RP manifested inflammatory vascular disease. The frequency of pseudotumour of the orbit and cochlear-labyrinthine dysfunction is also high and may be a manifestation of vasculitis. PMID:870159

  7. Prognosis and treatment after relapse of acute lymphoblastic leukemia and non-Hodgkin's lymphoma: 1985. A report from the Childrens Cancer Study Group

    SciTech Connect

    Bleyer, W.A.; Sather, H.; Hammond, G.D.

    1986-07-15

    Acute lymphoblastic leukemia and non-Hodgkin's lymphoma constitute 42% to 45% of the cancers in infants, children, and adolescents: In 1985, an estimated 2025 children were newly diagnosed with these two cancers and 900 (43%) of the pediatric cancer deaths in the United States have been projected to be due to these diseases. The single most important obstacle to preventing these deaths is relapse, and prevention of relapse or salvage of the patient who has had a relapse continues to be a major therapeutic challenge. The most important initial step in the treatment of the child whose disease has relapsed is to determine, to the extent possible, the prognosis. In a child with non-Hodgkin's lymphoma, a relapse confers an extremely poor prognosis, regardless of site of relapse, tumor histology, or other original prognostic factors, prior therapy, or time to relapse. In the child with acute lymphoblastic leukemia in relapse, the prognosis depends on multiple factors. The primary therapy is chemotherapy or chemoradiotherapy with marrow grafting. Other options exist, including no therapy, or investigational therapy. The therapy selected should be predicated on the prognosis. In the child with an isolated central nervous system (CNS) relapse off therapy, minimum therapy should be administered, particularly if the relapse occurred without prior cranial irradiation. In the child whose relapse is more than 6 months off therapy, conventional therapy should be considered. Also, a patient with an isolated CNS relapse on therapy after prior cranial irradiation should be given moderate therapy. Bone marrow transplantation or high-dose chemoradiotherapy with autologous marrow rescue should be reserved in children with a second or subsequent extramedullary relapse, and possibly for those with a first isolated overt testicular relapse on therapy.

  8. Aortic involvement in relapsing polychondritis.

    PubMed

    Le Besnerais, Maëlle; Arnaud, Laurent; Boutémy, Jonathan; Bienvenu, Boris; Lévesque, Hervé; Amoura, Zahir; Marie, Isabelle

    2017-05-17

    To assess prevalence of aortic involvement in relapsing polychondritis (RP) patients; to evaluate clinical features and long-term outcome of RP patients exhibiting aortitis, aortic ectasia and/or aneurysm. One hundred and seventy-two RP patients underwent aortic computed tomography (CT)-scan; they were seen in 3 medical centers. Eleven patients (6.4%) had aortic involvement, occurring within a median time of 2 years after RP diagnosis. CT-scan showed isolated aortitis (n=2); the 9 other patients exhibited: aortitis and aortic aneurysm (n=2) or ectasia (n=1), isolated aortic aneurysm (n=4) or ectasia (n=2); aortic localizations were as follows: thoracic (n=6), abdominal (n=2), thoracic and abdominal (n=4) aorta. Patients exhibited: resolution (n=3) improvement (n=3), stabilization (n=4) or deterioration (n=1) of aortic localization. Five patients experienced recurrence of aortic localization; one patient died of aortic abdominal aneurysm rupture. Predictive factors of death related to aortic complications were: aortitis on CT-scan, higher median levels of erythrocyte sedimentation rate. Predictive parameters of aortic relapses were: aortitis on CT-scan and involvement of the abdominal aorta. This study underlines that aortic involvement is severe in RP. Furthermore, we suggest that RP patients exhibiting poor prognostic factors, including panaortitis and higher values of ESR, may require more aggressive therapy. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  9. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

    PubMed

    Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

    2015-01-08

    Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

  10. The nature of relapse in schizophrenia

    PubMed Central

    2013-01-01

    Background Multiple relapses characterise the course of illness in most patients with schizophrenia, yet the nature of these episodes has not been extensively researched and clinicians may not always be aware of important implications. Methods We critically review selected literature regarding the nature and underlying neurobiology of relapse. Results Relapse rates are very high when treatment is discontinued, even after a single psychotic episode; a longer treatment period prior to discontinuation does not reduce the risk of relapse; many patients relapse soon after treatment reduction and discontinuation; transition from remission to relapse may be abrupt and with few or no early warning signs; once illness recurrence occurs symptoms rapidly return to levels similar to the initial psychotic episode; while most patients respond promptly to re-introduction of antipsychotic treatment after relapse, the response time is variable and notably, treatment failure appears to emerge in about 1 in 6 patients. These observations are consistent with contemporary thinking on the dopamine hypothesis, including the aberrant salience hypothesis. Conclusions Given the difficulties in identifying those at risk of relapse, the ineffectiveness of rescue medications in preventing full-blown psychotic recurrence and the potentially serious consequences, adherence and other factors predisposing to relapse should be a major focus of attention in managing schizophrenia. The place of antipsychotic treatment discontinuation in clinical practice and in placebo-controlled clinical trials needs to be carefully reconsidered. PMID:23394123

  11. Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin’s lymphoma

    PubMed Central

    Weide, Rudolf

    2008-01-01

    Bendamustine is an alkylating agent which also shows properties of a purine analog. Because of its unique mechanism of action it shows activity in relapsed indolent lymphomas which are resistant to alkylating agents, purine analogs, and rituximab. Bendamustine has a favorable toxicity profile causing no alopecia and only a moderate hematotoxicity and gastrointestinal toxicity. Combinations of bendamustine with mitoxantrone and rituximab and with rituximab alone have been shown to be highly active in relapsed/refractory indolent lymphomas and mantle cell lymphomas achieving long lasting complete remissions. Because of only moderate toxicity these combinations can be applied safely in elderly patients who can be treated in an outpatient setting. PMID:19209254

  12. The neurobiology of relapse in schizophrenia.

    PubMed

    Remington, Gary; Foussias, George; Agid, Ofer; Fervaha, Gagan; Takeuchi, Hiroyoshi; Hahn, Margaret

    2014-02-01

    Dopamine's proposed role in psychosis proved a starting point in our understanding of the neurobiology of relapse, fitting given the central role positive symptoms play. This link is reflected in early work examining neurotransmitter metabolite and drug (e.g. amphetamine, methylphenidate) challenge studies as a means of better understanding relapse and predictors. Since, lines of investigation have expanded (e.g. electrophysiological, immunological, hormonal, stress), an important step forward if relapse per se is the question. Arguably, perturbations in dopamine represent the final common pathway in psychosis but it is evident that, like schizophrenia, relapse is heterogeneous and multidimensional. In understanding the neurobiology of relapse, greater gains are likely to be made if these distinctions are acknowledged; for example, efforts to identify trait markers might better be served by distinguishing primary (i.e. idiopathic) and secondary (e.g. substance abuse, medication nonadherence) forms of relapse. Similarly, it has been suggested that relapse is 'neurotoxic', yet individuals do very well on clozapine after multiple relapses and the designation of treatment resistance. An alternative explanation holds that schizophrenia is characterized by different trajectories, at least to some extent biologically and/or structurally distinguishable from the outset, with differential patterns of response and relapse. Just as with schizophrenia, it seems naïve to conceptualize the neurobiology of relapse as a singular process. We propose that it is shaped by the form of illness and in place from the outset, modified by constitutional factors like resilience, as well as treatment, and confounded by secondary forms of relapse. © 2013 Elsevier B.V. All rights reserved.

  13. To Form a Favorable Idea of Chemistry

    ERIC Educational Resources Information Center

    Heikkinen, Henry W.

    2010-01-01

    "To confess the truth, Mrs. B., I am not disposed to form a very favorable idea of chemistry, nor do I expect to derive much entertainment from it." That 200-year-old statement by Caroline to Mrs. Bryan, her teacher, appeared on the first page of Jane Marcet's pioneering secondary school textbook, "Conversations on Chemistry". It was published 17…

  14. New Study Says CAI May Favor Introverts.

    ERIC Educational Resources Information Center

    Hopmeier, George

    1981-01-01

    A personality research study using the Myers-Briggs Type Indicator indicates that computer-assisted instruction programs favor introverts, i.e., those learners who can concentrate on details, memorize facts, and stay with a task until it is completed. (JJD)

  15. To Form a Favorable Idea of Chemistry

    ERIC Educational Resources Information Center

    Heikkinen, Henry W.

    2010-01-01

    "To confess the truth, Mrs. B., I am not disposed to form a very favorable idea of chemistry, nor do I expect to derive much entertainment from it." That 200-year-old statement by Caroline to Mrs. Bryan, her teacher, appeared on the first page of Jane Marcet's pioneering secondary school textbook, "Conversations on Chemistry". It was published 17…

  16. Prodromal Signs and Symptoms of Schizophrenic Relapse.

    ERIC Educational Resources Information Center

    Subotnik, Kenneth L.; Nuechterlein, Keith H.

    Increasing evidence that decompensation into acute psychosis by schizophrenics can often be avoided with active pharmacological and psychosocial intervention at the early signs of relapse has stimulated research into the signs and symptoms prodromal to acute psychosis. In this study, 6-week periods prior to 17 psychotic relapses and to 11 relapses…

  17. Preventing Adolescent Relapse: Concepts, Theories and Techniques.

    ERIC Educational Resources Information Center

    Mishra, Shitala P.; Ressler, Robert A.

    This chapter discusses adolescent drug abuse relapse prevention. It presents the following four conclusions regarding the efficacy of prevention programs. First, more controlled studies are needed to evaluate the long-term effectiveness of relapse prevention strategies with adolescents in reducing factors such as cravings and increasing their…

  18. Prodromal Signs and Symptoms of Schizophrenic Relapse.

    ERIC Educational Resources Information Center

    Subotnik, Kenneth L.; Nuechterlein, Keith H.

    Increasing evidence that decompensation into acute psychosis by schizophrenics can often be avoided with active pharmacological and psychosocial intervention at the early signs of relapse has stimulated research into the signs and symptoms prodromal to acute psychosis. In this study, 6-week periods prior to 17 psychotic relapses and to 11 relapses…

  19. [Relapsing polychondritis: report of 4 cases].

    PubMed

    Olival Costa, H; Alcantara Maia, R; Sakano, Y

    1989-01-01

    Four cases of Relapsing Polychondritis followed in the Hospital do Servidor Publico Estadual de Sao Paulo, since 1985, are reported and discussed. Relapsing Polychondritis, an auto-immune disease that destroys the pinnal and nasal cartilage has been observed occasionally around the world. Since it was first defined and described, in 1923, about 250 cases have been reported.

  20. Relapses in Patients With Giant Cell Arteritis

    PubMed Central

    Alba, Marco A.; García-Martínez, Ana; Prieto-González, Sergio; Tavera-Bahillo, Itziar; Corbera-Bellalta, Marc; Planas-Rigol, Ester; Espígol-Frigolé, Georgina; Butjosa, Montserrat; Hernández-Rodríguez, José; Cid, Maria C.

    2014-01-01

    Abstract Giant cell arteritis (GCA) is a relapsing disease. However, the nature, chronology, therapeutic impact, and clinical consequences of relapses have been scarcely addressed. We conducted the present study to investigate the prevalence, timing, and characteristics of relapses in patients with GCA and to analyze whether a relapsing course is associated with disease-related complications, increased glucocorticoid (GC) doses, and GC-related adverse effects. The study cohort included 106 patients, longitudinally followed by the authors for 7.8 ± 3.3 years. Relapses were defined as reappearance of disease-related symptoms requiring treatment adjustment. Relapses were classified into 4 categories: polymyalgia rheumatica (PMR), cranial symptoms (including ischemic complications), systemic disease, or symptomatic large vessel involvement. Cumulated GC dose during the first year of treatment, time required to achieve a maintenance prednisone dose <10 mg/d (T10), <5 mg/d (T5), or complete prednisone discontinuation (T0), and GC-related side effects were recorded. Sixty-eight patients (64%) experienced at least 1 relapse, and 38 (36%) experienced 2 or more. First relapse consisted of PMR in 51%, cranial symptoms in 31%, and systemic complaints in 18%. Relapses appeared predominantly, but not exclusively, within the first 2 years of treatment, and only 1 patient developed visual loss. T10, T5, and T0 were significantly longer in patients with relapses than in patients without relapse (median, 40 vs 27 wk, p  < 0.0001; 163 vs 89.5 wk, p = 0.004; and 340 vs 190 wk, p = 0.001, respectively). Cumulated prednisone dose during the first year was significantly higher in relapsing patients (6.2 ± 1.7 g vs 5.4 ± 0.78 g, p = 0.015). Osteoporosis was more common in patients with relapses compared to those without (65% vs 32%, p = 0.001). In conclusion, the results of the present study provide evidence that a relapsing course is associated

  1. Validation of histology image registration

    NASA Astrophysics Data System (ADS)

    Shojaii, Rushin; Karavardanyan, Tigran; Yaffe, Martin; Martel, Anne L.

    2011-03-01

    The aim of this paper is to validate an image registration pipeline used for histology image alignment. In this work a set of histology images are registered to their correspondent optical blockface images to make a histology volume. Then multi-modality fiducial markers are used to validate the alignment of histology images. The fiducial markers are catheters perfused with a mixture of cuttlefish ink and flour. Based on our previous investigations this fiducial marker is visible in medical images, optical blockface images and it can also be localized in histology images. The properties of this fiducial marker make it suitable for validation of the registration techniques used for histology image alignment. This paper reports on the accuracy of a histology image registration approach by calculation of target registration error using these fiducial markers.

  2. Predicting relapse among young adults: psychometric validation of the Advanced WArning of RElapse (AWARE) scale.

    PubMed

    Kelly, John F; Hoeppner, Bettina B; Urbanoski, Karen A; Slaymaker, Valerie

    2011-10-01

    Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure-the Advance WArning of RElapse (AWARE) scale (Miller & Harris, 2000) in an understudied but clinically important sample of young adults. Inpatient youth (N=303; Ages 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Lumpectomy Plus Tamoxifen or Anastrozole With or Without Whole Breast Irradiation in Women With Favorable Early Breast Cancer

    SciTech Connect

    Poetter, Richard . E-mail: Richard.Poetter@meduniwien.ac.at; Gnant, Michael; Kwasny, Werner; Tausch, Christoph; Handl-Zeller, Leonore; Pakisch, Brigitte; Taucher, Susanne; Hammer, Josef; Luschin-Ebengreuth, Gero; Schmid, Marianne; Kapp, Karin; Sedlmayer, Felix; Stierer, Michael; Reiner, Georg; Hofbauer, Friedrich; Rottenfusser, Andrea; Poestlberger, Sabine; Haider, Karin; Draxler, Wolfgang; Jakesz, Raimund

    2007-06-01

    Purpose: In women with favorable early breast cancer treated by lumpectomy plus tamoxifen or anastrazole, it remains unclear whether whole breast radiotherapy is beneficial. Methods and Material: Between January 1996 and June 2004, the Austrian Breast and Colorectal Cancer Study Group (ABCSG) randomly assigned 869 women to receive breast radiotherapy {+-} boost (n 414) or not (n = 417) after breast-conserving surgery (ABCSG Study 8A). Favorable early breast cancer was specified as tumor size <3 cm, Grading 1 or 2, negative lymph nodes, positive estrogen and/or progesterone receptor status, and manageable by breast-conserving surgery. Breast radiotherapy was performed after lumpectomy with 2 tangential opposed breast fields with mean 50 Gy, plus boost in 71% of patients with mean 10 Gy, in a median of 6 weeks. The primary endpoint was local relapse-free survival; further endpoints were contralateral breast cancer, distant metastases, and disease-free and overall survival. The median follow-up was 53.8 months. Results: The mean age was 66 years. Overall, there were 21 local relapses, with 2 relapses in the radiotherapy group (5-y rate 0.4%) vs. 19 in the no-radiotherapy group (5.1%), respectively (p = 0.0001, hazard ratio 10.2). Overall relapses occurred in 30 patients, with 7 events in the radiotherapy group (5-y rate 2.1%) vs. 23 events in the no-radiotherapy group (6.1%) (p = 0.002, hazard ratio 3.5). No significant differences were found for distant metastases and overall survival. Conclusion: Breast radiotherapy {+-} boost in women with favorable early breast cancer after lumpectomy combined with tamoxifen/anastrazole leads to a significant reduction in local and overall relapse.

  4. Salvage Treatment Improved Survival of Patients With Relapsed Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    SciTech Connect

    Zhang Xinxing; Xie Conghua; Xu Yong; Deng Di; Zhao Yanhai; Zou Bingwen; Zhou Lin; Li Mei; Wang Jin; Liu Weiping; Huang Meijuan

    2009-07-01

    Purpose: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type. Methods and Materials: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone. Results: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels. Conclusions: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.

  5. [Research and control of relapse tuberculosis cases].

    PubMed

    Yamagishi, Fumio; Toyota, Makoto

    2009-12-01

    With this symposium, we focused on the relapse of tuberculosis in Japan. Out of 19,893 tuberculosis patients registered in 2007 in Japan, 7.48% were classified as relapse cases. Relapse cases have the risk of acquired drug resistance. But we have few analyses of the proportion of relapse tuberculosis cases with standard short course regimens for six months, factors contributing to tuberculosis relapse and the proportion of drug resistance among relapse TB cases in Japan. Therefore we analyzed the relapse tuberculosis cases in two rural areas and three urban areas. We also analyzed the proportion of drug resistance among relapse cases with the data of drug susceptibility survey of Ryoken. 1. Research of relapse tuberculosis cases: Makoto TOYOTA (Kochi City Public Health Center). To clarify the relapse rate and factors contributing to tuberculosis relapse, we investigated the relapse tuberculosis cases in the municipality where the proportion of elderly tuberculosis patients was high. Out of 902 tuberculosis patients registered in Kochi City Public Health Center during 10 years, 20 pulmonary tuberculosis patients were confirmed relapse cases with initial registered records. Pretreatment cavitations, sputum culture positivity at 2 months, medical miss-management (e.g. number of doses, duration of therapy) and poor adherence were considered to be factors contributing to tuberculosis relapse. Out of 20 relapse cases, 12 cases were detected with symptoms, while only 3 cases were detected by examination in law. 2. A clinical study on relapse cases of pulmonary tuberculosis: Shuichi TAKIKAWA (National Hospital Organization Nishibeppu National Hospital). The relapse of pulmonary tuberculosis was investigated. In the cases with a treatment history before short course chemotherapy, drug resistance rate was high, and thus it needs to be cautious of drug resistance at the time of the retreatment. In the cases with a treatment history of short course chemotherapy, relapse cases

  6. Reoperative pulmonary metastasectomy for sarcomatous pediatric histologies.

    PubMed

    Temeck, B K; Wexler, L H; Steinberg, S M; McClure, L L; Horowitz, M A; Pass, H I

    1998-09-01

    The role for reoperative pulmonary metastasectomy in patients with "pediatric sarcomas" (osteosarcoma, nonrhabdomyosarcoma-soft tissue sarcoma, and Ewing's sarcoma) is undefined. We reviewed our results for patients with these histologic presentations (median age, 17.5 years; range, 6 to 32 years) having two (70), three (27), or four (10) metastasectomies between January 1965 and March 1995 to define postresection survival and potential prognostic factors. Simple wedges (88 thoracotomies, 84%) were performed more frequently than anatomic (17 thoracotomies, 16%) resections. With a median potential follow-up of 12.7 years, median survival was 2.25, 3.60, and 0.96 years from the second, third, and fourth explorations, respectively. Primary tumor site, sex, histology, age, maximal metastasis size, and systemic chemotherapy did not influence survival. Resectability was the most important prognostic factor (5.6 versus 0.7 years, 5.2 versus 2.5 years, 2.2 versus 0.2 years, resectable versus unresectable, median survival from second, third, and fourth thoracotomy, respectively). Unresectability, disease-free interval less than 6 months between initial (ie, first) pulmonary resection and the second thoracotomy, and two or more preoperative nodules noted on the right were simultaneously negatively associated with survival from the second thoracotomy. Unresectability or finding two or more metastases negatively affected survival from the third thoracotomy. These data imply that repeat metastasectomy can salvage a subset of patients with sarcomatous pediatric histologic presentations who retain favorable prognostic determinants.

  7. Relapsed duodenal ulcer after cure of Helicobacter pylori infection.

    PubMed

    Miwa, H; Matsushima, H; Terai, T; Tanaka, H; Kawabe, M; Namihisa, A; Watanabe, S; Sato, N

    1998-08-01

    We report a patient--a 42-year-old man--who had suffered from recurrent duodenal ulcer for about 20 years. Successful curative therapy for Helicobacter pylori infection was performed for 2 weeks with new triple omeprazole, anoxicillin, clarithromycin (OAC) treatment in October 1995, and cure of the infection was repeatedly confirmed by histology, culture, and the 13C urea breath test. One month after the curative therapy, recurrence of a small duodenal ulcer was observed and in February another duodenal ulcer and reflux esophagitis occurred, with severe symptoms, despite the continuous administration of ranitidine. None of the examinations to reconfirm cure of the infection revealed the presence of H. pylori. As the patient experienced continual psychological stress and smoked more frequently during the recurrent episode and had not used nonsteroidal anti-inflammatory drugs, stress and smoking appeared to play important roles in the relapse of duodenal ulcer in this patient after cure of H. pylori infection.

  8. Histology without xylene.

    PubMed

    Buesa, René J; Peshkov, Maxim V

    2009-08-01

    After the hazardous effects of xylene became indisputable in the 1970s, many potential substitutes became available, some with as many if not more hazards. This article discusses the inadequacy of 5 vegetable oils as substitutes, as well as the characteristics of 22 D-limonene-based substitutes, all less effective in their chemical role, some capable of inducing health problems, and costing more than twice as much as xylene. Some of the 35 alkane-based substitutes discussed are effective for tissue processing, less toxic, with a cost about the same as xylene, but are not very effective for dewaxing and other staining tasks. Isopropanol (2-propanol) alone or mixed with molten paraffin is a technically acceptable and cost-effective substitute for xylene for tissue processing, but in this study, we demonstrate that the best clearing agents from the sectioning quality and diagnostic value point of view, with automated or manual protocols, are mixtures of 5:1 and 2:1 isopropanol and mineral oil, followed by undiluted mineral oil, all at 50 degrees C, making them a safer and cheaper substitute than xylene. Using a 1.7% dishwasher soap aqueous solution at 90 degrees C to dewax before staining and oven drying the stained sections before coverslipping will eliminate xylene from the staining tasks. Tissue processors retorts and conduits can be dewaxed with a 2% solution of a strong glassware laboratory detergent. These 4 methodologies will make the histology laboratory xylene-free but, due to the natural resistance to change, many histotechs will be reluctant to adopt them if they think that their technical expertise could be jeopardized, and the only way these changes will succeed is if the pathologists, as stewards of the histology laboratory, commit to their implementation.

  9. Familial risk factors favoring drug addiction onset.

    PubMed

    Zimić, Jadranka Ivandić; Jukić, Vlado

    2012-01-01

    This study, primarily aimed at identification of familial risk factors favoring drug addiction onset, was carried out throughout 2008 and 2009. The study comprised a total of 146 addicts and 134 control subjects. Based on the study outcome, it can be concluded that in the families the addicts were born into, familial risk factors capable of influencing their psychosocial development and favoring drug addiction onset had been statistically more frequently encountered during childhood and adolescence as compared to the controls. The results also indicated the need for further research into familial interrelations and the structure of the families addicts were born into, as well as the need for the implementation of family-based approaches to both drug addiction prevention and therapy.

  10. Favorable Progress of English Education in Japan

    DTIC Science & Technology

    2009-02-20

    be a marvelous trigger for young children. Second, elementary school days are the right time to acquire proper pronunciation and better...listening capability. Some researchers say that below 12 or 13 years old is a favorable time to master natural pronunciation . They call this time...critical period”2. If they start to study English early, they will be able to acquire clear pronunciation and proper intonation. This time change

  11. How to predict clinical relapse in inflammatory bowel disease patients

    PubMed Central

    Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

    2016-01-01

    Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

  12. Management of relapsing Plasmodium vivax malaria

    PubMed Central

    Chu, Cindy S; White, Nicholas J

    2016-01-01

    ABSTRACT Introduction: Relapses are important contributors to illness and morbidity in Plasmodium vivax and P. ovale infections. Relapse prevention (radical cure) with primaquine is required for optimal management, control and ultimately elimination of Plasmodium vivax malaria. A review was conducted with publications in English, French, Portuguese and Spanish using the search terms ‘P. vivax’ and ‘relapse’. Areas covered: Hypnozoites causing relapses may be activated weeks or months after initial infection. Incidence and temporal patterns of relapse varies geographically. Relapses derive from parasites either genetically similar or different from the primary infection indicating that some derive from previous infections. Malaria illness itself may activate relapse. Primaquine is the only widely available treatment for radical cure. However, it is often not given because of uncertainty over the risks of primaquine induced haemolysis when G6PD deficiency testing is unavailable. Recommended dosing of primaquine for radical cure in East Asia and Oceania is 0.5 mg base/kg/day and elsewhere is 0.25 mg base/kg/day. Alternative treatments are under investigation. Expert commentary: Geographic heterogeneity in relapse patterns and chloroquine susceptibility of P. vivax, and G6PD deficiency epidemiology mean that radical treatment should be given much more than it is today. G6PD testing should be made widely available so primaquine can be given more safely. PMID:27530139

  13. The Wisconsin Predicting Patients' Relapse questionnaire

    PubMed Central

    Bolt, Daniel M.; McCarthy, Danielle E.; Japuntich, Sandra J.; Fiore, Michael C.; Smith, Stevens S.; Baker, Timothy B.

    2009-01-01

    Introduction: Relapse is the most common smoking cessation outcome. Accurate prediction of relapse likelihood could be an important clinical tool used to influence treatment selection or duration. The aim of this research was to develop a brief clinical relapse proneness questionnaire to be used with smokers interested in quitting in a clinical setting where time is at a premium. Methods: Diverse items assessing constructs shown in previous research to be related to relapse risk, such as nicotine dependence and self-efficacy, were evaluated to determine their independent contributions to relapse prediction. In an exploratory dataset, candidate items were assessed among smokers motivated to quit smoking who enrolled in one of three randomized controlled smoking cessation trials. A cross-validation dataset was used to compare the relative predictive power of the new instrument against the Fagerström Test for Nicotine Dependence (FTND) at 1-week, 8-week, and 6-month postquit assessments. Results: We selected seven items with relatively nonoverlapping content for the Wisconsin Predicting Patient's Relapse (WI-PREPARE) measure, a brief, seven-item questionnaire that taps physical dependence, environmental factors, and individual difference characteristics. Cross-validation analyses suggested that the WI-PREPARE demonstrated a stronger prediction of relapse at 1-week and 8-week postquit assessments than the FTND and comparable prediction to the FTND at a 6-month postquit assessment. Discussion: The WI-PREPARE is easy to score, suggests the nature of a patient's relapse risk, and predicts short- and medium-term relapse better than the FTND. PMID:19372573

  14. Prognostic factors and impact of adjuvant treatments on local and metastatic relapse of soft-tissue sarcoma patients in the competing risks setting.

    PubMed

    Italiano, Antoine; Le Cesne, Axel; Mendiboure, Jean; Blay, Jean-Yves; Piperno-Neumann, Sophie; Chevreau, Christine; Delcambre, Corinne; Penel, Nicolas; Terrier, Philippe; Ranchere-Vince, Dominique; Lae, Marick; Le Guellec, Sophie; Michels, Jean-Jacques; Robin, Yves Marie; Bellera, Carine; Bonvalot, Sylvie

    2014-11-01

    In the medical literature many analyses of outcomes of sarcoma patients were performed without regard to the problem of "competing risks." We analyzed local relapse-free and metastasis-free survival in a population of 3255 adult patients with a primary soft-tissue sarcoma (STS) included in the French Sarcoma Group database. Cumulative incidence of local and metastatic relapse was estimated by accounting for death as a competing event. On multivariate analysis, age, tumor site, histological subtype, and grade were independent adverse prognostic factors for local relapse, whereas tumor depth and size had no influence. Histological subtype, tumor depth, tumor size, and grade were independent adverse prognostic factors for metastatic relapse. Despite a higher incidence of competing deaths in patients managed with adjuvant radiotherapy than in patients not receiving radiotherapy, adjuvant radiotherapy was associated with a significant benefit in terms of local relapse-free survival. Despite a similar cumulative incidence of competing deaths in patients with grade 2 and grade 3 disease, we found that the benefit of adjuvant chemotherapy was present only in patients with grade 3 and not in patients with grade 2 disease. In the setting of competing risks, tumor biology reflected by histological grade is a crucial predictor of local relapse, whereas tumor depth and size have poor if any influence. Grade could also predict the benefit of adjuvant chemotherapy in patients with STS. © 2014 American Cancer Society.

  15. [Management of relapses in smoking dehabituation].

    PubMed

    Sanz Pozo, B; Camarelles Guillem, F; de Miguel Díez, J

    2006-03-01

    Due to the recurrent chronic nature of tobacco dependence, health care professionals should know the most common reasons for relapses and offer smokers who have stopped smoking a preventive treatment. In our setting, some authors state that the main causes for which smokers relapse are the negative emotional states and social pressures. Among the prevention strategies of relapse are providing the patient information, reinforcing his/her decision to stop smoking and helping the patient identify and face the danger situations for the maintenance of abstinence.

  16. Immunopathologic Studies in Relapsing Polychondritis

    PubMed Central

    Herman, Jerome H.; Dennis, Marie V.

    1973-01-01

    Serial studies have been performed on three patients with relapsing polychondritis in an attempt to define a potential immunopathologic role for degradation constituents of cartilage in the causation and/or perpetuation of the inflammation observed. Crude proteoglycan preparations derived by disruptive and differential centrifugation techniques from human costal cartilage, intact chondrocytes grown as monolayers, their homogenates and products of synthesis provided antigenic material for investigation. Circulating antibody to such antigens could not be detected by immunodiffusion, hemagglutination, immunofluorescence or complement mediated chondrocyte cytotoxicity as assessed by 51Cr release. Similarly, radiolabeled incorporation studies attempting to detect de novo synthesis of such antibody by circulating peripheral blood lymphocytes as assessed by radioimmunodiffusion, immune absorption to neuraminidase treated and untreated chondrocytes and immune coprecipitation were negative. Delayed hypersensitivity to cartilage constituents was studied by peripheral lymphocyte transformation employing [3H]thymidine incorporation and the release of macrophage aggregation factor. Positive results were obtained which correlated with periods of overt disease activity. Similar results were observed in patients with classical rheumatoid arthritis manifesting destructive articular changes. This study suggests that cartilage antigenic components may facilitate perpetuation of cartilage inflammation by cellular immune mechanisms. Images PMID:4265382

  17. Extramedullary (EMP) relapse in unusual locations in multiple myeloma: Is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome?

    PubMed

    Katodritou, E; Gastari, V; Verrou, E; Hadjiaggelidou, C; Varthaliti, M; Georgiadou, S; Laschos, K; Xirou, P; Yiannaki, E; Constantinou, N; Markala, D; Zervas, K

    2009-08-01

    Extramedullary relapse constitutes an uncommon manifestation of multiple myeloma (MM), characterized by highly malignant histology, special biological features, resistance to treatment and poor outcome. Its incidence has been increased during the last years, probably due to the introduction of novel strategies in the management of MM, including intensified treatment and immunomodulatory drugs. Here we report nine cases of extramedullary relapse of MM, presented in unusual locations, seven of which had previously been treated with thalidomide-containing regimens (TCR). Our aim was to explore the morphological, immunophenotypical, molecular and laboratory characteristics accompanying EMP-relapse and seek possible correlations with treatment and clinical outcome.

  18. Re-occurrence of the CD20 molecule expression subsequent to CD20-negative relapse in diffuse large B-cell lymphoma.

    PubMed

    Ferreri, A J; Dognini, G P; Verona, C; Patriarca, C; Doglioni, C; Ponzoni, M

    2007-01-01

    We report the first case of diffuse large B-cell lymphoma (DLBCL) of the stomach displaying CD20-negative relapse after rituximab-containing treatment and the re-appearance of CD20 expression at the second failure. The loss of CD20 expression in B-cell lymphomas relapsing after rituximab is a well-known phenomenon, but its actual impact in DLBCL is difficult to estimate. This paradigmatic case suggests that CD20-expression reappearance after purging of CD20-positive clones with rituximab might be an underestimated occurrence in B-cell lymphomas. Accordingly, every relapse, whenever possible, should be histologically assessed with diagnostic and immunophenotyping purposes.

  19. Ilizarov external fixation for management of severe relapsed clubfeet in older children.

    PubMed

    El-Sayed, Mohamed

    2013-09-01

    Although the standard treatment of clubfoot deformity is conservative by serial casting techniques, relapses are not uncommon. Management of relapsed clubfoot deformity in older children is an orthopedic challenge. There is a growing interest in management of such complex deformities using the Ilizarov technique. In this study, the Ilizarov frame was used to correct severe relapsed clubfoot deformities in older children, whom underwent previous surgical interventions. 42 relapsed clubfeet were included. The Dimeglio classification was used for clinical assessment of the relapsed feet pre-operatively as well as post-operatively. After an average follow-up period of 4.6 years, and according to the Beatson and Pearson numerical assessment, favorable results (excellent or good) were found in 37 feet, while poor results took place in only five feet. Based on the final clinical and radiographic results, the Ilizarov technique could be considered as a good management alternative for such severe deformities. Copyright © 2013 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  20. [Histologic studies on otomycosis].

    PubMed

    Vennewald, Irina; Schönlebe, J; Klemm, E

    2002-01-01

    Fungal infections of the ear are mostly described as mycoses of the auditory canal. The aim of our investigations was to find out how fungi colonize the ear in immunocompetent patients. In the years from 1993 to 2000, 128 patients suspected of having otomycosis were examined. Of these 115 patients suffered from chronic otitis media with persisting tympanum perforation and otorrhea. A further 13 patients had clinical signs of otitis externa only. In 54 out of 139 samples, fungi were found in the auditory canal, in five on the tympanic membrane, and in five in the middle ear. Two-thirds were isolated as moulds and one-third as yeasts. Dominating species were Aspergillus niger and Candida parapsilosis. Samples of 15 patients suspected of having mastoiditis or cholesteatoma were examined histologically. Fungal hyphae were observed in the middle ear cavity and/or between horny lamellae of cholesteatoma in 4 patients. In the middle ear of immunocompetent patients chronic-hyperplastic (polypous) inflammation was detected with increased production of mucus, which probably promotes the colonization with pathogenic fungi as in the middle ear just like in the auditory canal.

  1. Very delayed smoking relapse warrants research attention.

    PubMed

    Brandon, T H; Lazev, A B; Juliano, L M

    1998-08-01

    Recent findings suggest that former smokers remain at risk for relapse well beyond the traditional treatment follow-up period of one year. Although progress has been made in understanding factors involved in smoking cessation and short-term maintenance, very little attention has been paid to research on the process, predictors, and treatment implications of very delayed relapse. Possible research questions are offered to stimulate further investigation in this area.

  2. [A preliminary study on outpatient relapse prevention program for methamphetamine dependent patients: Serigaya Methamphetamine Relapse Prevention Program (SMARPP)].

    PubMed

    Kobayashi, Ohji; Matsumoto, Toshihiko; Otsuki, Masaki; Endo, Keiko; Okudaira, Kenichi; Harai, Hiroaki; Wada, Kiyoshi

    2007-10-01

    Although methamphetamine use disorder has been prevalent in Japan for more than fifty years, there have been hardly any effective medical treatment modalities other than improving methamphetamine-induced psychosis through hospitalization and/or participation in self help groups and private rehabilitation centers. As such limited social resources for recovering methamphetamine dependents are insufficient to prevent patients from relapse, there are growing needs for developing effective outpatient treatment program based on a chronic care perspective. We have developed a relapse prevention program for Japanese methamphetamine abusers, modifying "Matrix" model and incorporating other treatment materials. Then a preliminary study on implementing the program was conducted in an outpatient setting at Kanagawa Psychiatric Center, Serigaya Hospital. Of sixty eight methamphetamine dependent patients who visited the hospital for the first time between September 2006 and February 2007, four agreed to participate in the study. The program was manual- and workbook-based, and we suggested participants to attend to the session three-times per week for two months. Also participants were asked randomly to turn in urine samples once a week. The participants consisted of a female and three males, with an average age of thirty. The length of abstinent period since the last use varied substantially, from five days to more than four years. Three had the experience of serving in prison for violating the Stimulant Drugs Control Law. The results of the present study were that all four completed the program, and presented with negative urine samples throughout the period. However, in terms of treatment retention, two out of the four dropped out of the outpatient treatment within a month after the program termination. These outcomes suggest that a relapse prevention program may successfully be provided for Japanese methamphetamine abusers in an outpatient setting, with a favorable, treatment

  3. Relapsing catastrophic antiphospholipid syndrome potential role of microangiopathic hemolytic anemia in disease relapses.

    PubMed

    Espinosa, Gerard; Rodríguez-Pintó, Ignasi; Gomez-Puerta, José A; Pons-Estel, Guillermo; Cervera, Ricard

    2013-02-01

    To analyze the clinical and laboratory characteristics of patients with catastrophic antiphospholipid syndrome (APS) who suffer relapses. We analyzed the Web site--based international registry of patients with catastrophic APS ("CAPS Registry") http://infmed.fcrb.es/es/web/caps and selected those cases that relapsed. Relapses were reported in 9 of 282 (3.2%) patients with catastrophic APS. A total of 35 episodes of catastrophic APS were found: 6 patients presented 2 relapses, 2 patients suffered 3 relapses, and 1 patient developed 17 relapses. However, the last patient was not included in the statistical analysis because his clinical and immunologic characteristics were not fully described. Therefore, a total of 18 episodes were analyzed. In 9 (50%) episodes, a precipitating factor was identified. The most frequent precipitating factor, found in 5 (28%) episodes, was infection. Brain, kidney, heart, and lung were the most common organs involved. Laboratory features of microangiopathic hemolytic anemia (MHA) were present in 13 of 18 (72%) episodes (definitive in 9, corresponding to 4 patients, and probable in 4, corresponding to 2 patients). Three relapses did not present with features of MHA and in the remaining 2 these data were not reported. The mortality rate was 38%. Although relapses are rare in patients with catastrophic APS, these results support the hypothesis that an association between MHA and relapsing of catastrophic APS could be present. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Predictors of rapid relapse in bulimia nervosa.

    PubMed

    Olmsted, Marion P; MacDonald, Danielle E; McFarlane, Traci; Trottier, Kathryn; Colton, Patricia

    2015-04-01

    Relapse remains a significant concern in bulimia nervosa, with some patients relapsing within months of treatment completion. The purpose of the study was to identify predictors of relapse within the first 6 months following treatment. The 116 participants were bingeing and/or vomiting ≥ 8 times per month before day hospital (DH), and had ≤ 2 episodes per month in the last month of DH and the first month after DH. Rapid relapse was defined as ≥ 8 episodes per month for 3 months starting within 6 months. The rate of rapid relapse was 27.6%. Patients who relapsed soon after DH had higher frequencies of bingeing and vomiting before treatment, engaged in less body avoidance before treatment and were more likely to be slow responders to treatment. Weight and shape concerns and body checking were not significant predictors. More frequent bulimic symptoms accompanied by less body avoidance may indicate an entrenchment in the illness which in turn augurs a labored and transient response to DH treatment that is difficult to sustain after intensive treatment ends. © 2014 Wiley Periodicals, Inc.

  5. Modeling relapse situations in the human laboratory.

    PubMed

    Sinha, Rajita

    2013-01-01

    It is well known that alcoholism is a chronic relapsing illness. While stress significantly impacts alcoholism risk, there is also evidence that increasing levels of alcohol use affect peripheral and central stress and reward pathways thereby setting up a reciprocal relationship among the effects of alcohol consumption of the development, course of and recovery from alcoholism. This chapter reviews our efforts in assessing the integrity of stress pathways in alcoholism by examining whether altered responses of the stress pathways play a role in relapse risk. Using validated human laboratory procedures to model two of the most common situations that contribute to relapse risk, we review how such models in the laboratory can predict subsequent alcohol relapse. Empirical findings from human laboratory and brain imaging studies are reviewed to show that specific stress-related dysregulation accompanies the alcohol craving state in alcohol-dependent individuals, and such dysregulation along with increases in alcohol seeking are predictive of increased alcohol relapse risk. Finally, the significant implications of these findings for the development of novel treatment interventions that target stress processes and alcohol craving to improve alcoholism relapse outcomes are discussed.

  6. Invariant natural killer T infiltration in neuroblastoma with favorable outcome.

    PubMed

    Hishiki, Tomoro; Mise, Naoko; Harada, Kazuaki; Ihara, Fumie; Takami, Mariko; Saito, Takeshi; Terui, Keita; Nakata, Mitsuyuki; Komatsu, Shugo; Yoshida, Hideo; Motohashi, Shinichiro

    2017-10-10

    Tumor immunity has been suggested to play a key role in clinical and biological behavior of neuroblastomas. Given that CD1-restricted invariant natural killer T (iNKT) cells enhance both innate and acquired tumor immunity, we investigated the expression of the iNKT-cell-specific T-cell receptor Vα24-Jα18 in neuroblastoma tissues and its correlation with clinical and biological characteristics. Using real- time quantitative PCR, we quantified the expression of Vα24-Jα18 in untreated tumor samples from 107 neuroblastoma cases followed in our institution and analyzed the correlation between the presence of infiltrated iNKT cells and clinical characteristics or patients' outcome. Vα24-Jα18 receptor was detected in 62 untreated cases (57.9%). The expression was significantly higher in stages 1, 2, 3, or 4S (P = 0.0099), in tumors with low or intermediate risk (P = 0.0050), with high TrkA expression (P = 0.0229), with favorable histology (P = 0.0026), with aneuploidy (P = 0.0348), and in younger patients (P = 0.0036). The overall survival rate was significantly higher in patients with iNKT-cell infiltration (log-rank; P = 0.0089). Since tumor-infiltrating iNKT cells were predominantly observed in neuroblastomas undergoing spontaneous differentiation and/or regression, we suggest that iNKT cells might play a key role in these processes.

  7. Cytokine production profiles in chronic relapsing-remitting experimental autoimmune encephalomyelitis: IFN-γ and TNF-α are important participants in the first attack but not in the relapse.

    PubMed

    Hidaka, Yoshihiko; Inaba, Yuji; Matsuda, Kazuyuki; Itoh, Makoto; Kaneyama, Tomoki; Nakazawa, Yozo; Koh, Chang-Sung; Ichikawa, Motoki

    2014-05-15

    Multiple sclerosis (MS) is a chronic demyelinating disease often displaying a relapsing-remitting course of neurological manifestations that is mimicked by experimental autoimmune encephalomyelitis (EAE) in animal models of MS. In particular, NOD mice immunized with myelin oligodendrocyte glycoprotein peptide 35-55 develop chronic relapsing-remitting EAE (CREAE). To elucidate the mechanisms that cause MS relapse, we investigated the histopathology and cytokine production of spleen cells and mRNA expression levels in the central nervous system (CNS) of CREAE mice. During the first attack, inflammatory cell infiltration around small vessels and in the subarachnoid space was observed in the spinal cord. Spleen cell production and mRNA expression in the CNS of several cytokines, including IFN-γ, TNF-α, IL-6, IL-17, and CC chemokine ligand 2 (CCL2), were higher in CREAE mice than in controls. Afterwards, parenchymal infiltration and demyelination were observed histologically in the spinal cord and corresponded with the more severe clinical symptoms of the first and second relapses. IL-17 and CCL2, but not IFN-γ, TNF-α, or IL-6, were also produced by spleen cells during recurrences. Our results suggested that the immune mechanisms in relapses were different from those in the first attack for CREAE. Further investigation of CREAE mechanisms may provide important insights into successful therapies for human relapsing-remitting MS.

  8. Relapse Prevention with Substance Abusers: Clinical Issues and Myths.

    ERIC Educational Resources Information Center

    Daley, Dennis C.

    1987-01-01

    Discusses the problems of relapse with alcoholics and other drug abusers from three perspectives: client-related variables, common erroneous beliefs and myths held by professionals regarding relapse, and treatment system problems that may contribute to relapse. Offers proposed solutions and describes a relapse prevention model. (Author/ABB)

  9. Synaptic plasticity mediating cocaine relapse requires matrix metalloproteinases.

    PubMed

    Smith, Alexander C W; Kupchik, Yonatan M; Scofield, Michael D; Gipson, Cassandra D; Wiggins, Armina; Thomas, Charles A; Kalivas, Peter W

    2014-12-01

    Relapse to cocaine use necessitates remodeling excitatory synapses in the nucleus accumbens and synaptic reorganization requires matrix metalloproteinase (MMP) degradation of the extracellular matrix proteins. We found enduring increases in MMP-2 activity in rats after withdrawal from self-administered cocaine and transient increases in MMP-9 during cue-induced cocaine relapse. Cue-induced heroin and nicotine relapse increased MMP activity, and increased MMP activity was required for both cocaine relapse and relapse-associated synaptic plasticity.

  10. Gastrointestinal stromal tumor after tyrosine kinase inhibition therapy: a review of biopsies of 34 patients with clinically suspected relapse and/or progression of the tumor.

    PubMed

    Plank, L; Buzalkova, V; Szepe, P; Lasabova, Z; Jasek, K; Stanclova, A; Minarik, G; Sufliarsky, J

    2017-01-01

    Implementation of combined surgical and targeted therapy strategies using tyrosine kinase inhibitors improved the prognosis of patients with aggressive GISTs. The therapeutic answer may be individually different, some patients do not respond properly, or even progress in spite of the therapy. This together with intratumoral heterogeneity and possible development of secondary phenotypical and genetical changes represents a challenge for pathologists examining a biopsy of relapsed tumors and/or their metastases. For this study biopsy files of the national Slovak GIST registry were reviewed to identify patients examined bioptically both prior the therapy and during the TKI treatment due to suspected tumor relapse and/or progression. All the GIST biopsies were analyzed using a standardized algorithm of histological, immunohistochemical and molecular analyses of exon 7, 9, 11, 13 of c-KIT and exons 12, 14, and 18 of PDGFRA genes, with the aim to identify posttherapeutical changes of these parameters. From 34 patients fulfilling the criteria of selection, all were histologically examined during their clinically suspicious first GIST relaps, eight during the 2nd, three during 3rd and one during 4th and 5th relapse resp. All but one posttherapeutical biopsies showed "viable" GIST tissue and so 44 relapses of 33 patients could be evaluated in comparison with identical parameters of diagnostic biopsies. Distinguishing three major histological types (spindle-, epitheloid-cell and mixed cell type), a change of the GIST type was identified in 1/3 of 1st relapse and ¼ of all relapse biopsies. Evaluation of three phenotypical GIST parameters CD117, CD34 and DOG-1, showed that phenotype alteration was always represented by a single change. The most common was either a gain or loss of CD34 positivity appearing in 1/3 of 1st relapse biopsies, while a loss of CD117 positivity was identified in one patient´s biopsy only. Altogether, the phenotypical changes were in ¼ of all

  11. Cross platform analysis of methylation, miRNA and stem cell gene expression data in germ cell tumors highlights characteristic differences by tumor histology.

    PubMed

    Poynter, Jenny N; Bestrashniy, Jessica R B M; Silverstein, Kevin A T; Hooten, Anthony J; Lees, Christopher; Ross, Julie A; Tolar, Jakub

    2015-10-23

    Alterations in methylation patterns, miRNA expression, and stem cell protein expression occur in germ cell tumors (GCTs). Our goal is to integrate molecular data across platforms to identify molecular signatures in the three main histologic subtypes of Type I and Type II GCTs (yolk sac tumor (YST), germinoma, and teratoma). We included 39 GCTs and 7 paired adjacent tissue samples in the current analysis. Molecular data available for analysis include DNA methylation data (Illumina GoldenGate Cancer Methylation Panel I), miRNA expression (NanoString nCounter miRNA platform), and stem cell factor expression (SABiosciences Human Embryonic Stem Cell Array). We evaluated the cross platform correlations of the data features using the Maximum Information Coefficient (MIC). In analyses of individual datasets, differences were observed by tumor histology. Germinomas had higher expression of transcription factors maintaining stemness, while YSTs had higher expression of cytokines, endoderm and endothelial markers. We also observed differences in miRNA expression, with miR-371-5p, miR-122, miR-302a, miR-302d, and miR-373 showing elevated expression in one or more histologic subtypes. Using the MIC, we identified correlations across the data features, including six major hubs with higher expression in YST (LEFTY1, LEFTY2, miR302b, miR302a, miR 126, and miR 122) compared with other GCT. While prognosis for GCTs is overall favorable, many patients experience resistance to chemotherapy, relapse and/or long term adverse health effects following treatment. Targeted therapies, based on integrated analyses of molecular tumor data such as that presented here, may provide a way to secure high cure rates while reducing unintended health consequences.

  12. Medical treatment for biochemical relapse after radiotherapy.

    PubMed

    Quero, L; Hennequin, C

    2014-10-01

    This article's purpose was to review the medical data justifying the use of a medical treatment for biochemical relapse after external beam radiotherapy. The MEDLINE database was searched to identify relevant information with the following medical subject headings: "prostate cancer", "radiotherapy" and "biochemical relapse". Prognostic factors affecting the overall survival of patients with a biochemical relapse after external beam radiotherapy have been identified: short prostate specific antigen (PSA)-doubling time (< 12 months), high PSA value (> 10 ng/mL) and short interval between treatment and biochemical relapse (< 18 months). If a second local treatment is not feasible, timing to initiate a salvage medical treatment is not defined. Particularly, randomized trials did not demonstrate a significant benefit of an early initiation of androgen deprivation treatment. Some retrospective studies suggest that an early androgen deprivation is justified if poor prognostic factors are found. However, if an androgen deprivation treatment is prescribed, intermittent schedule is non-inferior to a continuous administration and seems to offer a better quality of life. Many non-hormonal treatments have also been evaluated in this setting: only 5-alpha-reductase inhibitors could be proposed in some specific situations. In conclusion, the judicious use of a medical treatment for biochemical relapse is still debated. Given the natural history of this clinical situation, a simple surveillance is justified in many cases.

  13. Pathological gambling: understanding relapses and dropouts.

    PubMed

    Aragay, Núria; Jiménez-Murcia, Susana; Granero, Roser; Fernández-Aranda, Fernando; Ramos-Grille, Irene; Cardona, Sara; Garrido, Gemma; Anisul Islam, Mohammed; Menchón, José M; Vallès, Vicenç

    2015-02-01

    There is little available information on the factors that influence relapses and dropouts during therapy for pathological gambling (PG). The aim of this study was to determine socio-demographic, clinical, personality, and psychopathological predictors of relapse and dropout in a sample of pathological gamblers seeking treatment. A total of 566 consecutive outpatients diagnosed with PG according to DSM-IV-TR criteria were included. All patients underwent an individualized cognitive-behavioral treatment program. We analyzed predictors of relapse during 6months of treatment and during the subsequent 6months of follow-up, and predictors of dropout over the entire therapeutic program. Eighty patients (14.1%) experienced at least one relapse during the entire follow-up of the study: 50 (8.8%) within the treatment period and 12 (2.1%) during the subsequent 6-month follow-up period. The main predictors of relapse were single marital status, spending less than 100euros/week on gambling, active gambling behavior at treatment inclusion, and high scores on the TCI-R Harm Avoidance personality dimension. One hundred fifty-seven patients (27.8%) missed 3 or more therapeutic sessions over the entire therapeutic program. The main predictors of dropout were single marital status, younger age, and high scores on the TCI-R Novelty Seeking personality dimension. The presence of these factors at inclusion should be taken into account by physicians dealing with PG patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

    Hasanjani Roushan, Mohammad Reza; Moulana, Zahra; Afshar, Zeinab Mohseni; Ebrahimpour, Soheil

    2016-01-01

    Background & Propose: Brucellosis is serious disease around the world, especially in underdeveloped countries. Relapse is major problem in therapy of brucellosis. This study aimed to evaluate risk factors of relapse after treatment in patients. Methods: It is a descriptive-analytic study from 1990 to 2014, in Ayatolla Rohani hospital in Babol, Iran. We studied 980 patients with brucellosis. The studied community included patients infected with brucellosis and the required information was gathered based on their hospital files. The base for recognizing Malta fever were clinical symptoms and Para-clinical sign congruent with infection like as, titer SAT>1:320 and 2-ME>1:160. Patients with relapse and patients without relapse were placed separately in two groups. The data were statistically compared with Spss 16, by Chi-square and Cox–regression tests. Results: Based on this study, treatment regimen is a preventive factor (P=0.000). Moreover, Based on some statistical methods, regimens no. 3 and 4 were introduce preventive factors (P=0.001) and (P=0.004). It should also be noted that findings the same statistical model, factors like gender, age, residence, professional contacts, complications and delay in treatment were also analyzed but none of them are considered as preventive factors. Conclusion: Based our finding, we suggest aminoglycosides (gentamicin or streptomycin with doxycycline) are associated with lower rate of relapse in brucellosis. PMID:26925907

  15. Retention and relapse in clinical practice.

    PubMed

    Littlewood, S J; Kandasamy, S; Huang, G

    2017-03-01

    Maintaining teeth in their corrected positions following orthodontic treatment can be extremely challenging. Teeth have a tendency to move back towards the original malocclusion as a result of periodontal, gingival, occlusal and growth related factors. However, tooth movement can also occur as a result of normal age changes. Because orthodontics is unable to predict which patients are at risk of relapse, those which will remain stable and the extent of relapse that will occur in the long-term, clinicians need to treat all patients as if they have a high potential to relapse. To reduce this risk, long term retention is advocated. This can be a significant commitment for patients, and so retention and the potential for relapse must form a key part of the informed consent process prior to orthodontic treatment. It is vital that patients are made fully aware of their responsibilities in committing to wear retainers as prescribed in order to reduce the chance of relapse. If patients are unable or unwilling to comply as prescribed, they must be prepared to accept that there will be tooth positional changes following treatment. There is currently insufficient high quality evidence regarding the best type of retention or retention regimen, and so each clinician's approach will be affected by their personal, clinical experience and expertise, and guided by their patients' expectations and circumstances.

