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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. 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.

  4. 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.

  5. 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.

  6. Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis

    PubMed Central

    Korelitz, Burton I; Sultan, Keith; Kothari, Megha; Arapos, Leo; Schneider, Judy; Panagopoulos, Georgia

    2014-01-01

    AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal. Two subgroups of patients were compared: group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD. RESULTS: Of 115 patients with longstanding UC reviewed, 68 patients met the inclusion criteria. Twenty patients were in group 1 and 48 in group 2. We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation. Overall, histological disease activity in the absence of gross/endoscopic disease was found in 31.2% (95%CI: 28%-35%) of colonoscopies performed on the entire cohort of 68 patients. Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients, 88% (95%CI: 72%-97%) vs 59% (95%CI: 53%-64%). Only 3/20 (15%) of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity (i.e., no endoscopic or histological activity) as compared to 37/48 (77%) of patients in group 2, and only 3.3% (95%CI: 0.09%-8.3%) of colonoscopies in group 1 had no histological inflammation compared to 23% (95%CI: 20%-27%) in group 2. CONCLUSION: Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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).

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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…

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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…

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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…

  5. 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…

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. [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.

  13. 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

  14. 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.

  15. 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)

  16. 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…

  17. [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.

  18. 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.

  19. 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.

  20. 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)

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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…

  12. 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…

  13. 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…

  14. 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.

  15. 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.

  16. [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.

  17. 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.

  18. 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…

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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…

  4. [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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. [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).

  19. 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.

  20. 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.

  1. 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

  2. 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

  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. 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".

  5. 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.

  6. 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

  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. 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.

  9. 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

  10. 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

  11. 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

  12. 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…

  13. 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…

  14. 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

  15. 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…

  16. 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…

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  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. 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.

  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. 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

  9. 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.

  10. 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,...

  11. 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 ...

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  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. 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

  10. 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

  11. 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

  12. 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…

  13. 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...

  14. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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...

  17. 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...

  18. 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,...

  19. 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,...

  20. 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,...

  1. 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,...

  2. 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,...

  3. 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...

  4. 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

  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. 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…

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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

  15. 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.

  16. 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

  17. 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

  18. Working Memory-Related Neural Activity Predicts Future Smoking Relapse

    PubMed Central

    Loughead, James; Wileyto, E Paul; Ruparel, Kosha; Falcone, Mary; Hopson, Ryan; Gur, Ruben; Lerman, Caryn

    2015-01-01

    Brief abstinence from smoking impairs cognition, particularly executive function, and this has a role in relapse to smoking. This study examined whether working memory-related brain activity predicts subsequent smoking relapse above and beyond standard clinical and behavioral measures. Eighty treatment-seeking smokers completed two functional magnetic resonance imaging sessions (smoking satiety vs 24 h abstinence challenge) during performance of a visual N-back task. Brief counseling and a short-term quit attempt followed. Relapse during the first 7 days was biochemically confirmed by the presence of the nicotine metabolite cotinine. Mean percent blood oxygen level-dependent (BOLD) signal change was extracted from a priori regions of interest: bilateral dorsolateral prefrontal cortex (DLPFC), medial frontal/cingulate gyrus, posterior cingulate cortex (PCC), and ventromedial prefrontal cortex. Signal from these brain regions and additional clinical measures were used to model outcome status, which was then validated with resampling techniques. Relapse to smoking was predicted by increased withdrawal symptoms, decreased left DLPFC and increased PCC BOLD percent signal change (abstinence vs smoking satiety). Receiver operating characteristic analysis demonstrated 81% area under the curve using these predictors, a significant improvement over the model with clinical variables only. The combination of abstinence-induced decreases in left DLPFC activation and reduced suppression of PCC may be a prognostic marker for poor outcome, specifically early smoking relapse. PMID:25469682

  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. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  11. Gestational Weight Gain in Japanese Women With Favorable Perinatal Outcomes

    PubMed Central

    Suzuki, Shunji

    2017-01-01

    Background We examined the optimal gestational weight gain (GWG) in the healthy Japanese women with favorable perinatal outcomes of singleton pregnancy. Methods We calculated the average GWG in the women whose height was 150 - 164 cm with favorable perinatal outcomes set for this study. The women were categorized to underweight, normal, overweight and obese based on the pre-pregnancy body mass index categories according to the Institute of Medicine guideline. Results The average GWG in the normal-weight women with the favorable perinatal outcomes was 11.4 ± 3.7 kg. It was not significantly different from that in the underweight and overweight women (12.0 ± 3.4 and 10.0 ± 4.8 kg) by Student’s t-test. The average GWG in the obese women was significantly lower than that in the other three groups (3.2 ± 2.2 kg, P < 0.01). Conclusion Based on the current results, the optimal GWG for the Japanese women without obesity was found to be 10 - 12 kg. PMID:27924177

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  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.

  9. 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.

  10. 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…

  11. 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

  12. 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…

  13. 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…

  14. 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

  15. 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…

  16. 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…

  17. 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…

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  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. 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.

  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. 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.

  8. 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.

  9. 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…

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  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. 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.

  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. 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

  1. 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.

  2. 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.

  3. 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

  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. 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...

  6. 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…

  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. 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

  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. 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.

  11. [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

  12. 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

  13. 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.

  14. 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-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing datasets of clinically informative samples enable the discovery of novel cancer genes and the network of relationships between the driver events and their impact on disease relapse and clinical outcome. PMID:26466571

  15. 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.

  16. 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.

  17. Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma

    PubMed Central

    Yang, Wen-Chi; Lin, Sheng-Fung

    2015-01-01

    Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM. PMID:26649299

  18. 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.

  19. 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%.

  20. 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

  1. 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.

  2. 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

  3. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    SciTech Connect

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  4. Cannabidiol reduces ethanol consumption, motivation and relapse in mice.

    PubMed

    Viudez-Martínez, Adrián; García-Gutiérrez, María S; Navarrón, Carmen María; Morales-Calero, María Isabel; Navarrete, Francisco; Torres-Suárez, Ana Isabel; Manzanares, Jorge

    2017-02-13

    This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling-induced convulsions associated to acute ethanol administration were evaluated. The two-bottle choice paradigm was performed to assess the effects of CBD (30, 60 and 120 mg/kg/day, i.p.) on ethanol intake and preference. In addition, an oral ethanol self-administration experiment was carried out to evaluate the effects of CBD [a single s.c. administration of a microparticle formulation providing CBD continuous controlled release (30 mg/kg/day)] on the reinforcement and motivation for ethanol. The effects of CBD (60 and 120 mg/kg/day, i.p.) on ethanol-induced relapse were also evaluated. Gene expression analyses of tyrosine hydroxylase in ventral tegmental area and μ-opioid (Oprm1), cannabinoid (CB1 r and CB2 r) and GPR55 receptors in nucleus accumbens (NAcc) were carried out by real-time polymerase chain reaction. Cannabidiol reduced the ethanol-induced hypothermia and handling-induced convulsion but failed to modify blood ethanol concentration. CBD reduced ethanol consumption and preference in the two-bottle choice, significantly decreased ethanol intake and the number of effective responses in the oral ethanol self-administration, and reduced ethanol-induced relapse. Furthermore, the administration of CBD significantly reduced relative gene expression of tyrosine hydroxylase in the ventral tegmental area, Oprm1, CB1 r and GPR55 in the NAcc and significantly increased CB2 r in the NAcc. Taken together, these results reveal that the administration of CBD reduced the reinforcing properties, motivation and relapse for ethanol. These findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.

  5. Stress enhancement of craving during sobriety: a risk for relapse.

    PubMed

    Breese, George R; Chu, Kathleen; Dayas, Christopher V; Funk, Douglas; Knapp, Darin J; Koob, George F; Lê, Dzung Anh; O'Dell, Laura E; Overstreet, David H; Roberts, Amanda J; Sinha, Rajita; Valdez, Glenn R; Weiss, Friedbert

    2005-02-01

    This report of the proceedings of a symposium presented at the 2004 Research Society on Alcoholism Meeting provides evidence linking stress during sobriety to craving that increases the risk for relapse. The initial presentation by Rajita Sinha summarized clinical evidence for the hypothesis that there is an increased sensitivity to stress-induced craving in alcoholics. During early abstinence, alcoholics who were confronted with stressful circumstances showed increased susceptibility for relapse. George Breese presented data demonstrating that stress could substitute for repeated withdrawals from chronic ethanol to induce anxiety-like behavior. This persistent adaptive change induced by multiple withdrawals allowed stress to induce an anxiety-like response that was absent in animals that were not previously exposed to chronic ethanol. Subsequently, Amanda Roberts reviewed evidence that increased drinking induced by stress was dependent on corticotropin-releasing factor (CRF). In addition, rats that were stressed during protracted abstinence exhibited anxiety-like behavior that was also dependent on CRF. Christopher Dayas indicated that stress increases the reinstatement of an alcohol-related cue. Moreover, this effect was enhanced by previous alcohol dependence. These interactive effects between stress and alcohol-related environmental stimuli depended on concurrent activation of endogenous opioid and CRF systems. A.D. Lê covered information that indicated that stress facilitated reinstatement to alcohol responding and summarized the influence of multiple deprivations on this interaction. David Overstreet provided evidence that restraint stress during repeated alcohol deprivations increases voluntary drinking in alcohol-preferring (P) rats that results in withdrawal-induced anxiety that is not observed in the absence of stress. Testing of drugs on the stress-induced voluntary drinking implicated serotonin and CRF involvement in the sensitized response