  16. Children's need for favorable acoustics in schools

    NASA Astrophysics Data System (ADS)

    Nelson, Peggy B.

    2003-10-01

    Children continue to improve their understanding of speech in noise and reverberation throughout childhood and adolescence. They do not typically achieve adult performance levels until their late teenage years. As a result, schools that are designed to be acoustically adequate for adult understanding may be insufficient for full understanding by young children. In addition, children with hearing loss, those with attention problems, and those learning in a non-native language require even more favorable signal-to-noise ratios. This tutorial will review the literature gathered by the ANSl/ASA working group on classroom acoustics that shaped the recommendations of the working group. Special topics will include speech perception data from typically developing infants and children, from children with hearing loss, and from adults and children listening in a non-native language. In addition, the tutorial will overview recommendations contained within ANSI standard 12.60-2002: Acoustical Performance Criteria, Design Requirements, and Guidelines for Schools. The discussion will also include issues related to designing quiet classrooms and working with local schools and professionals.

  17. Favorable outcome of epileptic blindness in children.

    PubMed

    Shahar, Eli; Barak, Shai

    2003-01-01

    Acute blindness is a rare presentation of epileptic seizures, referring to loss of sight without loss of consciousness associated with electroencephalographic (EEG) epileptic discharges, mainly representing an ictal phase but also either pre- or postictal. We report a series of 14 children with documented epileptic blindness, describing the accompanying fits and thereafter the response to therapy to resolve the blindness and control associated seizures. All patients experienced episodes of acute complete visual obscuration lasting for 1 to 10 minutes. Seven patients hadaccompanying generalized seizures, with a photosensitive response recorded in three of them. All of these seven children were treated with valproic acid, regaining full vision, and six of them became seizure free. Three patients with acute blindness who had accompanying focal motor seizures and unilateral temporooccipital posterior epileptic discharges were treated with carbamazepine regained full vision and complete seizure control. Four additional children had the constellation of migrainous headaches, focal motor phenomena, and complete blindness, along with occipital discharges compatible with Gastaut syndrome, benign childhood epilepsy with occipital paroxysms. All four patients were started on carbamazepine and became asymptomatic. Our overall experience suggests that epileptic blindness in children is associated with a favorable outcome when promptly diagnosed and treated appropriately, resulting in complete resolution of blindness in all children and satisfactory control of seizures in most of them. We therefore recommend performing a prompt EEG in any child presenting with acute visual obscuration, even in the absence of other epileptic phenomena.

  18. Colorectal tumors: the histology report.

    PubMed

    Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

    2011-03-01

    Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed.

  19. Histological evaluation of electrosurgery and formocresol pulpotomy techniques in primary teeth in dogs.

    PubMed

    El-Meligy, O; Abdalla, M; El-Baraway, S; El-Tekya, M; Dean, J A

    2001-01-01

    The purpose of this study was to compare pulpal and periapical tissue reactions to electrosurgery versus formocresol pulpotomy techniques in the primary teeth of dogs. The study was conducted on 33 primary teeth of three mongrel dogs between the ages of one to three months. Each dog had three teeth treated by Formocresol Pulpotomy with Mechanical Coronal Pulp Removal (FC), three teeth treated by Electrosurgery Pulpotomy with Mechanical Coronal Pulp Removal (ES/MCPR), three teeth treated by Electrosurgery Pulpotomy with Electrosurgical Coronal Pulp Removal (ES/ECPR), and two teeth serving as untreated Controls. Dogs one, two and three were sacrificed performing the pulpotomies at two, four and six weeks, respectively. The pulp, periapical tissue and after surrounding bone were submitted to histological examination and the histological reaction was recorded. The results were fourteen out of 18 unfavorable and zero out of three favorable histological reactions occurred in the FC treated teeth. Six out of 18 unfavorable and one out of three favorable histological reactions occurred in the ES/MCPR treated teeth. Nine out of 18 unfavorable and two out of three favorable histological reactions occurred in the ES/ECPR treated teeth. One out of 18 unfavorable and zero out of three favorable histological reactions occurred in the untreated Control teeth. The conclusion of this study is that of the three experimental groups, the teeth treated by Electrosurgery Pulpotomy with either Mechanical or Electrosurgical Coronal Pulp Removal exhibited less histopathological reaction than the teeth treated by Formocresol Pulpotomy.

  20. Mutational profiling of acute lymphoblastic leukemia with testicular relapse.

    PubMed

    Ding, Ling-Wen; Sun, Qiao-Yang; Mayakonda, Anand; Tan, Kar-Tong; Chien, Wenwen; Lin, De-Chen; Jiang, Yan-Yi; Xu, Liang; Garg, Manoj; Lao, Zhen-Tang; Lill, Michael; Yang, Henry; Yeoh, Allen Eng Juh; Koeffler, H Phillip

    2017-03-02

    Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (<1-2%). We selected two pediatric ALL patients who experienced testicular relapse and interrogated their leukemic cells with exome sequencing. The sequencing results and clonality analyses suggest that relapse of patient D483 directly evolved from the leukemic clone at diagnosis which survived chemotherapy. In contrast, relapse leukemia cells (both bone marrow and testis) of patient D727 were likely derived from a common ancestral clone, and testicular relapse likely arose independently from the bone marrow relapsed leukemia. Our findings decipher the mutational spectra and shed light on the clonal evolution of two cases of pediatric ALL with testicular relapse. Presence of CREBBP/NT5C2 mutations suggests that a personalized therapeutic approach should be applied to these two patients.

  1. Phase II study of recombinant interleukin 1alpha and etoposide in patients with relapsed osteosarcoma.

    PubMed

    Worth, L L; Jaffe, N; Benjamin, R S; Papadopoulos, N E; Patel, S; Raymond, A K; Jia, S F; Rodriguez, C; Gano, J; Gianan, M A; Kleinerman, E S

    1997-10-01

    A Phase II trial using interleukin 1alpha (IL-1alpha) and etoposide for patients with relapsed osteosarcoma (OS) was undertaken to assess the feasibility and tolerability of combination therapy with biotherapy and chemotherapy. Nine patients with histologically proven relapsed OS were treated with IL-1alpha immediately followed by etoposide daily for 5 days every 3 weeks. Surgical resection of lung metastasis or peripheral tumor was performed after two or three cycles. We observed three partial responses; disease was stable in another case. One case could not be evaluated. The side effects associated with combination therapy were as predicted from known side effects of the individual agents; however, more profound neutropenia was observed. Four patients exhibited clinical signs of capillary leak syndrome, i.e., hypotension, edema, and weight gain. The etiology of the capillary leak was unclear, because serum IL-1alpha, IL-2, tumor necrosis factor, and nitric oxide levels could not be used to predict which patients would develop capillary leak. Histological analysis of tumor specimens obtained after two or more courses of therapy showed changes consistent with a response to a biological response modifier: peripheral fibrosis surrounded the metastasis with infiltration of chronic and acute inflammatory cells. Because the response of relapsed OS to any type of salvage regimen has been poor, we interpret the clinical response of this therapy as good. However, the significant side effects associated with this therapy must also be taken into consideration before deciding to use this combination therapy. It is unfortunate that the study was stopped early due to halted production of IL-1alpha. If this agent is again manufactured for clinical use, we conclude that additional evaluation in patients with relapsed OS is warranted.

  2. Clinical Utility of Glatiramer Acetate in the Management of Relapse Frequency in Multiple Sclerosis

    PubMed Central

    Fernández, Oscar

    2012-01-01

    Glatiramer acetate (GA) represents one of the most common disease-modifying therapies for multiple sclerosis. GA is currently approved for patients at high risk of developing clinically definite multiple sclerosis (CDMS) after having experienced a well-defined first clinical episode (clinically isolated syndrome or CIS) and for patients with relapsing-remitting multiple sclerosis (RRMS). GA’s efficacy and effectiveness to reduce relapse frequency have been proved in placebo-controlled and observational studies. Comparative trials have also confirmed the lack of significant differences over other choices of treatment in the management of relapse frequency, and long-term studies have supported its effect at extended periods of time. Additionally, RRMS patients with suboptimal response to interferon β may benefit from reduced relapse rate after switching to GA, and those with clinically isolated syndrome may benefit from delayed conversion to CDMS. All these results, together with its proven long-term safety and positive effect on patients’ daily living, support the favorable risk-benefit of GA for multiple sclerosis treatment. PMID:23650472

  3. Relapsed chronic lymphocytic leukemia retreated with rituximab: interim results of the PERLE study.

    PubMed

    Chaoui, Driss; Choquet, Sylvain; Sanhes, Laurence; Mahé, Béatrice; Hacini, Maya; Fitoussi, Olivier; Arkam, Yazid; Orfeuvre, Hubert; Dilhuydy, Marie-Sarah; Barry, Marly; Jourdan, Eric; Dreyfus, Brigitte; Tempescul, Adrian; Leprêtre, Stéphane; Bardet, Aurélie; Leconte, Pierre; Maynadié, Marc; Delmer, Alain

    2017-06-01

    This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%). The overall response rate (ORR) was 74.6%, in favor of R-purine analogs (90%), R-bendamustine (75%), and R-alkylating agents (69%). Lower ORR in Del 17p patients (43%) and third time rituximab (31%). Most frequent adverse events were hematological (23% patients) including neutropenia (11%) and infections (12%); grade 3/4 AEs (23% patients), mainly hematological (18%); death during induction treatment (7%). This first large study focusing on relapsed/refractory CLL patients retreated with rituximab-based regimens is still ongoing.

  4. [Remission and relapse in the outpatient treatment of patients with schizophrenia. Outcomes at 3 years].

    PubMed

    Haro, J M; Ciudad, A; Alonso, J; Bousoño, M; Suárez, D; Novick, D; Gilaberte, I

    2008-01-01

    Three year data collected in the frame of the SOHO study within Spain were used to evaluate antipsychotic treatment outcomes by analyzing remission and relapse as well as the factors influencing them. The SOHO was a prospective, long-term, observational study of the outcomes of schizophrenia treatment in ambulatoty who initiated therapy or who changed to a new antipsychotic drug performed in 10 European countries, with a focus on olanzapine. This article reports the attainment of international schizophrenia clinical remission and relapse criteria and the associated correlates in these patients. A total of 2,020 patients were recruited in Spain. Almost 2/3 (60.1%) of the patients met the criteria for clinical remission. Factors that influence the likelihood of remission were identified, such as gender, baseline clinical and/or functional status, time since treatment initiation, treatment with olanzapine versus oral typical antipsychotics, duration of treatment, gender or the need for concomitant anxiolytics. Relapse occurred in 18.7% of patients. Treatment with quetiapine or the prescription of anticholinergics was associated with a greater risk of relapse. These results highlight some prognostic factors of the course of schizophrenia and underscore the importance of the antipsychotic choice and its maintenance to achieve favorable long-term clinical outcomes in routine practice.

  5. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

    PubMed Central

    Cohan, Stanley

    2016-01-01

    Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

  6. Neuromyelitis optica relapses: Race and rate, immunosuppression and impairment.

    PubMed

    Tackley, George; O'Brien, Fanny; Rocha, João; Woodhall, Mark; Waters, Patrick; Chandratre, Saleel; Halfpenny, Christopher; Hemingway, Cheryl; Wassmer, Evangeline; Wasiewski, Warren; Leite, Maria Isabel; Palace, Jacqueline

    2016-05-01

    Neuromyelitis optica (NMO) is a rare antibody-mediated CNS disease characterised by disabling relapses leading to high morbidity and mortality. Understanding relapse activity and severity is important for treatment decisions and clinical trial design. We assessed (1) whether clinical and demographic factors associate with different relapse rates and (2) the relative impact of immunosuppressive treatments on relapse rates and on attack-related residual disability. Clinical, demographic and treatment data were prospectively collected from 79 consecutive aquaporin 4 antibody positive patients seen in the nationally commissioned Oxford NMO service. The influence of clinical features on annualised relapse rates (using multiple regression) and the effect of immunosuppression on relapse-associated residual disability for transverse myelitis and optic neuritis attacks (using a mixed effect model) were analysed. The mean annualised relapse rate was 0.93. Relapse rates were significantly higher in Afro-Caribbeans, children and in those of shorter disease duration. Relapse rates reduced on treatment (from 0.87 to 0.42). Delay to first treatment did not influence eventual on-treatment relapse rate. Immunosuppressive treatment significantly reduced the residual disability from ON (p<0.01), and TM (p=0.029) attacks. Relapse rates in NMO are influenced by multiple factors, including age, ethnicity and disease duration. Current immunosuppressive treatments reduce but do not abolish relapses, however, they appear to additionally lessen the chronic disabling effect of a relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. The neurobiology of alcohol craving and relapse.

    PubMed

    Seo, Dongju; Sinha, Rajita

    2014-01-01

    A major block to recovery from alcoholism is substantial alcohol craving and the chronic relapsing nature of the illness. This chapter reviews relevant structural and functional neuroimaging studies and discusses neural mechanisms underlying alcohol craving and relapse in the context of influential risk factors (i.e., alcohol, alcohol cue, and stress). Review of neuroimaging studies suggests that neuroadaptations in the cortico-striatal-limbic circuit encompassing the medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, striatum, and amygdala significantly contribute to overwhelming alcohol craving and early relapse after a period of abstinence. The cortico-striatal-limbic circuit plays an important role in the modulation of emotion, reward, and decision making. As functional and structural chronic alcohol-related neuroadaptations are consistently reported in this circuit, it is likely that sensitization of this circuit from continued alcohol abuse may contribute to high alcohol craving and early relapse via impairments in the prefrontal executive function related to emotion regulation and decision making. This vulnerable neurobiologic state may be manifested as compulsive craving and intense urge to resume alcohol drinking in the face of environmental risk factors, including alcohol, alcohol cue, or stressful live events. © 2014 Elsevier B.V. All rights reserved.

  8. A Typology of Relapse Promoting Situations.

    ERIC Educational Resources Information Center

    Shiffman, Saul

    Outcome data on smoking cessation has emphasized that most people have difficulty not in quitting smoking, but in maintaining cessation. An attempt was made to develop a more meaningful typology of relapse-promoting situations using a sample of 183 exsmokers who called a telephone hotline seeking help to stay away from cigarettes. Two higher order…

  9. Immunotoxin Therapy for Relapsed Hairy Cell Leukemia

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have relapsed multiple times or not responded to prior chemotherapy will be treated with an experimental immunotoxin called moxetumomab pasudotox given intravenously on days 1, 3, and 5 of 28-day cycles

  10. Attributions and Relapse in Opiate Addicts.

    ERIC Educational Resources Information Center

    Bradley, Brendan P.; And Others

    1992-01-01

    Investigated whether attributions of opiate addicts would predict abstinence and reactions to abstinence violations. Found that addicts who at admission attributed to themselves greater responsibility for negative outcomes and who attributed relapse episodes to more personally controllable factors were subsequently more likely either to be…

  11. Resistance to Change and Relapse of Observing

    ERIC Educational Resources Information Center

    Thrailkill, Eric A.; Shahan, Timothy A.

    2012-01-01

    Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI…

  12. Resistance to Change and Relapse of Observing

    ERIC Educational Resources Information Center

    Thrailkill, Eric A.; Shahan, Timothy A.

    2012-01-01

    Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI…

  13. Comparison of relapse rates and of mucosal abnormalities after healing of duodenal ulceration and after one year's maintenance with cimetidine or sucralfate: a light and electron microscopy study.

    PubMed Central

    Tovey, F I; Husband, E M; Yiu, Y C; Baker, L; McPhail, G; Lewin, M R; Jayaraj, A P; Clark, C G

    1989-01-01

    Forty six patients with endoscopically diagnosed duodenal ulceration were randomly allocated to treatment with either sucralfate 1 g qds (n = 24) or cimetidine 200 mg tds and 400 mg nocte (n = 22). When the ulcers healed, a maintenance dose of sucralfate 1 g bd or cimetidine 400 mg nocte was given for one year (or until relapse if earlier). Biopsies of duodenal mucosa adjacent to ulcer sites for light and electron microscopy were obtained before and after healing and again after one year's maintenance if the ulcer remained healed. Duodenal biopsies were also taken from 20 age and sex matched controls. Rates of healing and relapse during maintenance did not differ between the two treatments, although relapses occurred earlier with cimetidine. In the three year post-maintenance follow up period 10/13 cimetidine patients relapsed compared with four of 11 sucralfate patients (p less than 0.05), the relapses occurring significantly earlier in the cimetidine treated patients (p less than 0.05). Mucosal biopsies from both treatment groups still showed considerable abnormalities after healing. During maintenance, however, the sucralfate scores fell significantly (p less than 0.02) to near control levels unlike the cimetidine scores which remained raised at pretreatment values. The histological and ultrastructural changes were not predictive of later relapse. These findings favour the use of sucralfate in preference to cimetidine for maintenance treatment in the prevention of relapse of healed duodenal ulcers. Images Fig. 1 Fig. 2 PMID:2731750

  14. Psychological and environmental determinants of relapse in crack cocaine smokers.

    PubMed

    Wallace, B C

    1989-01-01

    The paper reviews approaches to relapse in the treatment of cocaine abusers. Approaches reveal a common mechanism underlying relapse that involves drug craving, recall of euphoria, environmental cues, denial, myths of being able to sell or use drugs, and painful affect states necessitating use of a multifaceted clinical technique. Empirical validation of a common mechanism underlying relapse establishes a typology of psychological and environmental determinants of relapse for crack cocaine smokers (N = 35) who relapse after hospital detoxification and return a second time. Major findings are that relapse follows a painful emotional state (40%), failure to enter arranged aftercare treatment (37%), or encounters with conditioned environmental stimuli (34%), and involves narcissistic psychopathology and denial (28.5%) and interpersonal stress (24%); 85.7% involve multideterminants. Case examples illustrate the role of multideterminants in relapse. The paper educates clinicians to the integrated theory and multifaceted clinical technique necessary for efficacious treatment of cocaine patients, while the typology predicts probable relapse situations.

  15. mTOR pathway activation is a favorable prognostic factor in human prostate adenocarcinoma

    PubMed Central

    Stelloo, Suzan; Sanders, Joyce; Nevedomskaya, Ekaterina; de Jong, Jeroen; Peters, Dennis; van Leenders, Geert J.L.H.; Jenster, Guido; Bergman, Andries M.; Zwart, Wilbert

    2016-01-01

    Prostate cancer patients with localized disease are treated with curative intent. However, the disease will recur in approximately 30% of patients with a high incidence of morbidity and mortality. Prognostic biomarkers are needed to identify patients with high risk of relapse. mTOR pathway activation is reported in prostate cancer, but clinical trials testing efficacy of mTOR inhibitors were unsuccessful. To explain this clinical observation, we studied the expression and prognostic impact of mTOR-S2448 phosphorylation in localized prostate carcinomas. mTOR-S2448 phosphorylation is indicative for an activated mTOR pathway in prostate cancer. Surprisingly, the mTOR signaling pathway is activated specifically in prostate cancer patients with a favorable outcome. Since tumors from poor-outcome patients have low levels of mTOR-S2448 phosphorylation, this may explain why mTOR inhibitors proved unsuccessful in prostate cancer trials. PMID:27096957

  16. Histologic chorioamnionitis: different histologic features at different gestational ages.

    PubMed

    Torricelli, Michela; Voltolini, Chiara; Toti, Paolo; Vellucci, Francesca Letizia; Conti, Nathalie; Cannoni, Alice; Moncini, Irene; Occhini, Rossella; Severi, Filiberto Maria; Petraglia, Felice

    2014-06-01

    The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery. Three hundred and ninety-two women with singleton pregnancy with spontaneous onset of labor either prematurely or at term, with histologic diagnosis of HCA, were enrolled. Placentas were classified as: deciduitis and/or histologic chorioamnionitis within the membranes (HCA1); amnionitis or inflammation of the chorionic plate without funisitis (HCA2); and histologic chorioamnionitis with funisitis (HCA3). Microbiological culture was performed on both placental and fetal membrane samples. HCA1 was more frequent in women delivering at term than in preterm (p < 0.001). HCA2 was more represented in women delivering between 32 and 36 weeks (p < 0.001) and HCA3 occurred more frequently in those delivering within 32 weeks (p < 0.001). The positive bacterial culture was higher (p = 0.008) in presence of HCA3 in comparison with HCA1 and HCA2. This study showed a significantly different distribution of HCA grades in relation to gestational age at delivery. HCA may represent the expression of different subtending etiologies and may also reflect specific immune competence of gestational tissues at different gestational ages, strengthening as pregnancy advances.

  17. [Influence of KU-1257 on the recurrence and relapse of acetic acid-induced chronic gastric ulcers in rats].

    PubMed

    Sekiguchi, H; Ohsawa, A; Kobayashi, F; Ohkubo, H; Taga, F

    1996-02-01

    The influence of KU-1257 on the recurrence and relapse of acetic acid ulcers in rats was investigated grossly and histologically in comparison with that of cimetidine. The ulcer was induced by topical application of glacial acetic acid at the junction of the corpus and antrum on the anterior wall of the stomach. The drug was administered from the 5th to the 153rd day after the ulcer induction and then discontinued to the 238th day. The healing rates of the control groups (control) rose until the 119th day after the ulcer induction, followed by ups and downs. The quality of healing in the regenerated mucosa and the granulation tissue of the healed ulcer was poor, resulting in the recurrence and relapse of ulcers. The recurrence and relapse of ulcers also occurred in the cimetidine groups (CIM). On the other hand, the KU-1257 groups (KU-1257) showed much lower recurrence and relapse rates of ulcers than the control and CIM groups. Moreover, KU-1257, unlike CIM, improved the quality of ulcer healing throughout the period of its administration and even after it was discontinued. These results suggest that KU-1257 improves the quality of ulcer healing, and this may contribute to the low recurrence and relapse rates of ulcers.

  18. "Worried about relapse": Family members' experiences and perspectives of relapse in first-episode psychosis.

    PubMed

    Lal, Shalini; Malla, Ashok; Marandola, Gina; Thériault, Joanie; Tibbo, Phil; Manchanda, Rahul; Williams, Richard; Joober, Ridha; Banks, Nicola

    2017-05-19

    The purpose of this study was to gain an in-depth understanding on the subject of relapse from the perspectives of family members of young people receiving services for a first-episode psychosis (FEP). A qualitative descriptive approach, using focus group methods, was used to elicit experiences, understandings, and knowledge of relapse in FEP. Family members were recruited from 4 specialized early intervention programmes for psychosis in Canada. A total of 24 (6 male, 18 female) family members participated in the study. Thematic analysis was used to examine the data. The core underlying theme in all focus groups was worrying about relapse, which was often accompanied by significant levels of fear and anxiety, and was influenced by: (1) impact of an episode of psychosis; (2) limited confidence in recognizing and coping with relapse; (3) unmet needs for coping skills and emotional support and (4) unmet needs regarding frequency and continuity of communication with clinicians. Family members' unmet needs for relapse-focused education, support and communication with service providers and peers, can have a negative impact on relapse prevention. Addressing family members' education and support needs in a tailored manner (including preferences for types of peer support) can contribute positively to their confidence and ability to recognize and respond to relapse. This can help reduce fear and anxieties about relapse, and positively influence the ability to function as caregivers. Future research should focus on best approaches for providing education, sustained contact with the clinical team and family peer support. © 2017 John Wiley & Sons Australia, Ltd.

  19. Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis.

    PubMed

    Boster, Aaron L; Ford, Corey C; Neudorfer, Orit; Gilgun-Sherki, Yossi

    2015-06-01

    Glatiramer acetate (GA) is approved for relapsing-remitting multiple sclerosis in 57 countries worldwide, with more than 2 million patient-years of exposure and over 20 years of continuous clinical use without new safety concerns. GA has an overall favorable risk-benefit profile: 30% reduced annual relapse rate and decreased brain lesion activity. In clinically definite MS or clinically isolated syndrome, GA slows brain atrophy, which may be related to its unique anti-inflammatory and neuroprotective mechanisms of action. Early treatment with GA delays the onset of clinically definite MS more effectively than late treatment in clinically isolated syndrome. GA is not associated with immunosuppression, autoimmune disease, infections or development of neutralizing antibodies. A new three-times-weekly formulation of GA is available to potentially reduce the incidence of injection-related side effects. Other safety advantages of GA include its pregnancy rating (Category B) and limited uncontrolled data suggesting that tolerability is similar in children with MS.

  20. A double-blind, placebo-controlled, randomized trial of cladribine in relapsing-remitting multiple sclerosis.

    PubMed

    Romine, J S; Sipe, J C; Koziol, J A; Zyroff, J; Beutler, E

    1999-01-01

    We conducted an 18-month, placebo-controlled, double-blind study to evaluate cladribine in the treatment of 52 patients with relapsing-remitting multiple sclerosis. Patients received either placebo or cladribine 0.07 mg/kg/day by subcutaneous injection for 5 consecutive days as six monthly courses for a total cumulative dose of 2.1 mg/kg. Analysis of results revealed a statistically significant favorable effect of cladribine on the joint frequency and severity of relapses and magnetic resonance imaging (MRI) findings. MRI-enhancing lesions were completely suppressed in the cladribine patients by the sixth month of treatment. Mild segmental herpes zoster occurred in two cladribine-treated patients and one patient receiving placebo. Otherwise, there were no side effects or adverse events. We conclude that cladribine shows promise as a treatment for relapsing-remitting multiple sclerosis.

  1. Clinical and radiological control of highly active relapsing-remitting multiple sclerosis with first-line natalizumab.

    PubMed

    Meca-Lallana, José Eustasio; Carreón-Guarnizo, Ester; Hernández-Clares, Rocío; García-Molina, Estefanía; Díaz-Pérez, José; Leon-Hernández, Adelaida; Zamarro-Parra, Joaquín; Martín-Fernández, José Javier

    2017-06-01

    A 33-year-old man with gait instability, weakness of the left lower extremity, decreased visual acuity in the left eye, and urgency and urine incontinence was diagnosed of relapsing-remitting multiple sclerosis. He was treated with natalizumab (300 mg intravenously every 4 weeks) as first-line therapy, which reached at 6 months a favorable clinical evolution and dramatic radiological improvement (T2-weighted lesion load decreased by 50% and no gadolinium-enhancing T1 lesions) sustained over the course of 8 years. This clinical case shows the efficacy of natalizumab in a real-world setting and, particularly, the sustained effect of this drug in the long term as demonstrated by persistent radiological improvement. Natalizumab can be considered as the treatment of choice in relapsing-remitting multiple sclerosis forms presenting with two relapses and gadolinium-enhancing (Gd+) lesions.

  2. Isotretinoin and acne--a study of relapses.

    PubMed

    Chivot, M; Midoun, H

    1990-01-01

    A study was carried out involving 172 patients with acne which warranted treatment with isotretinoin. Patients were followed up for between 12 and 41 months after discontinuation of treatment and the number of relapses was assessed. 37 patients (21%) relapsed. These relapses were correlated with patients' age, length of disease progression prior to treatment, total dose received, daily dose, duration of treatment and severity of acne. It appeared that only young age and severity of acne influenced the percentage of relapse.

  3. Developing Cognitive Behavioral Therapy to Prevent Depressive Relapse in Youth

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Stewart, Sunita M.; Hughes, Jennifer L.; Jarrett, Robin B.; Emslie, Graham J.

    2008-01-01

    Relapse rates for children and adolescents with major depressive disorder (MDD) range from 30% to 40% within 1 to 2 years after acute treatment. Although relapse rates are high, there have been relatively few studies on the prevention of relapse in youth. While acute phase pharmacotherapy has been shown to reduce symptoms rapidly in depressed…

  4. Developing Cognitive Behavioral Therapy to Prevent Depressive Relapse in Youth

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Stewart, Sunita M.; Hughes, Jennifer L.; Jarrett, Robin B.; Emslie, Graham J.

    2008-01-01

    Relapse rates for children and adolescents with major depressive disorder (MDD) range from 30% to 40% within 1 to 2 years after acute treatment. Although relapse rates are high, there have been relatively few studies on the prevention of relapse in youth. While acute phase pharmacotherapy has been shown to reduce symptoms rapidly in depressed…

  5. Pure Testicular Seminoma Relapsing Late with Somatic Type Malignancy

    PubMed Central

    Anheuser, Petra; Gehrckens, Ralf; Wilczak, Waldemar; Sauter, Guido; Höflmayer, Doris

    2017-01-01

    Background. Somatic type malignancy (STM) occurs in 2% of all germ cell tumours (GCTs). The prognosis is unfavourable and the origin is poorly understood. Pathogenetic hypotheses involve direct transformation of teratoma, origin from totipotent cancer cells, or derivation from yolk sac tumour elements. Case Presentation. A 31-year-old patient was cured from testicular seminoma clinical stage IIc by orchiectomy and cisplatin-based chemotherapy. Nine years later, he experienced a late relapse with a mass sized 5 × 6 cm located at the former metastatic site. As no remission occurred after chemotherapy with three cycles of cisplatin, ifosfamide and etoposide, the mass was surgically resected. Histologically, the specimen consisted of neurofibroma with areas of malignant peripheral nerve sheath tumour and spots with mature bone formation. FISH analysis disclosed isochromosome 12p in the majority of evaluated cells suggesting somatic type malignancy (STM) of GCT. The patient is well 1 year after surgery. Conclusion. The pathogenesis of this STM remains enigmatic. The origin from GCT was evidenced by documentation of isochromosome 12p. Unrecognized teratomatous elements in the primary and totipotent cancer cells surviving the first chemotherapy could be hypothesized to represent the origin. STM developing from seminoma cells would be another novel hypothesis. PMID:28367345

  6. Reordering Histology to Enhance Engagement

    ERIC Educational Resources Information Center

    Amerongen, Helen

    2011-01-01

    In redesigning the preclinical curriculum and shifting from a discipline-based approach to an organ system-based approach, faculty at the University of Arizona College of Medicine in Tucson took the opportunity to restructure the sequence of introductory histology content to make it more engaging and relevant. In this article, the author describes…

  7. [Histology of keratoglobus (author's transl)].

    PubMed

    Knieper, P; Rochels, R; Nover, A

    1980-07-01

    The authors examined four cases of keratoglobus and report here on the histological changes found: degenerative alterations of the epithelium, characteristic changes of Bowman's membrane, such as thinning, detachment and wrinkling, alterations of the stroma and secondary alterations of the Descemet's membrane. These results indicate that keratoglobus is nearly an extreme variant of keratoconus.

  8. Reordering Histology to Enhance Engagement

    ERIC Educational Resources Information Center

    Amerongen, Helen

    2011-01-01

    In redesigning the preclinical curriculum and shifting from a discipline-based approach to an organ system-based approach, faculty at the University of Arizona College of Medicine in Tucson took the opportunity to restructure the sequence of introductory histology content to make it more engaging and relevant. In this article, the author describes…

  9. Regional Relapse After Intensity-Modulated Radiotherapy for Head-and-Neck Cancer

    SciTech Connect

    Duprez, Frederic; Bonte, Katrien; De Neve, Wilfried; Boterberg, Tom; De Gersem, Werner; Madani, Indira

    2011-02-01

    Purpose: To evaluate the regional relapse rate in the elective neck using intensity-modulated radiotherapy (IMRT) for head-and-neck cancer. Methods and Materials: We retrospectively analyzed the data from 285 patients treated with IMRT between 2000 and 2008. The median dose prescription to the primary tumor and involved lymph nodes was 69 Gy in 32 fractions. The elective neck was treated simultaneously according to Protocol 1 (multiple dose prescription levels of 56-69 Gy; 2-Gy normalized isoeffective dose, 51-70 Gy; 222 patients) or Protocol 2 (one dose prescription level of 56 Gy; 2-Gy normalized isoeffective dose, 51 Gy; 63 patients). Primary surgery or lymph node dissection was performed before IMRT in 72 (25%) and 157 (55%) patients, respectively. Also, 92 patients (32%) received concomitant chemotherapy. The median follow-up of living patients was 27.4 months (range, 0.3-99). Results: Regional, local, and distant relapse were observed in 16 (5.6%), 35 (12.3%), and 47 (16.5%) patients, respectively. The 2- and 5-year rate of regional relapse was 7% and 10%, respectively, with a trend favoring Protocol 2 (p = 0.06). Seven isolated regional relapses were detected at a median follow-up of 7.3 months in patients treated with Protocol 1 and none in those treated with Protocol 2. Percutaneous gastrostomy was required more frequently in patients who received Protocol 1 (p = 0.079). Conclusion: Isolated regional relapse is rare after IMRT for head-and-neck cancer. Elective neck node doses >51 Gy for a 2-Gy normalized isoeffective dose do not seem to improve regional control.

  10. Teriflunomide in relapsing multiple sclerosis: therapeutic utility.

    PubMed

    Freedman, Mark S

    2013-09-01

    Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent benefits on both clinical and magnetic resonance imaging outcomes. In long-term studies, teriflunomide treatment was associated with low rates of relapse and disability progression for up to 8 years. The safety profile of teriflunomide has been well characterized, with adverse events generally mild to moderate in nature and infrequently leading to permanent treatment discontinuation. The evidence reviewed here indicates that teriflunomide is an effective addition to the current DMTs used to treat RMS.

  11. Tickborne Relapsing Fever, Bitterroot Valley, Montana, USA

    PubMed Central

    Christensen, Joshua; Fischer, Robert J.; McCoy, Brandi N.; Raffel, Sandra J.

    2015-01-01

    In July 2013, a resident of the Bitterroot Valley in western Montana, USA, contracted tickborne relapsing fever caused by an infection with the spirochete Borrelia hermsii. The patient’s travel history and activities before onset of illness indicated a possible exposure on his residential property on the eastern side of the valley. An onsite investigation of the potential exposure site found the vector, Ornithodoros hermsi ticks, and 1 chipmunk infected with spirochetes, which on the basis of multilocus sequence typing were identical to the spirochete isolated from the patient. Field studies in other locations found additional serologic evidence and an infected tick that demonstrated a wider distribution of spirochetes circulating among the small mammal populations. Our study demonstrates that this area of Montana represents a previously unrecognized focus of relapsing fever and poses a risk for persons of acquiring this tickborne disease. PMID:25625502

  12. Switching to BCL-6 Negativity in Relapsed Diffuse Large B Cell Lymphoma Correlated with More Aggressive Disease Course.

    PubMed

    Todorović, Milena; Balint, Bela; Andjelic, Bosko; Radisavljevic, Ziv; Mihaljevic, Biljana

    2014-12-01

    Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6(+) protein expression into BCL-6(-) expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6(-) patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6(+) and BCL-6(-) groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.

  13. Relapses in multiple sclerosis: Relationship to disability.

    PubMed

    Goodin, Douglas S; Reder, Anthony T; Bermel, Robert A; Cutter, Gary R; Fox, Robert J; John, Gareth R; Lublin, Fred D; Lucchinetti, Claudia F; Miller, Aaron E; Pelletier, Daniel; Racke, Michael K; Trapp, Bruce D; Vartanian, Timothy; Waubant, Emmanuelle

    2016-03-01

    Multiple sclerosis (MS) is a recurrent inflammatory disease of the central nervous system, which ultimately causes substantial disability in many patients. A key clinical feature of this disease is the occurrence of relapses, consisting of episodes of neurological dysfunction followed by periods of remission. This review considers in detail the importance of the occurrence of relapses to the ultimate course of MS and the impact of relap setreatment (both acutely and prophylactically) on the long-term outcome for individuals. The ultimate goal of therapy in MS is the reduction of long-term disability. Clinical trials in MS, however, typically only extend for a very short time period compared to the time it takes for disability to evolve. Consequently, short-term outcome measures that are associated with, and predict, future disability need to be identified. In this regard, not only are relapses a characteristic feature of MS, they have also been proven to be associated with the occurrence of long-term disability. Moreover, treatments that reduce the number and severity of these attacks improve the long-term prognosis.

  14. Therapeutic options in relapsed or refractory peripheral T-cell lymphoma.

    PubMed

    Coiffier, Bertrand; Federico, Massimo; Caballero, Dolores; Dearden, Claire; Morschhauser, Franck; Jäger, Ulrich; Trümper, Lorenz; Zucca, Emanuele; Gomes da Silva, Maria; Pettengell, Ruth; Weidmann, Eckhart; d'Amore, Francesco; Tilly, Hervé; Zinzani, Pier Luigi

    2014-10-01

    Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas with a very poor prognosis. Current therapies, based on historical regimens for aggressive B-cell lymphomas, have resulted in insufficient patient outcomes. The majority of patients relapse rapidly, and current 5-year overall survival rates are only 10-30%. It is evident that new approaches to treat patients with PTCL are required. In recent years, prospective studies in PTCL have been initiated, mainly in patients with relapsed/refractory disease. In some of these, selected histologic subtypes have been evaluated in detail. As a consequence, numerous new therapies have been developed and shown activity in PTCL, including: agents targeting the immune system (e.g. brentuximab vedotin, alemtuzumab, lenalidomide); histone deacetylase inhibitors (romidepsin, belinostat); antifolates (pralatrexate); fusion proteins (denileukin diftitox); nucleoside analogs (pentostatin, gemcitabine); and other agents (e.g. alisertib, plitidepsin, bendamustine, bortezomib). A variety of interesting novel combinations is also emerging. It is hoped that these innovative approaches, coupled with a greater understanding of the clinicopathologic features, pathogenesis, molecular biology, and natural history of PTCL will advance the field and improve outcomes in this challenging group of diseases. This review summarizes the currently available clinical evidence on the various approaches to treating relapsed/refractory PTCL, including the role of stem cell transplantation, with an emphasis on potential new drug therapies. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

    PubMed Central

    Domingo-Domenech, J; Mellado, B; Ferrer, B; Truan, D; Codony-Servat, J; Sauleda, S; Alcover, J; Campo, E; Gascon, P; Rovira, A; Ross, J S; Fernández, P L; Albanell, J

    2005-01-01

    Nuclear factor (NF)-κB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-κB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-κB active state. Nuclear localisation of NF-κB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-κB was detected in 57 (66.3%) specimens, and nuclear NF-κB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-κB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-κB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P=0.02), Gleason score (P=0.03) and nuclear NF-κB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-κB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-κB is an independent prognostic factor of biochemical relapse in prostate cancer. PMID:16278667

  16. A solitary uterine relapse in T-cell Acute Lymphoblastic Leukaemia: CT features and pathologic correlation.

    PubMed

    Mazzei, M A; Bettini, G; Pozzessere, C; Guerrini, S; Defina, M; Ambrosio, M R; Aprile, L; Bocchia, M; Volterrani, L

    2016-01-01

    T-cell Acute Lymphoblastic Leukemia (T-cell ALL) is a rare haematological neoplasia, that affects children and less commonly adults. Female genital tract and particularly uterus involvement in acute ALL is rare. This report presents the CT features of a 64-year-old woman with uterine relapse of T-cell ALL, occurring 11 months after the diagnosis, as a second, unique relapse of disease. The patient was asymptomatic when a CT examination showed a homogenous thickness of the uterine wall in comparison with the previous CT examination. Histology from biopsy specimens, obtained through hysteroscopy, confirmed T-cell ALL localisation (TdT+, CD10+, CD3c+ and CD2+). The uterus could be a site of relapse in patients suffering from ALL. Even though an MRI examination could better demonstrate the disease in cases of suspected female genital tract involvement by ALL, the comparison of differences between a present and a previous CT examination is sufficient to suspect the diagnosis.

  17. Pathways Linking Socioeconomic Status and Postpartum Smoking Relapse

    PubMed Central

    Businelle, Michael S.; Kendzor, Darla E.; Reitzel, Lorraine R.; Vidrine, Jennifer Irvin; Castro, Yessenia; Mullen, Patricia Dolan; Velasquez, Mary M.; Cofta-Woerpel, Ludmila; Cinciripini, Paul M.; Greisinger, Anthony J.; Wetter, David W.

    2012-01-01

    Background Low socioeconomic status (SES) exacerbates the high rate of smoking relapse in women following childbirth. Purpose This study examined multiple models of potential mechanisms linking SES and postpartum smoking relapse among women who quit smoking due to pregnancy. Methods Participants were 251 women enrolled in a randomized clinical trial of a new postpartum smoking relapse prevention intervention. Four models of the prepartum mechanisms linking SES and postpartum smoking relapse were evaluated using a latent variable modeling approach. Results Each of the hypothesized models were a good fit for the data. As hypothesized, SES indirectly influenced postpartum smoking relapse through increased prepartum negative affect/stress, reduced sense of agency, and increased craving for cigarettes. However, the model that included craving as the sole final pathway between SES and relapse demonstrated superior fit when compared with all other models. Conclusions Findings have implications for future interventions that aim to reduce postpartum relapse. PMID:23086590

  18. Neurodynamics of relapse prevention: a neuronutrient approach to outpatient DUI offenders.

    PubMed

    Brown, R J; Blum, K; Trachtenberg, M C

    1990-01-01

    The central nervous system rewarding properties of ethanol, cocaine, and heroin may activate a common catecholaminergic reward system in the mesolimbic circuitry of the brain. Driving-under-the-influence (DUI) offenders with either alcohol- or cocaine-related problems were studied. The neuronutrients SAAVE and Tropamine significantly reduced relapse rates and enhanced recovery in these DUI outpatient offenders over a 10-week period. Follow-up on both the SAAVE and Tropamine groups after 10 months revealed a 73% and a 53% overall recovery rate, respectively. These clinical results favor the use of these neuronutrients as adjuncts to psychological therapeutic modalities.

  19. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.

    PubMed

    Hauser, Stephen L; Bar-Or, Amit; Comi, Giancarlo; Giovannoni, Gavin; Hartung, Hans-Peter; Hemmer, Bernhard; Lublin, Fred; Montalban, Xavier; Rammohan, Kottil W; Selmaj, Krzysztof; Traboulsee, Anthony; Wolinsky, Jerry S; Arnold, Douglas L; Klingelschmitt, Gaelle; Masterman, Donna; Fontoura, Paulo; Belachew, Shibeshih; Chin, Peter; Mairon, Nicole; Garren, Hideki; Kappos, Ludwig

    2017-01-19

    B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. In two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate. The annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; hazard ratio, 0.60; 95% CI, 0.43 to 0.84; P=0.003). The mean number of gadolinium-enhancing lesions per T1-weighted magnetic resonance scan was 0.02 with ocrelizumab versus 0.29 with interferon beta-1a in trial 1 (94% lower number of lesions with ocrelizumab, P<0.001) and 0.02 versus 0.42 in trial 2 (95% lower number of lesions, P<0.001). The change in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper-limb movements, and cognition; for this z score, negative values indicate worsening and positive values indicate improvement) significantly favored ocrelizumab over interferon beta-1a in trial 2 (0.28 vs. 0.17, P=0.004) but not in trial 1 (0.21 vs. 0.17, P=0.33). Infusion-related reactions occurred in 34.3% of the patients treated with ocrelizumab. Serious infection occurred in 1.3% of the patients treated with ocrelizumab and in 2.9% of those treated with interferon beta-1a. Neoplasms occurred

  20. Predictors of Relapse and Dropout During a 12-Week Relapse Prevention Program for Methamphetamine Users.

    PubMed

    Chen, Yi-Chih; Chen, Chih-Ken; Wang, Liang-Jen

    2015-01-01

    In this research, the possible neuropsychological predictors of relapse and dropout of group cognitive behavioral therapy (CBT) for methamphetamine (MA) users were explored. Participants were 42 MA users sentenced by the judicial system to take part in an out-patient relapse prevention program for MA abuse and dependence that employs a CBT model once a week over the course of 12 weeks. Baseline neuropsychological functions were evaluated with the Conners' Continuous Performance Test, Wisconsin Card Sorting Test, Iowa Gambling Task, and Barratt Impulsiveness Scale. All participants had to submit to urine drug tests every week. Of the 42 participants, 69.0% had a MA positive urine screening result at least once throughout the program (relapse), while 40.5% dropped out of the treatment program prior to its completion. Short duration of MA abstinence at baseline and poor attention predicted relapse. Predictors of dropout included being unmarried and having risky decision making. Findings may be helpful for clinicians, who can screen for the aforementioned risk factors and provide strategies for high-risk patients to help prevent relapse and dropout among MA users in treatment programs.

  1. Impact of multiple sclerosis relapse: The NARCOMS participant perspective.

    PubMed

    Nickerson, Molly; Cofield, Stacey S; Tyry, Tuula; Salter, Amber R; Cutter, Gary R; Marrie, Ruth Ann

    2015-05-01

    Acute relapses continue to be a significant aspect of multiple sclerosis (MS) on both the epidemiologic level and the individual patient level. Past work demonstrates residual disability from relapses as well as high patient-reported rates of ineffective relapse treatment. To better characterize the impact of MS relapses on the patient, a relapse-specific survey was administered through the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry to 1000 registry participants who had reported at least one relapse in the past 12 months. Thirty percent of respondents confirmed lack of relapse treatment efficacy at one month and at three months. Relapses also impacted socioeconomic measures; for individuals still going to school or working, more than half missed days and their average loss of school or work was 12.7 days. An impact on household tasks was reported by 68% of respondents. A healthcare facility such as a hospital, emergency room or urgent care center was utilized by 20.4% of respondents. The most common relapse symptoms were fatigue, weakness of the lower extremity, sensory symptoms, problems walking, and weakness of the upper extremity. Of the respondents who reported receiving corticosteroid treatment (53.3%), over half reported an adverse event. However, this was not a significant factor in dictating whether or not respondents would seek a different treatment on their next relapse, although 31% would choose a different treatment for their next relapse. Relapses continue to be an impactful experience that requires continued clinical attention. Improved follow-up from relapses and relapse treatment might be beneficial.

  2. Anal anatomy and normal histology.

    PubMed

    Pandey, Priti

    2012-12-01

    The focus of this article is the anatomy and histology of the anal canal, and its clinical relevance to anal cancers. The article also highlights the recent histological and anatomical changes to the traditional terminology of the anal canal. The terminology has been adopted by the American Joint Committee on Cancer, separating the anal region into the anal canal, the perianal region and the skin. This paper describes the gross anatomy of the anal canal, along with its associated blood supply, venous and lymphatic drainage, and nerve supply. The new terminology referred to in this article may assist clinicians and health care providers to identify lesions more precisely through naked eye observation and without the need for instrumentation. Knowledge of the regional anatomy of the anus will also assist in management decisions.

  3. Adapting lean to histology laboratories.

    PubMed

    Buesa, René J

    2009-10-01

    Histology laboratories (histolabs) can increase productivity and reduce turnaround time and errors by using any one of several available management tools. After a few years of operation, all histolabs develop workflow problems. Histology laboratories handling more than 20,000 cases per year benefit the most from implementing management tools, as occurred in the 25 facilities summarized in this article. Discontinuous workflow, lack of "pulling" between steps, accepting unavoidable waiting times while working with small batches within work cells, and a workflow with an uneven rate of completion, are some of the adaptations required by the Lean system when it is used in histology because 70% of the tasks are manual and the flow has to be interrupted to add value to the pieces of tissue during tissue processing, no matter how short that step is. After all these adaptations are incorporated, the histolab becomes as "Lean" as it can be, and the qualifier is also a recognition of the effort and personnel involvement in the implementation. Given its service nature, productivity increments do not expand the histolab customer base and could lead to staffing reductions. This is one of the causes of reluctance by some employees for implementing these techniques which are mostly driven by cost reductions sought by insurance companies and administrators, and not necessarily because of a real medical need to reduce the turnaround time. Finally, any histolab wanting to improve its workflow can follow some easy steps presented here as a guide to accomplish that objective. These steps stress the need for the supervisors to insure that the personnel in the histology laboratory are being paid at a comparable rate as other histolabs in the area.

  4. Ipilimumab for Patients with Relapse after Allogeneic Transplantation

    PubMed Central

    Davids, Matthew S.; Kim, Haesook T.; Bachireddy, Pavan; Costello, Caitlin; Liguori, Rebecca; Savell, Alexandra; Lukez, Alexander P.; Avigan, David; Chen, Yi-Bin; McSweeney, Peter; LeBoeuf, Nicole R.; Rooney, Michael S.; Bowden, Michaela; Zhou, Chensheng W.; Granter, Scott R.; Hornick, Jason L.; Rodig, Scott J.; Hirakawa, Masahiro; Severgnini, Mariano; Hodi, F. Stephen; Wu, Catherine J.; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Armand, Philippe; Streicher, Howard; Ball, Edward D.; Ritz, Jerome; Bashey, Asad; Soiffer, Robert J.

    2016-01-01

    BACKGROUND Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were

  5. Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

    PubMed

    Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

    2016-07-01

    The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    PubMed

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies.

  7. New findings on biological factors predicting addiction relapse vulnerability.

    PubMed

    Sinha, Rajita

    2011-10-01

    Relapse is a highly prevalent phenomenon in addiction. This paper examines the new research on identifying biological factors that contribute to addiction relapse risk. Prospective studies examining relapse risk are reviewed, and clinical, biological, and neural factors that predict relapse risk are identified. Clinical factors, patient-related factors, and subjective and behavioral measures such as depressive symptoms, stress, and drug craving all predict future relapse risk. Among biological measures, endocrine measures such as cortisol and cortisol/corticotropin (ACTH) ratio as a measure of adrenal sensitivity and serum brain-derived neurotrophic factor were also predictive of future relapse risk. Among neural measures, brain atrophy in the medial frontal regions and hyperreactivity of the anterior cingulate during withdrawal were identified as important in drug withdrawal and relapse risk. Caveats pertaining to specific drug abuse type and phase of addiction are discussed. Finally, significant implications of these findings for clinical practice are presented, with a specific focus on determining biological markers of relapse risk that may be used to identify those individuals who are most at risk of relapse in the clinic. Such markers may then be used to assess treatment response and develop specific treatments that will normalize these neural and biological sequelae so as to significantly improve relapse outcomes.

  8. Predictors of relapse in patients with major depressive disorder in a 52-week, fixed dose, double blind, randomized trial of selegiline transdermal system (STS).

    PubMed

    Jang, Saeheon; Jung, Sungwon; Pae, Chiun; Kimberly, Blanchard Portland; Craig Nelson, J; Patkar, Ashwin A

    2013-12-01

    We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment. After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥ 14 and a CGI-S score of ≥ 3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse. For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis. While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across

  9. [Relapse and insomnia in unipolar major depression].

    PubMed

    Falussy, Linda; Balla, Petra; Frecska, Ede

    2014-09-01

    The connection between mood and sleep disorders is highly complex and can be studied and interpreted in many respects. Epidemiologic data show that the co-occurrence of the two disorders is quite frequent. Thus an approach regarding them as a unit promotes biological psychiatric research by revealing new pathophysiological and therapeutic conclusions. Chronobiological results related to mood disorders have recently been described in excellent reviews including Hungarian ones. In the present review, the necessity of treatment of sleep disorders is evaluated in the context of relapse/remission/recurrence. Scientific data suggest that patients with insomnia have a ten-fold risk of developing depression, and insomnia plays an important role in depression relapses, recurrence of depressive episodes and becoming depression chronic. From neurobiological point of view, mood and sleep disorders have many features in common. Research has revealed decreased levels of melatonin and advanced sleep phases (shifted earlier) in depression, and altered and imbalanced monoaminergic pathways, and REM abnormalities in sleep disorders. Some authors suggest that REM abnormalities disappear along with the mood improvement, and the sleep structure can completely restore after remission. However, persistent abnormalities of REM sleep and slow wave sleep have also been found in remission, which increased the risk of the relapse and recurrence. Recently, there is an agreement as to the early treatment of insomnia can prevent the development of mood abnormalities. Alterations of cascades related to neural plasticity can also be a link between sleep and mood disorders. Neural plasticity is closely related to learning, sleeping, and cortisol regulation (coping with stress), and this draws the attention to comorbidity with further disorders (anxiety, dementia).

  10. Resistance to change and relapse of observing.

    PubMed

    Thrailkill, Eric A; Shahan, Timothy A

    2012-05-01

    Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI schedule (i.e., S+). The components differed in the rate of food arranged (Rich  = VI 30 s; Lean  =  VI 120 s). In Experiment 1, following baseline training, extinction of observing involved removal of both food and S+ deliveries, and reinstatement was examined by presenting either response-independent food or S+ deliveries. In Experiment 2, extinction involved removal of only food deliveries while observing responses continued to produce S+. Reinstatement was examined by delivering food contingent upon the first two food-key responses occurring in the presence of the S+. Experiment 3 assessed ABA renewal of observing by extinguishing food-key and observing responses in the presence of one contextual stimulus (i.e., B) and then returning to the original training context (i.e., A) during continued extinction. Experiment 4 examined resurgence by introducing food reinforcement for an alternative response during extinction, and subsequently removing that alternative source of food. Across experiments, relative resistance to extinction and relapse of observing tended to be greater in the component previously associated with the higher rate of primary reinforcement. Relapse of observing or attending to stimuli associated with primary reinforcement appears to be impacted by frequency of primary reinforcement in a manner similar to responding maintained directly by primary reinforcement.