  6. Relapse of Yellow Nail Syndrome with Pulmonary Lymphedema.

    PubMed

    Morimoto, Kozo; Saraya, Takeshi; Kurosaki, Atsuko; Yano, Ryozo; Sasaki, Yuka; Osawa, Takeshi; Kudoh, Shoji; Goto, Hajime

    2016-01-01

    Yellow nail syndrome (YNS) is a rare disorder characterized by the triad of yellow, thickened nails, lymphedema, and respiratory manifestations such as pleural effusions, bronchiectasis, and recurrent lower respiratory tract infections. We report a case of YNS showing pulmonary interlobular septal thickening on thoracic computed tomography, implying the presence of lymphatic edema. The patient showed both the remission and relapse of yellow nail with different lung treatments over a long clinical course.

  7. Relapses in bipolar patients: changes in social rhythm?

    PubMed

    Kadri, Nadia; Mouchtaq, Nadia; Hakkou, Farid; Moussaoui, Driss

    2000-03-01

    The Ramadan month represents a valuable opportunity to test the hypothesis that the course of the illness of bipolar patients can be disrupted by the change in social rhythm which usually occurs during this month. The objectives of this study were to follow up the mood state and blood lithium level of fasting Muslim bipolar patients who had been on lithium therapy for at least 3 months, and were clinically stable before being included in the study. Twenty bipolar patients were enrolled during the month of Ramadan in 1997. Diagnosis of bipolar disorder was according to ICD-10 criteria. Patients were assessed during the week before Ramadan, the second and the fourth weeks of the fasting month and the first week after its end, with the Hamilton Depression and Bech-Rafaelsen scales. The plasma concentration of lithium was also assessed. The main finding of the study was that 45% of the patients relapsed, 70% during the second week and the remaining patients at the end of Ramadan. These relapses were not related to plasma concentration of lithium. Most of the relapses were manic (71.4 %). Patients who did not relapse had insomnia and anxiety during the second and third weeks of the study. Side-effects of lithium increased and were observed in 48% of the sample, mostly dryness of the mouth with thirst and tremor. The result of this pilot study indicates that the Ramadan month may disrupt the mood state of bipolar patients. More studies are needed to confirm this observation and to evaluate the validity of the Ramadan model to study the impact of social rhythms on bipolar patients.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Menarche Increases Relapse Risk in Pediatric Multiple Sclerosis

    PubMed Central

    Lulu, Sabeen; Graves, Jennifer; Waubant, Emmanuelle

    2015-01-01

    Background Multiple sclerosis (MS) predominantly affects women with a sex ratio of 3:1 in contrast with a 1:1 sex ratio seen in pre-pubertal onset. Thus, puberty may influence MS risk differentially in males and females. How puberty may be associated with MS clinical features and disease course remains unknown. Objective To determine the association of menarche with disease course in girls with MS. Methods This is a longitudinal retrospective study from the UCSF Regional Pediatric MS Center database. We categorized patients by time of disease onset: pre-menarche, peri-menarche and post-menarche. Poisson regression models were used for within subject relapse analyses offset by follow-up time. Results Seventy six girls were included (pre-menarche onset=17; peri-menarche onset=9; post-menarche onset=50). Age of menarche was similar in all groups (Kruskal-Wallis p=0.19). Relapse rate was the same in all three groups during first 2 years of follow-up. In girls with follow-up overlapping at least two time periods, within-subject analyses showed increased relapses during peri-menarche compared to post-menarche period (adjusted IRR=8.5, 95%CI 2.5–28.7, p=0.001). Conclusion Pubertal status may influence MS course at least in female patients. Understanding how puberty influences MS clinical features may offer new insights in important factors regulating disease processes. PMID:25948626

  17. Improving service delivery for relapse management in multiple sclerosis.

    PubMed

    Warner, Richard; Thomas, Del; Martin, Roswell

    This action research study was conducted over an 18 month period within a district general hospital. The study has improved the quality of the service provided to people experiencing a relapse of multiple sclerosis. The authors now identify and treat a three-fold increase in relapse patients. At least 85% of these patients are treated within 10 days of reporting symptoms to a specialist nurse. Before the study, only 12% of patients received treatment within this time. The authors' data identify what patients valued about this service and also inform debate around distress associated with relapse and how services should develop to respond to this. The study is of particular importance to the UK because the National Institute for Clinical Excellence (NICE) has published guidance to the NHS about the management of this specific patient group (NICE, 2003). This study also clearly demonstrates how specialist nursing services can combine a substantial clinical role with instigating and managing change in service delivery that results in improvements in patient care.

  18. Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor encephalitis.

    PubMed

    Pillai, Sekhar C; Gill, Deepak; Webster, Richard; Howman-Giles, Robert; Dale, Russell C

    2010-09-01

    N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2) with relapsing NMDA receptor encephalitis each had the classic clinical features of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia, and mild autonomic dysfunction. Both patients had persistent neuropsychiatric disability, despite immune therapies. Positron emission tomography (PET) scans were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2). In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in the cerebral cortex, with the temporal regions being most affected. PET imaging was more sensitive than magnetic resonance imaging in these patients. In contrast, the one previous report of acute NMDA receptor encephalitis indicated cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with variable PET findings, possibly dependent upon the timing of the study, or other factors. Future studies should investigate whether cortical hypometabolism is associated with a relapsing course, and whether it is predictive of a poorer outcome in NMDA receptor encephalitis.

  19. Relapsed/refractory diffuse large B-cell lymphoma.

    PubMed

    Friedberg, Jonathan W

    2011-01-01

    Despite overall improvements in outcomes of diffuse large B-cell lymphoma (DLBCL), approximately one-third of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality. Novel insights from gene-expression analyses have increased our understanding of chemotherapy resistance and yielded rational targets for therapeutic intervention to both prevent and treat relapsed/refractory DLBCL. The clinical approach to relapsed/refractory DLBCL should include high-dose therapy and autologous stem cell transplantation (HD-ASCT) with curative intent in patients without comorbidities. Results from the recently reported CORAL study suggest that patients refractory to rituximab-containing regimens have inferior outcomes with HD-ASCT. Ongoing efforts to improve ASCT include novel conditioning regimens and evaluation of maintenance approaches after ASCT. Unfortunately, because the majority of patients are not eligible for ASCT due to refractory disease or age/comorbidities, these approaches have limited impact. The large group of patients not eligible for ASCT have incurable disease and should be referred for clinical trials of rationally targeted agents.

  20. A parametric estimation procedure for relapse time distributions.

    PubMed

    Ahlström, L; Olsson, M; Nerman, O

    1999-06-01

    In a relapse clinical trial patients who have recovered from some recurrent disease (e.g., ulcer or cancer) are examined at a number of predetermined times. A relapse can be detected either at one of these planned inspections or at a spontaneous visit initiated by the patient because of symptoms. In the first case the observations of the time to relapse, X, is interval-censored by two predetermined time-points. In the second case the upper endpoint of the interval is an observation of the time to symptoms, Y. To model the progression of the disease we use a partially observable Markov process. This approach results in a bivariate phase-type distribution for the joint distribution of (X, Y). It is a flexible model which contains several natural distributions for X, and allows the conditional distributions of the marginals to smoothly depend on each other. To estimate the distributions involved we develop an EM-algorithm. The estimation procedure is evaluated and compared with a non-parametric method in a couple of example based on simulated data.

  1. Changes in urinary metabolomic profile during relapsing renal vasculitis

    PubMed Central

    Al-Ani, Bahjat; Fitzpatrick, Martin; Al-Nuaimi, Hamad; Coughlan, Alice M.; Hickey, Fionnuala B.; Pusey, Charles D.; Savage, Caroline; Benton, Christopher M.; O’Brien, Eóin C.; O’Toole, Declan; Mok, Ken H.; Young, Stephen P.; Little, Mark A.