  11. Resistance to Change and Relapse of Observing

    PubMed Central

    Thrailkill, Eric A; Shahan, Timothy A

    2012-01-01

    Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI schedule (i.e., S+). The components differed in the rate of food arranged (Rich  = VI 30 s; Lean  =  VI 120 s). In Experiment 1, following baseline training, extinction of observing involved removal of both food and S+ deliveries, and reinstatement was examined by presenting either response-independent food or S+ deliveries. In Experiment 2, extinction involved removal of only food deliveries while observing responses continued to produce S+. Reinstatement was examined by delivering food contingent upon the first two food-key responses occurring in the presence of the S+. Experiment 3 assessed ABA renewal of observing by extinguishing food-key and observing responses in the presence of one contextual stimulus (i.e., B) and then returning to the original training context (i.e., A) during continued extinction. Experiment 4 examined resurgence by introducing food reinforcement for an alternative response during extinction, and subsequently removing that alternative source of food. Across experiments, relative resistance to extinction and relapse of observing tended to be greater in the component previously associated with the higher rate of primary reinforcement. Relapse of observing or attending to stimuli associated with primary reinforcement appears to be impacted by frequency of primary reinforcement in a manner similar to responding maintained directly by primary reinforcement. PMID:22693359

  12. HistoLogical, a computer atlas and drill of histology.

    PubMed

    Alper, E J; Cardasis, C

    1991-01-01

    An educational program has been developed to aid the instruction of Histology, a required course for the first year medical student. The program was developed using SuperCard on an Apple Macintosh IIci computer. It incorporates high quality color images with a hypermedia format, i.e. the student can jump from topic to topic as he/she wishes. The program has an "atlas," which provides information about each image and topic being discussed, and a "drill," which presents to the student a question about an image and provides feedback tailored to the student's answer. In the drill, the student is asked to type in responses to the questions; the answer is judged by text recognition. For each question, feedback is written for the correct answer, incorrect answer, and up to 10 "accessory answers" (answers which might be expected although they are not correct). The faculty of the UMMS Histology course has encouraged the use of this program in this years' course, and evaluation received from faculty and students has been quite positive.

  13. Staffing benchmarks for histology laboratories.

    PubMed

    Buesa, René J

    2010-06-01

    This article summarizes annual workloads for staff positions and work flow productivity (WFP) values from 247 human pathology, 31 veterinary, and 35 forensic histology laboratories (histolabs). There are single summaries for veterinary and forensic histolabs, but the data from human pathology are divided into 2 groups because of statistically significant differences between those from Spain and 6 Hispano American countries (SpHA) and the rest from the United States and 17 other countries. The differences reflect the way the work is organized, but the histotechnicians and histotechnologists (histotechs) from SpHA have the same task productivity levels as those from any other country (Buesa RJ. Productivity standards for histology laboratories. [YADPA 50,552]). The information is also segregated by groups of histolabs with increasing workloads; this aspect also showed statistical differences. The information from human pathology histolabs other than those from SpHA were used to calculate staffing annual benchmarks for pathologists (from 3700 to 6500 cases depending on the histolab annual workload), pathology assistants (20,000 cases), staff histotechs (9900 blocks), cutting histotechs (15,000 blocks), histotechs doing special procedures (9500 slides if done manually or 15,000 slides with autostainers), dieners (100 autopsies), laboratory aides and transcriptionists (15,000 cases each), and secretaries (20,000 cases). There are also recommendations about workload limits for supervisory staff (lead techs and supervisors) and when neither is required. Each benchmark was related with the productivity of the different tasks they include (Buesa RJ. Productivity standards for histology laboratories. [YADPA 50,552]) to calculate the hours per year required to complete them. The relationship between workload and benchmarks allows the director of pathology to determine the staff needed for the efficient operation of the histolab.

  14. Coeliac disease: the histology report.

    PubMed

    Villanacci, Vincenzo; Ceppa, Paola; Tavani, Enrico; Vindigni, Carla; Volta, Umberto

    2011-03-01

    To this day intestinal biopsy is justly considered the "gold standard" for the diagnosis of coeliac disease (CD). The aim of the authors in setting up these guidelines was to assist pathologists in formulating a more precise morphological evaluation of a duodenal biopsy in the light of clinical and laboratory data, to prepare histological samples with correctly oriented biopsies and in the differential diagnosis with other pathological entities and complications of the disease. A further intention was to promote the conviction for the need of a close collaborative relationship between different specialists namely the concept of a "multidisciplinary team".

  15. Gastric lymphoma: the histology report.

    PubMed

    Doglioni, Claudio; Ponzoni, Maurilio; Ferreri, Andrés J M; Savio, Antonella

    2011-03-01

    The diagnosis of gastric MALT lymphoma is frequently difficult for the general histopathologist. During recent years there have been relevant changes in the therapeutic approach to gastric MALT lymphoma and our knowledge about its pathogenesis has greatly improved. The management of this disease actually requires a close cooperation between the histopathologist and the clinicians. The histology report of biopsies of a newly diagnosed or of an already treated case implies information of clinical and therapeutical relevance. This paper aims at giving the histopathologist a general knowledge about the state of art of this disease and its management. The diagnostic process leading to a complete and competent report is then described step by step.

  16. Who Will Relapse? Symptoms of Nicotine Dependence Predict Long-Term Relapse after Smoking Cessation.

    ERIC Educational Resources Information Center

    Killen, Joel D.; And Others

    1992-01-01

    Conducted prospective examination of factors associated with smoking relapse. Findings from 618 subjects revealed that, at year 1, signal detection analysis (SDA) produced one subgroup with 25 percent nonrelapse rate and another with 9 percent nonrelapse rate. At year two, SDA produced one subgroup with 19 percent nonrelapse rate and another with…

  17. Relapsing herpes simplex encephalitis resulting in Kluver-Bucy syndrome.

    PubMed

    Ku, Bon D; Yoon, Sung Sang

    2011-01-01

    Relapsing herpes simplex encephalitis (HSE) rarely occurs after acyclovir treatment. We treated a patient with relapsing HSE of the contralateral temporal lobe, resulting in Klüver-Bucy syndrome, after a full-dose acyclovir treatment. This case suggests that physicians should consider sudden behavioral and emotional changes after HSE treatment as a possible indication of relapsing HSE, as well as possible temporal lobe epilepsy, and the need to administer longer acyclovir treatment for select patients.

  18. Internet-based relapse prevention for anorexia nervosa: nine- month follow-up

    PubMed Central

    2013-01-01

    Background To study the longer term effects of an internet-based CBT intervention for relapse prevention (RP) in anorexia nervosa. Methods 210 women randomized to the RP intervention group (full and partial completers) or the control group were assessed for eating and general psychopathology. Multiple regression analysis identified predictors of favorable course concerning Body Mass Index (BMI). Logistic regression analysis identified predictors of adherence to the RP program. Results Most variables assessed showed more improvement for the RP than for the control group. However, only some scales reached statistical significance (bulimic behavior and menstrual function, assessed by expert interviewers blind to treatment condition). Very good results (BMI) were seen for the subgroup of “full completers” who participated in all nine monthly RP internet-based intervention sessions. “Partial completers” and controls (the latter non-significantly) underwent more weeks of inpatient treatment during the study period than “full completers”, indicating better health and less need for additional treatment among the “full completers”. Main long-term predictors for favorable course were adherence to RP, more spontaneity, and more ineffectiveness. Main predictors of good adherence to RP were remission from lifetime mood and lifetime anxiety disorder, a shorter duration of eating disorder, and additional inpatient treatment during RP. Conclusions Considering the high chronicity of AN, internet-based relapse prevention following intensive treatment appears to be promising. PMID:24999404

  19. Treatment of relapsed and refractory multiple myeloma.

    PubMed

    Singhal, Seema; Mehta, Jayesh

    2003-06-01

    The definition of relapsed and refractory myeloma was straightforward when melphalan-prednisone constituted the mainstay of treatment and high-dose therapy with transplantation was rarely used in myeloma. However, several advances have occurred in the treatment of myeloma over the past decade. Most notably, high-dose therapy and transplantation have become broadly applicable, thalidomide has become available as effective salvage therapy, and several investigational agents with novel mechanisms of action appear to be very promising. Because of the differing properties of some of these agents, it is often possible to control the disease with an alternative treatment approach after the failure of one therapy. Some data indicate that combinations of these agents work when the drugs have failed individually. Therefore, refractory myeloma indicates disease unresponsive to the most recent therapy administered. Broadly, the salvage approaches that are used in patients with refractory or relapsed disease include high-dose dexamethasone, high-dose chemotherapy with autotransplantation, allogeneic hematopoietic stem cell transplantation, thalidomide-based therapies, and novel/investigational agents. The appropriate therapy for a given situation depends on the nature of the disease, age, organ function, bone marrow function, prior treatment, the availability of stem cell donors, and access to novel agents. A therapeutic trial of thalidomide is essential at some stage of the disease in all patients. High-dose therapy with autotransplantation is needed at some stage of the disease in most patients younger than 65 to 70 years.

  20. Risk of relapse after natalizumab withdrawal

    PubMed Central

    Vukusic, Sandra; Casey, Romain; Debard, Nadine; Stankoff, Bruno; Mrejen, Serge; Uhry, Zoe; Van Ganse, Eric; Castot, Anne; Clanet, Michel; Lubetzki, Catherine; Confavreux, Christian

    2016-01-01

    Objective: To assess disease activity within 12 months after natalizumab (NZ) discontinuation in a large French postmarketing cohort. Methods: In France, patients exposed at least once to NZ were included in the TYSEDMUS observational and multicenter cohort, part of the French NZ Risk Management Plan. Clinical disease activity during the year following NZ discontinuation was assessed in this cohort. Time to first relapse after NZ stop was analyzed using Kaplan-Meier method and potentially associated factors were studied using a multivariate Cox model. Results: Out of the 4,055 patients with multiple sclerosis (MS) included in TYSEDMUS, 1,253 discontinued NZ and 715 of them had relevant data for our study. The probability of relapse within the year after NZ stop was estimated at 45% (95% confidence interval 0.41–0.49). Conclusions: This large and systematic survey of patients with MS after NZ withdrawal allows quantifying the risk of increased disease activity following treatment discontinuation. This study provides large-scale, multicenter, systematic data after NZ cessation in real-life settings. PMID:27844037

  1. Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

    PubMed Central

    Olerup, O; Hillert, J; Fredrikson, S; Olsson, T; Kam-Hansen, S; Möller, E; Carlsson, B; Wallin, J

    1989-01-01

    HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities. Images PMID:2571150

  2. Histology of the first fish

    USGS Publications Warehouse

    Smith, M.P.; Sansom, I.J.; Repetski, J.E.

    1996-01-01

    THE first description of Anatolepis Bockelie & Fortey was from early Ordovician sediments of Ny Friesland, Spitsbergen1,2, but the genus is now known from many localities in North America and Greenland, ranging in age from the Late Cambrian period to the Early Ordovician3-6. Although initially interpreted as an agnathan fish2,3 that predated other representatives7, this has been widely disputed because the available histological data were unconvincing6,8-10 and the scales fell outside the known morphological range of other accepted early vertebrates9-11. Further doubt was cast upon the vertebrate affinity of Anatolepis when specimens from East Greenland were interpreted as the cuticular fragments of aglaspid arthropods6, although this interpretation has also been refuted12. Here we report on the morphology and histology of large collections of Anatolepis, and demonstrate the presence of dentine, a tissue unique to vertebrates, confirming that the taxon is both a vertebrate and the oldest known fish.

  3. Relapse situations according to Marlatt's taxonomy in smokers.

    PubMed

    Piñeiro, Bárbara; Becoña, Elisardo

    2013-01-01

    Relapse is common during the process of giving up smoking. The aim of the present study is to explore the relapse situations, according to Marlatt's relapse taxonomy, in a sample of 428 smokers (43.9% men and 56.1% women) who participated in a cognitive-behavior psychological treatment for quitting smoking. At the end of the treatment, 221 participants were abstinent, of whom 119 (41.2% men and 58.8% women) relapsed in the course of the 12-month follow-up, the majority in the first 3 months (69.74%). Most of the relapses were attributed to intrapersonal and environmental determinants (61.33%), the most common of which were "coping with negative emotional states" (38.65%), followed by "giving in to temptations or urges" (9.24%) and "testing personal control" (8.40%). Interpersonal determinants occurred in 38.66% of relapses, this percentage being made up mostly of "social pressure", which was the relapse situation in 34.46% of all relapses. These results, similar to those of Marlatt's original studies and others, contribute to improving our knowledge of the relapse situations process, with a view to interventions that may help to avoid it.

  4. Understanding Recovery Barriers: Youth Perceptions About Substance Use Relapse

    PubMed Central

    Gonzales, Rachel; Anglin, M. Douglas; Beattie, Rebecca; Ong, Chris Angelo; Glik, Deborah C.

    2014-01-01

    Objective To qualitatively explore how treatment-involved youth retrospectively contextualize relapse from substance use. Methods Fourteen focus groups were conducted with 118 youth (78.3% male; 66.1% Latino) enrolled in participating substance abuse treatment programs (4 young adult and 10 adolescent) throughout Los Angeles County. Transcripts were analyzed for relapse perception themes. Results Dominant relapse themes include emotional reasons (90%), life stressors (85%), cognitive factors (75%), socialization processes (65%), and environmental issues (55%). Conclusions Youth perceptions about relapse during treatment should be used to better inform clinical approaches and shape early-intervention recovery agendas for substance-abusing youth. PMID:22584088

  5. Patterns of disease relapse in primary extremity soft-tissue sarcoma.

    PubMed

    Smith, H G; Memos, N; Thomas, J M; Smith, M J F; Strauss, D C; Hayes, A J

    2016-10-01

    Extremity soft-tissue sarcomas comprise a range of distinct histological subtypes. This study aimed to characterize the patterns of disease relapse in patients undergoing resection of primary extremity soft-tissue sarcoma. All patients who had resection of primary extremity soft-tissue sarcoma at the Royal Marsden Hospital between January 2004 and January 2014 were identified from an institutional database. In the period examined, 556 patients underwent resection. The most common histological subtypes were undifferentiated pleomorphic sarcoma (169 patients, 30·4 per cent), well differentiated liposarcoma (63, 11·3 per cent), myxoid liposarcoma (62, 11·2 per cent), myxofibrosarcoma (54, 9·7 per cent) and leiomyosarcoma (39, 7·0 per cent). Local recurrence-free survival (LRFS) did not differ significantly between histological subtypes (P = 0·222). Distant metastasis-free survival (DMFS) and disease-specific survival (DSS) were found to differ significantly between subtypes (P < 0·001 for both DMFS and DSS), with the worst outcomes in patients with undifferentiated pleomorphic sarcoma (5-year survival rate: 56·8 (95 per cent c.i. 52·5 to 61·1) per cent for DMFS; 60·1 (55·6 to 64·6) per cent for DSS). However, on multivariable analysis, histological subtype was not found to be independently prognostic for LRFS, DMFS or DSS. Metastatic disease developed in 149 patients, with the lungs being the most common site of first metastasis (120 patients, 80·5 per cent). The site of first metastasis differed between subtypes, with extrapulmonary metastases predominant in myxoid liposarcoma (11 of 13 patients; P < 0·001). Although histological subtype was not found to be an independent prognostic factor for oncological outcomes, the site of first metastasis differed significantly between subtypes. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  6. Advances in the pathophysiology and treatment of relapsed/refractory Hodgkin’s lymphoma with an emphasis on targeted therapies and transplantation strategies

    PubMed Central

    Karantanos, Theodoros; Politikos, Ioannis; Boussiotis, Vassiliki A

    2017-01-01

    Hodgkin’s lymphoma (HL) is highly curable with first-line therapy. However, a minority of patients present with refractory disease or experience relapse after completion of frontline treatment. These patients are treated with salvage chemotherapy followed by autologous stem cell transplantation (ASCT), which remains the standard of care with curative potential for refractory or relapsed HL. Nevertheless, a significant percentage of such patients will progress after ASCT, and allogeneic hematopoietic stem cell transplantation remains the only curative approach in that setting. Recent advances in the pathophysiology of refractory or relapsed HL have provided the rationale for the development of novel targeted therapies with potent anti-HL activity and favorable toxicity profile, in contrast to cytotoxic chemotherapy. Brentuximab vedotin and programmed cell death-1-based immunotherapy have proven efficacy in the management of refractory or relapsed HL, whereas several other agents have shown promise in early clinical trials. Several of these agents are being incorporated with transplantation strategies in order to improve the outcomes of refractory or relapsed HL. In this review we summarize the current knowledge regarding the mechanisms responsible for the development of refractory/relapsed HL and the outcomes with current treatment strategies, with an emphasis on targeted therapies and hematopoietic stem cell transplantation. PMID:28701859

  7. Bilateral Maxillary, Sphenoid Sinuses and Lumbosacral Spinal Cord Extramedullary Relapse of CML Following Allogeneic Stem Cell Transplant

    PubMed Central

    Hosseini, Soudabeh; Ansari, Shahla; Vosough, Parvaneh; Bahoush, Gholamreza; Hamidieh, Amir Ali; Chahardouli, Bahram; Shamsizadeh, Morteza; Mehrazma, Mitra; Dorgalaleh, Akbar

    2016-01-01

    Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. There is a case report of a child who developed a granulocytic sarcoma of the maxillary and sphenoid sinuses and lumbosacral spinal cord mass 18 months after allogeneic bone marrow transplant for CML. He was presented with per orbital edema and neurological deficit of lower extremities and a mass lesion was found on spinal cord imaging. No evidence of hematologic relapse was identified at that time by bone marrow histology or cytogenetic. The patient died 1 month later with a picture of pneumonia, left ventricular dysfunction and a cardiopulmonary arrest on a presumed underlying sepsis with infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic bone marrow transplantation for CML, even if there is no evidence of bone marrow involvement. PMID:27252811

  8. Paediatric intracranial anaplastic ependymoma: the role of multiple surgical resections for disease relapse in maintaining quality of life and prolonged survival.

    PubMed

    Kitchen, William John; Pizer, Barry; Pettorini, Benedetta; Husband, David; Mallucci, Conor; Jenkinson, Michael D

    2015-01-01

    Ependymoma is the third most common intracranial glioma in children. The treatment of choice for these tumours remains gross total resection followed by radiotherapy. There are two principal histological subtypes, namely classic (∼70%) and anaplastic (∼30%) ependymoma. We present the case of a 12-year-old girl with an anaplastic ependymoma of the left temporal lobe. She underwent initial image-guided resection following biopsy. A postoperative MRI showed a macroscopic resection. She subsequently relapsed and indeed had 11 local and distant relapses managed by 12 separate craniotomies and tumour resection, 4 courses of radiotherapy and chemotherapy. For patients with multiple relapses, surgery should be considered primarily to re-resect any symptomatic lesion. This case demonstrates that multiple tumour resections can be undertaken with limited morbidity for the patient and with maintenance of quality of life. Repeated focal irradiation can also be used to control the disease with limited morbidity. © 2015 S. Karger AG, Basel.

  9. Daunorubicin, cytarabine, and cladribine regimen plus radiotherapy and donor lymphocyte infusion for extramedullary relapse of acute myeloid leukemia after hematopoietic stem cell transplantation.

    PubMed

    Sanna, Marco; Caocci, Giovanni; Vacca, Adriana; Piras, Eugenia; Orrù, Federica; La Nasa, Giorgio

    2013-01-01

    Myeloid sarcoma is a rare tumor consisting of myeloid blasts that involve anatomic sites outside the bone marrow. Fatal prognosis is inevitable in patients with extramedullary relapse after hematopoietic stem cell transplantation (HSCT), and no standard treatments are available yet. We report the first case of extramedullary relapse after HSCT treated with a combination of daunorubicin, cytarabine, and cladribine (DAC) regimen plus radiotherapy and donor lymphocyte infusion (DLI). This treatment induced a new and durable remission in our patient. The favorable toxicity profile and the reduced cost make this combination worthy of further investigations.

  10. Does the Pirani score predict relapse in clubfoot?

    PubMed

    Goriainov, Vitali; Judd, Julia; Uglow, Mike

    2010-10-01

    Presented here is a retrospective clinical audit of clubfoot patients to determine the value of the Pirani clubfoot scoring system at initial presentation in the estimation of subsequent relapse. All clubfoot patients treated by the same surgeon from 2002 to 2006 were included. The treatment adhered to the standard protocol, involving weekly stretching and casting until the foot was corrected, followed by Achilles tenotomy and plasters for 3 weeks. Thereafter, the child was placed in a foot abduction splint. The severity of clubfoot was assessed using the Pirani scoring system, consisting of two sub-scores-the midfoot contracture score (MFCS) and the hindfoot contracture score (HFCS). The MFCS and HFCS can each be 0.0-3.0, giving rise to a total Pirani score (TPS) of 0.0-6.0. Any recurrent deformity was classed as a relapse. Sixty-one clubfoot patients were treated. Five patients were lost to follow-up and six patients were excluded due to the presence of identified syndromes or having had primary treatment elsewhere. A total of 80 clubfeet were included. There were 17 relapses. The average interval between the initiation of foot abduction splint and relapse was 23 months. The median TPS was 3.5 in the no relapse group and 5.0 in the relapse group. The median MFCS was 1.5 in the no relapse group and 2.0 in the relapse group. The median HFCS was 2.0 in the no relapse group and 3.0 in the relapse group. Higher TPS and HFCS were statistically significant when the relapse group was analysed against the no relapse group (P = 0.05 × 10(-4) and 0.02 × 10(-4), respectively). Higher Pirani scores were associated with the late relapse group. The TPS and HFCS were shown to be statistically significant predictors of potential relapse. Closer follow-up is advised for patients at risk of relapse.

  11. Follicular porokeratosis: distinct clinical entity or histologic variant?

    PubMed

    Pongpudpunth, M; Farber, J; Mahalingam, M

    2009-11-01

    Various clinical subtypes of porokeratosis, clinically characterized by annular plaques with a normal or atrophic center and a distinctive keratotic ridge, are described based on the age of onset, size, number and distribution of the lesions. Follicular involvement, identified by follicular localization of cornoid lamellae, is uncommon and has only been reported in association with other subtypes such as disseminated superficial actinic porokeratosis and porokeratosis of Mibelli. We present a case of follicular porokeratosis in a 40-year-old male who presented initially with scaly red "papules" in a follicular distribution on the upper extremity. Microscopic examination of a punch biopsy specimen revealed parakeratosis confined to the follicle and mild interface change. A repeat biopsy performed in 2008 revealed identical histologic features. In terms of etiopathogenesis, a clone of cells at the base of the follicle demonstrating abnormal keratinization is not a novel concept and has been demonstrated in other porokeratotic dermatoses. However, the presence of lesions that are solely follicular based, in terms of clinical presentation and histologic findings, and static over a 3-year period favors the concept that follicular porokeratosis is a distinct clinical entity and not merely a histologic variant of the porokeratotic dermatoses described in the literature thus far.

  12. Most Americans Favor Larger Health Warnings on Cigarette Packs

    MedlinePlus

    ... html Most Americans Favor Larger Health Warnings on Cigarette Packs Even many smokers think these warnings should ... 31, 2017 FRIDAY, March 31, 2017 (HealthDay News) -- Cigarette packs carry health warnings, but many Americans think ...

  13. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... solicit from a person having business with the Council anything of value as a gift, gratuity, loan, entertainment, or favor for himself or another person, particularly one with whom he has family, business,...

  14. Histologic effects of resurfacing lasers.

    PubMed

    Freedman, Joshua R; Greene, Ryan M; Green, Jeremy B

    2014-02-01

    By utilizing resurfacing lasers, physicians can significantly improve the appearance of sun-damaged skin, scars, and more. The carbon dioxide and erbium:yttrium-aluminum-garnet lasers were the first ablative resurfacing lasers to offer impressive results although these earlier treatments were associated with significant downtime. Later, nonablative resurfacing lasers such as the neodymium:yttrium-aluminum-garnet laser proved effective, after a series of treatments with less downtime, but with more modest results. The theory of fractional photothermolysis has revolutionized resurfacing laser technology by increasing the safety profile of the devices while delivering clinical efficacy. A review of the histologic and molecular consequences of the resurfacing laser-tissue interaction allows for a better understanding of the devices and their clinical effects.

  15. Promising reciprocity: When proposing a favor for a request increases compliance even if the favor is not accepted.

    PubMed

    Guéguen, Nicolas; Meineri, Sébastien; Ruiz, Clément; Pascual, Alexandre

    2016-01-01

    Research has reported that reciprocity is an important social norm in relationships. In previous studies on reciprocity, participants' behavior was examined after receiving a favor from someone. In a series of field studies, we examined the effect of a statement that proved that a solicitor was someone who respected this principle. Confederates solicited participants for money or a cigarette in exchange for stamps or money, respectively. It was found that the participants complied more readily with the request in the promised favor condition, but most of them refused to take the promised favor. We conclude that individuals were led to help those who respected the putative norm of reciprocity in their social interaction.

  16. Wilms tumor gene 1 expression as a predictive marker for relapse and survival after hematopoietic stem cell transplantation for myelodysplastic syndromes.

    PubMed

    Yoon, Jae-Ho; Jeon, Young-Woo; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Yonggoo; Kim, Dong-Wook; Lee, Jong-Wook; Han, Kyungja; Min, Woo-Sung; Park, Chong-Won; Kim, Myungshin; Kim, Yoo-Jin

    2015-03-01

    Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is a major concern in myelodysplastic syndromes (MDS), but the role of Wilms tumor gene 1 (WT1) as a predictive marker for post-HSCT relapse remains to be validated. We measured WT1 transcript levels by real-time quantitative PCR from marrow samples of 82 MDS patients who underwent transplantation between 2009 and 2013. Pre-HSCT WT1 expression weakly correlated with marrow blast counts or International Prognostic Scoring System scores and failed to predict post-transplantation relapse. Regarding post-HSCT WT1, transcript levels of relapsed patients were significantly higher in comparison to those in remission. Further analysis using receiver operating characteristics curves showed that higher (>154 copies/10(4)ABL) 1-month post-HSCT WT1 resulted in a higher 3-year relapse rate (47.2% versus 6.9%, P < .001) with poorer disease-free survival (DFS) and overall survival at 3 years (41.7% versus 79.0% and 54.3% versus 82.1%, P = .003 and P = .033, respectively). Multivariate analysis after adjusting for pre-HSCT karyotype and chronic graft-versus-host disease (GVHD) also revealed that higher 1-month post-HSCT WT1 was an independent predictive marker for subsequent relapse (P = .002) and poorer DFS (P = .010). In the higher 1-month post-HSCT WT1 subgroup, patients with chronic GVHD showed lower relapse rate and favorable survival outcome. One month post-HSCT WT1 expression was a useful marker for minimal residual disease and relapse prediction in association with chronic GVHD in the context of HSCT for MDS. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: What is the role of elective neck irradiation?

    SciTech Connect

    Chen, Allen M. . E-mail: allenmchen@yahoo.com; Garcia, Joaquin; Lee, Nancy Y.; Bucci, M. Kara; Eisele, David W.

    2007-03-15

    Purpose: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). Methods and Materials: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinoma (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3-267 months). Results: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. Conclusion: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.

  18. Tick-borne relapsing fever in children.

    PubMed

    Le, C T

    1980-12-01

    Three cases of tick-borne fever diagnosed during the summer of 1979 are reported and the ecoepidemiology, clinical manifestations, and treatment of this infection are reviewed. Although challenging, the diagnosis can be made easily if specific historical clues are sought and the patient's blood smear is carefully examined. The diagnosis of this condition early in its course can save clinicians and patients the anxiety and cost of the work-up of a "fever of unknown origin." Since vacationing in the national parks and forests has become increasingly popular among many American families, tick-borne relapsing fever should be considered in any patient with an acute or recurrent fever of unknown origin who exhibits nonspecific symptoms of an undifferentiated "viral illness," and who gives a history of sleeping overnight in log cabins in the coniferous forests of the Western mountains of the United States.

  19. Mathematical Models of Tuberculosis Reactivation and Relapse

    PubMed Central

    Wallis, Robert S.

    2016-01-01

    The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiologic mechanism of tuberculosis in patients treated with tumor necrosis factor blockers, and predict the risk of relapse in persons undergoing tuberculosis treatment. These examples illustrate the power of various types of mathematic models to increase knowledge and thereby inform interventions in the present global tuberculosis epidemic. PMID:27242697

  20. Pemphigus erythematosus relapse associated with atorvastatin intake

    PubMed Central

    Lo Schiavo, Ada; Puca, Rosa Valentina; Romano, Francesca; Cozzi, Roberto

    2014-01-01

    Statins, also known as 3-hydroxy-3-methylglutaril-CoA reductase inhibitors, are well-tolerated drugs used for prevention of atherosclerosis and cardiovascular events. Although they are generally considered safe, some serious adverse effects, such as myositis, myopathy, and rhabdomyolysis can rarely occur. Furthermore, recent data from long-term follow-up on patients who have been taking statins for a long period of time suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reactions is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. Herein we report the case of a 70 year-old man who developed a relapse of pemphigus erythematosus, a syndrome with features of both lupus erythematosus and pemphigus, after atorvastatin intake. PMID:25258514

  1. Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

    SciTech Connect

    Pan, Hubert Y.; Morani, Ajaykumar; Wang, Wei-Lien; Hess, Kenneth R.; Paulino, Arnold C.; Ludwig, Joseph A.; Lin, Patrick P.; Daw, Najat C.; Mahajan, Anita

    2015-06-01

    Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant

  2. Prognostic factors and patterns of relapse in ewing sarcoma patients treated with chemotherapy and r0 resection.

    PubMed

    Pan, Hubert Y; Morani, Ajaykumar; Wang, Wei-Lien; Hess, Kenneth R; Paulino, Arnold C; Ludwig, Joseph A; Lin, Patrick P; Daw, Najat C; Mahajan, Anita

    2015-06-01

    To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant radiation therapy for patients who have poor histologic

  3. Louseborne Relapsing Fever among East African Refugees, Italy, 2015

    PubMed Central

    Lipani, Filippo; Costa, Cecilia; Scarvaglieri, Mariaelisabetta; Balbiano, Rosanna; Carosella, Sinibaldo; Calcagno, Andrea; Audagnotto, Sabrina; Barbui, Anna Maria; Brossa, Silvia; Ghisetti, Valeria; Dal Conte, Ivano; Caramello, Pietro; Di Perri, Giovanni

    2016-01-01

    During June 9–September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever. PMID:26812354

  4. Polysubstance Use and Heroin Relapse among Adolescents following Residential Treatment

    ERIC Educational Resources Information Center

    Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc

    2012-01-01

    This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…

  5. Maintenance, Generalization, and Treatment Relapse: A Behavioral Momentum Analysis

    ERIC Educational Resources Information Center

    Mace, F. Charles; Nevin, John A.

    2017-01-01

    Maintenance and generalization have been inconsistently defined in the behavior analytic literature. The term "treatment relapse" is used commonly in the medical and mental health literature to refer to the return of a condition that was previously considered successfully treated. Basic behavioral researchers have studied relapse related…

  6. Relapse Prevention Needs More Emphasis on Interpersonal Factors

    ERIC Educational Resources Information Center

    Stanton, Mark

    2005-01-01

    This article presents comments on "Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao," by Katie Witkiewitz and G.A. Marlatt. Stanton notes that the recent reconceptualization of relapse prevention by Witkiewitz and Marlatt enhances the model by "synthesizing recent empirical findings into a unified theory", but it does…

  7. Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

    2004-01-01

    This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

  8. Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

    PubMed

    Lucchini, Anna; Lipani, Filippo; Costa, Cecilia; Scarvaglieri, Mariaelisabetta; Balbiano, Rosanna; Carosella, Sinibaldo; Calcagno, Andrea; Audagnotto, Sabrina; Barbui, Anna Maria; Brossa, Silvia; Ghisetti, Valeria; Dal Conte, Ivano; Caramello, Pietro; Di Perri, Giovanni

    2016-02-01

    During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

  9. Impact of Life Events on the Relapse of Schizophrenic Patients

    ERIC Educational Resources Information Center

    Hussein, Hassan Ali; Jacoob, Shirooq; Sharour, Loai Abu

    2016-01-01

    Objectives: To investigate the relationship between stressful life events at the time of relapse in schizophrenic patients at psychiatric hospitals in Baghdad city. Methodology: A purposive (non-probability) sampling of 50 schizophrenic patients who have relapsed was involved in the present study. Data were collected through the use of the…

  10. Predictors of Exercise Relapse in a College Population.

    ERIC Educational Resources Information Center

    Sullum, Julie; Clark, Matthew M.; King, Teresa K.

    2000-01-01

    Investigated factors that predicted exercise relapse among college students. Physically active undergraduates completed questionnaires measuring Prochaska's 10 processes for change of exercise, self-efficacy, and decisional balance. Exercise levels were assessed at baseline and 8 weeks later. At baseline, relapsers had significantly lower…

  11. A case of late herpes simplex encephalitis relapse.

    PubMed

    Rigamonti, Andrea; Lauria, Giuseppe; Mantero, Vittorio; Salmaggi, Andrea

    2013-09-01

    Late relapse of herpes simplex encephalitis, defined as recurrence more than 3 months after the first initial encephalitic episode, is a rare condition. We describe the case of an adult patient who presented a relapse of herpes simplex encephalitis 8 years after the first episode occurred at the age of 57 years and review the literature of this topic.

  12. Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

    2004-01-01

    This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

  13. Polysubstance Use and Heroin Relapse among Adolescents following Residential Treatment

    ERIC Educational Resources Information Center

    Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc

    2012-01-01

    This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…

  14. Histological characterisation and prognostic evaluation of 62 gastric neuroendocrine carcinomas

    PubMed Central

    Chen, Xiaohui; Ye, Yuhong; Shi, Xi; Zhu, Kunshou; Huang, Liming; Zhang, Sheng; Ying, Mingang; Lin, Xuede

    2016-01-01

    Aim of the study To determine the significance of expression of synaptophysin, chromogranin A, and Ki-67 and their association with clinicopathological parameters, and to find out the possible prognostic factors in gastric neuroendocrine carcinoma (G-NEC). Material and methods We investigated the immunohistochemical features and prognosis of 62 G-NECs, and evaluated the association among expressions of synaptophysin, chromogranin A, and Ki-67, clinicopathological variables, and outcome. Results Chromogranin A expression was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p = 0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation analyses revealed that Ki-67 expression was significantly associated with mid-third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and had a trend of significant correlation with tumour relapse (p = 0.078). High expression of chromogranin A was significantly associated with histology of small-cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests, and as a result, early TNM staging and postoperative chemotherapy were found to be correlated with longer overall survival (p < 0.05). Univariate analysis revealed associations between poor prognosis in NECs and several factors, including high TNM staging (p = 0.048), vascular involvement (p = 0.023), relapse (p = 0.004), and microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate analysis, relapse was identified as the sole independent prognostic factor. Conclusions No significant correlation between survival and expression of synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study indicated that early diagnosis, no-residual-tumour resection, and postoperative chemotherapy were

  15. Relapse Prevention and the Five Rules of Recovery

    PubMed Central

    Melemis, Steven M.

    2015-01-01

    There are four main ideas in relapse prevention. First, relapse is a gradual process with distinct stages. The goal of treatment is to help individuals recognize the early stages, in which the chances of success are greatest. Second, recovery is a process of personal growth with developmental milestones. Each stage of recovery has its own risks of relapse. Third, the main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills. Fourth, most relapses can be explained in terms of a few basic rules. Educating clients in these rules can help them focus on what is important: 1) change your life (recovery involves creating a new life where it is easier to not use); 2) be completely honest; 3) ask for help; 4) practice self-care; and 5) don’t bend the rules. PMID:26339217

  16. Predictive factors for relapse in patients on buprenorphine maintenance.

    PubMed

    Ferri, Michael; Finlayson, Alistair J Reid; Wang, Li; Martin, Peter R

    2014-01-01

    Despite the dramatic increase in the use of buprenorphine for the treatment of opioid dependence, clinical outcomes of this treatment approach continue to need evaluation. This study examines factors associated with relapse and retention during buprenorphine treatment in a sample of opioid dependent outpatients. In a retrospective chart review of 62 patients with opioid dependence, relapse was determined by self-report, urine toxicology screens, and by checking the state controlled substance monitoring database. Data was analyzed using two-way tests of association and logistic regression. Patients with comorbid anxiety disorders, active benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were significantly more likely to relapse. Patients who relapsed were also more likely to be on a higher buprenorphine maintenance dose. This study identifies relapse risk factors during buprenorphine treatment for opioid dependence. Future research is needed to determine whether modifying these factors may lead to improved treatment outcomes. © American Academy of Addiction Psychiatry.

  17. Relapse Prevention and the Five Rules of Recovery.

    PubMed

    Melemis, Steven M

    2015-09-01

    There are four main ideas in relapse prevention. First, relapse is a gradual process with distinct stages. The goal of treatment is to help individuals recognize the early stages, in which the chances of success are greatest. Second, recovery is a process of personal growth with developmental milestones. Each stage of recovery has its own risks of relapse. Third, the main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills. Fourth, most relapses can be explained in terms of a few basic rules. Educating clients in these rules can help them focus on what is important: 1) change your life (recovery involves creating a new life where it is easier to not use); 2) be completely honest; 3) ask for help; 4) practice self-care; and 5) don't bend the rules.

  18. Spontaneously relapsing-remitting experimental autoimmune uveitis in rats allows successful therapeutic oral tolerance induction in ongoing disease.

    PubMed

    Huber, Andrea; Diedrichs-Möhring, Maria; Wildner, Gerhild

    2015-02-01

    Antigen-specific tolerance induction is a desired therapy for uveitis patients. Our relapsing-remitting rat model of experimental autoimmune uveitis (EAU) induced with IRBP peptide R14 enables us to test the effect of oral tolerance on the prevention of relapsing uveitis. We investigated several peptides overlapping the sequence of R14 for prevention and different doses of R14 for therapy to determine the tolerogenic epitope and the most effective therapeutic regimen for uveitis. Lewis rats were immunized with R14-CFA to induce EAU. Oral tolerance was induced prior to immunization (prevention) or after onset of EAU to prevent relapses (therapy). Therapeutic feeding was performed with high and/or low doses of oral antigen for clonal deletion of effector and induction of regulatory T cells. Uveitis was determined clinically and histologically; mesenteric lymph node (mLN) cells of tolerized rats were tested for surface markers, cytokines and Foxp3 expression. Preventive feeding of R14 and its major epitope R16, but none of the overlapping peptides significantly suppressed EAU and also prevented relapses, irrespective of their pathogenicity. Therapeutic feeding with R14 dramatically reduced relapses, while only the consecutive feeding of high and low-dose R14 had an ameliorating effect on the first course of disease. IL-10-producing T cells from mLN decreased after oral tolerization, and with R14-stimulation in vitro the TCRαβ+/Foxp3+ population increased in the low-dose fed group. No mLN population could be clearly assigned to successful oral tolerance induction during active autoimmune uveitis.

  19. Determinants of relapse periodicity in Plasmodium vivax malaria

    PubMed Central

    2011-01-01

    Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. Plasmodium vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites) which can be prevented only by 8-aminoquinoline anti-malarials. Tropical P. vivax relapses at three week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics P. vivax infections are characterized either by a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria control and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important

  20. Periodontal tissue reaction during orthodontic relapse in rat molars.

    PubMed

    Franzen, Tanya J; Brudvik, Pongsri; Vandevska-Radunovic, Vaska

    2013-04-01

    Relapse after orthodontic tooth movement (OTM) is an undesirable outcome that involves a number of factors. This study investigated the remodelling of the alveolar bone and related periodontal structures during orthodontic relapse in rat molars. The maxillary right first molars of 35 Wistar rats were moved mesially by a fixed orthodontic appliance for 10 days and the contralateral molars served as controls. The appliances were removed and six animals killed. The molars were allowed to relapse, and the remaining animals were sacrificed at 1, 3, 5, 7, 14, and 21 days. The jaws were sectioned and stained with haematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP). One day after appliance removal, the molars relapsed to a mean 62.5 per cent of the achieved OTM and then steadily relapsed to 86.1 per cent at 21 days. The number of osteoclasts situated along the alveolar bone of the first molars was highest at the end of active treatment and significantly decreased during the relapse period. In the OTM group, osteoclasts were most numerous in the pressure side of the periodontal ligament (PDL). As the molars relapsed over time, the osteoclast distribution shifted, and after 7 days of relapse, TRAP-positive cells were registered in previous pressure and tension sides of the first molars. After 21 days, these cells were concentrated in the distal parts of the PDL of all three maxillary right molars. These results indicate that orthodontic relapse in the rat model occurs rapidly and remodelling of the alveolar bone and PDL plays a central role in the relapse processes of both actively moved and adjacent teeth.

  1. Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.

    PubMed

    Guardiola, Jordi; Lobatón, Triana; Rodríguez-Alonso, Lorena; Ruiz-Cerulla, Alexandra; Arajol, Claudia; Loayza, Carolina; Sanjuan, Xavier; Sánchez, Elena; Rodríguez-Moranta, Francisco

    2014-11-01

    Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136-696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30-172 μg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Predictors of favorable results in pulmonary tuberculosis treatment (Recife, Pernambuco, Brazil, 2001-2004).

    PubMed

    Sassaki, Cinthia Midori; Scatena, Lucia Marina; Gonzales, Roxana Isabel Cardozo; Ruffino-Netto, Antonio; Hinos, Paula; Villa, Tereza Cristina Scatena

    2010-06-01

    Based on data available in the Information System for Notifiable Diseases, predictive factors of favorable results were identified in the treatment of pulmonary tuberculosis, diagnosed between 2001 and 2004 and living in Recife-PE, Brazil. Uni- and multivariate logistic regression methods were used. In multivariate analysis, the following factors remained: Age (years), 0 to 9 (OR = 4.27; p = 0.001) and 10 to 19 (OR = 1.78; p = 0.011), greater chance of cure than over 60; Education (years), 8 to 11 (OR = 1.52; p = 0.049), greater chance of cure than no education; Type of entry, ne wcase s (OR = 3.31; p < 0.001) and relapse (OR = 3.32; p < 0.001), greater chances of cure than restart after abandonment; Time (months) 2, 5--6 (OR = 9.15; p < 0.001); 6--9 (OR = 27.28; p < 0.001) and More than 9 (OR = 24.78; p < 0.001), greater chances of cure than less than 5; Health Unit District, DSII (OR = 1.60; p = 0.018) and DSIIV (OR = 2.87; p < 0.001), greater chance sof cure than DS II.

  3. Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient.

    PubMed

    Carbonelli, C; Roggeri, A; Cavazza, A; Zompatori, M; Zucchi, L

    2008-03-01

    Asthma is thought to be a Th2 disease while sarcoidosis is considered a Th1 granulomatous disorder. Organising pneumonia is a histologic pattern of lung injury. When it has no recognisable cause it is defined as cryptogenic organising pneumonia. We herein report the case of a patient with recurrent and steroid sensitive organising pneumonia associated with chronic sarcoidosis in an atopic, moderate persistent asthmatic patient. Each disease has been documented with transbronchial biopsies and recurrence of organising pneumonia was suggested by clinical features and by follow up HRCT which shows distinctive signs even in associated disease. Steroids are the mainstay of therapy for these disorders and especially for the consolidated processes typical of organising pneumonia but prognostic indices for relapse and progression are lacking.

  4. Metabolically dependent blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis.

    PubMed

    Hawkins, C P; Munro, P M; Landon, D N; McDonald, W I

    1992-01-01

    We have studied chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of immune-mediated demyelination, using gadolinium (Gd)-enhanced magnetic resonance imaging in vivo and the blood-brain barrier (BBB) markers, lanthanum nitrate and Gd nitrate, histologically. In regions of the spinal cord showing Gd enhancement, there was evidence for vesicular transport as a mechanism of BBB breakdown in CREAE, shown by an increased number of endothelial vesicles containing lanthanide (lanthanum or Gd, whichever had been perfused) and deposition of tracer in the perivascular space; tight interendothelial junctions remained intact. Prior perfusion with 2,4-dinitrophenol, a metabolic inhibitor, suppressed the appearance of endothelial vesicles containing lanthanide and tracer in the perivascular space. We conclude that an important contribution to BBB breakdown in CREAE is mediated by a metabolic change in the endothelial cells associated with increased vesicular transport.

  5. A very rare case of uterine PEComa HMB45 negative: primitive or relapse?

    PubMed Central

    Pecorino, Basilio; Scibilia, Giuseppe; Galia, Antonio; Scollo, Paolo

    2016-01-01

    Perivascular epithelioid cell tumors (PEComas) represent a rare group of tumours with uncertain malignancy potential exhibiting an immunophenotype characterized by actin and Human Melanoma Black 45 (HMB45) immunoreactivity. Our case concerns about a rare malignant uterine perivascular epithelioid cell tumour diagnosed in a patient underwent to subtotal hysterectomy with unclear diagnosis, 12 years before. Histological diagnosis after colposcopic exam with biopsy revealed a perivascular epithelioid cell tumor, with immunohistochemical profle negative for HMB45. Negativity for HMB45, already described in literature, could be due to important cellular modifcations of tumoral tissue. In our case, tumour was unresectable, progression of disease occurred during medical treatment and the patient died after 6 months. Lack of information about frst surgery doesn't allow to surely categorized the tumor as primitive or relapse. Further studies are necessary to understand some immunohistochemical anomaly like negativity for HMB45. PMID:26900338

  6. Histologic analysis of postmeniscectomy osteonecrosis.

    PubMed

    Higuchi, Hiroshi; Kobayashi, Yasukazu; Kobayashi, Atsushi; Hatayama, Kazuhisa; Kimura, Masashi

    2013-05-01

    Bone marrow signal changes on magnetic resonance imaging (MRI) after meniscectomy have been reported as evidence of postmeniscectomy osteonecrosis, but this pathology is unclear. We conducted a study to follow-up cases with bone marrow signal changes on MRI after meniscectomy and investigate the pathology of underlying lesions. Of 136 patients with no presurgical evidence of osteonecrosis, 29 had juxta-articular bone marrow signal changes on MRI after arthroscopic meniscectomy and subsequently underwent conservative therapy. In 6 of these 29 patients, clinical symptoms and radiographic changes began deteriorating. Based on the Koshino classification, 4 of the 6 patients had Stage-2 knee osteonecrosis and 2 had Stage-3. Arthroscopic and pathologic examinations were performed. Arthroscopic findings were fibrillation (all 6 cases), fissuring (4), ulceration (2), and eburnation (2). Histologic analysis confirmed subchondral bone fractures in all 6 cases, but osteonecrotic lesions were detected only in 2 cases with obvious radiologic deterioration. Postmeniscectomy osteonecrosis might result from subchondral bone fractures. Fracture healing is worse in patients with comorbidities than in those without it; comorbidities might be a risk factor for osteonecrosis.

  7. Next generation sequencing identifies ‘interactome’ signatures in relapsed and refractory metastatic colorectal cancer

    PubMed Central

    Cooke, Laurence; Mahadevan, Daruka

    2017-01-01

    Background In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. Methods Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms. Web-based bioinformatics tools (Reactome/Enrichr) were utilized to elucidate mutational profile linked pathways-networks that have the potential to guide therapy. Results Pts had progressed on fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, cetuximab and/or panitumumab. Most common histology was adenocarcinoma (colon N=29; rectal N=3). Of the mutations TP53 was the most common, followed by APC, KRAS, PIK3CA, BRAF, SMAD4, SPTA1, FAT1, PDGFRA, ATM, ROS1, ALK, CDKN2A, FBXW7, TGFBR2, NOTCH1 and HER3. Pts had on average had ≥5 unique mutations. The most frequent activated signaling pathways were: HER2, fibroblast growth factor receptor (FGFR), p38 through BRAF-MEK cascade via RIT and RIN, ARMS-mediated activation of MAPK cascade, and VEGFR2. Conclusions Dominant driver oncogene mutations do not always equate to oncogenic dependence, hence understanding pathogenic ‘interactome(s)’ in individual pts is key to both clinically relevant targets and in choosing the next best therapy. Mutational signatures derived from corresponding ‘pathway-networks’ represent a meaningful tool to (I) evaluate functional investigation in the laboratory; (II) predict response to drug therapy; and (III) guide rational drug combinations in relapsed and refractory mCRC pts. PMID:28280605

  8. VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma.

    PubMed

    Weng, Wen-Chin; Lin, Kuan-Hung; Wu, Pei-Yi; Ho, Ya-Hsuan; Liu, Yen-Lin; Wang, Bo-Jeng; Chen, Chien-Chin; Lin, Yueh-Chien; Liao, Yung-Feng; Lee, Wang-Tso; Hsu, Wen-Ming; Lee, Hsinyu

    2017-09-11

    Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in NB through mouse xenograft model and clinical analysis from NB patients. In xenograft experiments, CRT overexpression effectively inhibited the tumor growth. In addition, the mRNA and protein levels of VEGF and differentiation marker GAP-43 were upregulated by induced CRT expression. However, no significant correlation between the expression level of VEGF and microvessel density was observed in human NB tumors, suggesting a novel mechanism of VEGF participating in NB tumorigenesis through an angiogenesis-independent pathway. In NB patients' samples, mRNA expression levels of CRT and VEGF were positively correlated. Furthermore, positive VEGF expression by immunostaining of NB tumors was found to correlate well with histological grade of differentiation and predicted a favorable prognosis. In conclusion, our findings suggest that VEGF is a favorable prognostic factor of NB and might affect NB tumor behavior through CRT-driven neuronal differentiation rather than angiogenesis that might shed light on a novel therapeutic strategy to improve the outcome of NB.

  9. Correlation of ANXA1 expression with drug resistance and relapse in bladder cancer

    PubMed Central

    Yu, Shuliang; Meng, Qian; Hu, Huihui; Zhang, Man

    2014-01-01

    Objective: To investigate the expression of annexin a1 (ANXA1) in adriamycin-resistant human bladder cancer cell line (pumc-91/ADM) compared with the parental cell line (pumc-91) and its relevance to the drug resistance of bladder cancer, as well as explore the relevance of ANXA1 in recurrent bladder cancer tissues as pertinent to relapse. Methods: qRT-PCR and Western blot were implemented to research the level of ANXA1 in two cell lines (pumc-91/ADM and pumc-91). Immunohistochemistry was applied to explore ANXA1 expression in bladder cancer tissues of different intervals of relapse. The association of ANXA1 with clinicopathological parameters was analyzed. Results: The expression of ANXA1 was downregulated in drug-resistant cell line pumc-91/ADM compared to pumc-91. The bladder cancer tissues recurring two years later exhibited higher ANXA1 levels. ANXA1 expression level was positively correlated with T stage, while it was not connected with histological grade strongly. The expression level and influencing factors of ANXA1 in recurrent tissues of bladder cancer were clarified for the first time. Conclusion: ANXA1 may become a promising marker to predict the recurrence and drug resistance of bladder cancer and provide guidance for surveillance. PMID:25337195

  10. Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma

    PubMed Central

    Oki, Yasuhiro; Fanale, Michelle; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Copeland, Amanda; Samaniego, Felipe; Kwak, Larry W.; Neelapu, Sattva; Wang, Michael; Feng, Lei; Younes, Anas

    2017-01-01

    Summary We conducted a phase II study of the AKT inhibitor, MK2206 in patients with relapsed or refractory lymphoma of any histology excluding Burkitt lymphoma or lymphoblastic lymphoma. MK-2206 was administered orally at 200 mg once weekly in 28-d cycles up to 12 cycles in the absence of progression or significant toxicity. The dose was adjusted based on tolerance. A total of 59 patients were enrolled. The final doses patients received were 300 mg (n = 33), 250 mg (n = 2), 200 mg (n = 16) and 135 mg (n = 8). Based on intent-to-treat analysis, objective response was observed in 8 (14%) patients (2 complete response and 6 partial response), with median response duration of 5.8 months. The overall response rate was 20% in 25 patients with classical Hodgkin lymphoma. Rash was the most common toxicity (any grade 53%, Grade 3 in 15%) and was observed in a dose-dependent manner. The correlative cytokine analysis showed paradoxical increase in several cytokines, which may be explained by negative feedback mechanism induced by the on-target effect of AKT inhibitor. Our data demonstrate that MK2206 has a favourable safety profile with a modest activity in patients with relapsed Hodgkin lymphoma. The future studies should explore mechanism-based combinations (clinicaltrials.gov NCT01258998). PMID:26213141

  11. Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma.

    PubMed

    Oki, Yasuhiro; Fanale, Michelle; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Copeland, Amanda; Samaniego, Felipe; Kwak, Larry W; Neelapu, Sattva; Wang, Michael; Feng, Lei; Younes, Anas

    2015-11-01

    We conducted a phase II study of the AKT inhibitor, MK2206 in patients with relapsed or refractory lymphoma of any histology excluding Burkitt lymphoma or lymphoblastic lymphoma. MK-2206 was administered orally at 200 mg once weekly in 28-d cycles up to 12 cycles in the absence of progression or significant toxicity. The dose was adjusted based on tolerance. A total of 59 patients were enrolled. The final doses patients received were 300 mg (n = 33), 250 mg (n = 2), 200 mg (n = 16) and 135 mg (n = 8). Based on intent-to-treat analysis, objective response was observed in 8 (14%) patients (2 complete response and 6 partial response), with median response duration of 5·8 months. The overall response rate was 20% in 25 patients with classical Hodgkin lymphoma. Rash was the most common toxicity (any grade 53%, Grade 3 in 15%) and was observed in a dose-dependent manner. The correlative cytokine analysis showed paradoxical increase in several cytokines, which may be explained by negative feedback mechanism induced by the on-target effect of AKT inhibitor. Our data demonstrate that MK2206 has a favourable safety profile with a modest activity in patients with relapsed Hodgkin lymphoma. The future studies should explore mechanism-based combinations (clinicaltrials.gov NCT01258998). © 2015 John Wiley & Sons Ltd.