    2016-01-01

    Current biomarkers of renal disease in systemic vasculitis lack predictive value and are insensitive to early damage. To identify novel biomarkers of renal vasculitis flare, we analysed the longitudinal urinary metabolomic profile of a rat model of anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. Wistar-Kyoto (WKY) rats were immunised with human myeloperoxidase (MPO). Urine was obtained at regular intervals for 181 days, after which relapse was induced by re-challenge with MPO. Urinary metabolites were assessed in an unbiased fashion using nuclear magnetic resonance (NMR) spectroscopy, and analysed using partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLS-R). At 56 days post-immunisation, we found that rats with vasculitis had a significantly different urinary metabolite profile than control animals; the observed PLS-DA clusters dissipated between 56 and 181 days, and re-emerged with relapse. The metabolites most altered in rats with active or relapsing vasculitis were trimethylamine N-oxide (TMAO), citrate and 2-oxoglutarate. Myo-inositol was also moderately predictive. The key urine metabolites identified in rats were confirmed in a large cohort of patients using liquid chromatography–mass spectrometry (LC-MS). Hypocitraturia and elevated urinary myo-inositol remained associated with active disease, with the urine myo-inositol:citrate ratio being tightly correlated with active renal vasculitis. PMID:27905491

  2. Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia.

    PubMed

    van Delft, Frederik W; Horsley, Sharon; Colman, Sue; Anderson, Kristina; Bateman, Caroline; Kempski, Helena; Zuna, Jan; Eckert, Cornelia; Saha, Vaskar; Kearney, Lyndal; Ford, Anthony; Greaves, Mel

    2011-06-09

    B-cell precursor childhood acute lymphoblastic leukemia with ETV6-RUNX1 (TEL-AML1) fusion has an overall good prognosis, but relapses occur, usually after cessation of treatment and occasionally many years later. We have investigated the clonal origins of relapse by comparing the profiles of genomewide copy number alterations at presentation in 21 patients with those in matched relapse (12-119 months). We identified, in total, 159 copy number alterations at presentation and 231 at relapse (excluding Ig/TCR). Deletions of CDKN2A/B or CCNC (6q16.2-3) or both increased from 38% at presentation to 76% in relapse, suggesting that cell-cycle deregulation contributed to emergence of relapse. A novel observation was recurrent gain of chromosome 16 (2 patients at presentation, 4 at relapse) and deletion of plasmocytoma variant translocation 1 in 3 patients. The data indicate that, irrespective of time to relapse, the relapse clone was derived from either a major or minor clone at presentation. Backtracking analysis by FISH identified a minor subclone at diagnosis whose genotype matched that observed in relapse ∼ 10 years later. These data indicate subclonal diversity at diagnosis, providing a variable basis for intraclonal origins of relapse and extended periods (years) of dormancy, possibly by quiescence, for stem cells in ETV6-RUNX1(+) acute lymphoblastic leukemia.

  3. Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis.

    PubMed

    Yang, Xiao-Lai; Guo, Tian-Kang; Wang, Yan-Hong; Huang, Yan-Hui; Liu, Xia; Wang, Xiao-Xia; Li, Wan; Zhao, Xin; Wang, Li-Ping; Yan, Shuai; Wu, Di; Wu, Yong-Jie

    2012-02-01

    In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.

  4. American cutaneous leishmaniasis: use of a skin test as a predictor of relapse after treatment.

    PubMed Central

    Passos, V. M.; Barreto, S. M.; Romanha, A. J.; Krettli, A. U.; Volpini, A. C.; Lima e Costa, M. F.

    2000-01-01

    While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test has been described until now to predict such relapses. A cohort of 318 American cutaneous leishmaniasis patients was followed up for two years after treatment with meglumine antimoniate, during which time 32 relapses occurred, 30 in the first year and two in the second (accumulated risk: 10.5%). No association was found between these relapses and the parasite-specific antibody response before and after treatment, or between the relapses and stratification by sociodemographic and clinical characteristics. However when Leishmania was used as antigen, patients with a negative skin test at the time of diagnosis presented a 3.4-fold higher risk (hazard risk = 3.4; 95% confidence interval, 1.7-7.0) of American cutaneous leishmaniasis relapse, compared with patients with a positive response. This result shows that the skin test can be a predictor of American cutaneous leishmaniasis relapse after treatment. PMID:10994280

  5. Phase II study of bendamustine combined with rituximab in relapsed/refractory mantle cell lymphoma: efficacy, tolerability, and safety findings.

    PubMed

    Czuczman, Myron S; Goy, A; Lamonica, D; Graf, D A; Munteanu, M C; van der Jagt, R H

    2015-12-01

    In most cases of relapsed/refractory mantle cell lymphoma (MCL), patients respond to salvage therapy, though typically responses are partial and/or transient followed by disease progression, even with newer agents (e.g., ibrutinib). In this multicenter, open-label, single-arm, phase II study, patients with relapsed/refractory non-blastoid MCL received bendamustine 90 mg/m(2) (days 1 and 2) and rituximab 375 mg/m(2) (day 1) for 6 planned 28-day cycles. Functional imaging with 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) was conducted at baseline and after cycle 6. Forty-five patients were enrolled (median age, 70 years; 82 % stage IV disease; median number of prior chemotherapies, 2 [range, 1-4]), showing an overall response rate (ORR; primary efficacy measure) of 82 % (complete response [CR], 40 %; partial response, 42 %). In the 32 patients with complete 18F-FDG PET/CT data, 75 % achieved a complete metabolic response. Median duration of response was 1.6 years, 1-year progression-free survival was 67 %, and 3-year overall survival was 55 %. Main non-hematologic adverse events were nausea (69 %), fatigue (56 %), decreased appetite (42 %), constipation (38 %), diarrhea (36 %), vomiting (36 %), and decreased weight (31 %). Grade 3/4 neutropenia and lymphopenia occurred in 44 and 89 % of patients, respectively. ORR and CR rate compared favorably with single-agent ibrutinib (ORR, 67 %; CR, 23 %); bendamustine-rituximab is an effective therapy with manageable toxicity in relapsed/refractory MCL.

  6. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Kim, Ji Hyun; Stein, Anthony; Schultheiss, Timothy E.; Palmer, Joycelynne; Liu, An; Rosenthal, Joseph; Forman, Stephen J.

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  7. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma.

    PubMed

    García-Sanz, R; González-Porras, J R; Hernández, J M; Polo-Zarzuela, M; Sureda, A; Barrenetxea, C; Palomera, L; López, R; Grande-García, C; Alegre, A; Vargas-Pabón, M; Gutiérrez, O N; Rodríguez, J A; San Miguel, J F

    2004-04-01

    We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients, including a prognostic analysis to predict both response and survival. Patients received thalidomide at escalating doses (200-800 mg/day), daily cyclophosphamide (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an intention-to-treat basis and using the EBMT response criteria, 2% patients reached complete response (CR), 55% partial response (PR) and 26% minor response (MR) yielding a total response (CR+PR+MR) rate of 83% after 3 months of therapy. After 6 months of therapy, responses were maintained including a 10% CR. The 2-year progression free and overall survival were 57 and 66%, respectively. A favorable response was associated with beta2 microglobulin < or =4 mg/dl, platelets >80 x 10(9)/l and nonrefractory disease. Regarding survival, low beta2 microglobulin (< or =4 mg/dl), age (< or =65 years) and absence of extramedullary myelomatous lesion were associated with a longer survival. Major adverse effects included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%). Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral regimen that induces a high response rate and long remissions, particularly in relapsing patients with beta2 microglobulin < or =4 mg/dl and < or =65 years.

  8. Substance Abuse, Relapse, and Treatment Program Evaluation in Malaysia: Perspective of Rehab Patients and Staff Using the Mixed Method Approach

    PubMed Central

    Chie, Qiu Ting; Tam, Cai Lian; Bonn, Gregory; Dang, Hoang Minh; Khairuddin, Rozainee

    2016-01-01

    This study examined reasons for substance abuse and evaluated the effectiveness of substance treatment programs in Malaysia through interviews with rehab patients and staff. Substance rehab patients (aged 18–69 years; n = 30) and staff (ages 30–72 years; n = 10) participated in semi-structured interviews covering a range of topics, including family and peer relationships, substance use and treatment history, factors for substance use and relapse, motivation for entering treatment, work experience, job satisfaction, treatment evaluation, and patient satisfaction. Most patients did not demonstrate the substance progression trend and had normal family relationships. Most patients reported having peers from normal family backgrounds as well. Various environmental and personal factors was cited as contributing to substance abuse and relapse. There was no significant difference between patient and staff program evaluation scores although the mean score for patients was lower. A holistic treatment approach with a combination of cognitive–behavioral, medical, social, and spiritual components was favored by patients. Suggestions for improving existing programs include better tailoring treatment to individual needs, and providing more post-treatment group support. PMID:27303313

  9. 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

  10. 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

  11. Autologous transplant remains the preferred therapy for relapsed APL in CR2.

    PubMed

    Ganzel, C; Mathews, V; Alimoghaddam, K; Ghavamzadeh, A; Kuk, D; Devlin, S; Wang, H; Zhang, M-J; Weisdorf, D; Douer, D; Rowe, J M; Polge, E; Esteve, J; Nagler, A; Mohty, M; Tallman, M S

    2016-09-01

    Despite their favorable prognosis, 10-20% of acute promyelocytic leukemia (APL) patients relapse. Reinduction therapy is often followed by autologous hematopoietic cell transplantation (auto-HCT). Arsenic trioxide (ATO) has become part of standard reinduction and is often followed by auto-HCT. Data on patients in CR2 were collected from two large transplant registries (Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplant (EBMT)) and two specialty referral centers. The outcome of patients in CR2 who received only ATO-based therapy as reinduction was retrospectively compared with those who got an auto-HCT, with or without ATO. Prognostic factors included age, disease risk, extramedullary disease and duration of CR1. Of 207 evaluable patients, the median age was 31.5 years, 15.3% had extramedullary disease and median WBC at diagnosis was 4.8 × 10(9)/L. Sixty-seven patients received ATO alone and 140 underwent auto-HCT. The groups were comparable for age, gender, extramedullary disease, risk group and duration of CR1. At 5 years, overall survival (OS) was 42% and 78% for the ATO-only and auto-HCT groups, respectively (P<0.001). In addition, OS was associated with longer duration of CR1 (P=0.002), but not with disease risk at diagnosis. These data suggest that auto-HCT for APL patients in CR2 results in better OS than ATO-based therapy alone.