  12. A phase II clinical study on relapsed malignant gliomas treated with electro-hyperthermia.

    PubMed

    Fiorentini, Giammaria; Giovanis, Petros; Rossi, Susanna; Dentico, Patrizia; Paola, Raffaele; Turrisi, Gina; Bernardeschi, Paolo

    2006-01-01

    The purpose of this study was to evaluate the activity and toxicity of electro-hyperthermia (ET) on relapsed malignant glioma patients. Twelve patients with histologically diagnosed malignant glioma entered the study. Eight patients had glioblastoma multiforme, two had anaplastic astrocytoma grade III and two had anaplastic oligodendroglioma. All patients were pre-treated with temozolamide-based chemotherapy and radiotherapy. Hyperthermia with short radiofrequency waves of 13.56 MHz was applied using a capacitive coupling technique keeping the skin surface at 20 degrees C. The applied power ranged between 40-150 Watts and the calculated average equivalent temperature in the tumours was above 40 degrees C for more than 90% of the treatment duration. One complete remission and 2 partial remission were achieved, with a response rate of 25%. The median duration of response was 10 months (range 4-32). The median survival of the entire patient population was 9 months, with 25% survival rate at 1 year. ET appears to have some effectiveness in adults with relapsed malignant glioma.

  13. Pediatric Targeted Therapy: Clinical Feasibility of Personalized Diagnostics in Children with Relapsed and Progressive Tumors.

    PubMed

    Selt, Florian; Deiß, Alica; Korshunov, Andrey; Capper, David; Witt, Hendrik; van Tilburg, Cornelis M; Jones, David T W; Witt, Ruth; Sahm, Felix; Reuss, David; Kölsche, Christian; Ecker, Jonas; Oehme, Ina; Hielscher, Thomas; von Deimling, Andreas; Kulozik, Andreas E; Pfister, Stefan M; Witt, Olaf; Milde, Till

    2016-07-01

    The "pediatric targeted therapy" (PTT) program aims to identify the presence and activity of druggable targets and evaluate the clinical benefit of a personalized treatment approach in relapsed or progressive tumors on an individual basis. 10 markers (HDAC2, HR23B, p-AKT, p-ERK, p-S6, p-EGFR, PDGFR-alpha/beta, p53 and BRAFV600E) were analyzed by immunohistochemistry. Pediatric patients with tumors independent of the histological diagnosis, with relapse or progression after treatment according to standard protocols were included. N = 61/145 (42%) cases were eligible for analysis between 2009 and 2013, the most common entities being brain tumors. Immunohistochemical stainings were evaluated by the H-Score (0-300). In 93% of the cases potentially actionable targets were identified. The expressed or activated pathways were histone deacetylase (HDACs; 83.0% of cases positive), EGFR (87.2%), PDGFR (75.9%), p53 (50.0%), MAPK/ERK (43.3%) and PI3K/mTOR (36.1%). Follow-up revealed partial or full implementation of PTT results in treatment decision-making in 41% of the cases. Prolonged disease stabilization responses in single cases were noticed, however, response rates did not differ from cases treated with other modalities. Further studies evaluating the feasibility and clinical benefit of personalized diagnostic approaches using paraffin material are warranted.

  14. Conservatism in least favorable response analysis and testing

    SciTech Connect

    Paez, T L

    1980-01-01

    In order to assure that mechanical structures can meet design requirements it is desirable to test a structure using an input which is conservative but not a severe overtest. One method available for the specification of shock tests is the method of least favorable response. This method can be used analytically or in the laboratory and is guaranteed to provide tests which are conservative, at least in one sense. When the impulse response function, or equivalently the frequency response function, is available between a point of interest on a structure and the input point of the structure, and when we know the real function which envelops the modulus of the Fourier transform of all possible inputs which might excite the structure, then the method of least favorable response can be used to find an upper bound on the response which the point of interest on the structure can realize. We use this in the analysis of structural peak response. In the laboratory the least favorable response is generated experimentally, for example, by testing the structural unit on a shake table. If the structure survives the laboratory test, then we assume that it could survive any input in the class of inputs whose Fourier transform moduli are enveloped by the function used in the analysis. The objective of this study was to analyze the inherent conservatism of the method of least favorable response. A technique that can be used to do this is demonstrated. First, the method of least favorable response is reviewed and how it is used analytically and experimentally is demonstrated. Next the technique used to measure the conservatism in a least favorable response test is developed. Finally, the method is applied in some numerical examples where the degree of conservatism in the tests of some specific structures is measured. (LCL)

  15. Re-induction with L-DNR/FLAG improves response after AML relapse, but not long-term survival.

    PubMed

    Creutzig, U; Semmler, J; Kaspers, G L; Reinhardt, D; Zimmermann, M

    2014-11-01

    According to the results of the international study Relapsed AML 2001/01 response was better after re-induction with L-DNR/FLAG (liposomal daunorubicin, fludarabine, cytarabine, G-CSF) compared to FLAG only but survival rate was not improved. However, the findings might be group-specific. Patient characteristics, actual therapy given and long-term course of the disease in 155 pediatric patients (including non-randomized) with first relapse and 10 primary nonresponders treated in Germany were analyzed. Overall 4-year survival rates after relapse were similar in the 2 treatment groups L-DNR/FLAG and FLAG (0.43 ± 0.05 vs. 0.47 ± 0.06, p(log-rank)=0.47). The rate of randomization was low (65%) and 5% of the 101 randomized patients changed the treatment arm. Therefore, induction was based in 40% patients on an individual decision with preference for L-DNR/FLAG. There were less patients with favorable cytogenetics and morphology in the L-DNR/FLAG-group (p<0.04). Response to the first re-induction course at day 28 tended to be more unfavorable with FLAG only. In this patient group protocol intensifications were more frequent as compared to the L-DNR/FLAG-group (p=0.07), and late CR could be achieved after intensification in 9/18 poor responding patients. The initial selection bias of relapse patients with unfavorable risk factors to the disadvantage of the L-DNR/FLAG-group and the more drug- and time-intensive treatment after 1(st) re-induction given in the FLAG-group may have nullified the initial beneficial effect of L-DNR containing re-induction therapy and led to similar and relatively favorable survival rates in both treatment groups in Germany. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Normal karyotype acute myeloid leukemia patients with CEBPA double mutation have a favorable prognosis but no survival benefit from allogeneic stem cell transplant.

    PubMed

    Ahn, Jae-Sook; Kim, Jae-Young; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Lee, Seung-Shin; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Nan Young; Choi, Seung Hyun; Minden, Mark D; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Dennis Dong Hwan

    2016-01-01

    Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values <0.05). On multivariate analysis, CEBPA (dm) (p = 0.007, OR 39.593) was an independent risk factor for achievement of complete remission (CR). With a median follow-up of 40.1 months, CEBPA (dm) showed a favorable overall survival (OS), event-free survival (EFS), and lower relapse incidence (RI) in comparison with CEBPA (wild) (all p values <0.005). Comparison of clinical outcome analyses (consolidation chemotherapy vs. allogeneic hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML.

  17. Relapses in patients with Henoch–Schönlein purpura

    PubMed Central

    Calvo-Río, Vanesa; Hernández, José Luis; Ortiz-Sanjuán, Francisco; Loricera, Javier; Palmou-Fontana, Natalia; González-Vela, Maria C.; González-Lamuño, Domingo; González-López, Marcos A.; Armesto, Susana; Blanco, Ricardo; González-Gay, Miguel A.

    2016-01-01

    Abstract To further investigate into the relapses of Henoch–Schönlein purpura (HSP), we analyzed the frequency, clinical features, and predictors of relapses in series of 417 unselected patients from a single center. After a median follow-up of 12 (interquartile range [IQR]: 2–38) years, almost one-third of the 417 patients (n = 133; 32%; 85 men/48 women) had experienced at least 1 relapse. At the time of disease diagnosis, patients who later experienced relapses had less commonly infections than those who never suffered flares (30.8% vs 41.9%; P = 0.03). In contrast, patients who experienced relapses had a longer duration of the first episode of palpable purpura than those without relapses (palpable purpura lasting >7 days; 80.0% vs 68.1%; P = 0.04). Abdominal pain (72.3% vs 62.3%; P = 0.03) and joint manifestations (27.8% vs 15.5%; P = 0.005) were also more common in patients who later developed relapses. In contrast, patients who never suffered relapses had a slightly higher frequency of fever at the time of disease diagnosis (9.3% vs 3.8%; P = 0.06). At the time of disease diagnosis, corticosteroids were more frequently given to patients who later had relapses of the disease (44% vs 32% in nonrelapsing patients; P = 0.03). Relapses generally occurred soon after the first episode of vasculitis. The median time from the diagnosis of HSP to the first relapse was 1 (IQR: 1–2) month. The median number of relapses was 1 (IQR 1–3). The main clinical features at the time of the relapse were cutaneous (88.7%), gastrointestinal (27.1%), renal (24.8%), and joint (16.5%) manifestations. After a mean ± standard deviation follow-up of 18.9 ± 9.8 years, complete recovery was observed in 110 (82.7%) of the 133 patients who had relapses. Renal sequelae (persistent renal involvement) was found in 11 (8.3%) of the patients with relapses. The best predictive factors for relapse were joint and gastrointestinal manifestations at HSP diagnosis (odds ratio [OR]: 2

  18. [Novel treatment options in relapsed and refracter Hodgkin lymphomas].

    PubMed

    Illés, Árpád; Jóna, Ádám; Simon, Zsófia; Udvardy, Miklós; Miltényi, Zsófia

    2015-11-08

    Hodgkin lymphoma is a curable lymphoma with an 80-90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Retrospective analysis of data was performed. A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure.

  19. Relapse Experience in Iranian Opiate Users: a Qualitative Study

    PubMed Central

    Seyedfatemi, Naiemeh; Peyrovi, Hamid; Jalali, Amir

    2014-01-01

    Background: To understand the relapse process, it is required to notice the clients learned behaviors and environmental contexts. We aimed to explore and describe relapse experiences of Iranian drug users. Methods: This is a grounded theory study and twenty two participants were selected using purposive sampling, snowball and theoretical sampling. After obtaining written informed consent, data gathering was done by means of in-depth semi-structured interviews. According to Strauss and Corbin three phases of open coding, axial coding and selection coding were done for qualitative analysis and continuous comparison. During the research period Guba and Lincoln criteria were used to be reassured of the accuracy and rigor of the study findings. Results: The main categories of this study were craving and conflict, family stress and psychological indicators of relapse that emerged in three phases including recovery, tension and pre-relapse. High anxiety, withdrawal, rationalization and lying were the most common symptoms. Conclusion: Family reactions and social conditions play a key role in relapse. Relapse process is an active and multidimensional event in which the clients experience a psychosocial status continuum from recovery to relapse. Most psychological problems are seen in the tension phase. PMID:25349849

  20. Approaches to relapse after allogeneic stem cell transplantation.

    PubMed

    Kröger, Nicolaus

    2011-03-01

    Relapse has become the leading cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Despite improved understanding of the biology that underlies the graft-versus-leukemia/tumor effect the relapse rate did not decrease over the past 20 years. In general, prognosis is poor for patients who relapsed to an allograft since effective treatment options are limited. Here, we review the available and upcoming treatment approaches for relapse. Treatment of relapse after allogeneic HSCT has been rarely investigated systematically and results differ substantially from diseases. Withdrawal of immunosuppressive medication, donor lymphocyte infusions with or without chemotherapy and/or second allogeneic HSCT are the most used options. New specific cellular approaches such as disease-specific T-cells, alloreactive natural killer cells or vaccination strategies are under investigation. Novel agents such as tyrosine-kinase inhibitors, hypomethylating agents, monoclonal antibodies, immunomodulating drugs, or proteasome-inhibitors either alone or in combination with adoptive immunotherapy are upcoming promising options, but valid data are lacking so far. With some exceptions (chronic myeloid leukemia), treatment options for patients who relapse are limited. The results are poor and the majority of patients ultimately die of their disease. More effort and research is needed to prevent and treat relapse after allogeneic HSCT.

  1. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    SciTech Connect

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-10-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.

  2. Local salvage therapy for late (≥2 years) metastatic and local relapse of renal cell cancer is a potentially curative treatment irrespective of the site of recurrence.

    PubMed

    Grüllich, Carsten; Vallet, Sonia; Hecht, Christopher; Duensing, Stephan; Hadaschik, Boris; Jäger, Dirk; Hohenfellner, Markus; Pahernik, Sascha

    2016-05-01

    The primary treatment approach to locoregional renal cell carcinoma (RCC) is surgical resection. Most relapses occur within the first 2 years but some patients experience late recurrences. Surgical resection of oligometastatic disease may be considered a curative option for relapsed RCC. However, limited data are available of long-term follow-up of late relapse regarding treatment choice. We identified 104 patients with RCC from our database, who relapsed after≥2 years from resection of their primary tumor. Median age at primary diagnosis was 61 years and sex distribution was F:M = 40:64. Histology was clear cell, n = 103 and papillary, n = 1. Sites of relapse were local, n = 14 (13.4%); lung only, n = 25 (24.0%); or extrapulmonary, n = 65 (62.5%). Treatment at first relapse was local therapy (LT) in n = 60 (57.7%) patients, of these, n = 55 patients had surgery done and n = 5 patients had underwent radiotherapy. Systemic therapy was used in n = 9 (8.7%) patients. Overall, 35 patients received best supportive care (33.7%). We found a median overall survival (OS) of 49.8 months (95% CI: 29.3-70.2) and a progression-free survival (PFS) of 21.6 months (95% CI: 12.6-30.5) for all patients. Patients receiving LT had a median OS of 99.9 months (95% CI: 77.2-122.6) and a PFS of 31.1 months (95% CI: 21.5-40.7). Patients treated with systemic therapy, in turn, had an OS of 21.1 months (95% CI: 8.4-33.8) and a PFS of 4 months (95% CI: 1.0-6.2). Patients who received best supportive care had an OS of 10 months (95% CI: 1.3-18.7). This difference was highly significant (log rank for PFS: P<0.001; log rank for OS: P<0.003). Subgroup analysis of the LT group showed a superior outcome for local relapses (OS: not reached, PFS: 61.4mo [95% CI: 28.5-9.2]) compared to visceral relapses (OS: 35.5mo [95% CI: 17.9-53.1], PFS: 21.1mo [95% CI: 19.2-22.9]). Local salvage therapy should be considered the first therapeutic option in late relapse of RCC irrespective of the site of relapse

  3. Does rumination mediate the relationship between mindfulness and depressive relapse?

    PubMed

    Kearns, Nicole P; Shawyer, Frances; Brooker, Joanne E; Graham, Annette L; Enticott, Joanne C; Martin, Paul R; Meadows, Graham N

    2016-03-01

    Major depressive disorder is a significant mental illness that is highly likely to recur, particularly after three or more previous episodes. Increased mindfulness and decreased rumination have both been associated with decreased depressive relapse. The aim of this study was to investigate whether rumination mediates the relationship between mindfulness and depressive relapse. This prospective design involved a secondary data analysis for identifying causal mechanisms using mediation analysis. This study was embedded in a pragmatic randomized controlled trial of mindfulness-based cognitive therapy (MBCT) in which 203 participants (165 females, 38 males; mean age: 48 years), with a history of at least three previous episodes of depression, completed measures of mindfulness, rumination, and depressive relapse over a 2-year follow-up period. Specific components of mindfulness and rumination, being nonjudging and brooding, respectively, were also explored. While higher mindfulness scores predicted reductions in rumination and depressive relapse, the relationship between mindfulness and relapse was not found to be mediated by rumination, although there appeared to be a trend. Our results strengthen the argument that mindfulness may be important in preventing relapse but that rumination is not a significant mediator of its effects. The study was adequately powered to detect medium mediation effects, but it is possible that smaller effects were present but not detected. Mindfulness may be one of several components of MBCT contributing to prevention of depressive relapse. Although the original rationale for MBCT rested largely on a model of relapse causally linked to rumination, our findings suggest that the mechanism by which mindfulness impacts relapse is more complex than a simple effect on rumination. © 2015 The British Psychological Society.

  4. Comparative histology of pineal calcification.

    PubMed

    Vígh, B; Szél, A; Debreceni, K; Fejér, Z; Manzano e Silva, M J; Vígh-Teichmann, I

    1998-07-01

    The pineal organ (pineal gland, epiphysis cerebri) contains several calcified concretions called "brain sand" or acervuli (corpora arenacea). These concretions are conspicuous with imaging techniques and provide a useful landmark for orientation in the diagnosis of intracranial diseases. Predominantly composed of calcium and magnesium salts, corpora arenacea are numerous in old patients. In smaller number they can be present in children as well. The degree of calcification was associated to various diseases. However, the presence of calcified concretions seems not to reflect a specific pathological state. Corpora arenacea occur not only in the actual pineal tissue but also in the leptomeninges, in the habenular commissure and in the choroid plexus. Studies with the potassium pyroantimonate (PPA) method on the ultrastructural localization of free calcium ions in the human pineal, revealed the presence of calcium alongside the cell membranes, a finding that underlines the importance of membrane functions in the production of calcium deposits. Intrapineal corpora arenacea are characterized by a surface with globular structures. Meningeal acervuli that are present in the arachnoid cover of the organ, differ in structure from intrapineal ones and show a prominent concentric lamination of alternating dark and light lines. The electron-lucent lines contain more calcium than the dark ones. There is a correlation between the age of the subject and the number of layers in the largest acervuli. This suggests that the formation of these layers is connected to circannual changes in the calcium level of the organ. The histological organization of the human pineal is basically the same as that of mammalian experimental animals. Pineal concretions present in mammalian animal species are mainly of the meningeal type. Meningeal cells around acervuli contain active cytoplasmic organelles and exhibit alkaline phosphatase reaction in the rat and mink, an indication of a presumable

  5. Inframammary fold: a histologic reappraisal.

    PubMed

    Muntan, C D; Sundine, M J; Rink, R D; Acland, R D

    2000-02-01

    The inframammary fold is a defining element in the shape and structure of the female breast. It should be preserved whenever possible in ablative procedures and recreated accurately when the breast is reconstructed after mastectomy. To date, no accurate anatomic description of this essential structure exists. Previous studies have suggested that the fold is produced by a supporting ligament running from the dermis in the fold region to a variety of locations on the rib cage. This clinic's experience with mastectomy, augmentation mammaplasty, and breast reconstruction does not support the existence of a ligamentous structure. To define the structure of the inframammary fold, 10 female and 2 male cadavers were studied. The anterior chest wall was removed en bloc and frozen in orthostatic position. Parasagittal sections were made of the inframammary fold with the chest wall intact. After decalcification of the ribs and routine histologic preparation, thin sections were stained with Gomori's trichrome. On light microscopic examination, no demonstrable ligamentous structure of dense regular connective tissue could be identified in the fold region in any of the 12 specimens. Superficial and deep fascial layers were uniformly observed anterior to the pectoralis major and serratus anterior muscles. The superficial fascia was connected to the dermis in the fold region in a variety of configurations. In some cases, the deep fascia fused with the superficial fascia and dermis at the fold level. In other cases, bundles of collagen fibers arising from the superficial fascial layer were found to insert into the dermis at the inframammary fold, slightly inferior to it, or both. These bundles were observed consistently in sections from the sternum to the middle axillary line. They were distinct from Cooper's suspensory ligaments, which are seen more superiorly in the glandular tissue.

  6. Productivity standards for histology laboratories.

    PubMed

    Buesa, René J

    2010-04-01

    The information from 221 US histology laboratories (histolabs) and 104 from 24 other countries with workloads from 600 to 116 000 cases per year was used to calculate productivity standards for 23 technical and 27 nontechnical tasks and for 4 types of work flow indicators. The sample includes 254 human, 40 forensic, and 31 veterinary pathology services. Statistical analyses demonstrate that most productivity standards are not different between services or worldwide. The total workload for the US human pathology histolabs averaged 26 061 cases per year, with 54% between 10 000 and less than 30 000. The total workload for 70% of the histolabs from other countries was less than 20 000, with an average of 15 226 cases per year. The fundamental manual technical tasks in the histolab and their productivity standards are as follows: grossing (14 cases per hour), cassetting (54 cassettes per hour), embedding (50 blocks per hour), and cutting (24 blocks per hour). All the other tasks, each with their own productivity standards, can be completed by auxiliary staff or using automatic instruments. Depending on the level of automation of the histolab, all the tasks derived from a workload of 25 cases will require 15.8 to 17.7 hours of work completed by 2.4 to 2.7 employees with 18% of their working time not directly dedicated to the production of diagnostic slides. This article explains how to extrapolate this productivity calculation for any workload and different levels of automation. The overall performance standard for all the tasks, including 8 hours for automated tissue processing, is 3.2 to 3.5 blocks per hour; and its best indicator is the value of the gross work flow productivity that is essentially dependent on how the work is organized. This article also includes productivity standards for forensic and veterinary histolabs, but the staffing benchmarks for histolabs will be the subject of a separate article. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Relapse after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes: Analysis of Late Relapse Using Comparative Karyotype and Chromosome Genome Array Testing

    PubMed Central

    Fang, Min; Scott, Bart L.; Flowers, Mary E.D.; Gooley, Ted; Deeg, H. Joachim

    2016-01-01

    Relapse is a major cause of failure after allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndromes (MDS). We analyzed the relapse pattern in 1007 patients who underwent transplantation for MDS to identify factors that may determine the timing of relapse. Overall, 254 patients relapsed: 213 before 18 months and 41 later than 18 months after HCT, a time point frequently used in clinical trials. The hazard of relapse declined progressively with time since transplantation. A higher proportion of patients with early relapse had high-risk cytogenetics compared with patients with late relapse (P =.009). Patients with late relapse had suggestively longer postrelapse survival than patients who relapsed early, although the difference was not statistically significant (P =.07). Among 41 late relapsing patients, sequential cytogenetic data were available in 36. In 41% of these, new clonal abnormalities in addition to pre-HCT findings were identified at relapse; in 30% pre-HCT abnormalities were replaced by new clones, in 17.3% the same clone was present before HCT and at relapse, and in 9.7%, no abnormalities were present either before HCT or at relapse. Comparative chromosomal genomic array testing in 3 patients with late relapse showed molecular differences not detectable by cytogenetics between the pre-HCT clones and the clones at relapse. These data show that late relapses are not infrequent in patients who undergo transplantation for MDS. The pattern of new cytogenetic alterations at late relapse is similar to that observed in patients with early relapse and supports the concept that MDS relapse early and late after HCT is frequently due to the emergence of clones not detectable before HCT. PMID:25953732

  8. Preoperative lymphoscintigraphy and tumor histologic grade are associated with surgical detection of the sentinel lymph node.

    PubMed

    Arias Ortega, M; Torres Sousa, M Y; González García, B; Pardo García, R; González López, A; Delgado Portela, M

    2014-01-01

    To study which variables involved in the process of selective sentinel node biopsy (SSNB) influence the intraoperative detection of the sentinel lymph node. This was a prospective cross-sectional study in 210 patients (mean age, 54 years) diagnosed with breast cancer who underwent SSNB. We recorded clinical, radiological, radioisotope administration, surgical, and histological data as well as follow-up data. We did a descriptive analysis of the data and an associative analysis using multivariable regression. Deep injection alone was the most common route of radioisotope administration (72.7%). Most lesions were palpable (57.1%), presented as nodules (67.1%), measured less than 2 cm in diameter (64.8%), were located in the upper outer quadrant (49.1%), were ductal carcinomas (85.7%), were accompanied by infiltration (66.2%), and had a histologic grade of differentiation of ii (44.8%). Preoperative scintigraphy detected the sentinel node in 97.6% of cases and 95.7% were detected during the operation. One axillary relapse was observed. In the associative study, the variables "preoperative lymphoscintigraphy" and "histologic grade of differentiation of the tumor" were significantly associated with the detection of the sentinel lymph node during the operation. The probability of not detecting the sentinel lymph node during the surgical intervention is higher in patients with high histologic grade tumors or in patients in whom preoperative lymphoscintigraphy failed to detect the sentinel node. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  9. [Calcifying periarthropathy (radiologic-histological synopsis, terminology)].

    PubMed

    Dihlmann, W

    1981-01-01

    On the basis of a case of radiologically and histologically investigated calcifying periarthropathy in the tendon of the glutaeus medius muscle the histological appearance and the pathogenesis of pain associated with this process is considered. The transformation of tendon tissue into fibrous cartilage is emphasized.

  10. Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse

    DTIC Science & Technology

    2017-07-01

    AWARD NUMBER: W81XWH-14-1-0087 TITLE: Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse PRINCIPAL INVESTIGATOR: Dr. Masoud...SUBTITLE 5a. CONTRACT NUMBER Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse 5b. GRANT NUMBER W81XWH-14-1-0087 5c. PROGRAM...expedited tumor relapse. The purpose of the study  was to determine if transient blockade of autophagy by CQ was  associated  with anti‐inflammatory function

  11. Modeling diseases with latency and relapse.

    PubMed

    van den Driessche, P; Wang, Lin; Zou, Xingfu

    2007-04-01

    A general mathematical model for a disease with an exposed (la tent) period and relapse is proposed. Such a model is appropriate for tuberculosis, including bovine tuberculosis in cattle and wildlife, and for herpes. For this model with a general probability of remaining in the exposed class, the basic reproduction number R(0) is identified and its threshold property is discussed. In particular, the disease-free equilibrium is proved to be globally asymptotically stable if R(0) < 1. If the probability of remaining in the exposed class is assumed to be negatively exponentially distributed, then R(0) = 1 is a sharp threshold between disease extinction and endemic disease. A delay differential equation system is obtained if the probability function is assumed to be a step-function. For this system, the endemic equilibrium is locally asymptotically stable if R(0) > 1, and the disease is shown to be uniformly persistent with the infective population size either approaching or oscillating about the endemic level. Numerical simulations (for parameters appropriate for bovine tuberculosis in cattle) with R(0) > 1 indicate that solutions tend to this endemic state.

  12. A Motion Videogame for Opioid Relapse Prevention.

    PubMed

    Abroms, Lorien C; Leavitt, Leah E; Van Alstyne, Judy M; Schindler-Ruwisch, Jennifer M; Fishman, Marc J; Greenberg, Daniel

    2015-12-01

    This study examined the feasibility and acceptability of a body motion-activated videogame, targeting the prevention of opioid relapse among youth in the context of outpatient treatment. Participants attended four weekly gameplay sessions. Surveys were conducted at baseline and following each week's gameplay and assessed satisfaction with gameplay, craving intensity, and self-efficacy to refuse opioids. Participants expressed a high level of satisfaction with the videogame throughout the 4 weeks and agreed with the statement that they would be more likely to attend treatment sessions if the game was present (mean=4.6; standard deviation [SD]=0.7) and would recommend the videogame to other people in treatment (mean=4.2; SD=0.8). All participants recommended playing the videogame as part of treatment at least weekly, with a third recommending playing daily. Self-reported cravings declined over the 4-week period from baseline (mean=12.7; SD=8.4) to Week 4 (mean=9.8; SD=8.3), although the decline was not significant. Although participants stated that they liked the game, one-third of participants had dropped out of the study by the fourth session of gameplay. Preliminary evidence indicates that a motion videogame for addiction recovery may be feasible and acceptable within the context of outpatient treatment, although additional efforts are needed to keep youth in treatment. Future studies are needed to assess the impact of the game on long-term abstinence, treatment adherence, and engagement.

  13. Phylogenesis of relapsing fever Borrelia spp.

    PubMed

    Ras, N M; Lascola, B; Postic, D; Cutler, S J; Rodhain, F; Baranton, G; Raoult, D

    1996-10-01

    The phylogenetic relationships of 20 relapsing fever (RF) Borrelia spp. were estimated on the basis of the sequences of rrs genes. Complete sequences were aligned and compared with previously published sequences, and the similarity values were found to be 97.7 to 99.9%. Phylogenetic trees were constructed by using the three neighbor-joining, maximum-parsimony, and maximum-likelihood methods. The results of the comparative phylogenetic analysis divided the RF Borrelia spp. into three major clusters. One cluster included Borrelia crocidurae, Borrelia duttonii, Borrelia recurrentis, and Borrelia hispanica. Another cluster comprised tow main branches with Borrelia coriaceae, Borrelia lonestari, and Borrelia miyamotoi on one side and Borrelia parkeri, Borrelia turicatae, and Borrelia hermsii on the other side. Borrelia anserina constituted the third cluster. The phylogenetic position of Borrelia persica was more uncertain. These results suggested that the taxonomy of these spirochetes should be revised. To overcome the problems of culturing the spirochetes, RF Borrelia primers were defined. Following PCR amplification of the rrs gene, restriction length fragment polymorphism could be used to distinguish between RF Borrelia strains.

  14. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  15. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  16. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  17. 11 CFR 7.8 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Employees or Commissioners § 7.8 Gifts, entertainment, and favors. (a) A Commissioner or employee of the... affected by the performance or nonperformance of the Commissioner or employee's official duty. (b... persons concerned which are the motivating factors; (2) To the acceptance of food, refreshments,...

  18. 19 CFR 200.735-105 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Section 200.735-105 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION EMPLOYEE RESPONSIBILITIES AND CONDUCT Provisions Governing Ethical and Other Conduct and Responsibilities of Employees § 200.735... employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan,...

  19. 18 CFR 706.202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Employees § 706.202 Gifts, entertainment, and favors. (a) Except as provided in paragraphs (b) and (c) of this section, an employee shall... to: (1) Obvious family or personal relationships, such as those between the employee and his...

  20. 22 CFR 1203.735-305 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Gifts, entertainment, and favors. 1203.735-305 Section 1203.735-305 Foreign Relations UNITED STATES INTERNATIONAL DEVELOPMENT COOPERATION AGENCY EMPLOYEE RESPONSIBILITIES AND CONDUCT Ethical and Other Conduct and Responsibilities of Special Government Employees § 1203...

  1. Increasing long term response by selecting for favorable minor alleles

    USDA-ARS?s Scientific Manuscript database

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  2. 22 CFR 1203.735-305 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Gifts, entertainment, and favors. 1203.735-305 Section 1203.735-305 Foreign Relations UNITED STATES INTERNATIONAL DEVELOPMENT COOPERATION AGENCY EMPLOYEE... the Constitution and in 5 U.S.C. 7342, and the regulations promulgated thereunder pursuant to...

  3. 22 CFR 1203.735-305 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Gifts, entertainment, and favors. 1203.735-305 Section 1203.735-305 Foreign Relations UNITED STATES INTERNATIONAL DEVELOPMENT COOPERATION AGENCY EMPLOYEE... the Constitution and in 5 U.S.C. 7342, and the regulations promulgated thereunder pursuant to...

  4. Preschoolers Reduce Inequality While Favoring Individuals with More

    ERIC Educational Resources Information Center

    Li, Vivian; Spitzer, Brian; Olson, Kristina R.

    2014-01-01

    Inequalities are everywhere, yet little is known about how children respond to people affected by inequalities. This article explores two responses--minimizing inequalities and favoring those who are advantaged by them. In Studies 1a (N = 37) and 1b (N = 38), 4- and 5-year-olds allocated a resource to a disadvantaged recipient, but judged…

  5. An Evaluation of the Favorable Alternate Sites Project. Final Report.

    ERIC Educational Resources Information Center

    Kogan, Deborah; Vencill, Mary

    This final report describes and evaluates the Favorable Alternate Sites Project (FASP), developed in response to the oversettlement of refugees (particularly Southeast Asian refugees) in particular areas of the country. The project's goals were to reduce welfare dependency, increase the ability of FASP refugees to be self-supporting, and reduce…

  6. 12 CFR 560.110 - Most favored lender usury preemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 560.110 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY LENDING AND INVESTMENT Lending and Investment Provisions Applicable to all Savings Associations § 560.110 Most favored... lending institution by the law of that state. If state law permits different interest charges on specified...

  7. Filtering the Net in Libraries: The Case (Mostly) in Favor.

    ERIC Educational Resources Information Center

    Banks, Michael A.

    1998-01-01

    Examines issues and decision-making involved in restricting Internet access in libraries, for the most part favoring filtering devices. Questions to consider when selecting a filtering program are provided. Some of the better filtering programs are described, and Web addresses are included for each. Security risks associated with Java and…

  8. Filtering the Net in Libraries: The Case (Mostly) in Favor.

    ERIC Educational Resources Information Center

    Banks, Michael A.

    1998-01-01

    Examines issues and decision-making involved in restricting Internet access in libraries, for the most part favoring filtering devices. Questions to consider when selecting a filtering program are provided. Some of the better filtering programs are described, and Web addresses are included for each. Security risks associated with Java and…

  9. 25 CFR 700.519 - Gifts, entertainment and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Employee Responsibility and Conduct § 700.519 Gifts, entertainment and favors. (a) Acceptance of gratuities... individuals with whom Commission employees do business. This prohibition extends to the acceptance of meals and refreshments offered by individuals conducting or seeking business with the Commission...

  10. Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma--results of the UK HD3 relapse treatment strategy.

    PubMed

    Shankar, Ananth; Hayward, Janis; Kirkwood, Amy; McCarthy, Keith; Hewitt, Martin; Morland, Bruce; Daw, Stephen

    2014-05-01

    The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005, 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4-6 cycles of EPIC [etoposide, prednisolone, ifosfamide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5-year overall survival [OS] and progression-free survival from relapse was 75·8% [64·8-83·9] and 59·9% [48·3-69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19-1·18] for those with a time from end of treatment to relapse of 3-12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04-0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse. Survival outcome in children with primary refractory HL is poor. © 2014 John Wiley & Sons Ltd.

  11. Relapse dynamics during smoking cessation: Recurrent abstinence violation effects and lapse-relapse progression

    PubMed Central

    Kirchner, Thomas R.; Shiffman, Saul; Wileyto, E. Paul

    2012-01-01

    Smoking cessation is a process that unfolds over time and is characterized by intermittent lapses. Behavioral relapse prevention interventions commonly assume that lapse-relapse progression is driven by a set of psychological responses known as the Abstinence Violation Effect (AVE; Marlatt & Gordon, 1985), yet efforts to reduce the AVE have generally failed to affect clinical outcomes. We used parametric recurrent event survival analyses to better understand the dynamic relationship between a set of AVE responses to lapsing and subsequent lapse-relapse progression. Participants were 203 smokers who achieved abstinence and subsequently lapsed on one or more separate occasions. Using electronic diaries for ecological momentary assessment, participants responded to items assessing three core components of the AVE (internal attribution of self-blame for the lapse, abstinence self-efficacy and guilt) following a total of 1,001 smoking episodes in near real time. Contrary to hypothesis, neither self-blame, self-efficacy nor guilt following participants’ first lapse predicted relapse, and all three were overshadowed by responses to recurrent lapses that followed. Controlling for responses to their first lapse, responses to each additional lapse did prospectively predict lapse progression, such that drops in self-efficacy were associated with accelerated progression to a subsequent lapse (HR=1.09, CI=1.02–1.15), while increases in internal attributions of blame actually protected against lapsing (HR=0.98, CI=0.97–0.99). Treatment with nicotine patches slowed recurrent lapse progression (HR=0.58, CI=0.48–0.70), but this effect dissipated over multiple lapses, and was moderated by elevated ratings of post-lapse guilt (HR=1.08, CI=1.01–1.18), which predicted accelerated progression within the active patch group, while protecting against lapse in the placebo group. Results highlight the dynamic nature of lapse responses during smoking cessation, indicating that self

  12. Individualized relapse prediction: personality measures and striatal and insular activity during reward-processing robustly predict relapse*

    PubMed Central

    Gowin, Joshua L.; Ball, Tali M.; Wittmann, Marc; Tapert, Susan F.; Paulus, Martin P.

    2015-01-01

    Background Nearly half of individuals with substance use disorders relapse in the year after treatment. A diagnostic tool to help clinicians make decisions regarding treatment does not exist for psychiatric conditions. Identifying individuals with high risk for relapse to substance use following abstinence has profound clinical consequences. This study aimed to develop neuroimaging as a robust tool to predict relapse. Methods 68 methamphetamine-dependent adults (15 female) were recruited from 28-day inpatient treatment. During treatment, participants completed a functional MRI scan that examined brain activation during reward processing. Patients were followed 1 year later to assess abstinence. We examined brain activation during reward processing between relapsing and abstaining individuals and employed three random forest prediction models (clinical and personality measures, neuroimaging measures, a combined model) to generate predictions for each participant regarding their relapse likelihood. Results 18 individuals relapsed. There were significant group by reward-size interactions for neural activation in the left insula and right striatum for rewards. Abstaining individuals showed increased activation for large, risky relative to small, safe rewards, whereas relapsing individuals failed to show differential activation between reward types. All three random forest models yielded good test characteristics such that a positive test for relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood ratio of 0.48. Conclusions These findings suggest that neuroimaging can be developed in combination with other measures as an instrument to predict relapse, advancing tools providers can use to make decisions about individualized treatment of substance use disorders. PMID:25977206

  13. [Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].

    PubMed

    Klotz, L; Meuth, S G; Kieseier, B; Wiendl, H

    2013-08-01

    In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration < 5 years) were included, whereas CARE-MS-II investigated the effects of alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration < 10 years). These groups were compared to patients under treatment with frequently applied interferon β 1a (3 times  44 µg subcutaneous). Both studies clearly demonstrated a superiority of alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.

  14. Three-Drug Combination for Relapsed Multiple Myeloma

    Cancer.gov

    A summary of Interim results from an international, randomized phase III trial that suggest that adding carfilzomib (Kyprolis®) to a standard treatment improves outcomes for patients with multiple myeloma whose cancer has relapsed.

  15. Novel therapeutic options for relapsed hairy cell leukemia.

    PubMed

    Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

    2015-01-01

    The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

  16. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

  17. The effect of relapse on cognition in abstinent methamphetamine abusers.

    PubMed

    Simon, Sara L; Dacey, Jennifer; Glynn, Susan; Rawson, Richard; Ling, Walter

    2004-07-01

    Data from 75 participants in a longitudinal study of methamphetamine (MA) abuse were used to differentiate the cognitive performance of those who remained abstinent, relapsed, or continued to use during treatment. Participants were divided into three groups: continuous abstinence, initial abstinence but relapse, and continuous use. Groups did not differ on age, education, gender or ethnicity. Participants in the longitudinal study completed a battery of cognitive tests within 7 days of their last use of MA, then were re-tested monthly for up to 6 months (average time for this analysis was 92 days). For episodic memory, the relapse groups performance was worse than the abstinent and significantly worse than that of the continued use group who had the best performance on all measures. Relapse to methamphetamine use may affect episodic memory differently than it affects the other cognitive functions measured.

  18. Cognitive Therapy to Prevent Depressive Relapse in Adults

    PubMed Central

    2015-01-01

    The high prevalence, frequent relapse, and recurrence of major depressive disorder (MDD) increase its personal and societal costs. Cognitive therapy (CT) aims to decrease depressive symptoms and prevent relapse/recurrence. We review prevention evidence for acute, continuation, and maintenance CTs for patients whose depression is active, remitted, and recovered, respectively. Evidence suggests that patients relapse less often after discontinuing acute phase CT versus discontinuing pharmacotherapy. Continuation CT further decreases relapse relative to inactive controls and similarly to active pharmacotherapy. Maintenance CT may decrease recurrence but needs rigorous evaluation. Post-acute CT’s preventive effects appear greater for higher-risk patients (e.g., with residual depressive symptoms, unstable acute-phase treatment response, childhood trauma, more prior depressive episodes), although risks may vary by specific CTs. PMID:25729758

  19. Relapse in schizophrenia: Definitively not a bolt from the blue.

    PubMed

    Spaniel, Filip; Bakstein, Eduard; Anyz, Jiri; Hlinka, Jaroslav; Sieger, Tomas; Hrdlicka, Jan; Görnerová, Natálie; Höschl, Cyril

    2016-04-22

    Detailed study of the period before schizophrenic relapse when early warning signs (EWS) are present is crucial to effective pre-emptive strategies. To investigate the temporal properties of EWS self-reported weekly via a telemedicine system. EWS history was obtained for 61 relapses resulting in hospitalization involving 51 patients with schizophrenia. Up to 20 weeks of EWS history per case were evaluated using a non-parametric bootstrap test and generalized mixed-effects model to test the significance and homogeneity of the findings. A statistically significant increase in EWS sum score was detectable 5 weeks before hospitalization. However, analysis of EWS dynamics revealed a gradual, monotonic increase in EWS score across during the 8 weeks before a relapse. The findings-in contrast to earlier studies-suggest that relapse is preceded by a lengthy period during which pathophysiological processes unfold; these changes are reflected in subjective EWS.

  20. Association between specific plasmids and relapse in typhoid fever.

    PubMed Central

    Gotuzzo, E; Morris, J G; Benavente, L; Wood, P K; Levine, O; Black, R E; Levine, M M

    1987-01-01

    We studied isolates from 73 patients hospitalized with typhoid fever in Lima, Peru. Of these 73 patients, 11 (15%) suffered a clinical relapse, with fever and positive blood cultures, within 3 months of their original illness. Using plasmids as epidemiologic markers, we found that three patients who subsequently relapsed were initially infected with more than one strain of Salmonella typhi. There was a highly significant association between relapse and isolation of a strain containing either a 24- or a 38-kilobase plasmid at the time of the original infection; however, we were unable to show any evidence of homology between these two plasmids. Our data indicate that infection with multiple strains is not uncommon in this endemic area and suggest that relapse may be partly strain dependent. Images PMID:2821064

  1. Relapsing Whipple's disease presenting with hypopituitarism.

    PubMed

    Brändle, M; Ammann, P; Spinas, G A; Dutly, F; Galeazzi, R L; Schmid, C; Altwegg, M

    1999-03-01

    A 44-year-old man with a history of Whipple's disease 8 years ago presented with recurrent grand mal seizures and signs of hypopituitarism on physical examination. Magnetic resonance imaging of the brain revealed a hypothalamic lesion of 1 cm diameter in the region of the rostral infundibulum. Hypopituitarism was confirmed by low levels of serum cortisol, free testosterone and free thyroxine without an elevated TSH. Whipple encephalitis with hypothalamic involvement was suggested and verified by positive polymerase chain reaction (PCR) for Tropheryma whippelii in the cerebrospinal fluid. PCR for T. whippelii has become an important diagnostic tool for establishing the diagnosis of Whipple's disease especially in patients with unusual presentations and if the diagnosis cannot be confirmed histologically. Whipple's disease should be included in the differential diagnosis in hypopituitarism caused by infectious disease.

  2. A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors.

    PubMed

    Feldman, Darren R; Einhorn, Lawrence H; Quinn, David I; Loriot, Yohann; Joffe, Johnathan K; Vaughn, David J; Fléchon, Aude; Hajdenberg, Julio; Halim, Abdel-Baset; Zahir, Hamim; Motzer, Robert J

    2013-08-01

    Tivantinib is a selective, small-molecule inhibitor of the MET receptor tyrosine kinase. Preclinical and phase 1 data suggested a possible role for MET in the pathophysiology of germ cell tumors (GCTs) and a potential clinical benefit from tivantinib in patients with these tumors. Men (≥ 16 years) with relapsed or refractory, histologically confirmed, non-central nervous system GCTs received oral tivantinib 360 mg twice daily in 28-day cycles until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate in the first 4 cycles, with study termination for <2 responses among the first 21 patients. Secondary endpoints included 12-week progression-free survival (PFS), overall survival (OS), and safety. Twenty-seven patients were enrolled in 9 months (median age, 32 years). Most patients had tumors with nonseminoma histology (n = 25), and primary tumor sites were testis (n = 24) and mediastinum (n = 3). Among 25 evaluable patients, no objective responses were observed; accrual was halted when the 21st patient became evaluable. Best response was stable disease (n = 5). Median PFS was 1 month, the 12-week PFS rate was 21 %, and median OS was 6 months. Grade 3 or 4 adverse events considered related to study drug included grade 3 pneumonia and grade 3 syncope (n = 1, each). Tivantinib was well tolerated but did not demonstrate single-agent activity in patients with relapsed/refractory GCTs. Rapid accrual to this phase 2 trial was achieved in this rare patient population through multicenter collaboration.

  3. Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

    PubMed

    Peled, Jonathan U; Devlin, Sean M; Staffas, Anna; Lumish, Melissa; Khanin, Raya; Littmann, Eric R; Ling, Lilan; Kosuri, Satyajit; Maloy, Molly; Slingerland, John B; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Shono, Yusuke; Slingerland, Ann E; Docampo, Melissa D; Sung, Anthony D; Weber, Daniela; Alousi, Amin M; Gyurkocza, Boglarka; Ponce, Doris M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Taur, Ying; Pamer, Eric G; Jenq, Robert R; van den Brink, Marcel R M

    2017-03-15

    Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

  4. Assessing changes in relapse rates in multiple sclerosis.

    PubMed

    Inusah, Seidu; Sormani, Maria P; Cofield, Stacey S; Aban, Inmaculada B; Musani, Solomon K; Srinivasasainagendra, Vinodh; Cutter, Gary R

    2010-12-01

    Multiple Sclerosis (MS) annualized relapse rates (ARRs) in trials may be declining due to changes in diagnostic criteria, MS etiology, study criteria, and selection biases. This review examines if there is a trend in the ARR for relapsing-remitting MS patients (RRMS) over time and if so, why. A comprehensive literature search was performed using PubMed, Web of Science(®), and the Cochrane Library using electronic searches, screen scraping for abstracts, and hand searching of references for randomized trials conducted between 1960 and 2008. Out of 72 randomized trials, 56 (77.8%) defined relapse. This study uses 32 placebo relapsing-remitting studies out of the 37 (66.1%) with RRMS. The mean ARR for the treatment arms was 0.68 and the one for the placebo groups was 1.002. The year of publication was negatively associated with the ARR (p = 0.0001). The annual reduction amounts to 0.36 relapses over a 10-year period. Age and duration of symptoms were negatively associated with the ARR. Year of publication was significantly negatively associated with ARR after controlling for covariates. ARRs have fallen with relapse definition, entrance criteria remain important, but time exceeds all these variables and reflects two likely sources, selection of patients for trials by clinicians and rescue of patients truncating the number of multiple relapses. The impact of truncating the number of relapses on the falling rates is important, not only on the ARRs, but also on the impact of informative censoring in drop-outs.

  5. A Motion Videogame for Opioid Relapse Prevention

    PubMed Central

    Leavitt, Leah E.; Van Alstyne, Judy M.; Schindler-Ruwisch, Jennifer M.; Fishman, Marc J.; Greenberg, Daniel

    2015-01-01

    Abstract Objective: This study examined the feasibility and acceptability of a body motion–activated videogame, targeting the prevention of opioid relapse among youth in the context of outpatient treatment. Materials and Methods: Participants attended four weekly gameplay sessions. Surveys were conducted at baseline and following each week's gameplay and assessed satisfaction with gameplay, craving intensity, and self-efficacy to refuse opioids. Results: Participants expressed a high level of satisfaction with the videogame throughout the 4 weeks and agreed with the statement that they would be more likely to attend treatment sessions if the game was present (mean=4.6; standard deviation [SD]=0.7) and would recommend the videogame to other people in treatment (mean=4.2; SD=0.8). All participants recommended playing the videogame as part of treatment at least weekly, with a third recommending playing daily. Self-reported cravings declined over the 4-week period from baseline (mean=12.7; SD=8.4) to Week 4 (mean=9.8; SD=8.3), although the decline was not significant. Although participants stated that they liked the game, one-third of participants had dropped out of the study by the fourth session of gameplay. Conclusions: Preliminary evidence indicates that a motion videogame for addiction recovery may be feasible and acceptable within the context of outpatient treatment, although additional efforts are needed to keep youth in treatment. Future studies are needed to assess the impact of the game on long-term abstinence, treatment adherence, and engagement. PMID:26213838

  6. Integrins Modulate Relapse to Cocaine-Seeking

    PubMed Central

    Wiggins, Armina; Smith, Rachel J; Shen, Haowei; Kalivas, Peter W

    2012-01-01

    Relapse to cocaine seeking involves impairments in plasticity at glutamatergic synapses in the nucleus accumbens. Integrins are cell adhesion molecules that bind to the extracellular matrix and regulate aspects of synaptic plasticity, including glutamate receptor trafficking. To determine a role for integrins in cocaine-seeking, rats were trained to self-administer cocaine, the operant response extinguished, and cocaine-seeking induced by a conditioned cue or noncontingent cocaine injection. This cocaine self-administration protocol reduced the content of the beta3 integrin subunit in postsynaptic density (PSD) of the accumbens core at 24 hr after the last self-administration session. However, by 3 wks of forced abstinence plus extinction training the level of beta3 was elevated, and was further regulated over 120 min during cocaine-induced drug-seeking. A small peptide ligand (RGD) that mimics extracellular matrix protein binding to integrins was microinjected into the accumbens core during self-administration or extinction training, or just prior to cocaine-reinstated drug seeking. The daily RGD injections during self-administration or just prior to a reinstatement session inhibited cocaine-induced drug-seeking, while RGD microinjection during extinction training was without consequence on reinstated cocaine-seeking. Daily RGD during self-administration also prevented the enduring changes in beta3 levels. Finally, reduced surface expression of the GluR2 subunit of the AMPA receptor is associated with cocaine-seeking, and daily RGD microinjections during self-administration training normalized the surface expression of GluR2. Together these data indicate that the regulation integrins may contribute to cocaine-reinstated drug-seeking, in part by promoting reduced GluR2 surface expression. PMID:22072669

  7. Integrins modulate relapse to cocaine-seeking.

    PubMed

    Wiggins, Armina; Smith, Rachel J; Shen, Hao-Wei; Kalivas, Peter W

    2011-11-09

    Relapse to cocaine-seeking involves impairments in plasticity at glutamatergic synapses in the nucleus accumbens. Integrins are cell adhesion molecules that bind to the extracellular matrix and regulate aspects of synaptic plasticity, including glutamate receptor trafficking. To determine a role for integrins in cocaine-seeking, rats were trained to self-administer cocaine, the operant response extinguished, and cocaine-seeking induced by a conditioned cue or noncontingent cocaine injection. This cocaine self-administration protocol reduced the content of the β3 integrin subunit in postsynaptic density of the accumbens core at 24 h after the last self-administration session. However, after 3 weeks of forced abstinence plus extinction training, the level of β3 was elevated and was further regulated over 120 min during cocaine-induced drug-seeking. A small peptide ligand [arginine-glycine-aspartate (RGD)] that mimics extracellular matrix protein binding to integrins was microinjected into the accumbens core during self-administration or extinction training, or just before cocaine-reinstated drug seeking. The daily RGD injections during self-administration or just before a reinstatement session inhibited cocaine-induced drug-seeking, while RGD microinjection during extinction training was without consequence on reinstated cocaine-seeking. Daily RGD during self-administration also prevented the enduring changes in β3 levels. Finally, reduced surface expression of the GluR2 subunit of the AMPA receptor is associated with cocaine-seeking, and daily RGD microinjections during self-administration training normalized the surface expression of GluR2. Together, these data indicate that the regulation integrins may contribute to cocaine-reinstated drug-seeking, in part by promoting reduced GluR2 surface expression.

  8. The reliability of Marlatt's taxonomy for classifying relapses.

    PubMed

    Longabaugh, R; Rubin, A; Stout, R L; Zywiak, W H; Lowman, C

    1996-12-01

    Marlatt's focus on the relapse situation has had a major impact upon research and clinical practice in treating addictions. One component of his work was the development of a taxonomy for classifying precipitants of relapse. This taxonomy has been incorporated into the nomenclature of clinicians and clinical researchers as part of an explanatory framework for understanding relapses. Despite the taxonomy's influence it has never been examined for the reliability of its use across research studies. The present study compared the reliability of independent classifications of 149 relapse episodes by trained raters at three research laboratories. Despite considerable across-laboratory training, reliability was found to be inconsistent for research purposes. It is concluded that comparability of results based on Marlatt's relapse taxonomy across independent studies must be subject to question, and assumptions necessary for the aggregation of a knowledge base are not supported. Recommendations are offered for improving the reliability of the taxonomy and the methods used to collect taxonomy data. More generally, questions regarding the value of the specific relapse categories, as well as the overall taxonomy, are raised.

  9. Smoking increases the risk of relapse after successful tuberculosis treatment

    PubMed Central

    d’Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha

    2008-01-01

    Background Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. Methods A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001–2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Results Smoking (OR 2.53, 95% CI 1.23–5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46–8.93) were found to be independently associated with relapse of tuberculosis. Conclusions Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. PMID:18556729

  10. Mathematical model of Ebola transmission dynamics with relapse and reinfection.

    PubMed

    Agusto, F B

    2017-01-01

    The Ebola virus disease is caused by the Ebola virus which belongs to the filoviridae virus family. The 2014 outbreaks were estimated to have caused over 11,000 fatalities. In this paper, we formulate and analyze a system of ordinary differential equations which incorporates disease relapse and reinfection. The Ebola model with disease relapse and reinfection is locally-asymptotically stable when the basic reproduction number is less than unity. The model exhibits in the presence of disease reinfection, the phenomenon of backward bifurcation, where the stable disease-free equilibrium co-exists with a stable endemic equilibrium when the associated reproduction number is less than unity. The feasibility of backward bifurcation occurring increases with increasing values of both relapse and reinfection. The total number of new cases of Ebola-infected individuals increases with increasing values of the relapse and reinfection parameters. Further simulations show that Ebola transmission models that do not incorporate relapse and reinfection may under-estimate disease burden in the community. Similar under-estimation is observed in models that include only one infected and recovered classes. Using results obtained from sensitivity analysis indicates that Ebola (given disease relapse and reinfection) can be effectively curtailed in the community by using control measures with a high-effectiveness level. This strategy is more effective than either the moderate- or low-effectiveness levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

    PubMed Central

    Cohen, Jeffrey A.; Coles, Alasdair J.; Hartung, Hans-Peter; Havrdova, Eva; Selmaj, Krzysztof W.; Margolin, David H.; Lake, Stephen L.; Kaup, Susan M.; Panzara, Michael A.; Compston, D. Alastair S.

    2016-01-01

    Objective: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. Methods: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. Results: Alemtuzumab-treated patients were more likely than SC IFN-β-1a–treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a–treated patients. Conclusions: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities. Classification of evidence: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a

  12. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients.

    PubMed

    Giovannoni, Gavin; Cohen, Jeffrey A; Coles, Alasdair J; Hartung, Hans-Peter; Havrdova, Eva; Selmaj, Krzysztof W; Margolin, David H; Lake, Stephen L; Kaup, Susan M; Panzara, Michael A; Compston, D Alastair S

    2016-11-08

    To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients. In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities. This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a. © 2016 American Academy of Neurology.

  13. Multimodality therapy of favorable prognosis non-Hodgkin's lymphoma

    SciTech Connect

    Corder, M.P.; Leimert, J.T.; Tewfik, H.H.; Lovett, J.M.

    1983-07-01

    Twenty-seven previously untreated patients with favorable prognosis non-Hodgkin's lymphoma were treated with a combination of total body irradiation followed by cyclophosphamide - vincristine - prednisone (CVP). The dose of total body irradiation was planned to be 150 rad followed by 6 cycles of chemotherapy. The complete response rate was 59%; the complete plus partial response rate, 93%. The 50% disease-free survival was 8 months. The actuarial projected 5 year survival was 60% and the disease-free survival at 5 years was 27%. The program was well tolerated by the majority of patients. It is possible for some patients with favorable non-Hodgkin's lymphomas to achieve prolonged periods of disesase-free survival when treated with combinations of irradiation plus chemotherapy.

  14. Design integration of favorable geometry, structural support and containment

    SciTech Connect

    Purcell, J.A.; McGehee, G.A.

    1991-07-01

    In designs for fissile processes at Savannah River site, different approaches have been used to provide engineered margins of safety for criticality with containment and seismic resistance as additional requirements. These requirements are frequently at odds in engineered systems. This paper proposes a plan to take advantage of vessels with favorable geometry to provide seismic resistance and to support a glovebox for containment. Thin slab tanks, small diameter pencil tanks, annular tanks, and other novel designs have been used for criticality safety. The requirement for DBE seismic resistance and rigid control of dimensions leads the designer to consider annular tanks for meeting these requirements. The high strength of annular tanks may logically be used to support secondary containment. Hands-on access to all instruments, piping etc. within containment can be provided through gloveports, thus a specialized glovebox. This paper examines the advantages of using an annular tank design to provide favorable geometry, structural support and containment.

  15. Design integration of favorable geometry, structural support and containment

    SciTech Connect

    Purcell, J.A.; McGehee, G.A.

    1991-07-01

    In designs for fissile processes at Savannah River site, different approaches have been used to provide engineered margins of safety for criticality with containment and seismic resistance as additional requirements. These requirements are frequently at odds in engineered systems. This paper proposes a plan to take advantage of vessels with favorable geometry to provide seismic resistance and to support a glovebox for containment. Thin slab tanks, small diameter pencil tanks, annular tanks, and other novel designs have been used for criticality safety. The requirement for DBE seismic resistance and rigid control of dimensions leads the designer to consider annular tanks for meeting these requirements. The high strength of annular tanks may logically be used to support secondary containment. Hands-on access to all instruments, piping etc. within containment can be provided through gloveports, thus a specialized glovebox. This paper examines the advantages of using an annular tank design to provide favorable geometry, structural support and containment.

  16. Contact line pinning favors the mass production of monodisperse microbubbles.

    NASA Astrophysics Data System (ADS)

    Gordillo, Jose Manuel; Campo-Cortes, Francisco; Riboux, Guillaume

    2015-11-01

    A robust method for the generation of phospholipid covered monodisperse microbubbles of diameters ~10 microns at production rates exceeding 0.1 MHz, is presented here. We show that bubbles are periodically formed from the tip of a long and thin gas ligament stabilized thanks to both the strong favorable pressure gradient existing at the entrance region of a long rectangular PDMS-PDMS channel and to the pinning of the gas-liquid interface at a centered groove of several microns width placed on one of its walls. Moreover, the long exit channel incorporated in our design, favors the transport of phospholipid molecules towards the gas-liquid interface. Our experiments show that the resulting phospholipid shell inhibit both the diffusion of the gas in the surrounding liquid as well as the coalescence between contacting bubbles. These evidences indicate that the proposed method is suitable for the generation of monodisperse microbubbles for diagnosis or therapeutical applications.

  17. Expectant management with selective delayed intervention for favorable risk prostate cancer.

    PubMed

    Klotz, Laurence

    2002-01-01

    Management options for favorable risk prostate cancer are diverse, varying from a conservative approach (expectant management) to definitive treatment (radical prostatectomy or radiotherapy.) Several studies have suggested that expectant management provides similar 10-year survival rates and quality-adjusted life years compared with radical prostatectomy or radiotherapy. Expectant management alone clearly deprives some patients with potentially curable life-threatening disease of the opportunity for curative therapy. However, every series of conservative management contains a substantial subset of long-term survivors, particularly in the group with favorable clinical parameters. We have conducted a clinical study to evaluate a novel approach in which the choice between a definitive therapy and conservative policy is determined by the rate of PSA increase or the development of early, rapid clinical and/or histologic progression. This strategy, which has never been previously evaluated, offers the powerful attraction of individualizing therapy according to the biological behavior of the cancer. This would mean that patients with slowly growing malignancy would be spared the side effects of radical treatment, while those with more rapidly progressive cancer would still benefit from curative therapy. Doubling time varied widely. In this series of 200 patients, neither grade, stage, nor baseline PSA predicted the PSA doubling time. Thirty-three percent of patients had a PSA doubling time (T(D)) > 10 years. Doubling time appears to be a useful tool to guide treatment intervention for patients managed initially with expectant management. A doubling time of less than 2 years appears to identify patients at high risk for local progression in spite of otherwise favorable prognostic factors. Fifteen to 20% of patients will fall into this category. The remainder have a high chance of remaining free of recurrence and progression for many years. Watchful waiting is clearly

  18. Autophagy favors Brucella melitensis survival in infected macrophages.

    PubMed

    Guo, Fei; Zhang, Hui; Chen, Chuangfu; Hu, Shengwei; Wang, Yuanzhi; Qiao, Jun; Ren, Yan; Zhang, Ke; Wang, Yong; Du, Guoqing

    2012-06-01

    This study investigated the role of autophagy in the survival of the invasive bacterium Brucella melitensis strain 16M in murine macrophages. Here, Brucella melitensis 16M was found to trigger autophagosome formation, enhance autophagy flux and increase the expression level of the autophagy marker protein LC3-II. When autophagy was pharmacologically inhibited by 3-methyladenine (3-MA), Brucella replication efficiency was significantly decreased (p < 0.05). These results suggest that autophagy favors Brucella melitensis 16M survival in murine macrophages.

  19. Structured mixed phase is favored in neutron stars

    SciTech Connect

    Christiansen, Michael B.; Glendenning, Norman K.

    2003-01-01

    We give a general thermodynamical argument showing that in neutron stars, the Coulomb structured mixed phase is always favored for any first order phase transition involving systems in equilibrium with baryon number and electric charge as the two independent components. This finding is likely to have important consequences for many neutron star properties, e.g., glitch phenomena, transport and superfluid properties, r-mode instabilities, and the braking index.

  20. High expression of CD11c indicates favorable prognosis in patients with gastric cancer

    PubMed Central

    Wang, Yuan; Xu, Bin; Hu, Wen-Wei; Chen, Lu-Jun; Wu, Chang-Ping; Lu, Bin-Feng; Shen, Yue-Ping; Jiang, Jing-Ting

    2015-01-01

    : 0.23-0.67, P < 0.01) compared with patients with low CD11c expression after adjustment of potential confounders, with the exception of tumor size. However, the protective effect related to death (HR = 0.90, 95%CI: 0.49-1.67, P = 0.749) and relapse (HR = 0.65, 95%CI: 0.36-1.19, P = 0.160) disappeared when tumor size was incorporated into the model. CONCLUSION: High expression of CD11c decreased the risk of death and relapse, and may be regarded as an alternative indicator of favorable prognosis in patients with GC. PMID:26309367

  1. High expression of CD11c indicates favorable prognosis in patients with gastric cancer.

    PubMed

    Wang, Yuan; Xu, Bin; Hu, Wen-Wei; Chen, Lu-Jun; Wu, Chang-Ping; Lu, Bin-Feng; Shen, Yue-Ping; Jiang, Jing-Ting

    2015-08-21

    < 0.01) compared with patients with low CD11c expression after adjustment of potential confounders, with the exception of tumor size. However, the protective effect related to death (HR = 0.90, 95%CI: 0.49-1.67, P = 0.749) and relapse (HR = 0.65, 95%CI: 0.36-1.19, P = 0.160) disappeared when tumor size was incorporated into the model. High expression of CD11c decreased the risk of death and relapse, and may be regarded as an alternative indicator of favorable prognosis in patients with GC.

  2. Bioactive, mechanically favorable, and biodegradable copolymer nanocomposites for orthopedic applications.

    PubMed

    Victor, Sunita Prem; Muthu, Jayabalan

    2014-06-01

    We report the synthesis of mechanically favorable, bioactive, and biodegradable copolymer nanocomposites for potential bone applications. The nanocomposites consist of in situ polymerized biodegradable copolyester with hydroxyapatite (HA). Biodegradable copolyesters comprise carboxy terminated poly(propylene fumarate) (CT-PPF) and poly(trimethylol propane fumarate co mannitol sebacate) (TF-Co-MS). Raman spectral imaging clearly reveals a uniform homogenous distribution of HA in the copolymer matrix. The mechanical studies reveal that improved mechanical properties formed when crosslinked with methyl methacrylate (MMA) when compared to N-vinyl pyrrolidone (NVP). The SEM micrographs of the copolymer nanocomposites reveal a serrated structure reflecting higher mechanical strength, good dispersion, and good interfacial bonding of HA in the polymer matrix. In vitro degradation of the copolymer crosslinked with MMA is relatively more than that of NVP and the degradation decreases with an increase in the amount of the HA filler. The mechanically favorable and degradable MMA based nanocomposites also have favorable bioactivity, blood compatibility, cytocompatibility and cell adhesion. The present nanocomposite is a more promising material for orthopedic applications.

  3. Active Learning: A Small Group Histology Laboratory Exercise in a Whole Class Setting Utilizing Virtual Slides and Peer Education

    ERIC Educational Resources Information Center

    Bloodgood, Robert A.

    2012-01-01

    Histology laboratory instruction is moving away from the sole use of the traditional combination of light microscopes and glass slides in favor of virtual microscopy and virtual slides. At the same time, medical curricula are changing so as to reduce scheduled time for basic science instruction as well as focusing on student-centered learning…

  4. Active Learning: A Small Group Histology Laboratory Exercise in a Whole Class Setting Utilizing Virtual Slides and Peer Education

    ERIC Educational Resources Information Center

    Bloodgood, Robert A.

    2012-01-01

    Histology laboratory instruction is moving away from the sole use of the traditional combination of light microscopes and glass slides in favor of virtual microscopy and virtual slides. At the same time, medical curricula are changing so as to reduce scheduled time for basic science instruction as well as focusing on student-centered learning…

  5. In acute promyelocytic leukemia (APL) low BAALC gene expression identifies a patient group with favorable overall survival and improved relapse free survival.

    PubMed

    Nolte, Florian; Hecht, Anna; Reinwald, Mark; Nowak, Daniel; Nowak, Verena; Hanfstein, Benjamin; Faldum, Andreas; Büchner, Thomas; Spiekermann, Karsten; Sauerland, Cristina; Hofmann, Wolf-Karsten; Lengfelder, Eva

    2013-04-01

    We evaluated the prognostic value of BAALC expression in 86 patients with acute promyelocytic leukemia (APL). At 10 years, the overall survival (OS) was 66% in all patients and 75% in patients who achieved a complete remission (CR). Patients in the BAALC(low) group showed an OS of 87% as compared to 60% in the BAALC(high) group (p=0.019). This difference was more pronounced in treatment responders (92% vs. 70%; p=0.035). In multivariate analyses low BAALC expression retained its prognostic relevance. In conclusion, BAALC expression analysis might be useful in further risk stratification in APL patients.

  6. Prevalence and serological diagnosis of relapse in paracoccidioidomycosis patients.

    PubMed

    Sylvestre, Tatiane Fernanda; Franciscone Silva, Luciane Regina; Cavalcante, Ricardo de Souza; Moris, Daniela Vanessa; Venturini, James; Vicentini, Adriana Pardini; de Carvalho, Lídia Raquel; Mendes, Rinaldo Poncio

    2014-05-01

    A review of 400 clinical records of paracoccidioidomycosis (PCM) patients, 93 with the acute/subacute (AF) and 307 with the chronic form (CF), attended from 1977 to 2011, selected as to the schedule of release for study by the Office of Medical Records at the University Hospital of the Faculdade de Medicina de Botucatu-São Paulo State University--UNESP, was performed to detect cases in relapse. The control of cure was performed by clinical and serological evaluation using the double agar gel immunodiffusion test (DID). In the diagnosis of relapse, DID, enzyme-linked immunosorbent assay (ELISA) and immunoblotting assay (IBgp70 and IBgp43) were evaluated. Out of 400 patients, 21 (5.2%) went through relapse, 18 of them were male and 3 were female, 6∶1 male/female ratio. Out of the 21 patients in relapse, 15 (4.8%) showed the CF, and 6 (6.4%) the AF (p>0.05). The sensitivity of DID and ELISA before treatment was the same (76.1%). DID presented higher sensitivity in pre-treatment (80%) than at relapse (45%; p = 0.017), while ELISA showed the same sensitivity (80% vs 65%; p = 0.125). The serological methods for identifying PCM patients in relapse showed low rates of sensitivity, from 12.5% in IBgp70 to 65.0% in IBgp43 identification and 68.8% in ELISA. The sensitivity of ELISA in diagnosing PCM relapse showed a strong tendency to be higher than DID (p = 0.06) and is equal to IBgp43 (p = 0.11). In sum, prevalence of relapse was not high in PCM patients whose treatment duration was based on immunological parameters. However, the used methods for serological diagnosis present low sensitivity. While more accurate serological methods are not available, we pay special attention to the mycological and histopathological diagnosis of PCM relapse. Hence, direct mycological, cytopathological, and histopathological examinations and isolation in culture for P. brasiliensis must be appropriately and routinely performed when the hypothesis of relapse is considered.

  7. Prevalence and Serological Diagnosis of Relapse in Paracoccidioidomycosis Patients

    PubMed Central

    Sylvestre, Tatiane Fernanda; Silva, Luciane Regina Franciscone; Cavalcante, Ricardo de Souza; Moris, Daniela Vanessa; Venturini, James; Vicentini, Adriana Pardini; de Carvalho, Lídia Raquel; Mendes, Rinaldo Poncio

    2014-01-01

    A review of 400 clinical records of paracoccidioidomycosis (PCM) patients, 93 with the acute/subacute (AF) and 307 with the chronic form (CF), attended from 1977 to 2011, selected as to the schedule of release for study by the Office of Medical Records at the University Hospital of the Faculdade de Medicina de Botucatu – São Paulo State University – UNESP, was performed to detect cases in relapse. The control of cure was performed by clinical and serological evaluation using the double agar gel immunodiffusion test (DID). In the diagnosis of relapse, DID, enzyme-linked immunosorbent assay (ELISA) and immunoblotting assay (IBgp70 and IBgp43) were evaluated. Out of 400 patients, 21 (5.2%) went through relapse, 18 of them were male and 3 were female, 6∶1 male/female ratio. Out of the 21 patients in relapse, 15 (4.8%) showed the CF, and 6 (6.4%) the AF (p>0.05). The sensitivity of DID and ELISA before treatment was the same (76.1%). DID presented higher sensitivity in pre-treatment (80%) than at relapse (45%; p = 0.017), while ELISA showed the same sensitivity (80% vs 65%; p = 0.125). The serological methods for identifying PCM patients in relapse showed low rates of sensitivity, from 12.5% in IBgp70 to 65.0% in IBgp43 identification and 68.8% in ELISA. The sensitivity of ELISA in diagnosing PCM relapse showed a strong tendency to be higher than DID (p = 0.06) and is equal to IBgp43 (p = 0.11). In sum, prevalence of relapse was not high in PCM patients whose treatment duration was based on immunological parameters. However, the used methods for serological diagnosis present low sensitivity. While more accurate serological methods are not available, we pay special attention to the mycological and histopathological diagnosis of PCM relapse. Hence, direct mycological, cytopathological, and histopathological examinations and isolation in culture for P. brasiliensis must be appropriately and routinely performed when the hypothesis of relapse is

  8. A nomogram to predict brain metastasis as the first relapse in curatively resected non-small cell lung cancer patients.

    PubMed

    Won, Young-Woong; Joo, Jungnam; Yun, Tak; Lee, Geon-Kook; Han, Ji-Youn; Kim, Heung Tae; Lee, Jin Soo; Kim, Moon Soo; Lee, Jong Mog; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Sohee

    2015-05-01

    Development of brain metastasis results in a significant reduction in overall survival. However, there is no an effective tool to predict brain metastasis in non-small cell lung cancer (NSCLC) patients. We conducted this study to develop a feasible nomogram that can predict metastasis to the brain as the first relapse site in patients with curatively resected NSCLC. A retrospective review of NSCLC patients who had received curative surgery at National Cancer Center (Goyang, South Korea) between 2001 and 2008 was performed. We chose metastasis to the brain as the first relapse site after curative surgery as the primary endpoint of the study. A nomogram was modeled using logistic regression. Among 1218 patients, brain metastasis as the first relapse developed in 87 patients (7.14%) during the median follow-up of 43.6 months. Occurrence rates of brain metastasis were higher in patients with adenocarcinoma or those with a high pT and pN stage. Younger age appeared to be associated with brain metastasis, but this result was not statistically significant. The final prediction model included histology, smoking status, pT stage, and the interaction between adenocarcinoma and pN stage. The model showed fairly good discriminatory ability with a C-statistic of 69.3% and 69.8% for predicting brain metastasis within 2 years and 5 years, respectively. Internal validation using 2000 bootstrap samples resulted in C-statistics of 67.0% and 67.4% which still indicated good discriminatory performances. The nomogram presented here provides the individual risk estimate of developing metastasis to the brain as the first relapse site in patients with NSCLC who have undergone curative surgery. Surveillance programs or preventive treatment strategies for brain metastasis could be established based on this nomogram. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. The neuropharmacology of relapse to food seeking: methodology, main findings, and comparison with relapse to drug seeking

    PubMed Central

    Nair, Sunila G.; Adams-Deutsch, Tristan; Epstein, David H.; Shaham, Yavin

    2009-01-01

    Relapse to old, unhealthy eating habits is a major problem in human dietary treatments. The mechanisms underlying this relapse are unknown. Surprisingly, until recently this clinical problem has not been systematically studied in animal models. Here, we review results from recent studies in which a reinstatement model (commonly used to study relapse to abused drugs) was employed to characterize the effect of pharmacological agents on relapse to food seeking induced by either food priming (non-contingent exposure to small amounts of food), cues previously associated with food, or injections of the pharmacological stressor yohimbine. We also address methodological issues related to the use of the reinstatement model to study relapse to food seeking, similarities and differences in mechanisms underlying reinstatement of food seeking versus drug seeking, and the degree to which the reinstatement procedure provides a suitable model for studying relapse in humans. We conclude by discussing implications for medication development and future research. We offer three tentative conclusions: The neuronal mechanisms of food-priming- and cue-induced reinstatement are likely different from those of reinstatement induced by the pharmacological stressor yohimbine.The neuronal mechanisms of reinstatement of food seeking are possibly different from those of ongoing food-reinforced operant responding.The neuronal mechanisms underlying reinstatement of food seeking overlap to some degree with those of reinstatement of drug seeking. PMID:19497349

  10. Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG).

    PubMed

    Aparicio, J; Maroto, P; García del Muro, X; Sánchez-Muñoz, A; Gumà, J; Margelí, M; Sáenz, A; Sagastibelza, N; Castellano, D; Arranz, J A; Hervás, D; Bastús, R; Fernández-Aramburo, A; Sastre, J; Terrasa, J; López-Brea, M; Dorca, J; Almenar, D; Carles, J; Hernández, A; Germà, J R

    2014-11-01

    We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups. From 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS). After a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable). Long-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions

  11. Effect of fingolimod on diffuse brain tissue damage in relapsing-remitting multiple sclerosis patients.

    PubMed

    De Stefano, Nicola; Tomic, Davorka; Radue, Ernst-Wilhelm; Sprenger, Till; Meier, Daniela Piani; Häring, Dieter; Sormani, Maria Pia

    2016-05-01

    Multiple sclerosis (MS) affects all areas of the brain resulting in both focal and diffuse damage. In Phase 3 clinical trials, fingolimod showed significant reductions in both focal lesions and rate of brain volume loss (BVL) in patients with relapsing-remitting MS. To investigate if the effects of fingolimod 0.5mg on BVL are mediated exclusively through its effects on focal damage or if fingolimod also acts independently in reducing diffuse damage. This was a pooled post-hoc analysis of patients from two Phase 3 studies (FREEDOMS [N=1272] and FREEDOMS II [N=1083]), with no evidence of focal disease activity as defined by absence of gadolinium-enhancing lesions at baseline and new active lesions and clinical relapses at follow-up. The percent brain volume change (PBVC), as a measure of diffuse tissue damage, was assessed at Month (M) 12 and M24 by using the Structural Image Evaluation using Normalization of Atrophy (SIENA) method. A regression analysis was performed in the pooled intent-to-treat (ITT) population to quantify the treatment effect of fingolimod on BVL vs. placebo (PBO) in the overall population (unadjusted model), and whether this effect is sustained after adjusting for new active lesions and on-study relapses (adjusted model). Of 1088 patients, 638 (PBO, n=127; fingolimod, n=511) at M12 and 450 patients (PBO, n=68; fingolimod, n=382) at M24 showed no focal activity. Fingolimod significantly reduced PBVC by 65.5% over 12M (fingolimod vs. PBO: -0.16 vs. -0.45; p=0.001) and by 48.2% over 24M (-0.42 vs. -0.81; p=0.004). An absolute difference in PBVC of -0.27% (p<0.001) in favor of fingolimod vs. PBO over 24M was still evident in the pooled ITT population, after adjusting for active lesions and on-study relapses. The regression model suggests that 54% (-0.27%/-0.51%) of effects of fingolimod on PBVC are independent of its effects on visible focal damage. The effect of fingolimod on diffuse damage is partly independent of its treatment effect on focal

  12. Histologic progression in non-hodgkin's lymphoma

    SciTech Connect

    Hubbard, S.M.; Chabner, B.A.; DeVita, V.T., Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

    1982-02-01

    The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy.

  13. Graphs and Grammars for Histology: An Introduction

    PubMed Central

    Prewitt, Judith M. S.

    1979-01-01

    The invention of the microscope disclosed a whole new world, that of the hitherto invisibly small. Histologic evidence as revealed by the microscope has become a cornerstone of medical diagnosis, and efforts are now being made to lay foundations so that the medical visual information processing burden can be alleviated significantly by cost-effective automation. This paper lays image processing foundations by presenting a graph-theoretic and syntactic model for the analysis of histologic patterns, and presents results to date.

  14. [Histological findings in an irradiated choroidal melanoma].

    PubMed

    Koinzer, S; Hasselbach, H; Bräsen, J H; Leuschner, I; Roider, J

    2011-06-01

    Histological findings of choroidal melanomas after proton beam irradiation have been reported for complicated cases after enucleation. We present specimens of a tumor after transretinal probe excision. One year after irradiation, the biopsy was examined histologically. The specimens showed pigmented, spindle-shaped cells staining positively for Melan-A and HMB-45. Ki-67 showed low proliferation. Caspase-3 staining was normal. The melanoma still contained vital and even single proliferating cells, but regressed afterwards without additional therapy.

  15. Chondrosarcoma: correlation of radiological and histological grade

    SciTech Connect

    Rosenthal, D.I.; Schiller, A.L.; Mankin, H.J.

    1984-01-01

    The radiographic and CT appearance of 20 cases of chondrosarcoma were correlated with histological grade and type of matrix. Features which were useful in predicting histological grade included 1) margins between bone and tumor (radiograph), 2) morphology of calcification (radiograph, CT), 3) distribution of calcification within the lesion (radiograph, CT), 4) pattern of tumor growth within soft tissues (CT), and 5) presence of necrosis (CT). Tumor/soft-tissue margins were usually well defined on the CT scan regardless of grade.

  16. Classification of relapse pattern in clubfoot treated with Ponseti technique

    PubMed Central

    Bhaskar, Atul; Patni, Piyush

    2013-01-01

    Background: Relapse of clubfoot deformity following correction by Ponseti technique is not uncommon. The relapsed feet progress from flexible to rigid if left untreated and can become as severe as the initial deformity. No definitive classification exists to assess a relapsed clubfoot. Some authors have used the Pirani score to rate the relapse while others have used descriptive terms. The purpose of this study is to analyze the relapse pattern in clubfeet that have undergone treatment with the Ponseti method and propose a simple classification for relapsed clubfeet. Materials and Methods: Ninety-one children (164 feet) with idiopathic clubfeet who underwent treatment with Ponseti technique presented with relapse of the deformity. There were 68 boys and 23 girls. Mean age at presentation for casting was 10.71 days (range 7-22 days). Seventy three children (146 feet, 80%) had bilateral involvement and 18 (20%) had unilateral clubfeet. The mean Pirani Score was 5.6 and 5.5 in bilateral and unilateral groups respectively. Percutaneous heel cord tenotomy was done in 65 children (130 feet, 89%) in the bilateral group and in 12 children (66%) with unilateral clubfoot. Results: Five relapse patterns were identified at a mean followup of 4.5 years (range 3-5 years) which forms the basis of this study. These relapse patterns were classified as: Grade IA: decrease in ankle dorsiflexion from15 degrees to neutral, Grade IB: dynamic forefoot adduction or supination, Grade IIA – rigid equinus, Grade IIB – rigid adduction of forefoot/midfoot complex and Grade III: combination of two or more deformities: Fixed equinus, varus and forefoot adduction. In the bilateral group, 21 children (38 feet, 28%) had Grade IA relapse. Twenty four children (46 feet, 34%) had dynamic intoeing (Grade IB) on walking. Thirteen children (22 feet, 16%) had true ankle equinus of varying degress (Grade IIA); eight children (13 feet, 9.7%) had fixed adduction deformity of the forefoot (Grade IIB) and

  17. Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape.

    PubMed

    Sedov, Valeriy; Stuart, Robert K

    2017-06-01

    Treatment for acute myeloid leukemia (AML) generally consists of a combination of cytarabine and an anthracycline. Although induction therapy leads to complete remission (CR) for most patients, refractoriness to chemotherapy or relapse after initial response is associated with poor outcomes. The 1-year survival rates after first relapse have been reported at 29%, declining to 11% at 5 years. Prognosis is particularly poor among older patients whose higher prevalence of unfavorable cytogenetics and high frequency of comorbidities diminish their ability to tolerate intensive chemotherapy. There is no standard of care for relapsed/refractory (R/R) AML, and no new therapies have shown consistently superior outcomes in this setting in over two decades. Vosaroxin is an anticancer quinolone derivative (AQD) that was evaluated in combination with cytarabine for the treatment of R/R AML in the randomized, double-blind, placebo-controlled, phase III VALOR study (n = 711). Compared with placebo/cytarabine, the vosaroxin/cytarabine regimen demonstrated favorable CR rates and survival in patients ⩾60 years of age, with toxicities similar to other AML regimens. Here we review outcomes of recent studies of commonly used chemotherapy regimens for the treatment of R/R AML and evaluate the results of the VALOR trial in the context of the current treatment landscape.

  18. Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy.

    PubMed

    Santoni, Matteo; Buti, Sebastiano; Conti, Alessandro; Porta, Camillo; Procopio, Giuseppe; Sternberg, Cora N; Bracarda, Sergio; Basso, Umberto; De Giorgi, Ugo; Rizzo, Mimma; Derosa, Lisa; Ortega, Cinzia; Massari, Francesco; Milella, Michele; Bersanelli, Melissa; Cerbone, Linda; Muzzonigro, Giovanni; Burattini, Luciano; Montironi, Rodolfo; Santini, Daniele; Cascinu, Stefano

    2015-12-01

    We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected from 13 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 years after initial radical nephrectomy. One hundred fifty-one patients were included in this analysis. Among them, MSKCC risk score was favorable in 68 %, intermediate in 29 %, and poor in 3 %. Fifty-six patients (37 %) had NLR ≥3 at the start of VEGFR-TKI therapy (group A), while 95 had lower NLR (63 %, group B). The median overall survival (OS) was 28.8 months in group A and 68.7 months (95 % confidence interval (CI) 45.3-NA) in group B (p < 0.001). The median progression-free survival (PFS) was 15.8 months in group A and 25.1 months in group B (p = 0.03). At multivariate analysis, MSKCC risk group and NLR were independent prognostic factors for both OS and PFS. Pretreatment NLR is an independent prognostic factor for patients with late relapsing mRCC treated with first-line VEGFR-TKIs. A better characterization of baseline immunological impairment may optimize the management of this RCC subpopulation.

  19. Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT.

    PubMed

    Ruutu, T; de Wreede, L C; van Biezen, A; Brand, R; Mohty, M; Dreger, P; Duarte, R; Peters, C; Garderet, L; Schönland, S; Gratwohl, A; Niederwieser, D; de Witte, T; Kröger, N

    2015-12-01

    In patients treated with allogeneic stem cell transplantation (SCT) for malignant disease who suffer from a relapse after the transplantation, the role of second allogeneic SCT is often uncertain. In a retrospective analysis, 2632 second allogeneic transplantations carried out for a relapse after the first transplantation were analyzed to define indications and identify predictive factors. Fifteen percent of the patients remained relapse-free until 5 years after the second SCT. Patients with CML had a better survival than patients with other diseases. In a multivariate analysis, factors associated with better survival were low disease burden, longer remission duration after the first transplantation, longer interval between the transplantations, younger age, absence of grade II-IV acute GvHD or chronic GvHD after the first transplantation, and later year of transplantation. The European Society for Blood and Marrow Transplantation risk score predicted the outcome. Using the same donor as in the first transplantation vs another donor had no predictive value for survival. Sibling donor was a favorable predictive factor. In conclusion, second allogeneic SCT offers a reasonable option especially for young patients with a long remission after the first transplantation and a low disease burden. The present findings do not support the usefulness of changing the donor for the second transplantation.

  20. GRAPHIE: graph based histology image explorer

    PubMed Central

    2015-01-01

    Background Histology images comprise one of the important sources of knowledge for phenotyping studies in systems biology. However, the annotation and analyses of histological data have remained a manual, subjective and relatively low-throughput process. Results We introduce Graph based Histology Image Explorer (GRAPHIE)-a visual analytics tool to explore, annotate and discover potential relationships in histology image collections within a biologically relevant context. The design of GRAPHIE is guided by domain experts' requirements and well-known InfoVis mantras. By representing each image with informative features and then subsequently visualizing the image collection with a graph, GRAPHIE allows users to effectively explore the image collection. The features were designed to capture localized morphological properties in the given tissue specimen. More importantly, users can perform feature selection in an interactive way to improve the visualization of the image collection and the overall annotation process. Finally, the annotation allows for a better prospective examination of datasets as demonstrated in the users study. Thus, our design of GRAPHIE allows for the users to navigate and explore large collections of histology image datasets. Conclusions We demonstrated the usefulness of our visual analytics approach through two case studies. Both of the cases showed efficient annotation and analysis of histology image collection. PMID:26330277

  1. Diagnostic dry bone histology in human paleopathology.

    PubMed

    de Boer, H H Hans; Van der Merwe, A E Lida

    2016-10-01

    Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

  2. Reactivity to laboratory stress provocation predicts relapse to cocaine.

    PubMed

    Back, Sudie E; Hartwell, Karen; DeSantis, Stacia M; Saladin, Michael; McRae-Clark, Aimee L; Price, Kimber L; Moran-Santa Maria, Megan M; Baker, Nathaniel L; Spratt, Eve; Kreek, Mary Jeanne; Brady, Kathleen T

    2010-01-01

    Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1 microg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocortico-trophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants' cocaine use was monitored for approximately 1 month following testing. The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention. Published by Elsevier Ireland Ltd.

  3. Reactivity to Laboratory Stress Provocation Predicts Relapse to Cocaine

    PubMed Central

    Back, Sudie E.; Hartwell, Karen; DeSantis, Stacia M.; Saladin, Michael; McRae-Clark, Aimee L.; Price, Kimber L.; Maria, Megan M. Moran-Santa; Baker, Nathaniel L.; Spratt, Eve; Kreek, Mary Jeanne; Brady, Kathleen T.

    2009-01-01

    Background Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. Methods The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1ųg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocorticotrophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants’ cocaine use was monitored for approximately one month following testing. Results The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. Conclusions The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention. PMID:19726138

  4. Predictors of early relapse among adolescent crack users.

    PubMed

    Lopes-Rosa, Ronaldo; Kessler, Félix P; Pianca, Thiago G; Guimarães, Luciano; Ferronato, Pedro; Pagnussat, Esequiel; Moura, Helena; Pechansky, Flavio; von Diemen, Lisia

    2017-01-01

    Relapse is associated with a poor prognosis among drug users. Crack cocaine users are more prone to severe dependence because of the intensity of use. Additionally, initiating drug use during adolescence worsens users' prognosis due to the increased rates of impulsivity and other risk behaviors. This study aimed to identify the predictors of early relapse among adolescent crack users discharged from inpatient treatment. A cohort study was conducted with 89 psychiatric inpatients aged 12-17 years from two different hospitals in southern Brazil who met the criteria for crack abuse or dependence. Demographic data, substance use disorders, psychiatric comorbidities, and crack consumption profile were assessed during hospitalization using the Teen Addiction Severity Index, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime, and Crack Consumption Profile. Participants were re-assessed at 1 and 3 months after hospital discharge to determine their crack cocaine use based on self-report, family/caregiver information, and urine tests, whenever possible. There were extremely high rates of relapse (valid percent) in the first and third months, 65.9 and 86.4%, respectively. Statistically significant associations were observed between relapse in the first month and length of cocaine/crack cocaine use, and length of hospital stay. Data at 3 months were not analyzed because of the small number of patients who did not relapse. The high rates and significant associations found in this study suggest that intensive outpatient treatment strategies targeting this population should be developed and implemented to prevent early relapse after detoxification. One of the possible approaches, based on recent studies, might explore motivation as a strategy to reduce the rate of early relapse.

  5. Relapse to driving under the influence (DUI): a review.

    PubMed

    Nochajski, Thomas H; Stasiewicz, Paul R

    2006-03-01

    Driving under the influence (DUI) is a major public health problem. In 2003, there were 17,401 alcohol-related crash fatalities. Although there has been a large decrease in the fatality rates over the past two decades, further progress has stalled in recent years. This plateau in the injury and death rates resulting from impaired driving has been attributed, in part, to the persistent or repeat DUI offender. Broadly defined, repeat offenders are those individuals who, following an initial DUI arrest, relapse to driving under the influence of alcohol and other drugs. In this paper, we first provide a brief overview of several models of DUI relapse. We then review the empirical literature on DUI relapse, the data describing characteristics of first-time and repeat DUI offenders, and, especially, studies that have evaluated the impact of legal sanctions and rehabilitation programs on subsequent DUI behavior. The data reveal that DUI offenders are a heterogeneous group, and that simple models relying on only one or two behavioral domains (e.g., driving characteristics, demographics) to explain DUI relapse are insufficient to account for the DUI behavior of offenders. To advance our understanding of DUI relapse, we argue for development and testing of multifactorial models focusing on the interplay of legal, social and psychological factors that describe and explain relapse among DUI offenders. By recognizing the heterogeneity within the offender population it will be easier for researchers and clinicians to identify subgroups that are at high-risk for relapse and which should be targeted by prevention and intervention programs.

  6. Natalizumab for relapsing remitting multiple sclerosis.

    PubMed

    Pucci, Eugenio; Giuliani, Giorgio; Solari, Alessandra; Simi, Silvana; Minozzi, Silvia; Di Pietrantonj, Carlo; Galea, Ian

    2011-10-05

    Natalizumab (NTZ) (Tysabri(®)) is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier, thus reducing inflammation in central nervous system, and has been approved worldwide for the treatment of relapsing-remitting multiple sclerosis (RRMS). To evaluate the efficacy, tolerability and safety of NTZ in the treatment of patients with RRMS. We searched the Cochrane Multiple Sclerosis Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2010, Issue 1), MEDLINE (PubMed) and EMBASE, all up to 19 February 2010, and bibliographies of papers. Handsearching was carried out. Trialists and pharmaceutical companies were contacted. Furthermore, the websites of US Food and Drug Administration (FDA), the European Medicines Evaluation Agency (EMA) and the National Institute for health and Clinical Excellence (NICE) were also checked. All double-blind, randomised, controlled trials analysing more than a single infusion of NTZ (dosage > 3 mg/kg intravenous infusion every 4 weeks), also including its use as add-on treatment, versus placebo or other drugs in patients with RRMS. No restrictions on the basis of duration of treatment or length of follow up. Three reviewers independently selected articles which met the inclusion criteria. Disagreements were solved by discussion. Two reviewers independently extracted the data and assessed the methodological quality of each trial. Missing data was sought by contacting principal authors and Biogen Idec, through Biogen-Dompé Italia. Three studies met the inclusion criteria. These included one placebo-controlled trial (942 patients) and two add-on placebo-controlled trials, i.e. one plus glatiramer acetate (110 patients) and the second plus interferon beta-1a (1171 patients).This review assessed the efficacy, tolerability and safety of NTZ in patients with RRMS. Data was conclusive with respect to efficacy and tolerability, but not safety. As far as

  7. Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab.

    PubMed

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg; Sellebjerg, Finn; Oturai, Annette Bang

    2016-11-01

    Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity. To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in patients with relapsing-remitting MS (RRMS) and to examine the clinical effects associated with changes in 25(OH)D levels. In this prospective cohort study, baseline blood samples were collected from 170 natalizumab-treated RRMS patients during winter 2009-2010 and were repeated the following winter. Vitamin D supplements were recommended according to standard clinical practice in our clinic to patients with serum 25(OH)D<50nmol/l at baseline. Information was obtained on annualized relapse-rate (ARR) the year prior to baseline and the following year. We found that recommending vitamin D supplements in patients with vitamin D insufficiency was associated with a significant increase in serum 25(OH)D concentrations (p=5.1×10(-10)), which was significantly related with decreases in ARR; for each nmol/l increase in Δ25(OH)D a -0.014 (95% CI -0.026 to -0.003) decrease in ΔARR was observed, p=0.02. Correction of hypovitaminosis D in clinical practice by recommending oral D3 supplements resulted in increases in 25(OH)D levels in serum, which were associated with decreases in ARR in RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A Favorability Score for Vaginal Hysterectomy in a Statewide Collaborative.

    PubMed

    Skinner, Bethany D; Kamdar, Neil S; Mahnert, Nichole; Lim, Courtney S; Mullard, Andrew J; Campbell, Darrell A; As-Sanie, Sawsan; Morgan, Daniel M

    STUDY OBJECTIVE: Because it is associated with fewer complications and more rapid recovery, the vaginal approach is preferred for benign hysterectomy. Patient characteristics that traditionally favor a vaginal approach include adequate vaginal access, small uterine size, and low suspicion for extrauterine disease. However, the low proportion of hysterectomies performed vaginally in the United States suggests that these data are not routinely applied in clinical practice. We sought to analyze the association of parity, prior pelvic surgery, and uterine weight with the use of the vaginal, laparoscopic, robotic, and abdominal approaches to hysterectomy. A retrospective cohort study (Canadian Task Force classification II-2). The Michigan Surgical Quality Collaborative is a statewide organization of 52 academic and community hospitals in Michigan funded by Blue Cross and Blue Shield of Michigan/Blue Care Network, including patients from all insurance payers. Five thousand six hundred eight women undergoing hysterectomy for benign gynecologic conditions from January 1, 2013, through December 8, 2013, and included in the Michigan Surgical Quality Collaborative. To assess potential for vaginal hysterectomy, a favorability score of 0, 1, 2, or 3 was calculated by summing 1 point each for parity ≥1, no prior pelvic surgery, and uterine weight <250 g. Frequencies of surgical approaches to hysterectomy were compared using chi-square tests across favorability scores. The use of robotic hysterectomy was most frequent (41.9%, n = 2349/5608) followed by abdominal (19.7%, n = 1103/5608), laparoscopic (14.4%, n = 809/5608), vaginal (13.5%, n = 758/5608), and laparoscopic-assisted vaginal (10.5%, n = 589/5608) hysterectomy. With favorability scores of 0, 1, 2, and 3, vaginal hysterectomy was performed in 0.6% (n = 1/167), 5% (n = 66/1324), 13.7% (n = 415/3036), and 25.5% (n = 276/1081) of cases and abdominal hysterectomy in 41.9% (n = 70/167), 30.8% (n = 408

  9. Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

    PubMed

    Goldberg, Lawrence D D; Edwards, Natalie C; Fincher, Contessa; Doan, Quan V; Al-Sabbagh, Ahmad; Meletiche, Dennis M

    2009-09-01

    ). Medical savings were calculated as costs saved due to relapses avoided and prevention in disability progression steps. In the base case analysis, we assumed 89.4% persistence, a cost per relapse of $4,682, and a cost per disability progression step of $1,788. Monthly cost of therapy was defined as wholesale acquisition cost ($0 contractual discounts and $25 patient copayment assumed in the base case analysis) plus routine monitoring costs as assessed by an expert panel. The primary economic endpoint was cost per relapse avoided. Costs and outcomes occurring in the second year were discounted 3% to bring to 2008 present values. Oneway and multiway probabilistic (Monte Carlo) sensitivity analyses were conducted on key input variables to assess their impact on cost per relapse avoided. Without DMD treatment, patients were predicted to experience 2.55 relapses and 0.44 disability progression steps over a 2-year period (discounted values). The 2-year reductions in clinical relapses for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.66, 0.42, 0.74, and 0.70, respectively. The 2-year reductions in disability progression steps for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.05, 0.15, 0.12, and 0.11, respectively. In the base case analysis, IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate had the most favorable costs per relapse avoided ($80,589; $87,061; and $88,310; respectively) and IFN Beta-1a IM injection had the least favorable cost-effectiveness ratio ($141,721 per relapse avoided). Sensitivity analyses showed that these results were robust to changes in key input parameters, such as the number of relapses and disease progression steps in untreated patients, the RRR in clinical relapse and progression rates, the rate of persistence, the average cost of relapse, and the average cost of a disease progression step. This

  10. Early signet ring cell carcinoma of the stomach is related to favorable prognosis and low incidence of lymph node metastasis.

    PubMed

    Imamura, Taisuke; Komatsu, Shuhei; Ichikawa, Daisuke; Kawaguchi, Tsutomu; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Otsuji, Eigo

    2016-10-01

    The aim of this study was to evaluate the clinical characteristics of early signet ring cell carcinoma of the stomach (SRC) and to investigate the optimal treatment strategy for early SRC. A total of 746 patients with pT1 gastric cancer (GC), who had undergone surgical resection between 1997 and 2012 were analyzed. Of these, 190 patients with SRC were enrolled in this study. (i) The patients with SRC showed a significantly longer overall survival (P = 0.012) and disease free survival (P = 0.004) than patients with the other histological types. Multivariate analysis identified SRC as an independent factor predicting favorable prognosis in pT1 GC (HR = 0.38; 95% CI: 0.11-0.96; P = 0.041). Specifically, in undifferentiated pT1 GC, SRC was significantly less associated with lymph node metastasis (LNM) (OR = 0.39; 95% CI: 0.15-0.96; P = 0.042). (ii) From the viewpoint of a histological mixed-type, pure-SRC with pT1a was not associated with LNM regardless of tumor size (0.0%, 0/110), whereas mixed-SRC was an independent risk factor for LNM (OR = 7.19; 95% CI: 1.51-43.9; P = 0.012). Patients with early SRC have a favorable prognosis with a low incidence of LNM. However, care should be taken with mixed-SRC, which consists of SRC and other histological types. J. Surg. Oncol. 2016;114:607-612. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Clinical quality is independently associated with favorable bond ratings.

    PubMed

    Haydar, Ziad; Nicewander, David; Convery, Paul; Black, Michael; Ballard, David

    2010-01-01

    The relation between clinical quality and bond rating for nonprofit hospitals has been proposed but never fully studied. We analyzed the relation between bond rating, clinical quality measures (The Joint Commission/Centers for Medicare and Medicaid Services [CMS] core measures), and balance sheet and income statement financial measures of 236 hospitals across the United States that are rated by Moody's Investors Service and that reported clinical quality measures to CMS during the study period. We found a statistically significant relation between higher quality measures and more favorable bond ratings. This association remained significant after controlling for traditional financial parameters.

  12. Quality of life is predictive of relapse in schizophrenia.

    PubMed

    Boyer, Laurent; Millier, Aurelie; Perthame, Emeline; Aballea, Samuel; Auquier, Pascal; Toumi, Mondher

    2013-01-09

    The objective of this study was to evaluate whether quality of life (QoL), as measured by the SF36 and the Quality of Life Interview (QoLI), is predictive of relapse for patients with schizophrenia. Using data from a multicenter cohort study conducted in France, Germany, and the United-Kingdom (EuroSC), we performed Cox proportional-hazards models to estimate the associations between QoL at baseline and the occurrence of relapse over a 24-month period, with adjustment for age; gender; positive, negative and general psychopathology PANSS factors; functioning (GAF); medication; side-effects; and compliance measures. Our sample consisted of 1,024 patients; 540 (53%) had at least one period of relapse, and 484 (47%) had no relapse. QoL levels were the most important features predicting relapse. We found that a higher level of QoL predicts a lower rate of relapse at 24 months: HR = 0.82 (0.74; 0.91), p < 0.001 for the SF36-Physical Composite Score; and HR = 0.88 (0.81; 0.96), p = 0.002 for the SF36-Mental Composite Score. These results were not confirmed using the QoLI: HR = 0.91 (0.81; 1.01), p = 0.083. To a lesser extent, older age, better functioning, and a higher compliance score also predict a lower rate of relapse at 24 months (HRs from 0.97 to 0.98; p < 0.05). QoL, as assessed by the SF36, is an independent predictor of relapse at a 24-month follow-up in schizophrenia. This finding may have implications for future use of the QoL in psychiatry. Moreover, our findings may support the development and monitoring of complementary therapeutic approaches, such as 'recovery-oriented' combined with traditional mental health cares to prevent relapse.

  13. Quality of life is predictive of relapse in schizophrenia

    PubMed Central

    2013-01-01

    Background The objective of this study was to evaluate whether quality of life (QoL), as measured by the SF36 and the Quality of Life Interview (QoLI), is predictive of relapse for patients with schizophrenia. Methods Using data from a multicenter cohort study conducted in France, Germany, and the United-Kingdom (EuroSC), we performed Cox proportional-hazards models to estimate the associations between QoL at baseline and the occurrence of relapse over a 24-month period, with adjustment for age; gender; positive, negative and general psychopathology PANSS factors; functioning (GAF); medication; side-effects; and compliance measures. Results Our sample consisted of 1,024 patients; 540 (53%) had at least one period of relapse, and 484 (47%) had no relapse. QoL levels were the most important features predicting relapse. We found that a higher level of QoL predicts a lower rate of relapse at 24 months: HR = 0.82 (0.74; 0.91), p < 0.001 for the SF36-Physical Composite Score; and HR = 0.88 (0.81; 0.96), p = 0.002 for the SF36-Mental Composite Score. These results were not confirmed using the QoLI: HR = 0.91 (0.81; 1.01), p = 0.083. To a lesser extent, older age, better functioning, and a higher compliance score also predict a lower rate of relapse at 24 months (HRs from 0.97 to 0.98; p < 0.05). Conclusions QoL, as assessed by the SF36, is an independent predictor of relapse at a 24-month follow-up in schizophrenia. This finding may have implications for future use of the QoL in psychiatry. Moreover, our findings may support the development and monitoring of complementary therapeutic approaches, such as ‘recovery-oriented’ combined with traditional mental health cares to prevent relapse. PMID:23302219

  14. Postpartum relapse to cigarette smoking in inner city women.

    PubMed Central

    Hymowitz, Norman; Schwab, Maria; McNerney, Christopher; Schwab, Joseph; Eckholdt, Haftan; Haddock, Keith

    2003-01-01

    Past studies suggest that African American women who quit smoking during pregnancy are more likely to relapse during the postpartum period than white women, although it is not intuitively clear why this should be the case. To shed further light on this issue, two studies were carried out to determine factors that influence smoking cessation during pregnancy and postpartum relapse to smoking in a predominantly low-income African American population. In Study 1, the women were asked to fill out a written survey, and in Study 2, women participated in a structured interview. The same variables that influence smoking cessation and postpartum relapse in the general population, such as nicotine addiction levels, smoking by other members of the household, lack of social support, stress, weight gain, behavioral intentions to quit temporarily, and quitting for others, as opposed to one's self, influenced the behavior of low-income inner city residents. These findings suggest that the difference in rates of postpartum relapse to smoking in African American women and the general population is a matter of degree, rather than kind. The implications of these findings for understanding postpartum relapse in general and assisting low-income women in particular were discussed. PMID:12856912

  15. Rationalizations and identity conflict following smoking relapse: a thematic analysis

    PubMed Central

    Wee, Lei Hum; Binti Ithnin, Azlyn Azmainie; West, Robert; Mohammad, Nihayah; Chan, Caryn Mei Hsien; Hasan Nudin, Siti Saadiah

    2017-01-01

    Abstract Introduction: Little is known about how smokers respond cognitively and emotionally to the experience of “late” relapse after the acute withdrawal phase. This study assessed the kinds of thoughts and feelings that emerge in order to provide a basis for quantitative research assessing prevalence of different types of response and implications for future quit attempts. Methods: Face-to-face in-depth interviews were conducted among 14 people attending a quit smoking clinic in Malaysia who had relapsed after at least 6 weeks of abstinence. Transcripts were analyzed using thematic analysis to enable emergence of important aspects of the experience. Results: Following relapse, smokers often engaged in rationalizations and activities to minimize worry about the harmful effects of smoking by switching to a lower-tar cigarette, reducing the number of cigarette smoked, attempting to reduce cigarette smoke inhalation, comparing themselves with other smokers, and minimizing the health risks associated with smoking. In some cases, smokers retained a “non-smoker” identity despite having relapsed. Conclusion: Smoking relapsers rationalize their failure to quit and minimize their health risk in order to protect their image as non-smokers while it remains a source of identity conflict. PMID:28217031

  16. Clinical markers of slow healing and relapsing gastric ulcer.

    PubMed Central

    Battaglia, G; Di Mario, F; Piccoli, A; Vianello, F; Farinati, F; Naccarato, R

    1987-01-01

    The aim of the study was to identify the clinical markers useful in characterising slow healing and relapsing gastric ulcer patients. Ninety nine subjects entered the short term and 79 the long term study (12 months). The following parameters were taken into account: therapy, sex, age, smoking habit, alcohol consumption, analgesic intake, peptic ulcer family history and onset of the disease. Results of the studies were analysed by means of chi 2 test and logistic regression, both in stepwise and in specifying models. Cigarette smoking was found to be the most important risk factor of non-healing (p = 0.04). In women with late onset of the disease, cigarette smoking identified the gastric ulcer subjects at higher risk of non-healing with a predictive probability of 0.4679. Age under 50 years was found to be the most important risk factor of relapsing throughout the entire 12 month follow up period (p = 0.025). In those under 50 years, cigarette smoking and negative peptic ulcer family history in combination, identified the gastric ulcer subjects at higher risk of relapsing, the predicted probability being 0.6027. It is concluded that cigarette smoking is the most important risk factor for non-healing and those who relapse under the age of 50. The possibility of singling out categories of patients more prone not to heal and to relapse suggests new strategies in the management of gastric ulcer disease. PMID:3557191

  17. INSOMNIA, SELF-MEDICATION, AND RELAPSE TO ALCOHOLISM

    PubMed Central

    Brower, Kirk J.; Aldrich, Michael S.; Robinson, Elizabeth A. R.; Zucker, Robert A.; Greden, John F.