  12. Remission of Severe, Relapsed, and Refractory TTP after Multiple Cycles of Bortezomib

    PubMed Central

    Pandey, Manu R.; Ontiveros, Evelena P.

    2017-01-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by autoantibodies against a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Uncleaved von Willebrand factor (VWF) multimers accumulate and bind to platelets which causes spontaneous microthrombi ultimately causing microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia. Plasma exchange (PEX) with or without steroids constitutes standard first-line therapy with rituximab typically reserved for refractory cases. Therapies beyond rituximab lack strong evidence for routine use. Recently, bortezomib, a proteasome inhibitor used commonly in patients with multiple myeloma, was shown to induce remission in patients with refractory TTP. Here, we report a case of severe, relapsed TTP that was refractory to PEX, steroids, and rituximab that underwent remission following three cycles of bortezomib. We discuss the salient features of our case, the mechanism of action of bortezomib, and the very few other similar reports that exist in the literature. We conclude that bortezomib should be considered for patients with TTP refractory to PEX, steroids, and rituximab due to its efficacy and relatively favorable side effect profile. PMID:28367342

  13. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    ClinicalTrials.gov

    2017-03-17

    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  14. Understanding the molecular basis of histologic grade.

    PubMed

    Ignatiadis, M; Sotiriou, C

    2008-01-01

    Histologic grading in breast cancer is based on the evaluation of 3 morphologic features (tubule formation, nuclear pleomorphism and mitotic count), is essentially describing proliferation and differentiation in breast cancer, and is considered an important prognostic factor for this disease. It has been suggested that histologic grade 1 and 3 breast tumors are 2 different diseases that may have distinct molecular origins, pathogenesis and natural history. Different single markers like Ki-67, thymidine labeling index and S phase fraction/flow cytometry have been studied as markers of proliferation, but none of them, with the possible exception of Ki-67, is currently employed routinely in clinical practice. The advent of the powerful microarray technology has enabled scientists to comprehensively study proliferation in breast cancer on a genome-wide scale. A gene expression grade index (GGI) was developed that challenges the existence and clinical relevance of an intermediate grade 2 classification. The GGI could reclassify patients with histologic grade 2 tumors into 2 groups with high versus low risks of recurrence. GGI has also been used to define 2 clinically relevant subgroups in estrogen receptor-positive breast carcinomas. Finally, in the largest meta-analysis of publicly available gene expression and clinical data, 4 stable molecular subgroups of breast cancer have been identified, namely ER-/HER-, HER2+ and ER+/HER2-, which was divided into 2 subgroups (ER+/low proliferation and ER+/high proliferation). In this same meta-analysis, proliferation was shown to be the common driving force responsible for the performance of various breast cancer prognostic signatures.

  15. Histological characteristics of diffuse idiopathic skeletal hyperostosis.

    PubMed

    Kuperus, Jonneke S; Westerveld, L Anneloes; Rutges, Joost P H J; Alblas, Jacqueline; van Rijen, Mattie H P; Bleys, Ronald L A W; Öner, F Cumhur; Verlaan, Jorrit-Jan

    2017-01-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a predominantly radiographic diagnosis and histological knowledge of DISH is limited. The aim of this study was to describe the histological characteristics of DISH in the spinal column and to study the relation between DISH and intervertebral disc (IVD) degeneration. Therefore, 10 human cadaveric spines with fluoroscopic evidence of DISH were compared with 10 controls. Plain radiographs and computed tomography (CT) scans were obtained and tissue blocks were resected from three predefined levels of all specimens. The microscopic sections were scored by two blinded observers using a newly developed scoring system specific for characteristics of DISH and a validated scoring system for IVD degeneration. Maximum IVD height was measured on the CT scans. Analyses were performed using Fisher's exact test and Student's t-test. When compared to controls, the right sided sections from DISH specimens showed partial or complete bone bridges, consisting of cortical woven bone, accompanied by morphological changes in the adjoining part of the IVD. Using the histological scoring system for DISH, all parameters were significantly different between the DISH and control group (p < 0.01). The contralateral location did not show differences between the groups. The overall degree of IVD degeneration and height of IVD was comparable for the two groups. The histopathological changes observed in spines with DISH corresponded to the fluoroscopic images and CT scans. The degree of IVD degeneration and IVD height was comparable for both groups, suggesting a limited role for IVD degeneration in the pathogenesis of DISH. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:140-146, 2017.

  16. Definitions and drivers of relapse in patients with schizophrenia: a systematic literature review

    PubMed Central

    2013-01-01

    Relapse in patients with schizophrenia has devastating repercussions, including worsening symptoms, impaired functioning, cognitive deterioration and reduced quality of life. This progressive decline exacerbates the burden of illness on patients and their families. Relapse prevention is identified as a key therapeutic aim; however, the absence of widely accepted relapse definition criteria considerably hampers achieving this goal. We conducted a literature review in order to investigate the reporting of relapses and the validity of hospitalization as a proxy for relapse in patients with schizophrenia. The primary aim was to assess the range and validity of methods used to define relapse in observational or naturalistic settings. The secondary aim was to capture information on factors that predicted or influenced the risk of relapse. A structured search of the PubMed database identified articles that discussed relapse, and hospitalization as a proxy of relapse, in patients with schizophrenia. National and international guidelines were also reviewed. Of the 150 publications and guidelines identified, 87 defined relapse and 62% of these discussed hospitalization. Where hospitalization was discussed, this was as a proxy for, or a component of, relapse in the majority of cases. However, hospitalization duration and type varied and were not always well defined. Scales were used to define relapse in 53 instances; 10 different scales were used and multiple scales often appeared within the same definition. There were 95 references to factors that may drive relapse, including non-adherence to antipsychotic medication (21/95), stress/depression (11/95) and substance abuse (9/95). Twenty-five publications discussed the potential of antipsychotic therapy to reduce relapse rates—continuous antipsychotic therapy was associated with reduced frequency and duration of hospitalization. Non-pharmacological interventions, such as psychoeducation and cognitive behavioural therapy

  17. Integration of Histology Lectures and Practical Teaching in China

    ERIC Educational Resources Information Center

    Lu, Xiaoye; Cheng, Xin; Li, Ke; Lee, Kenneth Ka Ho; Yang, Xuesong

    2016-01-01

    Objectives: Human histology is a discipline concerning the study of microscopic structures of human tissues and organs--with the aid of light or electron microscopes. Traditional teaching of histology is composed of two separated components, theory and practice. The main disadvantage with traditional histology teaching is the detachment of theory…

  18. 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

  19. Mouse redox histology using genetically encoded probes.

    PubMed

    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.

  20. [Histological and molecular classification of gliomas].

    PubMed

    Figarella-Branger, D; Colin, C; Coulibaly, B; Quilichini, B; Maues De Paula, A; Fernandez, C; Bouvier, C

    2008-01-01

    Gliomas are the most frequent tumors of the central nervous system. The WHO classification, based on the presumed cell origin, distinguishes astrocytic, oligodendrocytic and mixed gliomas. A grading system is based on the presence of the following criteria: increased cellular density, nuclear atypias, mitosis, vascular proliferation and necrosis. The main histological subtype of grade I gliomas are pilocytic astrocytomas, which are benign. Diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas are low-grade (II) or high-grade (III and IV) tumors. Glioblastomas correspond to grade IV astrocytomas. C. Daumas-Duport et al. have proposed another classification based on histology and imaging data, which distinguishes oligodendrogliomas and mixed gliomas of grade A (without endothelial proliferation and/or contrast enhancement), oligodendrogliomas and mixed gliomas of grade B (with endothelial proliferation or contrast enhancement), glioblastomas and glioneuronal malignant tumors. Both classifications lack reproducibility. Many studies have searched for a molecular classification. Recurrent abnormalities in gliomas have been found. They encompassed recurrent chromosomal alterations, such as lost of chromosome 10, gain of chromosome 7, deletion of chromosome 1p and 19q, but also activation of the Akt pathway (amplification of EGFR), dysregulation of the cell cycle (deletion of p16, p53). These studies have enabled the description of two molecular subtypes for glioblastomas. De novo glioblastomas, which occur in young patients without of a prior history of brain tumor and harbor frequent amplification of EGFR, deletion of p16 and mutation of PTEN while mutation of p53 is infrequent. Secondary glioblastomas occur in the context of a preexisting low-grade glioma and are characterized by more frequent mutation of p53. On the other side, combined complete deletion of 1p and 19q as the result of the translocation t(1;19)(q10;p10) is highly specific of oligodendrogliomas

  1. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    SciTech Connect

    Moran, Meena S.; Yang Qifeng; Goyal, Sharad; Harris, Lyndsay; Chung, Gina; Haffty, Bruce G.