    2009-01-01

    Objective This study investigated the frequencies of insomnia and its self-medication with alcohol in a sample of alcoholic patients, as well as the relationship of these variables to alcoholic relapse. Method Subjects were 172 men and women receiving treatment for alcohol dependence. They completed a sleep questionnaire, measures of alcohol problem severity and depression severity, and polysomnograpy after at least two weeks of abstinence. Results Using eight items from the Sleep Disorders Questionnaire, >60% of subjects were classified as having symptomatic insomnia during the six months prior to treatment entry. Compared to patients without insomnia, patients with insomnia were more likely to report frequent alcohol use for sleep (55% vs. 28%; χ2=12.03, df=1, p=0.001), had significantly worse polysomnographic measures of sleep continuity, and had greater severity scores for both alcohol dependence and depression. Among 74 alcoholics who were followed a mean of five months after treatment, 60% with baseline insomnia vs. 30% without baseline insomnia relapsed to any use of alcohol (χ2=6.16, df=1, p=0.02). Insomnia remained a robust predictor of relapse after applying logistic regression analysis to control for other variables. A history of self-medicating insomnia with alcohol did not significantly predict subsequent relapse. Conclusions The majority of alcoholic patients entering treatment reported insomnia symptoms. Given the potential link between insomnia and relapse, routine questions about sleep in clinical and research settings are warranted. PMID:11229980

  18. Trazodone and alcohol relapse: a retrospective study following residential treatment.

    PubMed

    Kolla, Bhanu Prakash; Schneekloth, Terry D; Biernacka, Joanna M; Frye, Mark A; Mansukhani, Meghna P; Hall-Flavin, Daniel K; Karpyak, Victor M; Loukianova, Larissa L; Lesnick, Timothy G; Mrazek, David

    2011-01-01

    Trazodone is one of the most commonly prescribed hypnotic medications in patients with sleep disturbances in alcohol recovery. A recent study concluded that treating insomnia with trazodone in patients with alcohol dependence might impede improvements in alcohol consumption and lead to increased drinking when trazodone is stopped. We set out to investigate the relationship between trazodone use during alcoholism treatment and relapse rates in patients who were discharged from a residential alcohol treatment program. We retrospectively reviewed records of patients with a diagnosis of alcohol dependence in a residential addiction treatment center from 2005 to 2008 and analyzed the association of trazodone use at discharge and alcohol relapse at 6 months. We also assessed the association between trazodone use and relapse at 6 months adjusting for sex, drug dependence, nonsubstance use Axis I psychiatric diagnoses, patient self-report of difficulties with sleep, and anti-dipsotropic medication use at discharge and evaluated pair-wise interactions of trazodone use with the adjustment variables. Of 283 patients eligible for inclusion, 85 (30%) were taking trazodone at discharge. Older age, self-reported sleep problems, and having a nonsubstance use Axis I psychiatric diagnosis were associated with trazodone use. After discharge, 170 (60%) subjects responded to follow-up efforts. Neither intent to treat nor responder only analysis revealed any association between trazodone use and relapse. Our retrospective study of a complex patient population discharged from a residential treatment setting did not find an association between trazodone use at discharge and relapse rates at 6 months.

  19. Suppression of cancer relapse and metastasis by inhibiting cancer stemness.

    PubMed

    Li, Youzhi; Rogoff, Harry A; Keates, Sarah; Gao, Yuan; Murikipudi, Sylaja; Mikule, Keith; Leggett, David; Li, Wei; Pardee, Arthur B; Li, Chiang J

    2015-02-10

    Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemness-high cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis.

  20. Suppression of cancer relapse and metastasis by inhibiting cancer stemness

    PubMed Central

    Li, Youzhi; Rogoff, Harry A.; Keates, Sarah; Gao, Yuan; Murikipudi, Sylaja; Mikule, Keith; Leggett, David; Li, Wei; Pardee, Arthur B.; Li, Chiang J.

    2015-01-01

    Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemness-high cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis. PMID:25605917

  1. Drugs in development for relapsing multiple sclerosis.

    PubMed

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    drugs in development, and it is likely that BG-12 will be licensed this year. This has been licensed for psoriasis so there are good safety data in humans that may also hold true in MS; however, its three times daily dosage will probably impact on patient compliance. Laquinimod has lower efficacy than BG-12 but appears safe and could find a place as a first-line agent. Teriflunomide has just been licensed by the US FDA and may challenge the current injectable first-line therapies as it has a similar efficacy but the advantage of being taken orally. However, risk of teratogenicity may caution against its use in some women of child-bearing potential. This review will examine drugs that have been recently approved as well as those that are in late phase 2 or 3 development as treatment for relapsing MS, highlighting their mechanism of action as well as the clinical trial and safety data before discussing their potential for success in an increasingly florid and complex DMT armamentarium.

  2. Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection.

    PubMed Central

    Fouladi, M.; Jenkins, J.; Burger, P.; Langston, J.; Merchant, T.; Heideman, R.; Thompson, S.; Sanford, A.; Kun, L.; Gajjar, A.

    2001-01-01

    To describe the clinical features, histologic characteristics, and management of patients with pleomorphic xanthoastrocytoma (PXA), we reviewed data on 13 children who had histologically confirmed PXA and were referred to the neuro-oncology service between 1985 and 1999. Neuro-imaging with CT and/or MRI documented the anatomic location, tumor extent, and degree of resection. There were 3 males and 10 females; median age was 12.9 years (range, 8.2-17.2 years). The most frequent presentations included seizures (n = 8) and headache (n = 5). Tumor sites included temporal (n = 5), parietal (n = 3), frontal (n = 1), frontoparietal (n = 1), parietooccipital (n = 1), and temporoparietal (n = 1) lobes and the spinal cord (n = 1). CT/MRI revealed a cystic component in 6 patients, with cyst wall enhancement in 3 patients. The solid component was uniformly enhancing in 11 patients. Vasogenic edema was present in 9 patients, and calcification was noted in 4 patients. Histopathologic findings included meningeal invasion in 12 patients, calcifications in 4, and necrosis in 2. Mitotic figures (1-12 per high-power field) were seen in 8 patients. Gross total resection was achieved in 8 patients, near total resection in 1, and subtotal resection in 4. Ten patients were alive with a median follow-up of 41 months at this writing. Two patients died of progressive disease, and 1 died of an unrelated cause. In conclusion, pleomorphic xanthoastrocytoma is a rare neoplasm in childhood, commonly presenting with seizures. Gross total resection without adjuvant therapy provides prolonged disease control, as seen in 6 of 7 patients (85%) in our series. PMID:11465399

  3. Salinity inversions in the thermocline under upwelling favorable winds

    NASA Astrophysics Data System (ADS)

    Burchard, Hans; Basdurak, N. Berkay; Gräwe, Ulf; Knoll, Michaela; Mohrholz, Volker; Müller, Selina

    2017-02-01

    This paper discusses and explains the phenomenon of salinity inversions in the thermocline offshore from an upwelling region during upwelling favorable winds. Using the nontidal central Baltic Sea as an easily accessible natural laboratory, high-resolution transect and station observations in the upper layers are analyzed. The data show local salinity minima in the strongly stratified seasonal thermocline during summer conditions under the influence of upwelling favorable wind. A simple analytical box model using parameters (including variation by means of a Monte Carlo method) estimated from a hindcast model for the Baltic Sea is constructed to explain the observations. As a result, upwelled water with high salinity and low temperature is warmed up due to downward surface heat fluxes while it is transported offshore by the Ekman transport. The warming of upwelled surface water allows maintenance of stable stratification despite the destabilizing salinity stratification, such that local salinity minima in the thermocline can be generated. Inspection of published observations from the Benguela, Peruvian, and eastern tropical North Atlantic upwelling systems shows that also there salinity inversions occur in the thermocline, but in these cases thermocline salinity shows local maxima, since upwelled water has a lower salinity than the surface water. It is hypothesized that thermocline salinity inversions should generally occur offshore from upwelling regions whenever winds are steady enough and surface warming is sufficiently strong.

  4. HOW MUCH FAVORABLE SELECTION IS LEFT IN MEDICARE ADVANTAGE?

    PubMed

    Newhouse, Joseph P; Price, Mary; McWilliams, J Michael; Hsu, John; McGuire, Thomas G

    2015-01-01

    The health economics literature contains two models of selection, one with endogenous plan characteristics to attract good risks and one with fixed plan characteristics; neither model contains a regulator. Medicare Advantage, a principal example of selection in the literature, is, however, subject to anti-selection regulations. Because selection causes economic inefficiency and because the historically favorable selection into Medicare Advantage plans increased government cost, the effectiveness of the anti-selection regulations is an important policy question, especially since the Medicare Advantage program has grown to comprise 30 percent of Medicare beneficiaries. Moreover, similar anti-selection regulations are being used in health insurance exchanges for those under 65. Contrary to earlier work, we show that the strengthened anti-selection regulations that Medicare introduced starting in 2004 markedly reduced government overpayment attributable to favorable selection in Medicare Advantage. At least some of the remaining selection is plausibly related to fixed plan characteristics of Traditional Medicare versus Medicare Advantage rather than changed selection strategies by Medicare Advantage plans.

  5. Donepezil regulates energy metabolism and favors bone mass accrual.

    PubMed

    Eimar, Hazem; Alebrahim, Sharifa; Manickam, Garthiga; Al-Subaie, Ahmed; Abu-Nada, Lina; Murshed, Monzur; Tamimi, Faleh

    2016-03-01

    The autonomous nervous system regulates bone mass through the sympathetic and parasympathetic arms. The sympathetic nervous system (SNS) favors bone loss whereas the parasympathetic nervous system (PNS) promotes bone mass accrual. Donepezil, a central-acting cholinergic agonist, has been shown to down-regulate SNS and up-regulate PNS signaling tones. Accordingly, we hypothesize that the use of donepezil could have beneficial effects in regulating bone mass. To test our hypothesis, two groups of healthy female mice were treated either with donepezil or saline. Differences in body metabolism and bone mass of the treated groups were compared. Body and visceral fat weights as well as serum leptin level were increased in donepezil-treated mice compared to control, suggesting that donepezil effects on SNS influenced metabolic activity. Donepezil-treated mice had better bone quality than controls due to a decrease in osteoclasts number. These results indicate that donepezil is able to affect whole body energy metabolism and favors bone mass in young female WT mice.

  6. HOW MUCH FAVORABLE SELECTION IS LEFT IN MEDICARE ADVANTAGE?

    PubMed Central

    PRICE, MARY; MCWILLIAMS, J. MICHAEL; HSU, JOHN; MCGUIRE, THOMAS G.

    2015-01-01

    The health economics literature contains two models of selection, one with endogenous plan characteristics to attract good risks and one with fixed plan characteristics; neither model contains a regulator. Medicare Advantage, a principal example of selection in the literature, is, however, subject to anti-selection regulations. Because selection causes economic inefficiency and because the historically favorable selection into Medicare Advantage plans increased government cost, the effectiveness of the anti-selection regulations is an important policy question, especially since the Medicare Advantage program has grown to comprise 30 percent of Medicare beneficiaries. Moreover, similar anti-selection regulations are being used in health insurance exchanges for those under 65. Contrary to earlier work, we show that the strengthened anti-selection regulations that Medicare introduced starting in 2004 markedly reduced government overpayment attributable to favorable selection in Medicare Advantage. At least some of the remaining selection is plausibly related to fixed plan characteristics of Traditional Medicare versus Medicare Advantage rather than changed selection strategies by Medicare Advantage plans. PMID:26389127

  7. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China.

    PubMed

    Shi, Yuankai; Jia, Bo; Xu, Wei; Li, Wenyu; Liu, Ting; Liu, Peng; Zhao, Weili; Zhang, Huilai; Sun, Xiuhua; Yang, Haiyan; Zhang, Xi; Jin, Jie; Jin, Zhengming; Li, Zhiming; Qiu, Lugui; Dong, Mei; Huang, Xiaobing; Luo, Yi; Wang, Xiaodong; Wang, Xin; Wu, Jianqiu; Xu, Jingyan; Yi, Pingyong; Zhou, Jianfeng; He, Hongming; Liu, Lin; Shen, Jianzhen; Tang, Xiaoqiong; Wang, Jinghua; Yang, Jianmin; Zeng, Qingshu; Zhang, Zhihui; Cai, Zhen; Chen, Xiequn; Ding, Kaiyang; Hou, Ming; Huang, Huiqiang; Li, Xiaoling; Liang, Rong; Liu, Qifa; Song, Yuqin; Su, Hang; Gao, Yuhuan; Liu, Lihong; Luo, Jianmin; Su, Liping; Sun, Zimin; Tan, Huo; Wang, Huaqing; Wang, Jingwen; Wang, Shuye; Zhang, Hongyu; Zhang, Xiaohong; Zhou, Daobin; Bai, Ou; Wu, Gang; Zhang, Liling; Zhang, Yizhuo

    2017-03-15

    The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.

  8. RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

    PubMed Central

    Gianfelici, Valentina; Chiaretti, Sabina; Demeyer, Sofie; Di Giacomo, Filomena; Messina, Monica; La Starza, Roberta; Peragine, Nadia; Paoloni, Francesca; Geerdens, Ellen; Pierini, Valentina; Elia, Loredana; Mancini, Marco; De Propris, Maria Stefania; Apicella, Valerio; Gaidano, Gianluca; Testi, Anna Maria; Vitale, Antonella; Vignetti, Marco; Mecucci, Cristina; Guarini, Anna; Cools, Jan; Foà, Robin

    2016-01-01

    Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways. PMID:27151993

  9. Effect of modafinil on impulsivity and relapse in alcohol dependent patients: a randomized, placebo-controlled trial.

    PubMed

    Joos, Leen; Goudriaan, Anna E; Schmaal, Lianne; Fransen, Erik; van den Brink, Wim; Sabbe, Bernard G C; Dom, Geert

    2013-08-01

    Poor impulse control plays an important role in the development, course and relapse of substance use disorders. Therefore, improving impulse control may represent a promising approach in the treatment of alcohol dependence. This study aimed to test the effect of modafinil on impulse control and alcohol use in alcohol dependent patients (ADP) in a randomized, double-blind, placebo-controlled trial. Eighty-three abstinent ADP were randomized to 10 weeks modafinil (300 mg/d) or placebo. Alcohol use was quantified using the timeline follow-back method and was assessed until 6 months after treatment discontinuation. Impulsivity was assessed using self-report questionnaires (Barratt Impulsiveness Scale; State Impulsivity questionnaire) and neurocognitive tasks (Stop Signal Task; Delay Discounting Task) administered before, during and after treatment. Modafinil significantly improved self-report measures of state impulsivity, but had no effect on percentage of abstinent days or percentage of heavy drinking days, nor on the behavioral measures of impulsivity. However, subgroup analysis revealed that modafinil prolonged the time to relapse (p=.022) and tended to increase the percentage of abstinent days (p=.066) in ADP with poor response inhibition at baseline, whereas modafinil increased the percentage of heavy drinking days (p=.003) and reduced the percentage of abstinent days (p=.002) in patients with better baseline response inhibition. Overall results do not favor the use of modafinil in order to reduce relapse or relapse severity in ADP, and caution is required in prescribing modafinil to a non-selected sample of ADP. Further research on the effect of modafinil in ADP with poor baseline response inhibition is warranted.

  10. Echocardiographic versus histologic findings in Marfan syndrome.

    PubMed

    Gu, Xiaoyan; He, Yihua; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J V Ian

    2015-02-01

    This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved.

  11. Bone marrow histology in monoclonal macroglobulinemia.

    PubMed

    Rywlin, A M; Civantos, F; Ortega, R S; Dominguez, C J

    1975-06-01

    Rywlin, Arkadi, M., Civantos, Francisco, Ortega, Rolando S., and Dominguez, Carlos J.: Bone marrow histology in monoclonal macroglobulinemiamam J Clin Pathol 63. 769-778, 1975. Histologic sections and smears of aspirated bone marrow particles in 26 cases of monoclonal macroglobulinemia were studied. The bone marrows did not show uniform histologic features. Twenty-two patients had various degrees of lymphoid infiltration of the marrow, including nodules of malignant lymphoma, diffuse lymphocytic infiltration, nodular lymphoid hyperplasia, and normal lymphoid nodules. Four patients had no demonstrable lymphoid collections in the marrow. Additional histologic features of the marrows are summarized. A variant of a Dutcher body consisting of multiple PAS-positive inclusions that by light microscopy appear intranuclear is described. Even though the average macroglobulin levels were higher in patients with abnormal lymphoid infiltrates than in patients with noraml or no lymphoid collections, there was considerable overlap between individual patients values in the different groups. Similarly, no correlation between macroglobulin levels and other histologic features could be established. Patients with monoclonal macroglobulinemia represent a spectrum including benign monoclonal gammopathy, lymphoproliferative disorders of the marrow, nodal or extranodal lymphomas. The separation of Waldenström's macroglobulinemia by arbitrary criteria does not appear justified. (key words: Bone marrow; Monoclonal macroglobulinemia.

  12. Clinical and Histologic Mimickers of Celiac Disease.

    PubMed

    Kamboj, Amrit K; Oxentenko, Amy S

    2017-08-17

    Celiac disease is an autoimmune disorder of the small bowel, classically associated with diarrhea, abdominal pain, and malabsorption. The diagnosis of celiac disease is made when there are compatible clinical features, supportive serologic markers, representative histology from the small bowel, and response to a gluten-free diet. Histologic findings associated with celiac disease include intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy, and a chronic inflammatory cell infiltrate in the lamina propria. It is important to recognize and diagnose celiac disease, as strict adherence to a gluten-free diet can lead to resolution of clinical and histologic manifestations of the disease. However, many other entities can present with clinical and/or histologic features of celiac disease. In this review article, we highlight key clinical and histologic mimickers of celiac disease. The evaluation of a patient with serologically negative enteropathy necessitates a carefully elicited history and detailed review by a pathologist. Medications can mimic celiac disease and should be considered in all patients with a serologically negative enteropathy. Many mimickers of celiac disease have clues to the underlying diagnosis, and many have a targeted therapy. It is necessary to provide patients with a correct diagnosis rather than subject them to a lifetime of an unnecessary gluten-free diet.

  13. Echocardiographic versus Histologic Findings in Marfan Syndrome

    PubMed Central

    Gu, Xiaoyan; Li, Zhian; Han, Jiancheng; Chen, Jian; Nixon, J.V. (Ian)

    2015-01-01

    This retrospective study attempted to establish the prevalence of multiple-valve involvement in Marfan syndrome and to compare echocardiographic with histopathologic findings in Marfan patients undergoing valvular or aortic surgery. We reviewed echocardiograms of 73 Marfan patients who underwent cardiovascular surgery from January 2004 through October 2009. Tissue histology was available for comparison in 29 patients. Among the 73 patients, 66 underwent aortic valve replacement or the Bentall procedure. Histologic findings were available in 29 patients, all of whom had myxomatous degeneration. Of 63 patients with moderate or severe aortic regurgitation as determined by echocardiography, 4 had thickened aortic valves. The echocardiographic findings in 18 patients with mitral involvement included mitral prolapse in 15. Of 11 patients with moderate or severe mitral regurgitation as determined by echocardiography, 4 underwent mitral valve repair and 7 mitral valve replacement. Histologic findings among mitral valve replacement patients showed thickened valve tissue and myxomatous degeneration. Tricuspid involvement was seen echocardiographically in 8 patients, all of whom had tricuspid prolapse. Two patients had severe tricuspid regurgitation, and both underwent repair. Both mitral and tricuspid involvement were seen echocardiographically in 7 patients. Among the 73 patients undergoing cardiac surgery for Marfan syndrome, 66 had moderate or severe aortic regurgitation, although their valves manifested few histologic changes. Eighteen patients had mitral involvement (moderate or severe mitral regurgitation, prolapse, or both), and 8 had tricuspid involvement. Mitral valves were most frequently found to have histologic changes, but the tricuspid valve was invariably involved. PMID:25873795

  14. Comprehensive histological evaluation of bone implants

    PubMed Central

    Rentsch, Claudia; Schneiders, Wolfgang; Manthey, Suzanne; Rentsch, Barbe; Rammelt, Stephan

    2014-01-01

    To investigate and assess bone regeneration in sheep in combination with new implant materials classical histological staining methods as well as immunohistochemistry may provide additional information to standard radiographs or computer tomography. Available published data of bone defect regenerations in sheep often present none or sparely labeled histological images. Repeatedly, the exact location of the sample remains unclear, detail enlargements are missing and the labeling of different tissues or cells is absent. The aim of this article is to present an overview of sample preparation, staining methods and their benefits as well as a detailed histological description of bone regeneration in the sheep tibia. General histological staining methods like hematoxylin and eosin, Masson-Goldner trichrome, Movat’s pentachrome and alcian blue were used to define new bone formation within a sheep tibia critical size defect containing a polycaprolactone-co-lactide (PCL) scaffold implanted for 3 months (n = 4). Special attention was drawn to describe the bone healing patterns down to cell level. Additionally one histological quantification method and immunohistochemical staining methods are described. PMID:24504113

  15. Carfilzomib boosted combination therapy for relapsed multiple myeloma

    PubMed Central

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

    Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma. PMID:28243125

  16. Carfilzomib boosted combination therapy for relapsed multiple myeloma.

    PubMed

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

    Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma.

  17. STUDY OF RELAPSES IN SCHIZOPHRENIA USING THE LIFE TABLE METHOD

    PubMed Central

    Thara, R.; Raman, K.J.; Srinivasan, T.N.; Rajkumar, S.; Vijayalakshmi, V.

    1987-01-01

    SUMMARY The life table has been used to study mortality and survival in a population and also the pattern of course of various chronic medical illnesses. In this study, the life table has been applied to a cohort of well defined Schizophrenic patients undergoing a long term followup. The probability of occurence of relapses, time of maximum risk for occurence of relapses are estimated using the life table technique. The life table shows a steep fall in the percentage of Non-relapsers from 85% at the end of first year to 35% at the end of the third year. Projected survival rate at the end of 5 years, using the second degree parabola curve, is only 2 % which needs to be tested by further followup. PMID:21927250

  18. Relapse of Multiple Myeloma Presenting as Lower Lip Numbness

    PubMed Central

    Al-Riyami, Yusra M.; Bakathir, Abdulaziz; Al-Farsi, Khalil; Al-Azri, Faisal

    2016-01-01

    Multiple myeloma (MM) is an uncommon malignancy characterised by the proliferation of clonal plasma cells. There are few published reports describing the extramedullary presentation of MM manifesting primarily in the head and neck region. In addition, the occurrence of an isolated relapse of MM in these sites is exceedingly rare. We report a 56-year-old female who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2010 with sudden-onset numbness of the lower lip. She had a history of MM in remission following chemotherapy and a bone marrow transplant. Clinical and radiographic examinations were indicative of a possible relapse of MM, which was subsequently confirmed by bone marrow aspiration and histopathological evaluation. This unique case highlights the unusual site of relapse of a haematolymphoid malignancy. PMID:28003900

  19. Leprosy with Atypical Skin Lesions Masquerading as Relapsing Polychondritis

    PubMed Central

    Munganda, Hariharan; Bangia, Amit; Rani, Uma; Budhiraja, Rajesh; Brajpuriya, Swapnil

    2016-01-01

    Leprosy can present with a variety of clinical manifestations depending on the immune status of the individual. After dermatological and neurological involvement, rheumatic features specially various forms of arthritis are the third most common manifestation of the disease. We describe a unique case of a 22-year-old patient presenting with external ear involvement mimicking relapsing polychondritis along with inflammatory joint symptoms and skin lesions. Ear involvement in relapsing polychondritis characteristically is painful and spares the noncartilaginous ear lobules, in contrast to painless ear involvement in leprosy affecting the lobules as well. Histopathology confirmed the diagnosis, although the ear and skin lesions were not classical of leprosy. Such a presentation of leprosy closely mimicking relapsing polychondritis has not been described previously. Tissue diagnosis should always be attempted whenever possible in patients presenting with autoimmune features, so that inappropriate therapy with immunosuppressants is avoided. PMID:28116186

  20. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    PubMed

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

  1. Intratumoral lymphatic vessel density in vulvar squamous cell carcinomas: a possible association with favorable prognosis.

    PubMed

    Goes, Renata Sampaio; Carvalho, Jesus P; Almeida, Bernardo G L; Bacchi, Carlos E; Goes, Joao Carlos Sampaio; Calil, Marcelo Alvarenga; Baracat, Edmund C; Carvalho, Filomena M

    2012-01-01

    Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.

  2. Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors.

    PubMed

    Rössle, Matthias; Cathomas, Gieri; Bonapace, Laura; Sachs, Melanie; Dehler, Silvia; Storz, Martina; Huber, Gerhard; Moch, Holger; Junt, Tobias; Mertz, Kirsten D

    2016-08-01

    The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities-for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33-negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics. © The Author(s) 2016.

  3. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria.

    PubMed

    White, Michael T; Shirreff, George; Karl, Stephan; Ghani, Azra C; Mueller, Ivo

    2016-03-30

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.

  4. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

    PubMed Central

    White, Michael T.; Shirreff, George; Karl, Stephan; Ghani, Azra C.; Mueller, Ivo

    2016-01-01

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes. PMID:27030414

  5. Social partners prevent alcohol relapse behavior in prairie voles

    PubMed Central

    Hostetler, Caroline M.; Ryabinin, Andrey E.

    2013-01-01

    There is robust evidence for a protective role of interpersonal factors such as social support on alcohol relapse, but research on the mechanisms that social factors may be acting on to effectively protect individuals against relapse is lacking. Prairie voles are highly social, monogamous rodents that freely self-administer ethanol in high amounts, and are a useful model for understanding social influences on alcohol drinking. Here we investigated whether prairie voles can be used to model social influences on relapse using the alcohol deprivation effect, in which animals show a transient increase in ethanol drinking following deprivation. In Experiment I, subjects were housed alone during four weeks of 24-hour access to 10% ethanol in a two-bottle choice test. Ethanol was then removed from the cage for 72 hours. Animals remained in isolation or were then housed with a familiar same-sex social partner, and ethanol access was resumed. Animals that remained isolated showed an increase in ethanol intake relative to pre-deprivation baseline, indicative of relapse-like behavior. However, animals that were socially housed did not show an increase in ethanol intake, and this was independent of whether the social partner also had access to ethanol. Experiment II replicated the alcohol deprivation effect in a separate cohort of isolated animals. These findings demonstrate that prairie voles display an alcohol deprivation effect and suggest a ‘social buffering’ effect of relapse-like behavior in the prairie vole. This behavioral paradigm provides a novel approach for investigating the behavioral and neurobiological underpinnings of social influences on alcohol relapse. PMID:24275014

  6. Emergence of new ALK mutations at relapse of neuroblastoma.

    PubMed

    Schleiermacher, Gudrun; Javanmardi, Niloufar; Bernard, Virginie; Leroy, Quentin; Cappo, Julie; Rio Frio, Thomas; Pierron, Gaelle; Lapouble, Eve; Combaret, Valérie; Speleman, Frank; de Wilde, Bram; Djos, Anna; Ora, Ingrid; Hedborg, Fredrik; Träger, Catarina; Holmqvist, Britt-Marie; Abrahamsson, Jonas; Peuchmaur, Michel; Michon, Jean; Janoueix-Lerosey, Isabelle; Kogner, Per; Delattre, Olivier; Martinsson, Tommy

    2014-09-01

    In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000× deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions. © 2014 by American Society of Clinical Oncology.

  7. Relapsed small cell lung cancer: treatment options and latest developments

    PubMed Central

    Ohkuni, Yoshihiro; Kaneko, Norihiro; Yamaguchi, Etsuro; Kubo, Akihito

    2014-01-01

    According to recent analyses, there was a modest yet significant improvement in median survival time and 5-year survival rate of limited stage small cell lung cancer (SCLC) in North America, Europe, Japan and other countries over the last 30 years. The median survival time of limited stage SCLC is 15–20 months and 5-year survival rate is 15% or less. In terms of extensive stage SCLC, a median survival time of 9.4–12.8 months and 2-year survival of 5.2–19.5% are still disappointing. Despite being highly sensitive to first-line chemotherapy and radiotherapy treatments, most patients with SCLC experience relapse within 2 years and die from systemic metastasis. While several clinical trials of cytotoxic chemotherapies and molecular targeting agents have been investigated in the treatment of relapsed SCLC, none showed a significant clinical activity to be able to exceed topotecan as second-line chemotherapy. There are problematic issues to address for relapsed SCLC, such as standardizing the treatment for third-line chemotherapy. Topotecan alone was the first approved therapy for second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a variety of trials evaluating its efficacy have been carried out. Amrubicin has shown superiority to topotecan in a Japanese population, but was not superior in a study of western patients. There are some controversial issues for relapsed SCLC, such as treatment for older patients, third-line chemotherapy and efficacy of molecular targeting therapy. This article reviews current standard treatment, recent clinical trials and other topics on relapsed SCLC. PMID:24587832

  8. Antigenic variation among Borrelia spp. in relapsing fever.

    PubMed Central

    Kehl, K S; Farmer, S G; Komorowski, R A; Knox, K K

    1986-01-01

    Seven antigens of Borrelia hermsii, B. parkeri, and B. turicatae with isoelectric points in the range of 4.4 to 5.0 and molecular masses of 40 to 43 kilodaltons played a role in the relapse phenomenon of relapsing fever. Based upon location of the antigens in the outer envelope, the molecular weight, and Western blot analysis, the antigens from each phase of spirochetemia appeared to be a mixture of the serotype-specific antigens of cloned B. hermsii. Images PMID:3536750

  9. A simple technique for correction of relapsed overjet.

    PubMed

    Kakkirala, Neelima; Saxena, Ruchi

    2014-01-01

    Class III malocclusions are usually growth related discrepancies, which often become more severe when growth is completed Orthognathic surgery can be a part of the treatment plan, although a good number of cases can be treated non-surgically by camouflage treatment. The purpose of this report is to review the relapse tendency in patients treated non-surgically. A simple technique is described to combat one such post-treatment relapse condition in an adult patient who had undergone orthodontic treatment by extraction of a single lower incisor.

  10. Early aortic valve cusp rupture in relapsing polychondritis.

    PubMed Central

    Marshall, D A; Jackson, R; Rae, A P; Capell, H A

    1992-01-01

    Aortic regurgitation associated with relapsing polychondritis usually occurs late in the disease as a result of aortic root dilatation. A case where aortic regurgitation occurred early and was due to cusp rupture with a normal aortic root is reported. The patient required urgent aortic valve replacement within six weeks of developing a murmur despite apparent control of inflammation with immunosuppressive treatment. The possibility of cusp rupture with sudden haemodynamic deterioration should be considered in patients with relapsing polychondritis who develop aortic regurgitation. Images PMID:1575597

  11. Relapsed Pulmonary Cryptococcosis during Tumor Necrosis Factor α Inhibitor Treatment.

    PubMed

    Takazono, Takahiro; Sawai, Toyomitsu; Tashiro, Masato; Saijo, Tomomi; Yamamoto, Kazuko; Imamura, Yoshifumi; Miyazaki, Taiga; Suyama, Naofumi; Izumikawa, Koichi; Kakeya, Hiroshi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    A 35-year-old non-HIV patient developed pulmonary cryptococcosis after the initiation of infliximab. He recovered by fluconazole treatment and completed the therapy for a total of 6 months. However, he experienced a relapse 16 months later during retreatment with infliximab, revealing an interesting clinical course contradicting retreatment. This case also represents the first case of relapsed pulmonary cryptococcosis suspected during treatment with a biologic agent. Both of these aspects generated important clinical questions about the length of pulmonary cryptococcosis treatment and the necessity of introducing a second prophylaxis for such patients.

  12. Relapse among substance-abusing women: components and processes.

    PubMed

    Sun, An-Pyng

    2007-01-01

    This article is based on part of a project in which 32 women who experienced substance use-related problems were interviewed. The purpose of the article is to explore factors related to the women's relapse so that practitioners can better understand the nature of women's relapse and more effectively help them. Qualitative in-depth interviews were conducted, audiotaped (with the exception of three women), and transcribed. The interview was guided by open-ended questions - exploring factors that led to the women's initial substance use, abstinence, and relapse; factors that prompted them to come for treatment; and their experience with the treatment. These open-ended questions were supplemented with follow-up questions probing further critical elements shared by participants initially. The mean age of the sample was 34 years old, with over half being white, followed by Latina/Hispanic, African American, and Native American. Most women reported being poly-drug users, followed by methamphetamine/amphetamines, heroine, cocaine, and alcohol. The average number of years of education was 11 years. Four major themes representing factors contributing to the women's relapse were identified: (1) low self-worth and its connection to intimate relationships with men; (2) interpersonal conflicts and/or negative emotion; (3) less ability to sever the tie with the using network and to establish a tie with the non-using network; and (4) a lack of AOD-related knowledge and relapse prevention coping skills. The qualitative approach enables the study to report not only the four general themes but also the multiple dimensions and building blocks underlying each theme so that the pertinent contexts and specific meanings of women's relapses can be understood. Many of the factors appeared to be related to women's socialization and the gender-role formation process as well as their disadvantageous social reality. The study suggests several topics for inclusion in women's relapse prevention

  13. Relapsing cardial stenosis after laparoscopic nissen treated by esophageal stenting.

    PubMed

    Pouderoux, Philippe; Verdier, Eric; Courtial, Philippe; Bapin, Catherine; Deixonne, Bernard; Balmès, Jean-Louis

    2003-01-01

    Dysphagia after antireflux surgery is often a challenging situation. We report the case of a patient with relapsing cardial stricture and a weight loss of 24 kg following a laparoscopic Nissen procedure. Initial presentation was consistent with the diagnosis of pseudoachalasia and was resistant to endoscopic dilatation. Dysphagia was relieved by surgery, which showed cardial strangulation by tightly sutured diaphragmatic pillars. Symptoms and cardial stricture relapsed after a few months with no significant relief after repeated dilatations. Conservative treatment by endoscopic transcardial prosthesis for six weeks allowed a return to normal diet and a weight gain of 10 kg within a 30-month followup period.

  14. Relapsed Pulmonary Cryptococcosis during Tumor Necrosis Factor α Inhibitor Treatment

    PubMed Central

    Takazono, Takahiro; Sawai, Toyomitsu; Tashiro, Masato; Saijo, Tomomi; Yamamoto, Kazuko; Imamura, Yoshifumi; Miyazaki, Taiga; Suyama, Naofumi; Izumikawa, Koichi; Kakeya, Hiroshi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    2016-01-01

    A 35-year-old non-HIV patient developed pulmonary cryptococcosis after the initiation of infliximab. He recovered by fluconazole treatment and completed the therapy for a total of 6 months. However, he experienced a relapse 16 months later during retreatment with infliximab, revealing an interesting clinical course contradicting retreatment. This case also represents the first case of relapsed pulmonary cryptococcosis suspected during treatment with a biologic agent. Both of these aspects generated important clinical questions about the length of pulmonary cryptococcosis treatment and the necessity of introducing a second prophylaxis for such patients. PMID:27725552

  15. Tick-Borne Relapsing Fever Spirochetes in the Americas

    PubMed Central

    Lopez, Job E.; Krishnavahjala, Aparna; Garcia, Melissa N.; Bermudez, Sergio

    2017-01-01

    Relapsing fever spirochetes are tick- and louse-borne pathogens that primarily afflict those in impoverished countries. Historically the pathogens have had a significant impact on public health, yet currently they are often overlooked because of the nonspecific display of disease. In this review, we discuss aspects of relapsing fever (RF) spirochete pathogenesis including the: (1) clinical manifestation of disease; (2) ability to diagnose pathogen exposure; (3) the pathogen’s life cycle in the tick and mammal; and (4) ecological factors contributing to the maintenance of RF spirochetes in nature. PMID:28959690

  16. Histology image search using multimodal fusion.

    PubMed

    Caicedo, Juan C; Vanegas, Jorge A; Páez, Fabian; González, Fabio A

    2014-10-01

    This work proposes a histology image indexing strategy based on multimodal representations obtained from the combination of visual features and associated semantic annotations. Both data modalities are complementary information sources for an image retrieval system, since visual features lack explicit semantic information and semantic terms do not usually describe the visual appearance of images. The paper proposes a novel strategy to build a fused image representation using matrix factorization algorithms and data reconstruction principles to generate a set of multimodal features. The methodology can seamlessly recover the multimodal representation of images without semantic annotations, allowing us to index new images using visual features only, and also accepting single example images as queries. Experimental evaluations on three different histology image data sets show that our strategy is a simple, yet effective approach to building multimodal representations for histology image search, and outperforms the response of the popular late fusion approach to combine information.

  17. Habitat heterogeneity favors asexual reproduction in natural populations of grassthrips

    PubMed Central

    Lavanchy, Guillaume; Strehler, Marie; Llanos Roman, Maria Noemi; Lessard‐Therrien, Malie; Humbert, Jean‐Yves; Dumas, Zoé; Jalvingh, Kirsten; Ghali, Karim; Fontcuberta García‐Cuenca, Amaranta; Zijlstra, Bart; Arlettaz, Raphaël; Schwander, Tanja

    2016-01-01

    Explaining the overwhelming success of sex among eukaryotes is difficult given the obvious costs of sex relative to asexuality. Different studies have shown that sex can provide benefits in spatially heterogeneous environments under specific conditions, but whether spatial heterogeneity commonly contributes to the maintenance of sex in natural populations remains unknown. We experimentally manipulated habitat heterogeneity for sexual and asexual thrips lineages in natural populations and under seminatural mesocosm conditions by varying the number of hostplants available to these herbivorous insects. Asexual lineages rapidly replaced the sexual ones, independently of the level of habitat heterogeneity in mesocosms. In natural populations, the success of sexual thrips decreased with increasing habitat heterogeneity, with sexual thrips apparently only persisting in certain types of hostplant communities. Our results illustrate how genetic diversity‐based mechanisms can favor asexuality instead of sex when sexual lineages co‐occur with genetically variable asexual lineages. PMID:27346066

  18. Second octant favored for non-maximal 𝜃23

    NASA Astrophysics Data System (ADS)

    Frampton, Paul H.

    2017-06-01

    One of the most robust relationships predicted by binary tetrahedral (T‧) flavor symmetry relates the reactor neutrino angle 𝜃13 to the atmospheric neutrino angle 𝜃23, independently of 𝜃12. It has the form 𝜃13 = 2|π 4 - 𝜃23|. When this prediction first appeared in 2008, 𝜃13 was consistent with zero and 𝜃23 with π/4. Nonzero 𝜃13 was established by Daya Bay in 2012. Nonzero |π 4 - 𝜃23| is now favored by the NOνA experiment and, for 𝜃23, the aforementioned T‧ relation selects the second octant (𝜃23 > π 4 ) over the first octant (𝜃23 < π 4 ). This analysis initially assumes CP conservation in the lepton sector, but leptonic CP violation is discussed and it is shown that this specific T‧ relationship is invariant.

  19. On Favorable Thermal Fields for Detached Bridgman Growth

    NASA Technical Reports Server (NTRS)

    Stelian, Carmen; Volz, Martin P.; Derby, Jeffrey J.

    2009-01-01

    The thermal fields of two Bridgman-like configurations, representative of real systems used in prior experiments for the detached growth of CdTe and Ge crystals, are studied. These detailed heat transfer computations are performed using the CrysMAS code and expand upon our previous analyses [14] that posited a new mechanism involving the thermal field and meniscus position to explain stable conditions for dewetted Bridgman growth. Computational results indicate that heat transfer conditions that led to successful detached growth in both of these systems are in accordance with our prior assertion, namely that the prevention of crystal reattachment to the crucible wall requires the avoidance of any undercooling of the melt meniscus during the growth run. Significantly, relatively simple process modifications that promote favorable thermal conditions for detached growth may overcome detrimental factors associated with meniscus shape and crucible wetting. Thus, these ideas may be important to advance the practice of detached growth for many materials.

  20. Structures of Neural Correlation and How They Favor Coding

    PubMed Central

    Franke, Felix; Fiscella, Michele; Sevelev, Maksim; Roska, Botond; Hierlemann, Andreas; da Silveira, Rava Azeredo

    2017-01-01

    Summary The neural representation of information suffers from “noise”—the trial-to-trial variability in the response of neurons. The impact of correlated noise upon population coding has been debated, but a direct connection between theory and experiment remains tenuous. Here, we substantiate this connection and propose a refined theoretical picture. Using simultaneous recordings from a population of direction-selective retinal ganglion cells, we demonstrate that coding benefits from noise correlations. The effect is appreciable already in small populations, yet it is a collective phenomenon. Furthermore, the stimulus-dependent structure of correlation is key. We develop simple functional models that capture the stimulus-dependent statistics. We then use them to quantify the performance of population coding, which depends upon interplays of feature sensitivities and noise correlations in the population. Because favorable structures of correlation emerge robustly in circuits with noisy, nonlinear elements, they will arise and benefit coding beyond the confines of retina. PMID:26796692

  1. Does a Favor Request Increase Liking Toward the Requester?

    PubMed

    Niiya, Yu

    2016-01-01

    Although a request for help can impose a burden on the provider and has the potential of harming a relationship, the theory of amae suggests that in fact it could help promote a stronger relationship. In an experiment, both Japanese and American participants who were asked for help from a confederate increased their liking of the confederate relative to the baseline. Sociable impression of the confederate and perceived closeness of the relationship also increased relative to the baseline. There was, however, no such increase when participants helped the confederate without receiving a direct request. This study suggests that despite the potential risks to relationships, asking favors can provide opportunities for requesters to build and promote relationships.

  2. White House Budget Proposal Favorable Overall for Federal Science Agencies

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-02-01

    President Barack Obama's proposed federal budget of 3.8 trillion for fiscal year (FY) 2013, released on 13 February, provides an overall favorable funding picture for federal science agencies in a tight economic environment. However, there are also a number of proposed decreases, including a sharp cut to NASA's Planetary Science account. Overall, the budget proposal includes 140.8 billion for the federal investment in research and development, a 1.4% increase above the FY 2012 enacted level. Funding for federal basic and applied research would be 64 billion, 3.3% above FY 2012 enacted levels. Funding for defense research and development (R&D) would decrease to 75.9 billion, a drop of 1.5%; nondefense R&D would increase 5% to $64.9 billion.

  3. Reticulate evolution is favored in influenza niche switching

    PubMed Central

    Hill, Nichola J.; Zabilansky, Justin; Yuan, Kyle; Runstadler, Jonathan A.

    2016-01-01

    Reticulate evolution is thought to accelerate the process of evolution beyond simple genetic drift and selection, helping to rapidly generate novel hybrids with combinations of adaptive traits. However, the long-standing dogma that reticulate evolutionary processes are likewise advantageous for switching ecological niches, as in microbial pathogen host switch events, has not been explicitly tested. We use data from the influenza genome sequencing project and a phylogenetic heuristic approach to show that reassortment, a reticulate evolutionary mechanism, predominates over mutational drift in transmission between different host species. Moreover, as host evolutionary distance increases, reassortment is increasingly favored. We conclude that the greater the quantitative difference between ecological niches, the greater the importance of reticulate evolutionary processes in overcoming niche barriers. PMID:27114508

  4. Subchondral bone histology and grading in osteoarthritis

    PubMed Central

    Aho, Olli-Matti; Finnilä, Mikko; Thevenot, Jerome; Saarakkala, Simo; Lehenkari, Petri

    2017-01-01

    Objective Osteoarthritis (OA) has often regarded as a disease of articular cartilage only. New evidence has shifted the paradigm towards a system biology approach, where also the surrounding tissue, especially bone is studied more vigorously. However, the histological features of subchondral bone are only poorly characterized in current histological grading scales of OA. The aim of this study is to specifically characterize histological changes occurring in subchondral bone at different stages of OA and propose a simple grading system for them. Design 20 patients undergoing total knee replacement surgery were randomly selected for the study and series of osteochondral samples were harvested from the tibial plateaus for histological analysis. Cartilage degeneration was assessed using the standardized OARSI grading system, while a novel four-stage grading system was developed to illustrate the changes in subchondral bone. Subchondral bone histology was further quantitatively analyzed by measuring the thickness of uncalcified and calcified cartilage as well as subchondral bone plate. Furthermore, internal structure of calcified cartilage-bone interface was characterized utilizing local binary patterns (LBP) based method. Results The histological appearance of subchondral bone changed drastically in correlation with the OARSI grading of cartilage degeneration. As the cartilage layer thickness decreases the subchondral plate thickness and disorientation, as measured with LBP, increases. Calcified cartilage thickness was highest in samples with moderate OA. Conclusion The proposed grading system for subchondral bone has significant relationship with the corresponding OARSI grading for cartilage. Our results suggest that subchondral bone remodeling is a fundamental factor already in early stages of cartilage degeneration. PMID:28319157

  5. Favorable Geochemistry from Springs and Wells in COlorado

    DOE Data Explorer

    Zehner, Richard E.

    2012-02-01

    Citation Information: Originator: Geothermal Development Associates, Reno Nevada Originator: United States Geological Survey (USGS) Originator: Colorado Geological Survey Publication Date: 2012 Title: Favorable Geochemistry Edition: First Publication Information: Publication Place: Reno Nevada Publisher: Geothermal Development Associates, Reno, Nevada Description: This layer contains favorable geochemistry for high-temperature geothermal systems, as interpreted by Richard "Rick" Zehner. The data is compiled from the data obtained from the USGS. The original data set combines 15,622 samples collected in the State of Colorado from several sources including 1) the original Geotherm geochemical database, 2) USGS NWIS (National Water Information System), 3) Colorado Geological Survey geothermal sample data, and 4) original samples collected by R. Zehner at various sites during the 2011 field season. These samples are also available in a separate shapefile FlintWaterSamples.shp. Data from all samples were reportedly collected using standard water sampling protocols (filtering through 0.45 micron filter, etc.) Sample information was standardized to ppm (micrograms/liter) in spreadsheet columns. Commonly-used cation and silica geothermometer temperature estimates are included. Spatial Domain: Extent: Top: 4515595.841032 m Left: 149699.513964 m Right: 757959.309388 m Bottom: 4104156.435530 m Contact Information: Contact Organization: Geothermal Development Associates, Reno, Nevada Contact Person: Richard “Rick” Zehner Address: 3740 Barron Way City: Reno State: NV Postal Code: 89511 Country: USA Contact Telephone: 775-737-7806 Spatial Reference Information: Coordinate System: Universal Transverse Mercator (UTM) WGS’1984 Zone 13N False Easting: 500000.00000000 False Northing: 0.00000000 Central Meridian: -105.00000000 Scale Factor: 0.99960000 Latitude of Origin: 0.00000000 Linear Unit: Meter Datum: World Geodetic System 1984 (WGS ’1984) Prime Meridian: Greenwich

  6. High nevus counts confer a favorable prognosis in melanoma patients.

    PubMed

    Ribero, Simone; Davies, John R; Requena, Celia; Carrera, Cristina; Glass, Daniel; Rull, Ramon; Vidal-Sicart, Sergi; Vilalta, Antonio; Alos, Lucia; Soriano, Virtudes; Quaglino, Pietro; Traves, Victor; Newton-Bishop, Julia A; Nagore, Eduardo; Malvehy, Josep; Puig, Susana; Bataille, Veronique

    2015-10-01

    A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  7. Natal primary molar: clinical and histological aspects.

    PubMed

    Ruschel, Henrique C; Spiguel, Monica H; Piccinini, Daniela D; Ferreira, Simone H; Feldens, Eliane G

    2010-06-01

    The authors report a case of natal primary molar in a healthy 14-day-old child. The diagnosis of the case and the treatment plan are discussed, as well as histological analyses of the natal tooth. The tooth presented an immature appearance, with high mobility and insertion only in soft tissue, and therefore the clinical option adopted was dental extraction. Histological analyses revealed enamel hypoplasia and dentin showing a typical tubular pattern without alterations. The soft tissue had young and richly vascularized pulp with areas of chronic inflammatory infiltration.

  8. Relapse to drug seeking following prolonged abstinence: the role of environmental stimuli

    PubMed Central

    Fuchs, R.A.; Lasseter, H.C.; Ramirez, D.R.; Xie, X.

    2009-01-01

    Successful treatment of drug addiction must involve relapse prevention informed by our understanding of the neurobiological bases of drug relapse. In humans, exposure to drug-associated environmental stimuli can elicit drug craving and relapse. Because exposure to drug-paired stimuli similarly induces drug-seeking behavior in laboratory animals, several animal models of drug relapse have been developed. Here, we review animal models of cue-induced drug relapse and critically evaluate their validity and utility in addressing human relapse behaviors. PMID:20016771

  9. The Histologic Classifications of Lung Adenocarcinomas Are Discriminable by Unique Lineage Backgrounds.

    PubMed

    Hu, Haichuan; Sun, Zhengliang; Li, Yuan; Zhang, Yiliang; Li, Hang; Zhang, Yang; Pan, Yunjian; Shen, Lei; Wang, Rui; Sun, Yihua; Chen, Haiquan

    2016-12-01

    Lung adenocarcinomas are a heterogeneous set of diseases with distinct genetic and histologic characteristics. Besides the discovery of oncogenic mutations and introduction of the histologic classifications (2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society and 2015 WHO), increasing evidence has linked this intertumor heterogeneity to the lung lineage-specific pathways and lineage genes. Therefore, in this study, we assessed the gene expression of identified lung lineage genes to study their role in distinguishing lung adenocarcinoma diversities. A total of 278 surgically resected lung adenocarcinomas were included. Each case was evaluated for genetic mutations and histologic classification. Lineage genes associated with respiratory tract differentiation (NK2 homeobox 1 gene [NKX2-1], GATA protein binding 6 gene [GATA6], foxhead box J1 gene [FOXJ1], and SAM pointed domain containing ETS transcription factor gene [SPDEF]) and stem/basal-like status (inhibitor of DNA binding 2, HLH protein gene [ID2], POU class 5 homeobox 1 gene [POU5F1], SRY-box 2 gene [SOX2], and v-myc avian myelocytomatosis viral oncogene homolog gene [MYC]) were selected. mRNA expression of these genes in each tumor sample was assessed by quantitative real-time polymerase chain reaction and normalized to paired normal lung tissue. Distinct lineage gene expressions were found on the basis of genetic and histologic diversities. Expression of NKX2-1, GATA6, FOXJ1, and POU5F1 exhibited a significant linear relationship across histologic subgroups that was independent of genetic mutation status. Expression levels of NKX2-1 and POU5F1 were also associated with EGFR mutation status, independent of histologic subtypes. Further analysis revealed that the overexpression of SPDEF defined longer relapse-free survivals, especially in stage I disease. For the first time, we showed the unique lineage backgrounds of different histologic subtypes

  10. 3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

    PubMed Central

    Gibson, Eli; Gaed, Mena; Gómez, José A.; Moussa, Madeleine; Pautler, Stephen; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

    2013-01-01

    Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1) How does prostate tissue deform during histology processing? (2) What spatial misalignment of the tissue sections is induced by microtome cutting? (3) How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE) after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]). The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals), while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9° (angle) and 0.9-1.3 mm (depth). Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and should be

  11. Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.

    PubMed

    Messina, C; Valsecchi, M G; Aricò, M; Locatelli, F; Rossetti, F; Rondelli, R; Cesaro, S; Uderzo, C; Conter, V; Pession, A; Sotti, G; Loiacono, G; Santoro, N; Miniero, R; Dini, G; Favre, C; Meloni, G; Testi, A M; Werner, B; Silvestri, D; Arrighini, A; Varotto, S; Pillon, M; Basso, G; Zanesco, L

    1998-01-01

    The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

  12. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma

    PubMed Central

    Xie, Wanling; Jagannath, Sundar; Jakubowiak, Andrzej; Lonial, Sagar; Raje, Noopur S.; Alsina, Melissa; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Mazumder, Amitabha; Vesole, David H.; Kaufman, Jonathan L.; Colson, Kathleen; McKenney, Mary; Lunde, Laura E.; Feather, John; Maglio, Michelle E.; Warren, Diane; Francis, Dixil; Hideshima, Teru; Knight, Robert; Esseltine, Dixie-Lee; Mitsiades, Constantine S.; Weller, Edie; Anderson, Kenneth C.

    2014-01-01

    In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m2 (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomide-bortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with www.clinicaltrials.gov as #NCT00378209. PMID:24429336

  13. Randomized trial comparing mindfulness-based relapse prevention with relapse prevention for women offenders at a residential addiction treatment center.

    PubMed

    Witkiewitz, Katie; Warner, Kaitlin; Sully, Betsy; Barricks, Adria; Stauffer, Connie; Thompson, Brian L; Luoma, Jason B

    2014-04-01

    Reincarceration rates are high among substance-involved criminal offenders. This study (conducted during 2010-2011 in an urban area and funded by a Washington State University-Vancouver mini-grant) used a randomized design to examine the effectiveness of mindfulness-based relapse prevention (MBRP) as compared to relapse prevention (RP), as part of a residential addictions treatment program for women referred by the criminal-justice system (N = 105). At 15-week follow up, regression analyses found women in MBRP, compared to RP, reported significantly fewer drug use days and fewer legal and medical problems. Study limitations and future research directions for studying the efficacy of MBRP are discussed.

  14. Psychiatrist's adherence: a new factor in relapse prevention of schizophrenia. A randomized controlled study on relapse control through telemedicine system.