    2011-12-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  2. Breast Cancers Found with Digital Breast Tomosynthesis: A Comparison of Pathology and Histologic Grade.

    PubMed

    Wang, Wei-Shin; Hardesty, Lara; Borgstede, James; Takahashi, Jayme; Sams, Sharon

    2016-11-01

    To compare the pathology and histologic grading of breast cancers detected with digital breast tomosynthesis to those found with conventional digital mammography. The institutional review board approved this study. A database search for all breast cancers diagnosed from June 2012 through December 2013 was performed. Imaging records for these cancers were reviewed and patients who had screening mammography with tomosynthesis as their initial examination were selected. Five dedicated breast imaging radiologists reviewed each of these screening mammograms to determine whether the cancer was visible on conventional digital mammography or whether tomosynthesis was needed to identify the cancer. A cancer was considered mammographically occult if all five radiologists agreed that the cancer could not be seen on conventional digital mammography. The size, pathology and histologic grading for all diagnosed breast cancers were then reviewed. The Mann-Whitney U and Fisher exact tests were utilized to determine any association between imaging findings and cancer size, pathologic type and histologic grade. Sixty-five cancers in 63 patients were identified. Ten of these cancers were considered occult on conventional digital mammography and detected with the addition of tomosynthesis. These mammographically occult cancers were significantly associated with Nottingham grade 1 histologic pathology (p = 0.02), were smaller (median size: 6 mm versus 10 mm, p = 0.07) and none demonstrated axillary nodal metastases. Breast cancers identified through the addition of tomosynthesis are associated with Nottingham grade 1 histologic pathology and prognostically more favorable than cancers identified with conventional digital mammography alone.

  3. Classification of Tumor Histology via Morphometric Context.

    PubMed

    Chang, Hang; Borowsky, Alexander; Spellman, Paul; Parvin, Bahram

    2013-06-23

    Image-based classification of tissue histology, in terms of different components (e.g., normal signature, categories of aberrant signatures), provides a series of indices for tumor composition. Subsequently, aggregation of these indices in each whole slide image (WSI) from a large cohort can provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical and biological variations that are always present in a large cohort. In this paper, we propose two algorithms for classification of tissue histology based on robust representations of morphometric context, which are built upon nuclear level morphometric features at various locations and scales within the spatial pyramid matching (SPM) framework. These methods have been evaluated on two distinct datasets of different tumor types collected from The Cancer Genome Atlas (TCGA), and the experimental results indicate that our methods are (i) extensible to different tumor types; (ii) robust in the presence of wide technical and biological variations; (iii) invariant to different nuclear segmentation strategies; and (iv) scalable with varying training sample size. In addition, our experiments suggest that enforcing sparsity, during the construction of morphometric context, further improves the performance of the system.

  4. Tonsillotomy or tonsillectomy?--a prospective study comparing histological and immunological findings in recurrent tonsillitis and tonsillar hyperplasia.

    PubMed

    Reichel, Oliver; Mayr, Doris; Winterhoff, Jan; de la Chaux, Richard; Hagedorn, Hjalmar; Berghaus, Alexander

    2007-03-01

    We evaluated the differences in histological and immunological findings in children with recurrent tonsillitis and tonsillar hyperplasia and assessed the risk for relapsing tonsillar hyperplasia or recurrent tonsillitis after tonsillotomy in a prospective clinical study. Sixty-four children with recurrent tonsillitis underwent traditional (total) blunt dissection tonsillectomy between October 2003 and July 2004. Partial tonsillectomy (tonsillotomy) using CO(2)-laser technique was performed on 49 children with tonsillar hyperplasia and no history of recurrent tonsillitis between August 2003 and March 2005. The present study compares preoperative serum anti-streptolysin-O antibody and immunoglobulin levels (IgG, IgA and IgM), C-reactive protein levels (CRP) and blood leukocyte counts of the two study groups. Additionally the tonsillar tissue removed by tonsillotomy or tonsillectomy was histologically examined in order to determine the grade of hyperplasia, chronic inflammation and fibrosis. Furthermore, the grade of fresh inflammation within the tonsillar crypts of the specimens was analysed. The parents of 40 patients treated by laser tonsillotomy were surveyed in average 16 months. There was no statistically significant difference in preoperative serum anti-streptolysin-O antibody and immunoglobulin levels, C-reactive protein levels and blood leukocyte counts between the two study groups. All specimens showed the histological picture of hyperplasia. There was no statistically significant difference in the grades of hyperplasia between the two study groups. Signs of fresh but mild inflammation within the tonsillar crypts could be found in over 70% of both study groups. Fibrosis only occurred in children with recurrent tonsillitis (9%). In all specimens signs of chronic inflammation could be detected. The histological examinations of specimens from children with repeated throat infections more frequently showed a moderate chronic inflammation of the tonsillar tissue

  5. [Relapsing viral hepatitis type A complicated with renal failure].

    PubMed

    Tagle, Martin; Barriga, Jose A; Gutierrez, Sussy; Valdez, Luis Manuel; Castle, James; Antunez De Mayolo, Antonio; Scavino Levy, Yolanda; León Barúa, Raúl; Mendoza, Carlos; Cajas, Lucy; Santibáñez, Vilma

    2004-01-01

    We report the case of a 42-year old male with an episode of relapsing hepatitis A of cholestatic pattern, which clinic course was complicated by fever, anemia and renal failure, requiring hemodialysis. The occurrence of cryglobulins and diminished complement levels was detected. A kidney biopsy was performed showing evidence of thrombotic microangiopathy. The patient had a good therapeutic response to corticosteroids, although he developed recurrence of fever and a palpable purpuric rush over his lower extremities when dose was reduced. A skin biopsy found leukocytoclastic vasculitis. Symptoms and physical findings improved when therapy with cycloposphamide was started and the dose of corticosteroids was increased. Hepatitis A virus infection usually has a benign course, although complications may occasionally develop. The relapsing form can be seen in 3-20% of the case; it can appear with a cholestatic pattern and most of the time it has a mild clinic development. Unlike hepatitis B, extra-hepatic manifestations are unusual in hepatitis A, and renal manifestations are even more infrequent. Acute renal failure (ARF) in non-fulminating hepatitis A has been reported only occasionally and its etiology remains unclear. Several hypotheses have been proposed, including renal toxicity due to hyperuricemia or increased bilirrubin, cryoglobulinemia, alterations in the renal blood flow due to endotoxemia or peripheral immune complex-mediated damage when hypocomplementemia is found. Kidney biopsy showed evidence of thrombotic microangiopathy, which raised the hypothesis of a Hemolytic Uremic Syndrome (HUS). An association with HUS has been described in a patient with surface antigen for hepatitis B (HBsAg) and anomalies in the hepatic biochemical tests, but as far as we know this is the first case of relapsing hepatitis A associated with a confirmed microangiopathic renal involvement.

  6. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma

    PubMed Central

    Stadtmauer, Edward A.; Abonour, Rafat; Cohen, Adam D.; Bensinger, William I.; Gasparetto, Cristina; Kaufman, Jonathan L.; Lentzsch, Suzanne; Vogl, Dan T.; Gomes, Christina L.; Pascucci, Natalia; Smith, David D.; Orlowski, Robert Z.; Durie, Brian G. M.

    2015-01-01

    Treatment options for patients with heavily pretreated relapsed and/or refractory multiple myeloma remain limited. We evaluated a novel therapeutic regimen consisting of carfilzomib, pomalidomide, and dexamethasone (CPD) in an open-label, multicenter, phase 1, dose-escalation study. Patients who relapsed after prior therapy or were refractory to the most recently received therapy were eligible. All patients were refractory to prior lenalidomide. Patients received carfilzomib IV on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m2), pomalidomide once daily on days 1 to 21 (4 mg as the initial dose level), and dexamethasone (40 mg oral or IV) on days 1, 8, 15, and 22 of 28-day cycles. The primary objective was to evaluate the safety and determine the maximum tolerated dose (MTD) of the regimen. A total of 32 patients were enrolled. The MTD of the regimen was dose level 1 (carfilzomib 20/27 mg/m2, pomalidomide 4 mg, dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in ≥60% of all patients, including 11 patients with grade ≥3 anemia. Dyspnea was limited to grade 1/2 in 10 patients. Peripheral neuropathy was uncommon and limited to grade 1/2. Eight patients had dose reductions during therapy, and 7 patients discontinued treatment due to AEs. Two deaths were noted on study due to pneumonia and pulmonary embolism (n = 1 each). The combination of CPD is well-tolerated and highly active in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT01464034. PMID:26384354

  7. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma.

    PubMed

    Shah, Jatin J; Stadtmauer, Edward A; Abonour, Rafat; Cohen, Adam D; Bensinger, William I; Gasparetto, Cristina; Kaufman, Jonathan L; Lentzsch, Suzanne; Vogl, Dan T; Gomes, Christina L; Pascucci, Natalia; Smith, David D; Orlowski, Robert Z; Durie, Brian G M

    2015-11-12

    Treatment options for patients with heavily pretreated relapsed and/or refractory multiple myeloma remain limited. We evaluated a novel therapeutic regimen consisting of carfilzomib, pomalidomide, and dexamethasone (CPD) in an open-label, multicenter, phase 1, dose-escalation study. Patients who relapsed after prior therapy or were refractory to the most recently received therapy were eligible. All patients were refractory to prior lenalidomide. Patients received carfilzomib IV on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m(2)), pomalidomide once daily on days 1 to 21 (4 mg as the initial dose level), and dexamethasone (40 mg oral or IV) on days 1, 8, 15, and 22 of 28-day cycles. The primary objective was to evaluate the safety and determine the maximum tolerated dose (MTD) of the regimen. A total of 32 patients were enrolled. The MTD of the regimen was dose level 1 (carfilzomib 20/27 mg/m(2), pomalidomide 4 mg, dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in ≥60% of all patients, including 11 patients with grade ≥3 anemia. Dyspnea was limited to grade 1/2 in 10 patients. Peripheral neuropathy was uncommon and limited to grade 1/2. Eight patients had dose reductions during therapy, and 7 patients discontinued treatment due to AEs. Two deaths were noted on study due to pneumonia and pulmonary embolism (n = 1 each). The combination of CPD is well-tolerated and highly active in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT01464034.

  8. Incidence and management of renal adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib.

    PubMed

    Shah, Jatin J

    2013-12-01

    Patients with multiple myeloma (MM) frequently experience renal dysfunction owing to patient-specific risk factors, the pathophysiology of MM, and treatment-related adverse events. The presence of renal complications in patients with MM may be associated with advanced disease and is a negative prognostic factor for survival. Frequently these patients receive reduced or modified dosing regimens, which can result in under-dosing and may adversely affect treatment efficacy. Consequently, there is a need for effective therapies with favorable renal safety profiles. Carfilzomib is a selective proteasome inhibitor approved in the United States as a single agent for the treatment of relapsed and refractory MM. Safety studies have demonstrated that single-agent carfilzomib is well tolerated in patients with relapsed and/or refractory MM and concomitant renal dysfunction. This article reviews the etiology and incidence of renal adverse events in patients with MM, the renal safety profile of single-agent carfilzomib from four phase II studies in patients with relapsed and/or refractory MM, and the management of patients with MM who receive carfilzomib and are at risk for renal complications.

  9. Gastric ulcer healing with tripotassium dicitrato bismuthate and subsequent relapse.

    PubMed

    Sutton, D R

    1982-07-01

    Fifty patients with endoscopically proven gastric ulcers completed a one month double-blind randomised trial of tripotassium dicitrato bismuthate (TBD) (DeNol) compared with an identical placebo. Ulcer healing occurred in 18 (72%) of the 25 patients given TDB and in nine (36%) of the patients given placebo. The TDB group experienced significantly less pain than the placebo group. During a follow-up of 29 patients with healed ulcers for up to 44 months, relapse occurred in 13 (45%). It was highest in the first three months (27%) and had risen to 41% at two years.

  10. Direct resin composite approach to orthodontic relapse. Case report.

    PubMed

    Sabatini, Camila

    2012-03-01

    The treatment of malaligned teeth represents a challenge, especially in the presence of root resorption. Options to improve aesthetics are limited and often involve high costs. Direct composite restorations offer an alternative for the realignment of orthodontic-relapsed teeth where orthodontic retreatment is not indicated. Their reasonable cost, conservativeness and excellent aesthetics have allowed resin composites to gain popularity in recent years. This report describes a direct composite approach to the realignment of teeth with anterior root resorption. Furthermore, the article describes the use of a "silicon lingual matrix" to facilitate the polychromatic layering of composite and the manipulation of illusions to improve perception of tooth alignment.

  11. Cutaneous metastasis revealing a relapse of gastric linitis: Another case

    PubMed Central

    Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

    2012-01-01

    INTRODUCTION Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. PRESENTATION OF CASE We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. DISCUSSION Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. CONCLUSION This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. PMID:23276763

  12. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

    Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease. PMID:27478601

  13. Relapsing Polychondritis Presented with Encephalitis Followed by Brain Atrophy

    PubMed Central

    Park, Moo-Seok; Jeong, Hae-Bong; Kwon, Oh-Sang; Yoon, Byung-Nam; Kim, Hee Sung; Choi, Sang Tae

    2017-01-01

    Relapsing polychondritis (RP) is a rare autoimmune disease that is characterized by inflammatory reaction of unknown etiology and destruction of cartilaginous structures. Characteristic symptoms of this disease include cartilage inflammation of the ear, nose, larynx, trachea, bronchi, joints, eyes, heart and skin. Concomitance with neurologic symptom is very rare in RP, and the detailed underlying mechanism of neurological involvement associated with RP is not fully understood. We herein described an unusual recurrent case of inflammatory brain lesions associated with RP, with attention to clinical manifestations, autoimmune disease involvement, and therapeutic effects. PMID:28243168

  14. Borrelia miyamotoi: a widespread tick-borne relapsing fever spirochete.

    PubMed

    Wagemakers, Alex; Staarink, Pieter J; Sprong, Hein; Hovius, Joppe W R

    2015-06-01

    Borrelia miyamotoi is a relapsing fever spirochete that has only recently been identified as a human pathogen. Borrelia miyamotoi is genetically and ecologically distinct from Borrelia burgdorferi sensu lato, while both are present in Ixodes ticks. Over 50 patients with an acute febrile illness have been described with a B. miyamotoi infection, and two infected immunocompromised patients developed a meningoencephalitis. Seroprevalence studies indicate exposure in the general population and in specific risk groups, such as patients initially suspected of having human granulocytic anaplasmosis. Here, we review the available literature on B. miyamotoi, describing its presence in ticks, reservoir hosts, and humans, and discussing its potential impact on public health.

  15. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL

    PubMed Central

    Li, Benshang; Li, Hui; Bai, Yun; Kirschner-Schwabe, Renate; Yang, Jun J; Chen, Yao; Lu, Gang; Tzoneva, Gannie; Ma, Xiaotu; Wu, Tongmin; Li, Wenjing; Lu, Haisong; Ding, Lixia; Liang, Huanhuan; Huang, Xiaohang; Yang, Minjun; Jin, Lei; Kang, Hui; Chen, Shuting; Du, Alicia; Shen, Shuhong; Ding, Jianping; Chen, Hongzhuan; Chen, Jing; von Stackelberg, Arend; Gu, Longjun; Zhang, Jinghui; Ferrando, Adolfo; Tang, Jingyan; Wang, Shengyue; Zhou, Bin-Bing S.

    2015-01-01

    Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in the backbone of ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in phosphoribosyl pyrophosphate synthetase 1 (PRPS1), a rate-limiting purine biosynthesis enzyme, in 24/358 (6.7%) relapse B-ALL cases. All individuals who harbored PRPS1 mutations relapsed early on-treatment, and mutated ALL clones expanded exponentially prior to clinical relapse. Our functional analyses of PRPS1 mutants uncovered a new chemotherapy resistance mechanism involving reduced feedback inhibition of de novo purine biosynthesis and competitive inhibition of thiopurine activation. Notably, the de novo purine synthesis inhibitor lometrexol can effectively abrogate PRPS1 mutant-driven drug resistance. Overall these results highlight the importance of constitutive activation of de novo purine pathway in thiopurine resistance, and offer therapeutic strategies for the treatment of relapsed and resistant ALL. PMID:25962120

  16. Are We Throwing Histology out with the Microscope? A Look at Histology from the Physician's Perspective

    ERIC Educational Resources Information Center

    Pratt, Rebecca L.

    2009-01-01

    A trend in medical schools across the United States is the refurbishing of histology laboratories with digital microscopy systems. Although such systems may reduce curricular time, they do not teach basic microscope skills, and students who learn solely with these systems may be less prepared for their practices or specialties, particularly in…

  17. High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML).

    PubMed

    Graf, M; Reif, S; Hecht, K; Pelka-Fleischer, R; Kroell, T; Pfister, K; Schmetzer, H

    2005-05-01

    Costimulatory molecules such as lymphocyte function-associated antigen (LFA)-1 (CD11a), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), neuronal cell adhesion molecule (NCAM) (CD56), B7-1 (CD80), or B7-2 (CD86) are important regulatory elements in healthy immunological cascades, but their role in acute myeloid leukemia (AML) has only been rarely investigated. We studied their expression on mononuclear bone marrow (BM) cells from 105 patients with AML at initial diagnosis and evaluated their prognostic significance. Fluorescence-activated cell sorter (FACS) analyses were performed using antibodies directly conjugated with fluorescein. A BM sample was considered positive if more than 20% of the cells in the blast containing gate expressed the respective marker. The surface expression of CD11a (27 of 29 cases positive with an average of 71% positive blasts; 27(+)/29, 71%), CD54 (23(+)/33, 37%), CD56 (24(+)/93, 20%), CD58 (29(+)/29, 95%), CD80 (13(+)/28, 30%), and CD86 (19(+)/29, 39%) was measured. The expression of these markers in different French-American-British (FAB) classification types (M0-M5) was heterogeneous, except for CD56, which showed a higher proportion of positive cells in monocytic subtypes of AML. In addition, cases with a "poor risk" karyotype as well as patients succumbing to "early death" after double induction therapy according to the AML Cooperative Group (CG) protocol were characterized by a high expression of CD56. Relapse-free survival analyses demonstrated that patients with more than 8% CD56(+) cells in the BM relapsed significantly sooner. CD54 was preferentially expressed in AML M4(eo) and in addition in "favorable" cytogenetic risk groups and in cases that had responded to AML-CG therapy. Only very high proportions (>60%) of CD54(+) cells were associated with a lower probability for relapse-free survival. CD80 and CD86 expressions were similar in all FAB types. Patients who had responded to AML-CG therapy showed higher CD80

  18. Relapse following mandibular advancement with dental plus skeletal maxillomandibular fixation.

    PubMed

    Ellis, E; Gallo, W J

    1986-07-01

    This study examines the short-term stability of the mandible following mandibular advancement surgery in which skeletal suspension wires were used in addition to dental maxillomandibular fixation. Twenty adults underwent sagittal ramus osteotomies. No concomitant surgical procedures were performed. Maxillomandibular fixation consisted of wiring between the upper and lower orthodontic brackets and circummandibular wires connected to the piriform aperture or anterior nasal spine wires for eight weeks. Cephalograms were analyzed during this period to evaluate skeletal stability. A statistically insignificant mean horizontal relapse of 8.9% was found at pogonion during the period of fixation. Significant vertical intrusion of the anterior mandible occurred, however, with a mean superior movement of pogonion of 0.83 mm (P less than or equal to 0.05). Dental changes noted were uprighting of the maxillary incisors and flaring of the mandibular incisors. In comparison with the results of other studies in which dental maxillomandibular fixation was used alone, the results of this study indicate that the use of skeletal suspension wires is advantageous in the prevention of horizontal skeletal relapse.

  19. Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma

    PubMed Central

    Ramani, Vishnu C.; Zhan, Fenghuang; He, Jianbo; Barbieri, Paola; Noseda, Alessandro; Tricot, Guido; Sanderson, Ralph D.

    2016-01-01

    In most myeloma patients, even after several rounds of intensive therapy, drug resistant tumor cells survive and proliferate aggressively leading to relapse. In the present study, gene expression profiling of tumor cells isolated from myeloma patients after sequential rounds of chemotherapy, revealed for the first time that heparanase, a potent promoter of myeloma growth and progression, was elevated in myeloma cells that survived therapy. Based on this clinical data, we hypothesized that heparanase was involved in myeloma resistance to drug therapy. In several survival and viability assays, elevated heparanase expression promoted resistance of myeloma tumor cells to chemotherapy. Mechanistically, this enhanced survival was due to heparanase-mediated ERK signaling. Importantly, use of the heparanase inhibitor Roneparstat in combination with chemotherapy clearly diminished the growth of disseminated myeloma tumors in vivo. Moreover, use of Roneparstat either during or after chemotherapy diminished regrowth of myeloma tumors in vivo following therapy. These results provide compelling evidence that heparanase is a promising, novel target for overcoming myeloma resistance to therapy and that targeting heparanase has the potential to prevent relapse in myeloma and possibly other cancers. PMID:26624982

  20. Statins Reduce the Risks of Relapse to Addiction in Rats.

    PubMed

    Chauvet, Claudia; Nicolas, Celine; Lafay-Chebassier, Claire; Jaber, Mohamed; Thiriet, Nathalie; Solinas, Marcello

    2016-05-01

    Statins are drugs that have been used for decades in humans for the treatment of hypercholesterolemia. More recently, several lines of evidence demonstrate that statins, in addition to their peripheral effects, produce a wide variety of effects in the brain and may be beneficial in neurological and psychiatric conditions. In this study, we allowed rats to self-administer cocaine for several weeks and, at the end of self-administration training, we treated them with low doses of statins daily for a 21-day period of abstinence. Chronic administration of brain-penetrating statins, simvastatin (1 mg/kg) and atorvastatin (1 mg/kg), reduced cocaine seeking compared with vehicle, whereas administration of pravastatin (2 mg/kg), a statin with low brain penetrability, did not. Importantly, the effects of brain-penetrating statins persisted even after discontinuation of the treatment and were specific for drug seeking because drug taking was not altered by simvastatin treatment. Finally, the effects of simvastatin were found to generalize to another drug of abuse such as nicotine, but not to food reward, and to reinstatement of cocaine seeking induced by stress. These results demonstrate that brain-penetrating statins can reduce risks of relapse to addiction. Given their well-known safety profile in humans, statins could be a novel effective treatment for relapse to cocaine and nicotine addiction and their use could be implemented in clinical settings without major health risks.

  1. Leptin influence in craving and relapse of alcoholics and smokers.

    PubMed

    Aguiar-Nemer, Aline S; Toffolo, Mayla C F; da Silva, Claudio Jeronimo; Laranjeira, Ronaldo; Silva-Fonseca, Vilma A

    2013-06-01

    Leptin inhibits signaling of dopamine in the nucleus accumbens, suggesting its role in regulating stress and its possible involvement in the neurobiology of reward system. The aim of this study was to review of the literature on the influence of leptin in the craving for alcohol and tobacco and whether there is already evidence that leptin may be a biomarker to indicate risk for craving and relapse. The review used as data bases Medline, LILACS and SciElo in the period between 2000 and 2012. Keywords were leptin, substance use disorders, craving and withdrawal, in Portuguese and English. Only 12 articles were met the inclusion criteria, relating leptin with craving in alcoholics (n = 10) and smokers (n = 2). No studies were found in the LILACS database. Leptin levels increase during abstinence and this may be related to a reduction of dopaminergic action in mesolimbic system, resulting in a greater intensity of craving and maintenance of addictive behavior. Although there are few studies, the most recent results indicate the usefulness of leptin as a marker of risk for relapse among smokers and alcoholics in abstinence.

  2. Clinical translation of animal models of treatment relapse.

    PubMed

    Pritchard, Duncan; Hoerger, Marguerite; Mace, F Charles; Penney, Heather; Harris, Brian

    2014-05-01

    Behavioral Momentum Theory (BMT) has inspired animal models of treatment relapse. We translated the models of reinstatement and resurgence into clinical procedures to test whether relapse tests would replicate behavior pattern found in basic research. Following multiple schedule baseline reinforcement of a 16-year-old male's problem behavior at equal rates by two therapists, treatment was introduced using a variable-interval, variable-time (VI VT) schedule arrangement with therapists delivering reinforcers at different rates. Despite the differing rates of VI VT reinforcers, the treatment produced comparable reductions in problem behavior. Following successful treatment, the two therapists discontinued treatment and resumed reinforcement of problem behavior at equal rates that constituted a reinstatement of baseline conditions. As predicted by BMT, reinstatement resulted in an immediate return of high rates of problem behavior but was 2.6 times higher for the therapist using the higher rate VI VT treatment. A second treatment phase was implemented followed by a test of resurgence in a single extended extinction session conducted separately for each therapist. The unequal VI VT treatment rates by therapists resulted in 2.1 times greater responding in the resurgence test for the therapist who implemented the higher rate VI VT procedure. These results are consistent with basic research studies and BMT.