    PubMed

    Spaniel, F; Novak, T; Bankovska Motlova, L; Capkova, J; Slovakova, A; Trancik, P; Matejka, M; Höschl, C

    2015-12-01

    Exposure to psychotic states has detrimental effects on the long-term outcome of schizophrenia and brain integrity. Therefore, improving relapse prevention is a key component of long-term management of schizophrenia. Previous studies using continuous monitoring of an individual's early signs of relapse and adopting preventative pharmacological interventions, when early signs are detected, showed promising clinical results in terms of relapse risk reduction. This 18-month multi-centre parallel randomized controlled, open label, trial with telemedicine relapse prevention programme ITAREPS failed to show superiority of maintenance plus prodrome-based targeted medication strategy over treatment as usual. The study, marked by low investigator's adherence, confirmed that absence of pharmacological intervention at early stage of prodrome, critically influenced the risk of relapse. This and previous randomized controlled trials with telemedicine programme ITAREPS suggested that substantial improvement in relapse prevention in schizophrenia is likely to be unattainable under current clinical settings. Future preventive strategies in schizophrenia would require rapid pharmacological intervention upon occurrence of subclinical prodromal symptoms that are undetectable under conventional outpatient practice. Studies with ITAREPS suggested that integration of telemedicine relapse prevention systems and visiting nurse service might together represent practical solution capable to address those requirements. The Information Technology Aided Relapse Prevention Programme in Schizophrenia (ITAREPS) presents a telemedicine solution for weekly monitoring and management of schizophrenia. This study aims to evaluate the effectiveness of the programme in reducing the number of hospitalizations during the 18-month multi-centre parallel randomized controlled, open label, trial. Outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n = 74) or control group

  15. Smoking relapse situations among a community-recruited sample of Spanish daily smokers.

    PubMed

    Piñeiro, Bárbara; López-Durán, Ana; Martínez-Vispo, Carmela; Fernández Del Río, Elena; Martínez, Úrsula; Rodríguez-Cano, Rubén; Míguez, M Carmen; Becoña, Elisardo

    2017-12-01

    Relapse is a common factor within the behavior change process. However, there is scarce and limited knowledge of smoking relapse situations in population-based samples. The aim of this study was to identify smoking relapse situations among a sample of Spanish relapsers from the general population. A sample of 775 relapsers was recruited among the general population using a snowball method. Participants completed a survey including sociodemographic, smoking-related and psychopathology variables. Smoking relapse situations were identified through specific questions assessing different aspects related to the last relapse episode. The majority of smoking relapse situations were attributed to positive affect (36.6%) and negative affect (34.3%), followed by lack of control (10.1%), smoking habit (6.7%), craving or nicotine withdrawal (6.3%), and social pressure (5.9%). Being unemployed and having a mental disorder in the past increased the likelihood of relapse in situations of negative affect. Being single and having quit smoking to save money were associated with an increased likelihood of relapse in situations of positive affect. Affect plays a significant role in smoking relapse among a community sample of unassisted Spanish smokers. Relapse may be much more of an affective and situational process than a habit, physiological or social pressure. Findings from this study may help develop tailored community smoking relapse prevention strategies or programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Histology. Notes for Students of Animal Husbandry.

    ERIC Educational Resources Information Center

    Price, Charles J.; Reed, Josephine E.

    This document approaches the subject of Histology by way of simple independent unicellular organisms through the lower levels of cell organization and specialization to a detailed study of the highly complex tissues of vertebrate animals. Emphasis is placed on structure, but function is explained in some detail. The relationships between tissues…

  17. Abdominal and pelvic tumors with musculoskeletal histology.

    PubMed

    Dyrstad, Sara W; Fowler, Amy M; Jokerst, Clint E; Baker, Jonathan C; Hillen, Travis J; Menias, Christine

    2014-01-01

    This article is a case-based review of the broad spectrum of tumors with musculoskeletal histology that can arise in the abdomen or pelvis and involve the soft tissues, muscle, and bone. In this article, pathology-proven cases are presented with a focus on radiographic, computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography findings. The imaging features that differentiate tumors with musculoskeletal histology from more common abdominal tumors are discussed. Representative cases include malignant fibrous histiocytoma, chondrosarcoma, Ewing sarcoma, hemangiopericytoma, desmoplastic fibroma, neurofibrosarcoma, osteosarcoma, intimal sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, teratoma, and chordoma. A variety of tumors with musculoskeletal histology can arise in the abdomen and pelvis. In some cases, unique imaging characteristics allow a confident diagnosis, whereas other cases have a more nonspecific appearance. Recognition of imaging features that suggest a musculoskeletal tumor including direct extension from a bone or neural foramen, the presence of cartilaginous or osseous matrix, or macroscopic fat would allow the radiologist to suggest the proper diagnosis. Recognizing imaging characteristics of tumors with musculoskeletal histology is important clinically as management and prognosis differ from that of more common abdominal tumors. © 2013 Published by Elsevier Inc.

  18. The histological diagnosis of toxoplasmic lymphadenitis

    PubMed Central

    Stansfeld, A. G.

    1961-01-01

    The commonest presenting sign of acquired toxoplasmosis in man is enlargement of superficial lymph nodes. The persistence of the nodes may lead to a suspicion of malignant lymphoma and the diagnosis then hinges on the lymph node biopsy. Three cases of toxoplasmic lymphadenitis are described in each of which the diagnosis was unsuspected clinically. The chance discovery of a toxoplasma cyst in the lymph node section of Case 1 led to the correct diagnosis, after an initial diagnosis of Hodgkin's disease had been made. In the other two, strikingly similar histological changes in the lymph node biopsies suggested the diagnosis, which was confirmed serologically in each case. The histological changes are described and the clinical and pathological aspects of toxoplasmic lymphadenitis are briefly reviewed, with special reference to the differentiation from malignant lymphomatous conditions and to the specificity of the histological picture. It is concluded that the histology is, in many instances, sufficiently distinctive for a tentative diagnosis of toxoplasmic lymphadenitis to be made on the lymph node biopsy. The diagnosis should always be confirmed by isolation of the parasite or by serological tests. It is exceedingly rare for toxoplasma cysts to be found in lymph nodes and only one previous observation of this kind has been reported. Images PMID:16810977

  19. Developing the eHistology Atlas.

    PubMed

    Richardson, Lorna; Graham, Liz; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Baldock, Richard A

    2015-01-01

    The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook 'The Atlas of Mouse Development' by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.php.

  20. Histology. Notes for Students of Animal Husbandry.

    ERIC Educational Resources Information Center

    Price, Charles J.; Reed, Josephine E.

    This document approaches the subject of Histology by way of simple independent unicellular organisms through the lower levels of cell organization and specialization to a detailed study of the highly complex tissues of vertebrate animals. Emphasis is placed on structure, but function is explained in some detail. The relationships between tissues…

  1. Developing the eHistology Atlas

    PubMed Central

    Richardson, Lorna; Graham, Liz; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Baldock, Richard A.

    2015-01-01

    The eMouseAtlas project has undertaken to generate a new resource providing access to high-resolution colour images of the slides used in the renowned textbook ‘The Atlas of Mouse Development’ by Matthew H. Kaufman. The original histology slides were digitized, and the associated anatomy annotations captured for display in the new resource. These annotations were assigned to objects in the standard reference anatomy ontology, allowing the eHistology resource to be linked to other data resources including the Edinburgh Mouse Atlas Gene-Expression database (EMAGE) an the Mouse Genome Informatics (MGI) gene-expression database (GXD). The provision of the eHistology Atlas resource was assisted greatly by the expertise of the eMouseAtlas project in delivering large image datasets within a web environment, using IIP3D technology. This technology also permits future extensions to the resource through the addition of further layers of data and annotations to the resource. Database URL: www.emouseatlas.org/emap/eHistology/index.php PMID:26500249

  2. Histological subtypes of periocular basal cell carcinoma.

    PubMed

    Wu, Albert; Sun, Michelle T; Huilgol, Shyamala C; Madge, Simon; Selva, Dinesh

    2014-01-01

    To determine the proportion of different subtypes of periocular BCC in South Australia. Retrospective review. One thousand seven hundred thirteen consecutive periocular basal cell carcinoma (BCC) excision specimens. Histological analysis of consecutive periocular BCC specimens. Date of resection, patient age at resection, gender, tumour location, histological subtype and perineural invasion. From 2006 to 2012, a total of 1713 consecutive periocular BCC excision specimens were analysed. The mean age at resection was 68.8 years (median: 71, range: 21-101). Most specimens (56.4%) were removed from male patients. 52.7% involved the lower eyelid, 29.0% the medial canthus, 10.9% the lateral canthus and 7.5% the upper eyelid. The main histological subtypes identified were nodular (65.7%), infiltrative (17.5%), superficial (12.6%) and micronodular (4.2%). Of the specimens, 25.6% had more than one subtype. The most common subtype combinations were nodular with infiltrative (49.7%), and nodular with superficial (26.0%). The majority of periocular BCC were located on the lower lid and classified histologically as nodular. Infiltrative BCC occurred more frequently than the superficial subtype. As the proportion of mixed BCC containing aggressive subtypes is high, surgical excision with margin control should be considered for periocular BCC. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

  3. Segmentation of histological structures for fractal analysis

    NASA Astrophysics Data System (ADS)

    Dixon, Vanessa; Kouznetsov, Alexei; Tambasco, Mauro

    2009-02-01

    Pathologists examine histology sections to make diagnostic and prognostic assessments regarding cancer based on deviations in cellular and/or glandular structures. However, these assessments are subjective and exhibit some degree of observer variability. Recent studies have shown that fractal dimension (a quantitative measure of structural complexity) has proven useful for characterizing structural deviations and exhibits great potential for automated cancer diagnosis and prognosis. Computing fractal dimension relies on accurate image segmentation to capture the architectural complexity of the histology specimen. For this purpose, previous studies have used techniques such as intensity histogram analysis and edge detection algorithms. However, care must be taken when segmenting pathologically relevant structures since improper edge detection can result in an inaccurate estimation of fractal dimension. In this study, we established a reliable method for segmenting edges from grayscale images. We used a Koch snowflake, an object of known fractal dimension, to investigate the accuracy of various edge detection algorithms and selected the most appropriate algorithm to extract the outline structures. Next, we created validation objects ranging in fractal dimension from 1.3 to 1.9 imitating the size, structural complexity, and spatial pixel intensity distribution of stained histology section images. We applied increasing intensity thresholds to the validation objects to extract the outline structures and observe the effects on the corresponding segmentation and fractal dimension. The intensity threshold yielding the maximum fractal dimension provided the most accurate fractal dimension and segmentation, indicating that this quantitative method could be used in an automated classification system for histology specimens.

  4. Reptilian spermatogenesis: A histological and ultrastructural perspective.

    PubMed

    Gribbins, Kevin M

    2011-07-01

    Until recently, the histology and ultrastructural events of spermatogenesis in reptiles were relatively unknown. Most of the available morphological information focuses on specific stages of spermatogenesis, spermiogenesis, and/or of the mature spermatozoa. No study to date has provided complete ultrastructural information on the early events of spermatogenesis, proliferation and meiosis in class Reptilia. Furthermore, no comprehensive data set exists that describes the ultrastructure of the entire ontogenic progression of germ cells through the phases of reptilian spermatogenesis (mitosis, meiosis and spermiogenesis). The purpose of this review is to provide an ultrastructural and histological atlas of spermatogenesis in reptiles. The morphological details provided here are the first of their kind and can hopefully provide histological information on spermatogenesis that can be compared to that already known for anamniotes (fish and amphibians), birds and mammals. The data supplied in this review will provide a basic model that can be utilized for the study of sperm development in other reptiles. The use of such an atlas will hopefully stimulate more interest in collecting histological and ultrastructural data sets on spermatogenesis that may play important roles in future nontraditional phylogenetic analyses and histopathological studies in reptiles.

  5. Lord Byron's death: a case of late malarial relapse?

    PubMed

    Tsiamis, Costas; Piperaki, Evangelia Theophano; Kalantzis, George; Poulakou Rebelakou, Effie; Tompros, Nikolaos; Thalassinou, Eleni; Spilipoulou, Chara; Tsakris, Athanassios

    2015-09-01

    The study examines the pathological circumstances related to Byron's death, the primary issue being malaria. Lord Byron died during the Greek War of Independence against the Ottoman Empire, in Messolonghi on 19 April 1824. Byron's medical profile consists of recurrent onsets of fever, which gave rise to the issue of malaria relapses. According to Byron's letters he reported crises of fever in Greece (1810), Malta (1811), Italy (1817-1819) and England. Evidence from Byron's autopsy, specifically the absence of hepatosplenomegaly, does not support a hypothetical diagnosis of malaria. Nonetheless, the relapsing fevers cannot be ignored and the same applies to the possibility of malaria relapse or re-infection in line with the endemic nature of the Messolonghi area. Our research on the chronologies of Byron's reported fevers found that new attacks occurred at intervals of 540 days on average. Moreover, the most outstanding feature of Plasmodium vivax and Plasmodium ovale is their ability to form dormant forms of hypnozoites in the liver which, when reactivated (110-777 days), cause true relapses of clinical disease. Of course, an ex post facto diagnosis is under debate, because the diagnosis is not clinical but microscopic. Byron's example raises alarm over a current medical problem, i.e. the diagnosis of unexplained fevers, and the need for a detailed travel or immigration history, which will include malaria in the differential diagnosis.

  6. Social Resource Characteristics and Adolescent Substance Abuse Relapse.

    ERIC Educational Resources Information Center

    Vik, Peter W.; And Others

    1992-01-01

    Examined social resource network characteristics of adolescent substance abusers (n=19). Perceived similarity to one's social network emerged as important moderator of whether social network provided support to remain abstinent or elevated risk for relapse. Increased perceived support predicted continued posttreatment abstinence when recovering…

  7. Hereditary neuralgic amyotrophy associated with a relapsing multifocal sensory neuropathy.

    PubMed Central

    Thomas, P K; Ormerod, I E

    1993-01-01

    A family with neuralgic amyotrophy (idiopathic brachial plexus neuropathy) associated with a multifocal sensory neuropathy is described. Four members over two generations were affected by neuralgic amyotrophy, inherited as an apparent autosomal dominant trait; two also had a multifocal relapsing sensory neuropathy with the clinical features of Wartenberg's migrant neuropathy. PMID:8429311

  8. Preventing Relapse to Cigarette Smoking by Behavioral Skill Training.

    ERIC Educational Resources Information Center

    Hall, Sharon M.; And Others

    Although smoking cessation techniques have been effective, few programs have long term results. To investigate the effectiveness of a tobacco dependence relapse prevention program, 123 adult smokers (51 male, 72 female) voluntarily participated in one of four small group treatment conditions (6 or 30 second aversive smoking plus skill training, or…

  9. [Risk factors for persistent and relapsed childhood-onset asthma].

    PubMed

    Tsukioka, Kazuharu; Toyabe, Shin-ichi; Akazawa, Kouhei

    2010-06-01

    The aim of this study was to identify factors responsible for childhood-onset persistent asthma and childhood-onset asthma relapsing in adulthood. We compared a number of potential risk factors for asthma among 608 patients with childhood-onset persistent asthma (onset at 15 years of age or younger) and 286 patients with childhood-onset asthma (onset at 20 years or younger) that had relapsed after a period of remission longer than 2 years. Multiple linear regression analysis revealed that the factors associated with childhood-onset persistent asthma were a past or present history of allergic rhinitis (p=0.001) and high serum total IgE concentration (> or =300 IU/ml; p=0.007). The factors associated with relapse of childhood-onset asthma were female sex (p=0.001), younger onset age (p=0.036), and smoking (current or former; p<0.001). Our findings indicate that a past or present history of allergic rhinitis and high serum IgE level are significant risk factors for childhood-onset persistent asthma, and that female sex and a history of smoking are risk factors for relapse of childhood-onset asthma. Fortunately, exposure to tobacco smoke is a controllable risk factor.

  10. Alcohol relapses associated with September 11, 2001: a case report.

    PubMed

    Zywiak, William H; Stout, Robert L; Trefry, Winston B; LaGrutta, Joy E; Lawson, Constance C; Khan, Nazia; Swift, Robert M; Schneider, Robert J

    2003-06-01

    The timing of the terrible events of September 11, 2001 (9-11), and an ongoing randomized clinical trial of case monitoring have allowed a prospective examination of the effects of trauma upon the relapse rates of a group of clients following alcohol detoxification. The clients studied in this report were enrolled in case monitoring prior to 9-11. Case monitoring consists of telephone contacts on a tapering schedule designed to help clients avoid relapses, reduce the severity of relapses that do occur, and get clients back into treatment, at less intense levels, than would occur without case monitoring. For those clients completing a telephone contact before and a telephone contact after 9-11, none of the clients drank between detox discharge and 9-11, while 42% drank by the first telephone contact after 9-11. Data from another study were analyzed and results counter the rival hypothesis that the case monitoring study results reflect an annual seasonal effect. Results suggest that terrorist events may lead to a greater likelihood of relapse for those in alcohol recovery. These effects may be ameliorated by public education and outreach.

  11. Advances in the Treatment of Relapsed or Refractory Hodgkin's Lymphoma

    PubMed Central

    2012-01-01

    Hodgkin's lymphoma (HL) is diagnosed in 20,000 men and women annually in North America and Europe. Despite treatment advancements for HL resulting in an overall survival rate of 80%, patients with advanced stage disease continue to have suboptimal outcomes, with relapse rates of 30%–40%. An additional 10%–15% of patients present with primary refractory disease. For patients who relapse after initial treatment, salvage chemotherapy followed by autologous stem cell transplant in those with chemotherapy-sensitive disease is the standard of care. Patients who relapse after second-line therapy have a median survival time in the range of 6–36 months, and the optimal management of these patients remains unclear. Unfortunately, there have been no new agents approved for relapsed HL treatment since the 1970s. Consequently, clinical decision making in this population is difficult. Recently however, several agents have emerged that have shown clinical promise in this poor-risk population. This review discusses the management of these patients and also discusses several newer agents showing clinical promise in the treatment of HL. PMID:22387318

  12. Schizophrenia relapse, patient considerations, and potential role of lurasidone

    PubMed Central

    Citrome, Leslie

    2016-01-01

    When treating persons with schizophrenia, delaying time to relapse is a main goal. Antipsychotic medication has been the primary treatment approach, and there are a variety of different choices available. Lurasidone is a second-generation (atypical) antipsychotic agent that is approved for the treatment of schizophrenia and bipolar depression. Three long-term studies of lurasidone have examined time to relapse in persons with schizophrenia, including a classic placebo-controlled randomized withdrawal study and two 12-month active comparator studies (vs risperidone and vs quetiapine extended-release). Lurasidone 40–80 mg/d evidenced superiority over placebo (number needed to treat [NNT] vs placebo for relapse, 9). Lurasidone 40–160 mg/d was noninferior to quetiapine extended-release 200–800 mg/d on the outcome of relapse, and was superior on the outcome of avoidance of hospitalization (NNT 8) and the outcome of remission (NNT 7). Lurasidone demonstrated a lower risk for long-term weight gain than the active comparators. Demonstrated differences in tolerability profiles among the different choices of antipsychotics make it possible to attempt to match up an individual patient to the best choice for such patient based on past history of tolerability, comorbidities, and personal preferences, potentially improving adherence. PMID:27563237

  13. A Qualitative Exploration of Drug Abuse Relapse Following Treatment

    ERIC Educational Resources Information Center

    Islam, Manirul; Hashizume, Masahiro; Yamamoto, Taro; Alam, Faruq; Rabbani, Golam

    2012-01-01

    Drug use is an alarming issue in Bangladesh. Most drug users return to drugs after treatment, in what becomes a vicious cycle of treatment and relapse. This study explored why they return and what pathways they follow. We carried out 5 key informant interviews, 10 in-depth interviews, 2 focus group discussions, 3 case studies, 8 observations, and…

  14. Relapsing fever group Borrelia in Southern California rodents.

    PubMed

    Nieto, Nathan C; Teglas, Mike B

    2014-09-01

    Wild rodent reservoir host species were surveyed prospectively for infection with Borrelia hermsii, the causative agent of tick-borne relapsing fever in the western United States. Trapping occurred during the summer of 2009-2012 at field sites surrounding Big Bear Lake, CA, a region where human infection has been reported for many years. Using quantitative polymerase chain reaction (qPCR), we tested 207 rodents from 11 species and found chipmunks (Tamias spp.) and a woodrat (Neotoma macrotis) infected. Chipmunks represented the majority of captures at these sites. Sixteen of the 207 (7.7%; CI = 4.6-12.4) animals were qPCR-positive for Borrelia spp. associated with relapsing fever, and of those, we obtained bacterial DNA sequences from eight. The phylogram made from these sequences depict a clear association with B. hermsii genomic group I. In addition, we identified an infection with Borrelia coriaceae in a Tamias merriami, a potentially nonpathogenic member of the tick-borne relapsing fever group. Our findings support the hypothesis that chipmunk species play an important role in the maintenance of Borrelia species that cause tick-borne relapsing fever in the western United States, and therefore the risk of infection to people.

  15. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

    PubMed Central

    Madan, V; Shyamsunder, P; Han, L; Mayakonda, A; Nagata, Y; Sundaresan, J; Kanojia, D; Yoshida, K; Ganesan, S; Hattori, N; Fulton, N; Tan, K-T; Alpermann, T; Kuo, M-C; Rostami, S; Matthews, J; Sanada, M; Liu, L-Z; Shiraishi, Y; Miyano, S; Chendamarai, E; Hou, H-A; Malnassy, G; Ma, T; Garg, M; Ding, L-W; Sun, Q-Y; Chien, W; Ikezoe, T; Lill, M; Biondi, A; Larson, R A; Powell, B L; Lübbert, M; Chng, W J; Tien, H-F; Heuser, M; Ganser, A; Koren-Michowitz, M; Kornblau, S M; Kantarjian, H M; Nowak, D; Hofmann, W-K; Yang, H; Stock, W; Ghavamzadeh, A; Alimoghaddam, K; Haferlach, T; Ogawa, S; Shih, L-Y; Mathews, V; Koeffler, H P

    2016-01-01

    Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential. PMID:27063598

  16. An Ecological Momentary Assessment of Relapse Crises in Dieting

    ERIC Educational Resources Information Center

    Carels, Robert A.; Douglass, Olivia M.; Cacciapaglia, Holly M.; O'Brien, William H.

    2004-01-01

    Much of the research on relapse crises in dieting has focused on isolated lapse events and relied heavily on retrospective self-report data. The present study sought to overcome these limitations by using ecological momentary assessment (EMA) techniques to examine situations of dietary temptation and lapse with a sample of obese, formerly…

  17. A Qualitative Exploration of Drug Abuse Relapse Following Treatment

    ERIC Educational Resources Information Center

    Islam, Manirul; Hashizume, Masahiro; Yamamoto, Taro; Alam, Faruq; Rabbani, Golam

    2012-01-01

    Drug use is an alarming issue in Bangladesh. Most drug users return to drugs after treatment, in what becomes a vicious cycle of treatment and relapse. This study explored why they return and what pathways they follow. We carried out 5 key informant interviews, 10 in-depth interviews, 2 focus group discussions, 3 case studies, 8 observations, and…

  18. Couples Relapse Prevention Sessions as a Maintenance Strategy for Alcoholics.

    ERIC Educational Resources Information Center

    Cutter, Henry S. G.; And Others

    This study evaluated whether alcoholics who receive relapse prevention (RP) sessions in the year after a short-term behavioral marital therapy (BMT) do better at long-term follow-up than do those not receiving the additional RP. Sixty couples with an alcoholic husband, after participating in 10 weekly BMT couples group sessions, were assigned…

  19. Understanding Recovery Barriers: Youth Perceptions about Substance Use Relapse

    ERIC Educational Resources Information Center

    Gonzales, Rachel; Anglin, M. Douglas; Beattie, Rebecca; Ong, Chris Angelo; Glik, Deborah C.

    2012-01-01

    Objective: To qualitatively explore how treatment-involved youth retrospectively contextualize relapse from substance use. Methods: Fourteen focus groups were conducted with 118 youth (78.3% male; 66.1% Latino) enrolled in participating substance abuse treatment programs (4 young adult and 10 adolescent) throughout Los Angeles County. Transcripts…

  20. Non-Hodgkin lymphoma with relapses in the lacrimal glands

    PubMed Central

    Couceiro, Rita; Proença, Helena; Pinto, Filomena; Fonseca, Ana; Monteiro-Grillo, Manuel

    2015-01-01

    Objective: To report an unusual case of systemic non-Hodgkin lymphoma (NHL) with repeated relapse in the lacrimal glands, in spite of complete remission for several years after treatment. Methods: A 78-year-old male with small lymphocytic B cell NHL, stage IV disease (lung invasion), was submitted to surgery and chemotherapy in 2001, with complete remission of the disease. In 2003 he developed a nodular lesion in the right lacrimal fossa. Pathology results revealed a local relapse of NHL. Radiation and chemotherapy were initiated and complete remission was again achieved. In 2012 the patient developed a new nodular lesion located in the left lacrimal fossa, resulting in diplopia, ptosis and proptosis of the left eye. Orbital computerized tomography (CT), ocular ultrasound and incisional biopsy were performed. Results: Orbital CT revealed a lesion infiltrating the left lacrimal gland and encircling the globe. Biopsy results confirmed a local relapse of B cell NHL. The patient was submitted to local radiation therapy with progressive resolution of ptosis, proptosis and diplopia. Response to treatment was monitored with ocular ultrasound. Conclusions: Patients with NHL diagnosis should be immediately investigated if ophthalmic or orbital symptoms develop. NHL extension to the orbit and adnexa is infrequent (5% of NHL cases) but may occur at any stage of the disease, including as a relapse site. In such cases, radiation and chemotherapy achieve good results, inducing long periods of remission. PMID:27625948

  1. Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma.

    PubMed

    Moskowitz, Alison J; Schöder, Heiko; Gavane, Somali; Thoren, Katie L; Fleisher, Martin; Yahalom, Joachim; McCall, Susan J; Cadzin, Briana R; Fox, Stephanie Y; Gerecitano, John; Grewal, Ravinder; Hamlin, Paul A; Horwitz, Steven M; Kumar, Anita; Matasar, Matthew; Ni, Andy; Noy, Ariela; Palomba, M Lia; Perales, Miguel-Angel; Portlock, Carol S; Sauter, Craig; Straus, David; Younes, Anas; Zelenetz, Andrew D; Moskowitz, Craig H

    2017-09-05

    Identification of prognostic factors for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase II study of PET-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, etoposide (augICE) we assessed clinical factors, quantitative PET assessments, and cytokines/chemokine values. Transplant-eligible patients with rel/ref HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative (Deauville ≤ 2) patients proceeded to autologous stem cell transplant (ASCT) while PET-positive patients received augICE before ASCT. Serum cytokine and chemokine levels were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis were measured at baseline, after BV and after augICE. 65 patients enrolled (45 cohort 1, 20 cohort 2); 49 (75%) achieved CR and 64 proceeded to ASCT. 3-year overall survival and EFS were 95% and 82%. Factors predictive for EFS by multivariate analysis were baseline MTV (bMTV) (p<0.001) and refractory disease (p=0.003). Low bMTV (<109.5cm(3)) and relapsed disease identified a favorable group (3-yr EFS 100%). For transplanted patients, bMTV and pre-ASCT PET were independently prognostic; 3-year EFS for pre-ASCT PET-positive patients with low bMTV was 86%. In this phase II study of PET-adapted therapy with BV and augICE for rel/ref HL, bMTV and refractory disease were independent prognostic factors for EFS. Furthermore, bMTV improved the predictive power of pre-ASCT PET. Future studies should optimize efficacy and tolerability of salvage therapy by stratifying patients according to risk factors such as bMTV. Copyright © 2017 American Society of Hematology.

  2. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images

    PubMed Central

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K.; Schad, Lothar R.; Zöllner, Frank Gerrit

    2015-01-01

    Background Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. Methods and Results In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin—3,3’-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. Validation To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Context Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics. PMID:26717571

  3. New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images.

    PubMed

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K; Schad, Lothar R; Zöllner, Frank Gerrit

    2015-01-01

    Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin-3,3'-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics.

  4. Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome

    PubMed Central

    Ostrovnaya, Irina; Rubnitz, Kaitlyn R.; Ali, Siraj M.; Miller, Vincent A.; Mossé, Yael P.; Maris, John M.

    2016-01-01

    Neuroblastoma is characterized by a relative paucity of recurrent somatic mutations at diagnosis. However, recent studies have shown that the mutational burden increases at relapse, likely as a result of clonal evolution of mutation-carrying cells during primary treatment. To inform the development of personalized therapies, we sought to further define the frequency of potentially actionable mutations in neuroblastoma, both at diagnosis and after chemotherapy. We performed a retrospective study to determine mutation frequency, the only inclusion criterion being availability of cancer gene panel sequencing data from Foundation Medicine. We analyzed 151 neuroblastoma tumor samples: 44 obtained at diagnosis, 42 at second look surgery or biopsy for stable disease after chemotherapy, and 59 at relapse (6 were obtained at unknown time points). Nine patients had multiple tumor biopsies. ALK was the most commonly mutated gene in this cohort, and we observed a higher frequency of suspected oncogenic ALK mutations in relapsed disease than at diagnosis. Patients with relapsed disease had, on average, a greater number of mutations reported to be recurrent in cancer, and a greater number of mutations in genes that are potentially targetable with available therapeutics. We also observed an enrichment of reported recurrent RAS/MAPK pathway mutations in tumors obtained after chemotherapy. Our data support recent evidence suggesting that neuroblastomas undergo substantial mutational evolution during therapy, and that relapsed disease is more likely to be driven by a targetable oncogenic pathway, highlighting that it is critical to base treatment decisions on the molecular profile of the tumor at the time of treatment. However, it will be necessary to conduct prospective clinical trials that match sequencing results to targeted therapeutic intervention to determine if cancer genomic profiling improves patient outcomes. PMID:27997549

  5. Bone health in patients with multiple sclerosis relapses.

    PubMed

    Murphy, Olwen; Zandi, Michael S; Lindenberg, Nitzan; Murphy, Elaine; Chataway, Jeremy

    2016-03-01

    To evaluate the bone health and vitamin D levels of a cohort of patients with relapses of multiple sclerosis (MS) and to propose an algorithm for the management of bone health in this patient group. We prospectively studied 56 consecutive patients from our acute relapse clinic. 3 patients were excluded from analysis as they were not deemed to have experienced an acute MS relapse. Bone health was assessed with vitamin D levels and Dual Energy X-ray Absorptiometry (DEXA) scanning (10 patients failed to attend for DEXA). Statistical analyses were used to compare groups and identify predictive variables. A review of the literature led to a proposed management protocol. Pre-relapse the baseline EDSS was ≤6.5 in all subjects, and <4.0 in the majority (66%). Most received corticosteroids. 51% had low bone mineral density (BMD) as defined by a T-score less than -1.0 on DEXA scanning. Three were osteoporotic (T-score less than -2.5). Thirty one of fifty (62%) subjects were Vitamin D deficient (25(OH)D less than 50nmol/L). A range of variables, including previous corticosteroid usage, were not significantly predictive of reduced BMD. There was a high frequency of both low BMD and Vitamin D deficiency in this cohort of relatively young and largely ambulatory patients experiencing MS relapses. Current tools, such as the WHO FRAX algorithm, are inadequate in assessing bone status and fracture risk in this patient group, predominantly as they are focused on older age groups. We propose a simple clinical management algorithm. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Primaquine treatment and relapse in Plasmodium vivax malaria

    PubMed Central

    2016-01-01

    The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once ‘neglected’ species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients’ G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe. PMID:27077309

  7. Primaquine treatment and relapse in Plasmodium vivax malaria.

    PubMed

    Rishikesh, Kumar; Saravu, Kavitha

    2016-01-01

    The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once 'neglected' species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients' G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe.

  8. Predicting relapse following medical therapy for Graves' disease

    SciTech Connect

    McKillop, J.H.; Wilson, R.; Pearson, D.W.; Cuthbert, G.F.; Jenkins, C.; Caine, S.; Thomson, J.A.

    1984-01-01

    In 40 patients with Graves' disease (35 female, 5 male; mean age at presentation = 38 yrs) the authors examined the ability of thyroidal /sup 99m/Tc uptake and serum thyroid stimulating immunoglobins (TSI) to identify patients who would relapse after a course of medical therapy. Serum TSI and 20 minute thyroidal /sup 99m/Tc uptake were estimated every 3 months during a 12 month course of carbimazole and tri iodothyronine. TSI levels were estimated by inhibition of receptor binding and expressed as an index (normal value <25). 17 patients (Group 1) remained biochemically euthyroid for at least 1 year after cessation of therapy. 23 (Group II) developed recurrent thyrotoxicosis. Thyroid hormone level did not differ between Groups I and II at presentation. /sup 99m/Tc uptake did not differ significantly in the two groups at presentation and overlap of values persisted throughout therapy. 3 patients had undetectable TSI levels at presentation and throughout follow-up. In the remaining 37, TSI levels at presentation were significantly higher in Group II and all 7 patients with initial values >80 relapsed. After 12 months therapy a TSI level of >25 was present in 1 Group I patient and 16 Group II patients who had detectable TSI at presentation. /sup 99m/Tc uptake was a poor predictor of relapse of thyrotoxicosis. A very high TSI level at presentation (>80) was associated with relapse. An abnormal TSI on completion of 12 months medical therapy had a sensitivity of 86% and a specificity of 94% for prediction of relapse of thyrotoxicosis in the subsequent year.

  9. African relapsing Fever borreliae genomospecies revealed by comparative genomics.

    PubMed

    Elbir, Haitham; Abi-Rached, Laurent; Pontarotti, Pierre; Yoosuf, Niyaz; Drancourt, Michel

    2014-01-01

    Relapsing fever borreliae are vector-borne bacteria responsible for febrile infection in humans in North America, Africa, Asia, and in the Iberian Peninsula in Europe. Relapsing fever borreliae are phylogenetically closely related, yet they differ in pathogenicity and vectors. Their long-term taxonomy, based on geography and vector grouping, needs to be re-apprised in a genomic context. We therefore embarked into genomic analyses of relapsing fever borreliae, focusing on species found in Africa. Genome-wide phylogenetic analyses group Old World Borrelia crocidurae, Borrelia hispanica, B. duttonii, and B. recurrentis in one clade, and New World Borrelia turicatae and Borrelia hermsii in a second clade. Accordingly, average nucleotide identity is 99% among B. duttonii, B. recurrentis, and B. crocidurae and 96% between latter borreliae and B. hispanica while the similarity is 86% between Old World and New World borreliae. Comparative genomics indicates that the Old World relapsing fever B. duttonii, B. recurrentis, B. crocidurae, and B. hispanica have a 2,514-gene pan genome and a 933-gene core genome that includes 788 chromosomal and 145 plasmidic genes. Analyzing the role that natural selection has played in the evolution of Old World borreliae species revealed that 55 loci were under positive diversifying selection, including loci coding for membrane, flagellar, and chemotaxis proteins, three categories associated with adaption to specific niches. Genomic analyses led to a reappraisal of the taxonomy of relapsing fever borreliae in Africa. These analyses suggest that B. crocidurae, B. duttonii, and B. recurrentis are ecotypes of a unique genomospecies, while B. hispanica is a distinct species.

  10. African Relapsing Fever Borreliae Genomospecies Revealed by Comparative Genomics

    PubMed Central

    Elbir, Haitham; Abi-Rached, Laurent; Pontarotti, Pierre; Yoosuf, Niyaz; Drancourt, Michel

    2014-01-01

    Background: Relapsing fever borreliae are vector-borne bacteria responsible for febrile infection in humans in North America, Africa, Asia, and in the Iberian Peninsula in Europe. Relapsing fever borreliae are phylogenetically closely related, yet they differ in pathogenicity and vectors. Their long-term taxonomy, based on geography and vector grouping, needs to be re-apprised in a genomic context. We therefore embarked into genomic analyses of relapsing fever borreliae, focusing on species found in Africa. Results: Genome-wide phylogenetic analyses group Old World Borrelia crocidurae, Borrelia hispanica, B. duttonii, and B. recurrentis in one clade, and New World Borrelia turicatae and Borrelia hermsii in a second clade. Accordingly, average nucleotide identity is 99% among B. duttonii, B. recurrentis, and B. crocidurae and 96% between latter borreliae and B. hispanica while the similarity is 86% between Old World and New World borreliae. Comparative genomics indicates that the Old World relapsing fever B. duttonii, B. recurrentis, B. crocidurae, and B. hispanica have a 2,514-gene pan genome and a 933-gene core genome that includes 788 chromosomal and 145 plasmidic genes. Analyzing the role that natural selection has played in the evolution of Old World borreliae species revealed that 55 loci were under positive diversifying selection, including loci coding for membrane, flagellar, and chemotaxis proteins, three categories associated with adaption to specific niches. Conclusion: Genomic analyses led to a reappraisal of the taxonomy of relapsing fever borreliae in Africa. These analyses suggest that B. crocidurae, B. duttonii, and B. recurrentis are ecotypes of a unique genomospecies, while B. hispanica is a distinct species. PMID:25229054

  11. Competition favors elk over beaver in a riparian willow ecosystem

    USGS Publications Warehouse

    Baker, B.W.; Peinetti, H.R.; Coughenour, M.C.; Johnson, T.L.

    2012-01-01

    Beaver (Castor spp.) conservation requires an understanding of their complex interactions with competing herbivores. Simulation modeling offers a controlled environment to examine long-term dynamics in ecosystems driven by uncontrollable variables. We used a new version of the SAVANNA ecosystem model to investigate beaver (C. Canadensis) and elk (Cervus elapses) competition for willow (Salix spp.). We initialized the model with field data from Rocky Mountain National Park, Colorado, USA, to simulate a 4-ha riparian ecosystem containing beaver, elk, and willow. We found beaver persisted indefinitely when elk density was or = 30 elk km_2. The loss of tall willow preceded rapid beaver declines, thus willow condition may predict beaver population trajectory in natural environments. Beaver were able to persist with slightly higher elk densities if beaver alternated their use of foraging sites in a rest-rotation pattern rather than maintained continuous use. Thus, we found asymmetrical competition for willow strongly favored elk over beaver in a simulated montane ecosystem. Finally, we discuss application of the SAVANNA model and mechanisms of competition relative to beaver persistence as metapopulations, ecological resistance and alternative state models, and ecosystem regulation.

  12. Favorable selection, risk adjustment, and the Medicare Advantage program.

    PubMed

    Morrisey, Michael A; Kilgore, Meredith L; Becker, David J; Smith, Wilson; Delzell, Elizabeth

    2013-06-01

    To examine the effects of changes in payment and risk adjustment on (1) the annual enrollment and switching behavior of Medicare Advantage (MA) beneficiaries, and (2) the relative costliness of MA enrollees and disenrollees. From 1999 through 2008 national Medicare claims data from the 5 percent longitudinal sample of Parts A and B expenditures. Retrospective, fixed effects regression analysis of July enrollment and year-long switching into and out of MA. Similar regression analysis of the costliness of those switching into (out of) MA in the 6 months prior to enrollment (after disenrollment) relative to nonswitchers in the same county over the same period. Payment generosity and more sophisticated risk adjustment were associated with substantial increases in MA enrollment and decreases in disenrollment. Claims experience of those newly switching into MA was not affected by any of the policy reforms, but disenrollment became increasingly concentrated among high-cost beneficiaries. Enrollment is very sensitive to payment levels. The use of more sophisticated risk adjustment did not alter favorable selection into MA, but it did affect the costliness of disenrollees. © Health Research and Educational Trust.

  13. Habitat heterogeneity favors asexual reproduction in natural populations of grassthrips.

    PubMed

    Lavanchy, Guillaume; Strehler, Marie; Llanos Roman, Maria Noemi; Lessard-Therrien, Malie; Humbert, Jean-Yves; Dumas, Zoé; Jalvingh, Kirsten; Ghali, Karim; Fontcuberta García-Cuenca, Amaranta; Zijlstra, Bart; Arlettaz, Raphaël; Schwander, Tanja

    2016-08-01

    Explaining the overwhelming success of sex among eukaryotes is difficult given the obvious costs of sex relative to asexuality. Different studies have shown that sex can provide benefits in spatially heterogeneous environments under specific conditions, but whether spatial heterogeneity commonly contributes to the maintenance of sex in natural populations remains unknown. We experimentally manipulated habitat heterogeneity for sexual and asexual thrips lineages in natural populations and under seminatural mesocosm conditions by varying the number of hostplants available to these herbivorous insects. Asexual lineages rapidly replaced the sexual ones, independently of the level of habitat heterogeneity in mesocosms. In natural populations, the success of sexual thrips decreased with increasing habitat heterogeneity, with sexual thrips apparently only persisting in certain types of hostplant communities. Our results illustrate how genetic diversity-based mechanisms can favor asexuality instead of sex when sexual lineages co-occur with genetically variable asexual lineages. © 2016 The Author(s) Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  14. Coevolution of robustness, epistasis, and recombination favors asexual reproduction.

    PubMed

    MacCarthy, Thomas; Bergman, Aviv

    2007-07-31

    The prevalence of sexual reproduction remains one of the most perplexing phenomena in evolutionary biology. The deterministic mutation hypothesis postulates that sexual reproduction will be advantageous under synergistic epistasis, a condition in which mutations cause a greater reduction in fitness when combined than would be expected from their individual effects. The inverse condition, antagonistic epistasis, correspondingly is predicted to favor asexual reproduction. To assess this hypothesis, we introduce a finite population evolutionary process that combines a recombination modifier formalism with a gene-regulatory network model. We demonstrate that when reproductive mode and epistasis are allowed to coevolve, asexual reproduction outcompetes sexual reproduction. In addition, no correlation is found between the level of synergistic epistasis and the fixation time of the asexual mode. However, a significant correlation is found between the level of antagonistic epistasis and asexual mode fixation time. This asymmetry can be explained by the greater reduction in fitness imposed by sexual reproduction as compared with asexual reproduction. Our findings present evidence and suggest plausible explanations that challenge both the deterministic mutation hypothesis and recent arguments asserting the importance of emergent synergistic epistasis in the maintenance of sexual reproduction.

  15. Adaptation of Cupriavidus necator to conditions favoring polyhydroxyalkanoate production.

    PubMed

    Cavalheiro, João M B T; de Almeida, M Catarina M D; da Fonseca, M Manuela R; de Carvalho, Carla C C R

    2012-12-15

    The fatty acid (FA) composition of the bacterial membrane of Cupriavidus necator DSM 545 was assessed during the time course of two-stage fed-batch cultivations for the production of short-chain polyhydroxyalkanoates (PHA). Changes in the relative proportion of straight, methyl and cyclopropyl saturated, unsaturated, hydroxy substituted and polyunsaturated FA were observed, depending on the C sources and cultivation conditions used to favor the synthesis of poly(3-hydroxybutyrate) (P(3HB)), poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) or poly(3-hydroxybutyrate-4-hydroxybutyrate-3-hydroxyvalerate) (P(3HB-4HB-3HV)), under N limiting conditions. The relative percentage of each FA class was studied using glucose or waste glycerol (GRP), as main C source for P(3HB) production. The FA profile was also assessed when GRP was used together with i) γ-butyrolactone (GBL) (precursor of 4HB monomers) for P(3HB-4HB) synthesis and ii) GBL and propionic acid (PA) (3HV precursor) to yield P(3HB-4HB-3HV). The effect of GBL and PA utilization as PHA monomer precursors on the FA profile of the cell membrane was studied under two different dissolved oxygen concentrations (DOC). Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Paleozoic unconformities favorable for uranium concentration in northern Appalachian basin

    SciTech Connect

    Dennison, J.M.

    1986-05-01

    Unconformities can redistribute uranium from protore rock as ground water moves through poorly consolidated strata beneath the erosion surface, or later moves along the unconformity. Groundwater could migrate farther than in present-day lithified Paleozoic strata in the Appalachian basin, now locally deformed by the Taconic and Allegheny orogenies. Several paleoaquifer systems could have developed uranium geochemical cells. Sandstone mineralogy, occurrences of fluvial strata, and reduzate facies are important factors. Other possibilities include silcrete developed during desert exposure, and uranium concentrated in paleokarst. Thirteen unconformities are evaluated to determine favorable areas for uranium concentration. Cambrian Potsdam sandstone (New York) contains arkoses and possible silcretes just above crystalline basement. Unconformities involving beveled sandstones and possible fluvial strata include Cambrian Hardyston sandstone (New Jersey), Cambrian Potsdam Sandstone (New York), Ordovician Oswego and Juniata formations (Pennsylvania and New York), Silurian Medina Group (New York), and Silurian Vernon, High Falls, and Longwood formations (New York and New Jersey). Devonian Catskill Formation is beveled by Pennsylvanian strata (New York and Pennsylvania). The pre-Pennsylvanian unconformity also bevels Lower Mississippian Pocono, Knapp, and Waverly strata (Pennsylvania, New York, and Ohio), truncates Upper Mississippian Mauch Chunk Formation (Pennsylvania), and forms paleokarst on Mississippian Loyalhanna Limestone (Pennsylvania) and Maxville Limestone (Ohio). Strata associated with these unconformities contain several reports of uranium. Unconformities unfavorable for uranium concentration occur beneath the Middle Ordovician (New York), Middle Devonian (Ohio and New York), and Upper Devonian (Ohio and New York); these involve marine strata overlying marine strata and probably much submarine erosion.

  17. Phenotypic selection favors missing trait combinations in coexisting annual plants.

    PubMed

    Kimball, Sarah; Gremer, Jennifer R; Huxman, Travis E; Lawrence Venable, D; Angert, Amy L

    2013-08-01

    Trade-offs among traits are important for maintaining biodiversity, but the role of natural selection in their construction is not often known. It is possible that trade-offs reflect fundamental constraints, negative correlational selection, or directional selection operating on costly, redundant traits. In a Sonoran Desert community of winter annual plants, we have identified a trade-off between relative growth rate and water-use efficiency among species, such that species with high relative growth rate have low water-use efficiency and vice versa. We measured selection on water-use efficiency, relative growth rate, and underlying traits within populations of four species at two study sites with different average climates. Phenotypic trait correlations within species did not match the among-species trade-off. In fact, for two species with high water-use efficiency, individuals with high relative growth rate also had high water-use efficiency. All populations experienced positive directional selection for water-use efficiency and relative growth rate. Selection tended to be stronger on water-use efficiency at the warmer and drier site, and selection on relative growth rate tended to be stronger at the cooler and wetter site. Our results indicate that directional natural selection favors a phenotype not observed among species in the community, suggesting that the among-species trade-off could be due to pervasive genetic constraints, perhaps acting in concert with processes of community assembly.

  18. Favorable Selection, Risk Adjustment, and the Medicare Advantage Program

    PubMed Central

    Morrisey, Michael A; Kilgore, Meredith L; Becker, David J; Smith, Wilson; Delzell, Elizabeth

    2013-01-01

    Objectives To examine the effects of changes in payment and risk adjustment on (1) the annual enrollment and switching behavior of Medicare Advantage (MA) beneficiaries, and (2) the relative costliness of MA enrollees and disenrollees. Data From 1999 through 2008 national Medicare claims data from the 5 percent longitudinal sample of Parts A and B expenditures. Study Design Retrospective, fixed effects regression analysis of July enrollment and year-long switching into and out of MA. Similar regression analysis of the costliness of those switching into (out of) MA in the 6 months prior to enrollment (after disenrollment) relative to nonswitchers in the same county over the same period. Findings Payment generosity and more sophisticated risk adjustment were associated with substantial increases in MA enrollment and decreases in disenrollment. Claims experience of those newly switching into MA was not affected by any of the policy reforms, but disenrollment became increasingly concentrated among high-cost beneficiaries. Conclusions Enrollment is very sensitive to payment levels. The use of more sophisticated risk adjustment did not alter favorable selection into MA, but it did affect the costliness of disenrollees. PMID:23088500

  19. Increasing Spring temperature favors oak seed production in temperate areas

    NASA Astrophysics Data System (ADS)

    Caignard, Thomas; Kremer, Antoine; Firmat, Cyril; Nicolas, Manuel; Venner, Samuel; Delzon, Sylvain

    2017-04-01

    Although changes in vegetative phenology have considerable consequences for ecosystem functioning, little is known about how tree reproduction responds to climate change, while reproductive traits are key determinants of plant fitness. Assessing the response of tree reproduction to climate variations is needed for understanding tree and forest adaptation to environmental changes. We analyzed an extensive dataset of tree reproduction in 28 temperate oak forests distributed throughout France and examined how seed production responded to temperature variations over 14 years In addition, a "space-for-time" substitution experiment has been used to quantify the temperature sensitivity of acorn production. The amount of acorn produced in 10 Q. petraea populations along two parallel elevation gradients in Southern France were quantified from 2012 to 2015. During the past two decades, we observed a significant increase in reproductive effort for Q. petraea that correlates with a rise in spring temperature. Although no significant trend over time has been observed for Q. robur, a significant increase in seed production was also found with spring temperature. Such sensitivity to temperature of seed production has been confirmed along the elevational gradients. Our findings show that increasing spring temperature favors oak reproductive effort in temperate ecosystems. Nevertheless, while fitness can be enhanced by higher seed production, it also depends on the frequency and on the synchronization of mast seeding production that climate change may influence too.

  20. Gender bias in food intake favors male preschool Guatemalan children.

    PubMed

    Frongillo, E A; Bégin, F

    1993-02-01

    Gender bias in food intake and its subsequent effects on growth and illness were examined using data from rural Guatemalan children. Multiple regression controlled for energy requirements, illness, and maternal and economic factors. Gender bias in energy and protein intake favored boys; the magnitude for ages 2-5 y was 247 kJ/d. Analysis of subsequent effects showed that boys had higher rates of weight gain due to gender bias in energy intake than did girls for ages 1-2 y (0.27-0.97 kg/y), when there were no differences in illness rates due to gender bias in energy intake. For age 3-5 y, boys and girls did not differ in weight gain due to gender bias in energy intake. For ages 1-2 y for weight and stature, the growth rate for boys was faster than that of girls by 6-49% due to gender bias. This study provides evidence of gender bias in food intake in a Latin American population, but more work on the existence of and reasons for gender bias in food intake is needed before advocating that education or health programs should focus on this issue.

  1. Cardiac arrest at high elevation with a favorable outcome.

    PubMed

    Yanagawa, Youichi; Omori, Kazuhiko; Takeuchi, Ikuto; Jitsuiki, Kei; Yoshizawa, Toshihiko; Ishikawa, Kouhei; Kando, Yumi; Fukata, Mutsumu; Ohsaka, Hiromichi

    2017-04-01

    A 36-year-old man started to climb Mount Fuji (3776m above sea level: ASL), from the Gotemba new fifth station (2400m ASL). He had no significant medical history, and this was his first attempt to climb such a high mountain. He began feeling chest discomfort but continued to climb. When he reached the ninth station of the mountain (3600mASL), he lost consciousness. One individual immediately provided basic life support using an automated external defibrillator (AED) that was located in the station. After electroshocks, he regained consciousness. He was transported to the fifth station, where an ambulance could approach, in a large crawler. When the medical staff, who were transported via helicopter and ambulance, examined him near the fifth station, he still complained of chest discomfort. A single spray of nitroglycerin and aspirin (200mg) was administered. He was transported to the Cardiac Care Unit via ambulance and helicopter under escort by a physician. A chest computed tomography angiogram indicated triple-vessel disease. He was discharged without any neurological deficits after undergoing bypass surgery. In high mountains that can be easily accessed by amateur climbers who may have cardiac disease, the placement of AED devices and the establishment of the chain of survival from the scene to the intensive care unit are essential for obtaining a favorable outcome when a climber suffers cardiac arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Musical FAVORS: Reintroducing music to adult cochlear implant users.

    PubMed

    Plant, Geoff

    2015-09-01

    Music represents a considerable challenge for many adult users of cochlear implants (CIs). Around half of adult CI users report that they do not find music enjoyable, and, in some cases, despite enhanced speech perception skills, this leads to considerable frustration and disappointment for the CI user. This paper presents suggestions to improve the musical experiences of deafened adults with CIs. Interviews with a number of adult CI users revealed that there were a number of factors which could lead to enhanced music experiences. The acronym FAVORS (familiar music, auditory-visual access, open-mindedness, and simple arrangements) summarizes the factors that have been identified, which can help CI users in their early music listening experiences. Each of these factors is discussed in detail, along with suggestions for how they can be used in therapy sessions. The use of a group approach (music focus groups) is also discussed and an overview of the approach and exercises used is presented. The importance of live music experiences is also discussed.

  3. Favorable outcome in open globe injuries with low OTS score.

    PubMed

    Cillino, Giovanni; Ferraro, Lucia; Casuccio, Alessandra; Cillino Salvatore

    2014-09-01

    Open globe eye injuries can have profound social and economic consequences. Here, we describe two cases of war and outdoor activity open globe eye injury where, despite a low OTS score, current microsurgical technology allowed for a favorable outcome. A 33-year-old Libyan soldier had been treated for an open-globe grenade blast trauma to his left eye, which showed light perception and OTS score 2. He had undergone a lensectomy and PPV with silicone oil tamponade. Surgical treatment included scleral buckling, cornea trephination, temporary Eckardt keratoprosthesis, PPV revision, intraocular lens (IOL) implantation, and corneal grafting. Six months later, his VA was improved to 20/70. CASE REPORT 2: A 35-year-old man presented with a corneal laceration in his left eye from a meat skewer, with marked hypotony and LP. After primary corneal wound closure, B-scan ultrasonography revealed massive vitreous hemorrhage (OTS score 2). The patient underwent open cataract extraction with IOL implantation, 23 gauge PPV, laser photocoagulation of the retinochoroidal laceration, and a gas tamponade. After three weeks, the patient underwent a 2nd 23G PPV due to a fibrinous reaction. Six month later, the patients exhibited 20/25 VA. These cases confirm that even for patients with a low OTS and poor visual prognosis, an up-to-date surgery protocol may achieve visual results adequate for leading an autonomous daily life.