  3. Behavioral momentum and relapse of extinguished operant responding.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2009-11-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a stimulus depends on the rate of reinforcement associated with that stimulus, even if some of those reinforcers occur independently of the behavior. We present three experiments examining whether the rate of reinforcement in the presence of a stimulus similarly modulates the relative relapse of operant behavior produced by reinstatement, resurgence, and renewal paradigms. During baseline conditions, pigeons responded for food reinforcement on variable-interval 120-sec schedules in alternating periods of exposure to two stimuli arranged by a multiple schedule. Additional response-independent food presentations were also delivered in the presence of one of the multiple-schedule stimuli. Consistent with previous research, baseline response rates were lower in the presence of the stimulus with the added response-independent reinforcement, and relative resistance to extinction was greater in the presence of that stimulus. In addition, following extinction, the relative relapse of responding produced by reinstatement, resurgence, and renewal paradigms was greater in the presence of the stimulus associated with the higher rate of reinforcement. We suggest that a model of extinction from behavioral momentum theory may be useful for understanding these results.

  4. Predicting relapse risk in childhood acute lymphoblastic leukaemia.

    PubMed

    Teachey, David T; Hunger, Stephen P

    2013-09-01

    Intensive multi-agent chemotherapy regimens and the introduction of risk-stratified therapy have substantially improved cure rates for children with acute lymphoblastic leukaemia (ALL). Current risk allocation schemas are imperfect, as some children are classified as lower-risk and treated with less intensive therapy relapse, while others deemed higher-risk are probably over-treated. Most cooperative groups previously used morphological clearance of blasts in blood and marrow during the initial phases of chemotherapy as a primary factor for risk group allocation; however, this has largely been replaced by the detection of minimal residual disease (MRD). Other than age and white blood cell count (WBC) at presentation, many clinical variables previously used for risk group allocation are no longer prognostic, as MRD and the presence of sentinel genetic lesions are more reliable at predicting outcome. Currently, a number of sentinel genetic lesions are used by most cooperative groups for risk stratification; however, in the near future patients will probably be risk-stratified using genomic signatures and clustering algorithms, rather than individual genetic alterations. This review will describe the clinical, biological, and response-based features known to predict relapse risk in childhood ALL, including those currently used and those likely to be used in the near future to risk-stratify therapy.

  5. Late relapse of imported Plasmodium ovale malaria: a case report.

    PubMed

    Siala, Emna; Gastli, Mondher; Essid, Rym; Jemal, Sana; Ben Abdallah, Rym; Ben Abda, Imène; Aoun, Karim; Bouratbine, Aida

    2015-06-01

    We report the first case of an imported Plasmodium ovale relapse in a Tunisian man who developed malaria three years after leaving sub- Saharan Africa. A 29-year-old Tunisian man consulted in September 2011 because of a fever, myalgia, and headache that had begun eight days earlier and persisted despite treatment with oral antibiotics. On questioning, the patient stated that he had resided three years ago for six months in Ivory Coast, where he acquired malaria. He was treated with artemether-lumefantrine. The patient said he had no recent travel to any other malaria-endemic area and had not received a blood transfusion. A first microscopy of peripheral blood smears was negative for malaria parasites. The diagnosis was established 17 days after onset of symptoms. A repeat microscopic examination of blood smears confirmed the presence of Plasmodium ovale with a parasitemia lower than 0.1%. The patient was treated with artemether lumefantrine, followed by primaquine. This case emphasizes the possibility of relapse of some plasmodial species. It highlights the importance of repeating microscopic examination of blood when the diagnosis of malaria is suspected.

  6. Minor clone provides a reservoir for relapse in multiple myeloma.

    PubMed

    Magrangeas, F; Avet-Loiseau, H; Gouraud, W; Lodé, L; Decaux, O; Godmer, P; Garderet, L; Voillat, L; Facon, T; Stoppa, A M; Marit, G; Hulin, C; Casassus, P; Tiab, M; Voog, E; Randriamalala, E; Anderson, K C; Moreau, P; Munshi, N C; Minvielle, S

    2013-02-01

    Recent studies have provided direct evidence for genetic variegation in subclones for various cancer types. However, little is known about subclonal evolutionary processes according to treatment and subsequent relapse in multiple myeloma (MM). This issue was addressed in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. As MM is a highly heterogeneous disease associated with a large number of chromosomal abnormalities, a subset of secondary genetic events that seem to reflect progression, 1q21 gain, NF-κB-activating mutations, RB1 and TP53 deletions, was examined. By using high-resolution single-nucleotide polymorphism arrays, subclones were identified with nonlinear complex evolutionary histories. Such reordering of the spectrum of genetic lesions, identified in a third of MM patients during therapy, is likely to reflect the selection of genetically distinct subclones, not initially competitive against the dominant population but which survived chemotherapy, thrived and acquired new anomalies. In addition, the emergence of minor subclones at relapse appeared to be significantly associated with bortezomib treatment. These data support the idea that new strategies for future clinical trials in MM should combine targeted therapy and subpopulations' control to eradicate all myeloma subclones in order to obtain long-term remission.

  7. Beyond the Ubiquitous Relapse Curve: A Data-Informed Approach

    PubMed Central

    Zywiak, William H.; Kenna, George A.; Westerberg, Verner S.

    2011-01-01

    Relapse to alcohol and other substances has generally been described by curves that resemble one another. However, these curves have been generated from the time to first use after a period of abstinence without regard to the movement of individuals into and out of drug use. Instead of measuring continuous abstinence, we considered post-treatment functioning as a more complicated phenomenon, describing how people move in and out of drinking states on a monthly basis over the course of a year. When we looked at time to first drink we observed the ubiquitous relapse curve. When we classified clients (N = 550) according to drinking state however, they frequently moved from one state to another with both abstinent and very heavy drinking states as being rather stable, and light or moderate drinking and heavy drinking being unstable. We found that clients with a family history of alcoholism were less likely to experience these unstable states. When we examined the distribution of cases crossed by the number of times clients switched states we found that a power function explained 83% of that relationship. Some of the remainder of the variance seems to be explained by the stable states of very heavy drinking and abstinence acting as attractors. PMID:21556282

  8. Obinutuzumab for relapsed or refractory indolent non-Hodgkin's lymphomas.

    PubMed

    Gabellier, Ludovic; Cartron, Guillaume

    2016-04-01

    The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin's lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc-Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma.

  9. Acid ceramidase in prostate cancer radiation therapy resistance and relapse

    NASA Astrophysics Data System (ADS)

    Cheng, Joseph C.

    Prostate tumor cell escape from ionizing radiation (IR)-induced killing can lead to disease progression and relapse. Sphingolipids such as ceramide and sphingosine 1-phosphate influence signal transduction pathways that regulate stress response in cancer cells. In particular, metabolism of apoptotic ceramide constitutes an important survival adaptation. Assessments of enzyme activity, mRNA, and protein demonstrated preferential upregulation of the ceramide deacylating enzyme acid ceramidase (AC) in irradiated cancer cells. Promoter-reporter and ChIP-qPCR assays revealed AC transcription by activator protein 1 (AP-1) is sensitive to pharmacological inhibition of de novo ceramide biosynthesis, identifying a protective feedback mechanism that mitigates the effects of IR-induced ceramide. Deregulation of c-Jun, in particular, induced marked radiosensitization in vitro and in vivo, which was rescued by ectopic AC over-expression. AC over-expression in prostate cancer clonogens surviving 80 Gray fractionated irradiation was associated with increased radioresistance and proliferation, suggesting a role in radiotherapy failure and relapse. Indeed, immunohistochemical analysis of human prostate cancer tissues revealed higher levels of AC after radiotherapy failure than therapy-naive adenocarcinoma, PIN, or benign tissues. By genetically downregulating AC with small interfering RNA (siRNA), we observed radiosensitization of cells using clonogenic and cytotoxicity assays. Finally, treatment with lysosomotropic small molecule inhibitors of AC, LCL385 or LCL521, induced prostate cancer xenograft radiosensitization and long-term suppression, suggesting AC is a tractable target for adjuvant radiotherapy.

  10. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-11-08

    Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder

  11. A cross-sectional, multicentre study of the therapeutic management of multiple sclerosis relapses in Italy.

    PubMed

    Annovazzi, Pietro; Tomassini, Valentina; Bodini, Benedetta; Boffa, Laura; Calabrese, Massimiliano; Cocco, Eleonora; Cordioli, Cinzia; De Luca, Giovanna; Frisullo, Giovanni; Gallo, Antonio; Malucchi, Simona; Paolicelli, Damiano; Pesci, Ilaria; Radaelli, Marta; Ragonese, Paolo; Roccatagliata, Luca; Tortorella, Carla; Vercellino, Marco; Zipoli, Valentina; Gasperini, Claudio; Rodegher, Mariaemma; Solaro, Claudio

    2013-02-01

    Despite the existence of therapeutic guidelines, management of multiple sclerosis relapse remains heterogeneous. Optimisation of relapse outcome demands an improved understanding of the neurologist's therapeutic attitude towards relapse management, which is the aim of this study. Neurologists from 13 multiple sclerosis