  4. Sperm competition favors harmful males in seed beetles.

    PubMed

    Hotzy, Cosima; Arnqvist, Göran

    2009-03-10

    One of the most enigmatic observations in evolutionary biology is the evolution of morphological or physiological traits in one sex that physically injure members of the other sex. Such traits occur in a wide range of taxa and range from toxic ejaculate substances to genital or external spines that wound females during copulation. Current hypotheses for the adaptive evolution of such injurious traits rest entirely on the assumption that they are beneficial to their bearer by aiding in reproductive competition. Here, we assess this key assumption in seed beetles where genital spines in males physically injure females. We demonstrate that male spine length is positively correlated with harm to females during mating but also that males with longer spines are more successful in sperm competition. This is the first complete support for the proposal that sexual selection by sperm competition can favor morphological traits in males that inflict injury upon females. However, our results suggest that harm to females is a pleiotropic by-product, such that genital spines in males elevate success in sperm competition by means other than by causing harm.

  5. Surgery for retroperitoneal relapse in the setting of a prior retroperitoneal lymph node dissection for germ cell tumor

    PubMed Central

    Gotto, Geoffrey T.; Carver, Brett S.; Sogani, Pramod; Sheinfeld, Joel

    2010-01-01

    Recognition of the therapeutic role of retroperitoneal lymph node dissection (RPLND) in the setting of testicular germ cell tumors (GCTs) is of utmost importance. Although the histologic findings of RPLND provide diagnostic and prognostic information, the adequacy of initial RPLND is an independent predictor of clinical outcome. Despite the advent of effective cisplatin-based chemotherapy for testicular GCTs, patients who have undergone suboptimal surgery at the time of initial RPLND are compromised. Despite the initial enthusiasm surrounding anatomic mapping studies, the use of modified RPLND templates has the potential to leave a significant number of patients with unresected retroperitoneal disease. Teratomatous elements are particularly common. Patients with retroperitoneal relapse following initial RPLND should be treated with reoperative RPLND and chemotherapy and can expect long term survival rates nearing 70% when treated in tertiary centers by experienced surgeons. PMID:20535295

  6. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.

    PubMed

    Kalincik, Tomas; Vivek, Vino; Jokubaitis, Vilija; Lechner-Scott, Jeannette; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Grand'maison, Francois; Hupperts, Raymond; Oreja-Guevara, Celia; Bergamaschi, Roberto; Iuliano, Gerardo; Alroughani, Raed; Van Pesch, Vincent; Amato, Maria Pia; Slee, Mark; Verheul, Freek; Fernandez-Bolanos, Ricardo; Fiol, Marcela; Spitaleri, Daniele La; Cristiano, Edgardo; Gray, Orla; Cabrera-Gomez, Jose Antonio; Shaygannejad, Vahid; Herbert, Joseph; Vucic, Steve; Needham, Merilee; Petkovska-Boskova, Tatjana; Sirbu, Carmen-Adella; Duquette, Pierre; Girard, Marc; Grammond, Pierre; Boz, Cavit; Giuliani, Giorgio; Rio, Maria Edite; Barnett, Michael; Flechter, Shlomo; Moore, Fraser; Singhal, Bhim; Bacile, Elizabeth Alejandra; Saladino, Maria Laura; Shaw, Cameron; Skromne, Eli; Poehlau, Dieter; Vella, Norbert; Spelman, Timothy; Liew, Danny; Kilpatrick, Trevor J; Butzkueven, Helmut

    2013-12-01

    The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.

  7. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations | Office of Cancer Genomics

    Cancer.gov

    The majority of patients with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas showed clonal evolution from the diagnostic tumor, with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK pathway.

  8. A comparison of patients relapsing to addictive drug use with non-relapsing patients following residential addiction treatment in Antigua.

    PubMed

    Martin, T C; Josiah-Martin, J A; Kosakoski, J; Norton, K; Sinnott, T

    2005-06-01

    The outcome of a 29-day residential addiction treatment programme for persons from Antigua and Barbuda with addiction to drugs or alcohol was assessed. All 100 patients entering the drug and alcohol treatment programme at Crossroads Centre Antigua between November 1998 and October 2002 were included. All patients were assessed with regards to drug or alcohol use or abstinence in November 2002 using telephone and mail follow-up as well as informal follow-up with families and other community contacts. Crossroads Centre Antigua is a 35 bed, 29-day residential treatment centre for drug and alcohol addiction serving patients from developed countries (85%) and from the Caribbean region (15%). Patients records were also reviewed to obtain age, gender, ethnicity, drug of choice, years of problematic use, completion of the 29 day programme, family member participation at Crossroads Centre Antigua (a four-day programme) and acceptance of halfway house placement. Of the 100 Antiguan patients admitted, 46 (46%) were abstinent (non-relapsers) at average 20.7+/-14.7 months after treatment. Abstinence did not have to be continuous. Forty-nine were known to be using drug or alcohol (49%) and five (5%) were lost to follow-up and considered to be using drugs (relapsers). Age (37.5 vs 41.1 years), gender (28% vs 22% female), ethnicity (87% vs 87% Afro-Caribbean), years of harmful use (12.7 vs 12.5 years) did not differ significantly between relapsers and non-relapsers. Crack cocaine use (67% vs 65%) and alcohol use (26% vs 31%) as primary addiction did not differ significantly between relapsers and non-relapsers. Relapsers were significantly less likely to complete the 29- day programme (81% vs 100%, p < 0.01), have family members participate at Crossroads (32% vs 54%, p < 0.05) or accept halfway house placement (4% vs 54%, p < 0.001). In conclusion, abstinence was achieved in 46% of those entering treatment, in 51% completing treatment, in 60% whose families participated and in 92

  9. Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer.

    PubMed

    O'Brien, Catherine; True, Lawrence D; Higano, Celestia S; Rademacher, Brooks L S; Garzotto, Mark; Beer, Tomasz M

    2010-04-01

    Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high-risk prostate cancer. Little is known about the clinical significance of postchemotherapy tumor histopathologic features. We assessed the prognostic and predictive value of histologic features (intraductal carcinoma, vacuolated cell morphologic features, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with preprostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) rates at 2 and 5 years were 65% and 49%, respectively. In univariate analyses (using the Kaplan-Meier method and log-rank tests), intraductal (P = .001) and cribriform (P = .014) histologic features were associated with shorter RFS. In multivariate analyses, using the Cox proportional hazards regression, baseline prostate-specific antigen (P = .004), lymph node metastases (P < .001), and cribriform histologic features (P = .007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (P = .007) predicted lymph node metastases. Intraductal and cribriform histologic features apparently predict postchemotherapy outcome.

  10. Histological changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in high-risk prostate cancer patients

    PubMed Central

    O’Brien, Catherine; True, Lawrence D.; Higano, Celestia S.; Rademacher, Brooks L. S.; Garzotto, Mark; Beer, Tomasz M.

    2011-01-01

    Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high risk prostate cancer. Little is known about the clinical significance of post-chemotherapy tumor histopathology. We assessed the prognostic and predictive value of histological features (intraductal carcinoma, vacuolated cell morphology, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with pre-prostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) at 2 and 5 years was 65% and 49%, respectively. In univariate analyses (using Kaplan-Meier method and log-rank tests) intraductal (p=0.001) and cribriform (p=0.014) histologies were associated with shorter RFS. In multivariate analyses, using Cox’s proportional hazards regression, baseline PSA (p=0.004), lymph node metastases (p<0.001), and cribriform histology (p=0.007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (p=0.007) predicted lymph node metastases. Intraductal and cribriform histologies apparently predict post-chemotherapy outcome. PMID:20231619

  11. What favors the occurrence of subduction mega-earthquakes?

    NASA Astrophysics Data System (ADS)

    Brizzi, Silvia; Funiciello, Francesca; Corbi, Fabio; Sandri, Laura; van Zelst, Iris; Heuret, Arnauld; Piromallo, Claudia; van Dinther, Ylona

    2017-04-01

    Most of mega-earthquakes (MEqs; Mw > 8.5) occur at shallow depths along the subduction thrust fault (STF). The contribution of each subduction zone to the globally released seismic moment is not homogenous, as well as the maximum recorded magnitude MMax. Highlighting the ingredients likely responsible for MEqs nucleation has great implications for hazard assessment. In this work, we investigate the conditions favoring the occurrence of MEqs with a multi-disciplinary approach based on: i) multivariate statistics, ii) analogue- and iii) numerical modelling. Previous works have investigated the potential dependence between STF seismicity and various subduction zone parameters using simple regression models. Correlations are generally weak due to the limited instrumental seismic record and multi-parameter influence, which make the forecasting of the potential MMax rather difficult. To unravel the multi-parameter influence, we perform a multivariate statistical study (i.e., Pattern Recognition, PR) of the global database on convergent margins (Heuret et al., 2011), which includes seismological, geometrical, kinematic and physical parameters of 62 subduction segments. PR is based on the classification of objects (i.e., subduction segments) belonging to different classes through the identification of possible repetitive patterns. Tests have been performed using different MMax datasets and combination of inputs to indirectly test the stability of the identified patterns. Results show that the trench-parallel width of the subducting slab (Wtrench) and the sediment thickness at the trench (Tsed) are the most recurring parameters for MEqs occurrence. These features are mostly consistent, independently of the MMax dataset and combination of inputs used for the analysis. MEqs thus seem to be promoted for high Wtrench and Tsed, as their combination may potentially favor extreme (i.e., in the order of thousands of km) trench-parallel rupture propagation. To tackle the

  12. Ground states of stealthy hyperuniform potentials: I. Entropically favored configurations.

    PubMed

    Zhang, G; Stillinger, F H; Torquato, S

    2015-08-01

    Systems of particles interacting with "stealthy" pair potentials have been shown to possess infinitely degenerate disordered hyperuniform classical ground states with novel physical properties. Previous attempts to sample the infinitely degenerate ground states used energy minimization techniques, introducing algorithmic dependence that is artificial in nature. Recently, an ensemble theory of stealthy hyperuniform ground states was formulated to predict the structure and thermodynamics that was shown to be in excellent agreement with corresponding computer simulation results in the canonical ensemble (in the zero-temperature limit). In this paper, we provide details and justifications of the simulation procedure, which involves performing molecular dynamics simulations at sufficiently low temperatures and minimizing the energy of the snapshots for both the high-density disordered regime, where the theory applies, as well as lower densities. We also use numerical simulations to extend our study to the lower-density regime. We report results for the pair correlation functions, structure factors, and Voronoi cell statistics. In the high-density regime, we verify the theoretical ansatz that stealthy disordered ground states behave like "pseudo" disordered equilibrium hard-sphere systems in Fourier space. The pair statistics obey certain exact integral conditions with very high accuracy. These results show that as the density decreases from the high-density limit, the disordered ground states in the canonical ensemble are characterized by an increasing degree of short-range order and eventually the system undergoes a phase transition to crystalline ground states. In the crystalline regime (low densities), there exist aperiodic structures that are part of the ground-state manifold but yet are not entropically favored. We also provide numerical evidence suggesting that different forms of stealthy pair potentials produce the same ground-state ensemble in the zero

  13. Evoked and spontaneous transmission favored by distinct sets of synapses.

    PubMed

    Peled, Einat S; Newman, Zachary L; Isacoff, Ehud Y

    2014-03-03

    Spontaneous "miniature" transmitter release takes place at low rates at all synapses. Long thought of as an unavoidable leak, spontaneous release has recently been suggested to be mediated by distinct pre- and postsynaptic molecular machineries and to have a specialized role in setting up and adjusting neuronal circuits. It remains unclear how spontaneous and evoked transmission are related at individual synapses, how they are distributed spatially when an axon makes multiple contacts with a target, and whether they are commonly regulated. Electrophysiological recordings in the Drosophila larval neuromuscular junction, in the presence of the use-dependent glutamate receptor (GluR) blocker philanthotoxin, indicated that spontaneous and evoked transmission employ distinct sets of GluRs. In vivo imaging of transmission using synaptically targeted GCaMP3 to detect Ca(2+) influx through the GluRs revealed little spatial overlap between synapses participating in spontaneous and evoked transmission. Spontaneous and evoked transmission were oppositely correlated with presynaptic levels of the protein Brp: synapses with high Brp favored evoked transmission, whereas synapses with low Brp were more active spontaneously. High-frequency stimulation did not increase the overlap between evoked and spontaneous transmission, and instead decreased the rate of spontaneous release from synapses that were highly active in evoked transmission. Although individual synapses can participate in both evoked and spontaneous transmission, highly active synapses show a preference for one mode of transmission. The presynaptic protein Brp promotes evoked transmission and suppresses spontaneous release. These findings suggest the existence of presynaptic mechanisms that promote synaptic specialization to either evoked or spontaneous transmission. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Evoked and spontaneous transmission favored by distinct sets of synapses

    PubMed Central

    Peled, Einat S.; Newman, Zachary L.; Isacoff, Ehud Y.

    2014-01-01

    Summary Background Spontaneous “miniature” transmitter release takes place at low rates at all synapses. Long thought as an unavoidable leak, spontaneous release has recently been suggested to be mediated by distinct pre- and post-synaptic molecular machineries and to have a specialized role in setting up and adjusting neuronal circuits. It remains unclear how spontaneous and evoked transmission are related at individual synapses, how they are distributed spatially when an axon makes multiple contacts with a target and whether they are commonly regulated. Results Electrophysiological recordings in the Drosophila larval neuromuscular junction, in the presence of the use-dependent glutamate receptor (GluR) blocker Philanthotoxin, indicated that spontaneous and evoked transmission employ distinct sets of GluRs. In vivo imaging of transmission using synaptically-targeted GCaMP3 to detect Ca2+ influx through the GluRs revealed little spatial overlap between synapses participating in spontaneous and evoked transmission. Spontaneous and evoked transmission were oppositely correlated with presynaptic levels of the protein Brp: synapses with high Brp favored evoked transmission, whereas synapses with low Brp were more active spontaneously. High frequency stimulation did not increase the overlap between evoked and spontaneous transmission, and instead decreased the rate of spontaneous release from synapses that were highly active in evoked transmission. Conclusions While individual synapses can participate in both evoked and spontaneous transmission, highly-active synapses show a preference for one mode of transmission. The presynaptic protein Brp promotes evoked transmission and suppresses spontaneous release. These findings suggest the existence of presynaptic mechanisms that promote synaptic specialization to either evoked or spontaneous transmission. PMID:24560571

  15. Alkaline diets favor lean tissue mass in older adults1234

    PubMed Central

    Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa

    2008-01-01

    Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women. PMID:18326605

  16. Alkaline diets favor lean tissue mass in older adults.

    PubMed

    Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa

    2008-03-01

    Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid-producing protein and cereal grains relative to their content of net alkali-producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Subjects were 384 men and women > or =65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight/weight x 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. At baseline, the mean urinary potassium excretion was 67.0 +/- 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (beta = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 +/- 3.6%. Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women.

  17. Patients with Spinal Cord Injuries Favor Administration of Methylprednisolone

    PubMed Central

    Bowers, Christian A.; Kundu, Bornali; Rosenbluth, Jeffrey; Hawryluk, Gregory W. J.

    2016-01-01

    Methylprednisolone sodium succinate (MPSS) for treatment of acute spinal cord injury (SCI) has been associated with both benefits and adverse events. MPSS administration was the standard of care for acute SCI until recently when its use has become controversial. Patients with SCI have had little input in the debate, thus we sought to learn their opinions regarding administration of MPSS. A summary of the published literature to date on MPSS use for acute SCI was created and adjudicated by 28 SCI experts. This summary was then emailed to 384 chronic SCI patients along with a survey that interrogated the patients’ neurological deficits, communication with physicians and their views on MPSS administration. 77 out of 384 patients completed the survey. 28 respondents indicated being able to speak early after injury and of these 24 reported arriving at the hospital within 8 hours of injury. One recalled a physician speaking to them about MPSS and one patient reported choosing whether or not to receive MPSS. 59.4% felt that the small neurological benefits associated with MPSS were ‘very important’ to them (p<0.0001). Patients had ‘little concern’ for potential side-effects of MPSS (p = 0.001). Only 1.4% felt that MPSS should not be given to SCI patients regardless of degree of injury (p<0.0001). This is the first study to report SCI patients’ preferences regarding MPSS treatment for acute SCI. Patients favor the administration of MPSS for acute SCI, however few had input into whether or not it was administered. Conscious patients should be given greater opportunity to decide their treatment. These results also provide some guidance regarding MPSS administration in patients unable to communicate. PMID:26789007

  18. Mechanical Heterogeneity Favors Fragmentation of Strained Actin Filaments

    PubMed Central

    De La Cruz, Enrique M.; Martiel, Jean-Louis; Blanchoin, Laurent

    2015-01-01

    We present a general model of actin filament deformation and fragmentation in response to compressive forces. The elastic free energy density along filaments is determined by their shape and mechanical properties, which were modeled in terms of bending, twisting, and twist-bend coupling elasticities. The elastic energy stored in filament deformation (i.e., strain) tilts the fragmentation-annealing reaction free-energy profile to favor fragmentation. The energy gradient introduces a local shear force that accelerates filament intersubunit bond rupture. The severing protein, cofilin, renders filaments more compliant in bending and twisting. As a result, filaments that are partially decorated with cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric shape deformations and energy profiles distinct from mechanically homogenous (i.e., uniform), bare actin, or saturated cofilactin filaments. The local buckling strain depends on the relative size of the compliant segment as well as the bending and twisting rigidities of flanking regions. Filaments with a single bare/cofilin-decorated boundary localize energy and force adjacent to the boundary, within the compliant cofilactin segment. Filaments with small cofilin clusters were predicted to fragment within the compliant cofilactin rather than at boundaries. Neglecting contributions from twist-bend coupling elasticity underestimates the energy density and gradients along filaments, and thus the net effects of filament strain to fragmentation. Spatial confinement causes compliant cofilactin segments and filaments to adopt higher deformation modes and store more elastic energy, thereby promoting fragmentation. The theory and simulations presented here establish a quantitative relationship between actin filament fragmentation thermodynamics and elasticity, and reveal how local discontinuities in filament mechanical properties introduced by regulatory proteins can modulate both the severing efficiency

  19. Mechanical heterogeneity favors fragmentation of strained actin filaments.

    PubMed

    De La Cruz, Enrique M; Martiel, Jean-Louis; Blanchoin, Laurent

    2015-05-05

    We present a general model of actin filament deformation and fragmentation in response to compressive forces. The elastic free energy density along filaments is determined by their shape and mechanical properties, which were modeled in terms of bending, twisting, and twist-bend coupling elasticities. The elastic energy stored in filament deformation (i.e., strain) tilts the fragmentation-annealing reaction free-energy profile to favor fragmentation. The energy gradient introduces a local shear force that accelerates filament intersubunit bond rupture. The severing protein, cofilin, renders filaments more compliant in bending and twisting. As a result, filaments that are partially decorated with cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric shape deformations and energy profiles distinct from mechanically homogenous (i.e., uniform), bare actin, or saturated cofilactin filaments. The local buckling strain depends on the relative size of the compliant segment as well as the bending and twisting rigidities of flanking regions. Filaments with a single bare/cofilin-decorated boundary localize energy and force adjacent to the boundary, within the compliant cofilactin segment. Filaments with small cofilin clusters were predicted to fragment within the compliant cofilactin rather than at boundaries. Neglecting contributions from twist-bend coupling elasticity underestimates the energy density and gradients along filaments, and thus the net effects of filament strain to fragmentation. Spatial confinement causes compliant cofilactin segments and filaments to adopt higher deformation modes and store more elastic energy, thereby promoting fragmentation. The theory and simulations presented here establish a quantitative relationship between actin filament fragmentation thermodynamics and elasticity, and reveal how local discontinuities in filament mechanical properties introduced by regulatory proteins can modulate both the severing efficiency

  20. Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, Alan G.

    2004-01-01

    Relapse prevention, based on the cognitive-behavioral model of relapse, has become an adjunct to the treatment of numerous psychological problems, including (but not limited to) substance abuse, depression, sexual offending, and schizophrenia. This article provides an overview of the efficacy and effectiveness of relapse prevention in the…

  1. Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, Alan G.

    2004-01-01

    Relapse prevention, based on the cognitive-behavioral model of relapse, has become an adjunct to the treatment of numerous psychological problems, including (but not limited to) substance abuse, depression, sexual offending, and schizophrenia. This article provides an overview of the efficacy and effectiveness of relapse prevention in the…

  2. Comparison of PR3-ANCA and MPO-ANCA Epitope Specificity upon Disease Relapse

    EPA Science Inventory

    BACKGROUND Relapse is a major clinical problem in ANCA vasculitis that causes increased morbidity and mortality. Compared to MPO-ANCA patients, patients with PR3-ANCA run a significantly increased risk of experiencing relapses. We hypothesized that a relapsing patient is produ...

  3. Comparison of PR3-ANCA and MPO-ANCA Epitope Specificity upon Disease Relapse

    EPA Science Inventory

    BACKGROUND Relapse is a major clinical problem in ANCA vasculitis that causes increased morbidity and mortality. Compared to MPO-ANCA patients, patients with PR3-ANCA run a significantly increased risk of experiencing relapses. We hypothesized that a relapsing patient is produ...

  4. Retrospective and Prospective Reports of Precipitants to Relapse in Pathological Gambling

    ERIC Educational Resources Information Center

    Hodgins, David C.; el-Guebaly, Nady

    2004-01-01

    A prospective design was used to explore the precipitants of relapse in a naturalistic sample of pathological gamblers (N = 101) who had recently quit gambling. Relapse rates were high; only 8% were entirely free of gambling during the 12-month follow-up. Relapses were highly variable but occurred most frequently in the evening, when the person…

  5. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.

    PubMed

    Hogan, Laura E; Meyer, Julia A; Yang, Jun; Wang, Jinhua; Wong, Nicholas; Yang, Wenjian; Condos, Gregory; Hunger, Stephen P; Raetz, Elizabeth; Saffery, Richard; Relling, Mary V; Bhojwani, Deepa; Morrison, Debra J; Carroll, William L

    2011-11-10

    Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (< 36 months) and late (≥ 36 months) relapse. CNA analysis discovered CNAs that were shared at diagnosis and relapse and others that were new lesions acquired at relapse. DNA methylation analysis found increased promoter methylation at relapse. There were many genetic alterations that evolved from diagnosis to relapse, and in some cases these genes had previously been associated with chemoresistance. Integration of the results from all 3 platforms identified genes of potential interest, including CDKN2A, COL6A2, PTPRO, and CSMD1. Although our results indicate that a diversity of genetic changes are seen at relapse, integration of gene expression, CNA, and methylation data suggest a possible convergence on the WNT and mitogen-activated protein kinase pathways.

  6. Retrospective and Prospective Reports of Precipitants to Relapse in Pathological Gambling

    ERIC Educational Resources Information Center

    Hodgins, David C.; el-Guebaly, Nady

    2004-01-01

    A prospective design was used to explore the precipitants of relapse in a naturalistic sample of pathological gamblers (N = 101) who had recently quit gambling. Relapse rates were high; only 8% were entirely free of gambling during the 12-month follow-up. Relapses were highly variable but occurred most frequently in the evening, when the person…

  7. Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

    2008-01-01

    The outcome of a sequential treatment strategy that included cognitive behavioral therapy (CBT) in the prevention of major depressive disorder relapse among 46 youths is examined. Results show that youths under the antidepressant medication management plus relapse prevention CBT treatment was at lower risk for relapse than those under the…

  8. Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

    2008-01-01

    The outcome of a sequential treatment strategy that included cognitive behavioral therapy (CBT) in the prevention of major depressive disorder relapse among 46 youths is examined. Results show that youths under the antidepressant medication management plus relapse prevention CBT treatment was at lower risk for relapse than those under the…

  9. Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

    SciTech Connect

    Kahn, Shannon; Flowers, Christopher; Xu Zhiheng; Esiashvili, Natia

    2011-09-01

    Purpose: To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Methods and Materials: Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. Results: There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p = 0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p = 0.032) and 0.383 (p = 0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p < 0.001), observed only in patients receiving a busulfan-based conditioning regimen. Conclusion: Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative

  10. Does the addition of involved field radiotherapy to high-dose chemotherapy and stem cell transplantation improve outcomes for patients with relapsed/refractory Hodgkin lymphoma?

    PubMed

    Kahn, Shannon; Flowers, Christopher; Xu, Zhiheng; Esiashvili, Natia

    2011-09-01

    To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p=0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p=0.032) and 0.383 (p=0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p<0.001), observed only in patients receiving a busulfan-based conditioning regimen. Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative chemotherapy conditioning regimens should be considered

  11. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

    PubMed Central

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-01

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

  12. Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico-laboratory and histological characteristics.

    PubMed

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-07

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.

  13. [Relapse prevention program consisting of coping skills training, cue exposure treatment, and letter therapy for Japanese alcoholic men who relapsed after standard cognitive-behavioral therapy].

    PubMed

    Yokoyama, Akira; Matsushita, Sachio; Toyama, Tomomi; Nakayama, Hideki; Takimura, Tsuyoshi; Kimura, Mitsuru; Yoneda, Junichi; Maesato, Hitoshi; Mizukami, Takeshi; Higuchi, Susumu; Yokoyama, Tetsuji

    2015-04-01

    Coping skills training (CST) and cue exposure treatment (CET) have yielded favorable outcomes when used to treat alcoholics. We conducted 6-week inpatient programs that consisted of 9 CST group sessions (n = 117) during 2005-2009 and 9 CST group sessions plus 4 CET group sessions (n = 49) during 2009-2011 and subsequent 1-year letter therapy for Japanese alcoholic men who had relapsed and been readmitted after standard cognitive-behavioral inpatient therapy. When patients received a letter containing encouraging words every 2 weeks, they were asked to reread their CST and CET records and to respond to the letter by marking drinking days on a calendar and naming the skills on a list of the 9 CST themes and CET that were useful for maintaining abstinence during that 2-week period. The estimated percentages of achievement of 30 or fewer drinking days during the one year of letter therapy were 36.1 - 45.8%. 'Non-smoking', '2nd admission', and 'After age-limit job retirement' were significant factors in achieving good outcomes. The 'usefulness' responses for 'Increasing pleasant activities', 'CET', 'Anger management', ' Managing negative thinking', 'Problem solving', and ' Seemingly irrelevant decisions' as percentages of overall responses to the letters were significantly higher, in order of decreasing percentages, in the achiever group than in the non-achiever group, but the differences between the groups in ' Managing urges to drink', ' Drink refusal skills', ' Planning for emergencies', and ' Receiving criticism about drinking' were not significant. The odds ratios for achievement of 30 or fewer drinking days during the 1-year period increased significantly by 1.15 -1.31 fold per 10% increment in the 'usefulness' ratio for 'Increasing pleasant activities'. The difference in percentage achievement between the group treated by CST alone and the group treated by CST plus CET was not significant. In conclusion, some coping skills were more useful for relapse prevention

  14. Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats.

    PubMed

    Le Berre, Ludmilla; Godfrin, Yann; Günther, Eberhard; Buzelin, Françoise; Perretto, Sabine; Smit, Helga; Kerjaschki, Dontscho; Usal, Claire; Cuturi, Cristina; Soulillou, Jean-Paul; Dantal, Jacques

    2002-02-01

    Buffalo/Mna rats spontaneously develop a focal segmental glomerulosclerosis with a histological pattern similar to the human disease. In this study, we investigated the potential of recurrence of the disease by transplantation of normal kidneys into Buffalo/Mna recipients. Kidneys from healthy LEW.1W rats were grafted into proteinuric 6-month-old Buffalo/Mna rats without or with specific tolerance induction following donor-specific transfusion (DST) aimed at controlling host anti-donor immune responses. The inverse combination was carried out to determine whether a proteinuric Buffalo/Mna kidney can recover its permselectivity in a normal environment. As a control, LEW.1W kidneys were grafted into Wistar Furth recipients. After transplantation without DST, recurrence of proteinuria in LEW.1W kidneys appeared at approximately 10 days, possibly associated with rejection of the graft. In the same combination with DST, proteinuria occurred after 20 days, and the attendant glomerular damage suggested that the initial kidney disease had recurred. Transplanted control animals remained free of proteinuria. In the opposite combination, the proteinuria and the lesions of Buffalo/Mna kidneys regressed after transplantation into healthy LEW.1W rats. The recurrence of proteinuria after transplantation in Buffalo/Mna and the remission of lesions in Buffalo/Mna kidneys transplanted into normal hosts suggests that Buffalo/Mna rats express circulating albuminuric factors, which may be relevant to the relapse of idiopathic nephrotic syndrome in humans.

  15. Importance of Histologic Verification of Positive Positron Emission Tomography/Computed Tomography Findings in the Follow-Up of Patients With Malignant Lymphoma.

    PubMed

    Nakayama, Hitomi; Aisa, Yoshinobu; Ito, Chisako; Shimazaki, Kengo; Katsumata, Yasushi; Hayashi, Hiroyuki; Nakazato, Tomonori

    2015-12-01

    Posttherapy positron emission tomography/computed tomography (PET/CT) scanning in patients with malignant lymphoma remains controversial. We aimed to evaluate the utility of achieving histologic verification of positive PET/CT findings in the follow-up of patients with malignant lymphoma. A total of 771 PET/CT scans were performed as posttherapy follow-up in 190 lymphoma patients who had experienced a complete remission at our institution. Fifty-two patients (27.3%) had (18)F-fludeoxyglucose-positive lesions on posttherapy PET/CT, and a histologic diagnosis was carried out in 32 cases (16.8%). Ten patients (5.2%) exhibited relapse of lymphoma. Twelve lesions in 11 patients (5.8%) were proven to be second primary malignancies (SPM). Eleven patients (5.8%) were proven to have benign or normal tissue lesions. Among the 32 histologically verified PET/CT-positive patients, the symptomatic PET/CT-positive patients (n = 10; 4 SPM, 6 lymphoma relapse) had a significantly shorter overall survival rate than the asymptomatic PET/CT-positive patients (n = 22; 7 SPM, 4 lymphoma relapse, 11 benign/normal tissue lesions) (2-year overall survival, 48.2% vs. 100%, respectively; P < .001). This study emphasizes that the histologic diagnosis should be confirmed in posttherapy PET/CT-positive patients via biopsy before adjusting the treatment regimen as a result of the high false-positive rate, including unexpected SPM or benign/normal tissue lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Breast Cancer Classification From Histological Images with Multiple Features and Random Subspace Classifier Ensemble

    NASA Astrophysics Data System (ADS)

    Zhang, Yungang; Zhang, Bailing; Lu, Wenjin

    2011-06-01

    Histological image is important for diagnosis of breast cancer. In this paper, we present a novel automatic breaset cancer classification scheme based on histological images. The image features are extracted using the Curvelet Transform, statistics of Gray Level Co-occurence Matrix (GLCM) and Completed Local Binary Patterns (CLBP), respectively. The three different features are combined together and used for classification. A classifier ensemble approach, called Random Subspace Ensemble (RSE), are used to select and aggregate a set of base neural network classifiers for classification. The proposed multiple features and random subspace ensemble offer the classification rate 95.22% on a publically available breast cancer image dataset, which compares favorably with the previously published result 93.4%.

  17. Randomized trial of oral teriflunomide for relapsing multiple sclerosis.

    PubMed

    O'Connor, Paul; Wolinsky, Jerry S; Confavreux, Christian; Comi, Giancarlo; Kappos, Ludwig; Olsson, Tomas P; Benzerdjeb, Hadj; Truffinet, Philippe; Wang, Lin; Miller, Aaron; Freedman, Mark S

    2011-10-06

    Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis. We concluded a randomized trial involving 1088 patients with multiple sclerosis, 18 to 55 years of age, with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years. Patients were randomly assigned (in a 1:1:1 ratio) to placebo, 7 mg of teriflunomide, or 14 mg of teriflunomide once daily for 108 weeks. The primary end point was the annualized relapse rate, and the key secondary end point was confirmed progression of disability for at least 12 weeks. Teriflunomide reduced the annualized relapse rate (0.54 for placebo vs. 0.37 for teriflunomide at either 7 or 14 mg), with relative risk reductions of 31.2% and 31.5%, respectively (P<0.001 for both comparisons with placebo). The proportion of patients with confirmed disability progression was 27.3% with placebo, 21.7% with teriflunomide at 7 mg (P=0.08), and 20.2% with teriflunomide at 14 mg (P=0.03). Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging (MRI). Diarrhea, nausea, and hair thinning were more common with teriflunomide than with placebo. The incidence of elevated alanine aminotransferase levels (≥1 times the upper limit of the normal range) was higher with teriflunomide at 7 mg and 14 mg (54.0% and 57.3%, respectively) than with placebo (35.9%); the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group (6.3%, 6.7%, and 6.7%, respectively). Serious infections were reported in 1.6%, 2.5%, and 2.2% of patients in the three groups, respectively. No deaths occurred. Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. (Funded by Sanofi

  18. [Cerebral primitive osteosarcoma, a radiological and histological atypia].

    PubMed

    Ahanogbe, K M H; Ibahioin, K; Karkouri, M; Dianka, M B; Akpo, W; El Azhari, A

    2016-10-01

    Osteosarcoma is a malignant mesenchymal tumor including cells that present an osteoblastic differentiation. On the skull, it has often extra-axial development associated with bone reaction. We report an atypical and rare case of intracranial or cerebral osteosarcoma underline the radiological and pathological diagnostic difficulties. Our case concerns a primary osteosarcoma without bone involvement in a 10-year old boy who was admitted for intracranial hypertension with progressive worsening and brachial monoparesis. Subtotal resection was performed but the postoperative course was not favorable. The child died five months after the initial surgery. Its radiological aspect prompted us evoke several diagnoses including glioma or meningioma. On the histological level, osteosarcoma, especially with poorly differentiated cells, can be deceiving with other processes, including a gliosarcoma that was revealed by simple microscopic reading before being confirmed by an immunohistochemical study. In the absence of any bone reaction or known extra-cranial location, it can be difficult to suggest the diagnosis of osteosarcoma based on imagery alone. Immunohistochemistry is essential for an accurate diagnosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Clinical and histological features of nonalcoholic steatohepatitis in Iranian patients

    PubMed Central

    Bahrami, Hossein; Daryani, Nasser Ebrahimi; Mirmomen, Shahram; Kamangar, Farin; Haghpanah, Babak; Djalili, Mehdi

    2003-01-01

    Background Although several studies have been performed on risk factors and natural course of NASH, it seems that NASH tends to be more than a disease confined to strict boundaries. The objective of this study was to assess the clinical and paraclinical features and risk factors for non-alcoholic steatohepatitis (NASH) patients in an Iranian population Methods Patients with histologically confirmed NASH who had elevated liver aminotransaminases, negative serologic markers of viral or autoimmune hepatitis and no findings in favor of metabolic liver disease were enrolled. A careful history was taken regarding alcohol intake. Results 53 patients consisting of 32 male and 21 female entered the study. The mean age was 37.8 ± 11.3 years. Twenty-six patients (55.3%) were overweight, 15 (31.9%) obese, 40 (75.5%) dyslipidemic, and three patients (5.7%) were diabetic. Liver biopsy showed mild steatosis in 35.7%, moderate steatosis in 53.6%, and severe forms in 10.7%. In 80.2% of patients, portal inflammation was present, and 9.4% had cirrhosis. The amount of increase in liver enzymes bore no relationship with fibrosis, portal inflammation, and degree of steatosis. Conclusions The patients in our study showed a male predominancy and were somewhat younger than other studies. PMID:14561231

  20. A histological study of cerebral aqueduct.

    PubMed

    Stanković, Gordana; Nikolić, Valentina; Puskas, Laslo; Filipović, Branislav; Stojsić-Dzunja, Ljubica; Krivokuća, Dragan

    2005-01-01

    Cerebral (sylvian) aqueduct is a narrow channel in the mesencephalon. It lies between the tectum and the tegmentum of the mesencephalon and is surrounded by the periaqueductal gray matter. The aim of this study was to determine the shape of the aqueduct of sylvius and the structure of its walls in a series of transverse histological sections. Serial transverse sections of the mesencephalon were examined in twenty adult brains of both sexes. Six sections were stained by the hematoxylin-eosin method. The rostral part of the the aqueduct has a triangular shape with dorsal concavity caused by retrocommissural fossae. In the middle, its shape is oval to irregular, the rostral part has a T shape due to isthmic recess on the floor. Walls of the aqueduct are coated with a layer of prismatic cells. Determination of the morphological and histological features of the mesencephalic aqueduct is important for differentiation between physiological and pathological processes in this region.

  1. Histological structure affects recellularization of decellularized arteries.

    PubMed

    Negishi, Jun; Hashimoto, Yoshihide; Yamashita, Akitatsu; Kimura, Tsuyoshi; Kishida, Akio; Funamoto, Seiichi

    2017-01-01

    Decellularized arteries were prepared to evaluate the in vivo recellularization of biological material after implantation. Porcine aortas and radial arteries were decellularized using high-hydrostatic pressure to form materials with histologically-different structures. Successful removal of cells from decellularized arteries was evaluated by hematoxylin-eosin staining and measurement of residual DNA. Cell remnants were eliminated completely from the decellularized arteries, and histological structures were preserved. Cells adhered to all decellularized artery samples, but infiltration of cells was observed only from the adventitial side of the decellularized radial artery. Rats were implanted subcutaneously with a decellularized aorta or radial artery to evaluate in vivo performance. Decellularized aortic tissue prevented cell infiltration better than that of the decellularized radial artery, suggesting that the elastin lamina in decellularized tissues prevents cell infiltration and suppresses recellularization. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Graves' disease associated with histologic Hashimoto's thyroiditis.

    PubMed

    Falk, S A; Birken, E A; Ronquillo, A H

    1985-02-01

    The microscopic slides of 16 patients who underwent bilateral subtotal thyroidectomy for hyperthyroid Graves' disease were reviewed and classified into three groups: I, Hashimoto's thyroiditis; II, Graves' disease; and III, both Hashimoto's thyroiditis and Graves' disease. Three patients were classified as group I, 10 as group II, and three as group III. In 38% of the patients with clinical Graves' disease the histologic evidence of Hashimoto's thyroiditis could be found either alone or in combination with histologic evidence of Graves' disease (groups I and III). One patient in group I, four in group II, and three in group III had infiltrative ophthalmopathy (50% of total). Hyperthyroid Graves' disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis can occur all together, in duads, or individually at a specific time in a patient's life.

  3. A focus group study of predictors of relapse in electronic gaming machine problem gambling, part 2: factors that 'pull' the gambler away from relapse.

    PubMed

    Oakes, J; Pols, R; Battersby, M; Lawn, S; Pulvirenti, M; Smith, D

    2012-09-01

    This study aimed to develop an empirically based description of relapse in Electronic Gaming Machine (EGM) problem gambling (PG) by describing the processes and factors that 'pull' the problem gambler away from relapse contrasted with the 'push' towards relapse. These conceptualisations describe two opposing, interacting emotional processes occurring within the problem gambler during any relapse episode. Each relapse episode comprises a complex set of psychological and social behaviours where many factors interact sequentially and simultaneously within the problem gambler to produce a series of mental and behaviour events that end (1) with relapse where 'push' overcomes 'pull' or (2) continued abstinence where 'pull' overcomes 'push'. Four focus groups comprising thirty participants who were EGM problem gamblers, gamblers' significant others, therapists and counsellors described their experiences and understanding of relapse. The groups were recorded, recordings were then transcribed and analysed using thematic textual analysis. It was established that vigilance, motivation to commit to change, positive social support, cognitive strategies such as remembering past gambling harms or distraction techniques to avoid thinking about gambling to enable gamblers to manage the urge to gamble and urge extinction were key factors that protected against relapse. Three complementary theories emerged from the analysis. Firstly, a process of reappraisal of personal gambling behaviour pulls the gambler away from relapse. This results in a commitment to change that develops over time and affects but is independent of each episode of relapse. Secondly, relapse may be halted by interacting factors that 'pull' the problem gambler away from the sequence of mental and behavioural events, which follow the triggering of the urge and cognitions to gamble. Thirdly, urge extinction and apparent 'cure' is possible for EGM gambling. This study provides a qualitative, empirical model for

  4. Histologic changes in previously irradiated thyroid glands

    SciTech Connect

    Valdiserri, R.O.; Borochovitz, D.

    1980-03-01

    Thyroid tissue from 90 patients with a history of therapeutic irradiation to the head and neck in childhood and adolescence was examined microscopically. In addition to the well-known observation that these individuals have an increased incidence of primary thyroid carcinoma, it was also demonstrated that they have an increased incidence of benign histologic changes. These changes represent a spectrum from nonspecific hyperplastic lesions to benign neoplasis and thyroidltis.

  5. Normal Vulvar Histology: Variation by Site.

    PubMed

    Day, Tania; Holland, Seán M; Scurry, James

    2016-01-01

    The aim of the study was to assess the histology of normal vulvar skin with attention to anatomic location and epithelium type. We performed a retrospective histologic review of 118 vulvar biopsies and excisions obtained between 2010 and 2014 with adjacent normal skin or mucosa. Exclusions included age younger than 18 years, vestibulectomy, labiaplasty, inflammatory dermatoses, and insufficient normal tissue for assessment. Stratum corneum morphology was assessed as basket weave, compact, or intermediate. Stratum granulosum cell layer number and epithelial thickness were recorded. Dermal lymphocytic infiltrate was described as nil, sparse, moderate, or dense. Fischer exact test, Pearson χ, and Student t test were used for statistical analysis. There were 7 cases from mons pubis, 11 from perineum, 83 from labia, and 17 from vestibule. In the skin, the stratum corneum morphology was basket weave in 31%, compact in 35%, and intermediate in 34%. Stratum corneum at the mons pubis was uniformly basket weave, whereas at perineum, it was either compact or intermediate (7/7 vs 0/11; p < .001); the labia demonstrated all 3 morphologies. Parakeratosis (PK) was identified at the specimen edge in 4 cases of hairless skin and 7 cases of squamous mucosa. Mean epithelial thickness and dermal lymphocytic infiltration were similar in specimens with and without PK. Compact stratum corneum of vulvar skin and a zone of PK at the mucocutaneous junction may be normal histological findings. Pathologists need to be aware of site-related differences of the vulvar epithelium to avoid overdiagnosis of pathological conditions.

  6. Anatomy and histology of Virchow's node.

    PubMed

    Mizutani, Masaomi; Nawata, Shin-ichi; Hirai, Ichiro; Murakami, Gen; Kimura, Wataru

    2005-12-01

    A regional lymphatic system is composed of the first, second, third and even fourth or much more intercalated nodes along the lymptatic route from the periphery to the venous angle or the thoracic duct. The third or fourth node is usually termed the last-intercalated node or end node along the route. Similarly, one of the supraclavicular nodes is known to correspond to the end node along the thoracic duct. It is generally called 'Virchow's node', in which the famous 'Virchow's metastasis' of advanced gastric cancer occurs. The histology of this node has not been investigated, although region-specific differences in histology are evident in human lymph nodes. We found macroscopically the end node in five of 30 donated cadavers. Serial sections were prepared for these five nodes and sections stained with hematoxylin and eosin. Histological investigation revealed that, on the inferior or distal side of the end node, the thoracic duct divided into three to 10 collateral ducts and these ducts surrounded the node. The node communicated with the thoracic duct and its collaterals at multiple sites in two to three hilus-like portions, as well as along the subcapsular sinus. Thus, the end node was aligned parallel to the thoracic duct. Moreover, the superficial and deep cortex areas of the end node were fragmented to make an island-like arrangement, which may cause the short-cut intranodal shunt. Consequenly, the filtration function of most of Virchow's node seemed to be quite limited.

  7. Histological changes of kidney in diabetic nephropathy

    PubMed Central

    Pourghasem, Mohsen; Shafi, Hamid; Babazadeh, Zahra

    2015-01-01

    Diabetes mellitus is the most common cause of chronic renal disorders and end-stage kidney disease in developed countries. It is the major cause of dialysis and transplantation. Failure in renal function causes wide disorders in the body. Diabetes results in wide range of alterations in the renal tissue. It is believed that early histological changes in diabetic nephropathy are detectable 2 years after diabetes is diagnosed. The glomerular alterations are the most important lesions in the diabetic nephropathy (DN). The Renal Pathology Society provides a new pathological classification for the detection of histopathology of DN. It divides diabetic nephropathy into four hierarchical glomerular lesions. Alloxan or streptozotocin induced diabetic rat is the one most widely used specie to study DN. Histological changes in the rat DN closely resemble the human disease and the most information of this review was obtained through the study of rat DN. All cell types of the kidney such as mesangial cells, podocytes and tubulointerstitial cells are liable to be affected in the event of DN. Severity of renal lesions is associated to the clinical aspect of renal outcome, but the aim of this article was only to review the histological changes of kidney in diabetes mellitus. PMID:26644877

  8. Charcoal kiln relicts - a favorable site for tree growth?

    NASA Astrophysics Data System (ADS)

    Buras, Allan; Hirsch, Florian; van der Maaten, Ernst; Takla, Melanie; Räbiger, Christin; Cruz Garcia, Roberto; Schneider, Anna; Raab, Alexandra; Raab, Thomas; Wilmking, Martin

    2015-04-01

    Soils with incompletely combusted organic material (aka 'black carbon') are considered fertile for plant growth. Considerable enrichment of soils with black carbon is known from Chernozems, from anthropogenic induced altering of soils like the 'Terra Preta' in South America (e.g. Glaser, 2001), and from charcoal kiln relicts. Recent studies have reported a high spatial frequency of charcoal kiln relicts in the Northeastern German lowlands (Raab et al., 2015), which today are often overgrown by forest plantations. In this context the question arises whether these sites are favorable for tree growth. Here we compare the performance of 22 Pinus sylvestris individuals - a commonly used tree species in forestry - growing on charcoal kiln relicts with 22 control trees. Growth performance (height growth and diameter growth) of the trees was determined using dendrochronological techniques, i.e. standard ring-width measurements were undertaken on each two cores per tree and tree height was measured in the field. Several other wood properties such as annual wood density, average resin content, as well as wood chemistry were analyzed. Our results indicate that trees growing on charcoal kiln relicts grow significantly less and have a significantly lower wood density in comparison with control trees. Specific chemical components such as Manganese as well as resin contents were significantly higher in kiln trees. These results highlight that tree growth on charcoal kiln relicts is actually hampered instead of enhanced. Possibly this is a combined effect of differing physical soil properties which alter soil water accessibility for plants and differing chemical soil properties which may negatively affect tree growth either if toxic limits are surpassed or if soil nutrient availability is decreased. Additional soil analyses with respect to soil texture and soil chemistry shall reveal further insight into this hypothesis. Given the frequent distribution of charcoal kiln relicts in

  9. Peripheral blood eosinophilia has a favorable prognostic impact on transplant outcomes after allogeneic peripheral blood stem cell transplantation.

    PubMed

    Kim, Dong Hwan; Popradi, Gizelle; Xu, Wei; Gupta, Vikas; Kuruvilla, John; Wright, Janice; Messner, Hans A; Lipton, Jeffrey H

    2009-04-01

    Peripheral eosinophilia after allogeneic stem cell transplant (ASCT) may reflect the activation of the Th2 cytokine pathway. A retrospective analysis was performed to evaluate the impact of early- (before day 100: EEo) or late-onset (beyond day 100: LEo) eosinophilia (> or =0.5 x 10(9)/L in peripheral blood) on transplant outcomes after peripheral blood SCT (PBSCT) in 237 patients. The incidence of EEo and LEo was 43% at day 100 and 62% at 2 years, respectively. Compared with patients without LEo, improved transplant outcomes were observed in patients with LEo: better overall survival (OS; 86% versus 41%, P = 5 x 10(-11)), lower nonrelapse mortality (NRM; 10% versus 37%, P = 3 x 10(-6)), lower relapse incidence (11% versus 31%, P = 3 x 10(-5)), and higher GVHD-specific survival (GSS; 90% versus 64%, P = 1 x 10(-6)) were observed. In addition, similar finding was observed when transplant outcomes were analyzed according to the occurrence of eosinophilia at the onset of cGVHD. The multivariate analyses confirmed a favorable implication of LEo on OS, NRM, and GSS. LEo was associated with: (1) less severe chronic GVHD (cGVHD), (2) higher prevalence of autoantibodies, and (3) rapid lymphocyte count recovery after ASCT. In summary, the development of eosinophila after allogeneic PBSCT seemed to be a prognostic marker for improving transplant outcome.

  10. Genetic and epigenetic heterogeneity and the impact on cancer relapse.

    PubMed

    Hassan, Ciaran; Afshinnekoo, Ebrahim; Li, Sheng; Wu, Shixiu; Mason, Christopher E

    2017-10-01

    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with an exceedingly poor prognosis: a 5-year overall survival rate of 40%-45% in the young and a 5-year survival rate of less than 10% in the elderly (>60 years of age). Although a high percentage of patients enters complete remission after chemotherapeutic intervention, the majority of patients relapse within 3 years. Such stark prognostic outcomes highlight the need for additional clinical research, basic discovery, and molecular delineation of the etiologies and mechanisms behind responses to therapy that lead to relapse. Here, we summarize recent discoveries in tumor heterogeneity at the genetic and epigenetic levels and their independent molecular trajectories and dynamics in response to therapy. These new discoveries may have significant implications for understanding, monitoring, and treating leukemia and other cancers. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  11. Using conditioned place preference to identify relapse prevention medications.

    PubMed

    Napier, T Celeste; Herrold, Amy A; de Wit, Harriet

    2013-11-01

    Stimuli, including contexts, which predict the availability or onset of a drug effect, can acquire conditioned incentive motivational properties. These conditioned properties endure after withdrawal, and can promote drug-seeking which may result in relapse. Conditioned place preference (CPP) assesses the associations between drugs and the context in which they are experienced. Here, we review the potential utility of CPP procedures in rodents and humans to evaluate medications that target conditioned drug-seeking responses. We discuss the translational potential of the CPP procedure from rodents to humans, and review findings with FDA-approved treatments that support the use of CPP to develop relapse-reduction medications. We also discuss challenges and methodological questions in applying the CPP procedure to this purpose. We argue that an efficient and valid CPP procedure in humans may reduce the burden of full clinical trials with drug-abusing patients that are currently required for testing promising treatments.

  12. Relapsing Fever: Diagnosis Thanks to a Vigilant Hematology Laboratory.

    PubMed

    Fuchs, Inbal; Tarabin, Salman; Kafka, Michael

    2015-07-01

    Three cases of relapsing fever from southern Israel were diagnosed promptly thanks to vigilance of the hematology laboratory technicians. In this region of Israel, patients presenting with prolonged fever and leukopenia without localizing symptoms are generally suspected of having brucellosis or a rickettsial disease. Pediatric patients with prolonged fever, cytopenias, and negative aforementioned serologies are often hospitalized for further work-up. Because of the policy of performing a manual blood smear when results of the automated blood count demonstrate severe anemia and abnormal platelet and/or white blood cell counts, a diagnosis of tick-borne relapsing fever was confirmed and promptly relayed to the physician. This routine prevented unnecessary examinations and hospitalization days and provided important information to regional epidemiology and public health authorities.

  13. Genomic Evolution of Breast Cancer Metastasis and Relapse

    DOE PAGES

    Yates, Lucy R.; Knappskog, Stian; Wedge, David; ...

    2017-08-14

    Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

  14. Effectiveness of adding relapse prevention materials to telephone counseling

    PubMed Central

    Sheffer, Christine E.; Stitzer, Maxine; Brandon, Thomas; Bursac, Zoran

    2012-01-01

    The purpose of this study was to examine the effectiveness of adding the Forever Free relapse prevention materials to telephone counseling provided by the Arkansas quitline. Results suggest that the addition of Forever Free materials to telephone counseling does not improve abstinence rates for those participants who receive at least one session of counseling and nicotine patches; however, for those participants unwilling or unable to receive nicotine patches, the addition of the Forever Free relapse prevention materials doubled the abstinence rate and increased the odds of abstinence by nearly 70% 6 months after treatment (20.9% versus 10.6%; OR=1.69; CI=1.02–2.78; p=0.04). Given the recent proliferation of quitline services and the variety of services provided, these results can address concerns about enhancing treatment outcomes for certain groups. PMID:20682187

  15. Mutations driving CLL and their evolution in progression and relapse

    PubMed Central

    Landau, Dan A.; Tausch, Eugen; Taylor-Weiner, Amaro N; Stewart, Chip; Reiter, Johannes G.; Bahlo, Jasmin; Kluth, Sandra; Bozic, Ivana; Lawrence, Mike; Böttcher, Sebastian; Carter, Scott L.; Cibulskis, Kristian; Mertens, Daniel; Sougnez, Carrie; Rosenberg, Mara; Hess, Julian M.; Edelmann, Jennifer; Kless, Sabrina; Kneba, Michael; Ritgen, Matthias; Fink, Anna; Fischer, Kirsten; Gabriel, Stacey; Lander, Eric; Nowak, Martin A.; Döhner, Hartmut; Hallek, Michael; Neuberg, Donna; Getz, Gad; Stilgenbauer, Stephan; Wu, Catherine J.

    2015-01-01

    SUMMARY Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. We identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized cancer drivers (RPS15, IKZF3) and collectively identify RNA processing and export, MYC activity and MAPK signaling as central pathways involved in CLL. Clonality analysis of this large dataset further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatme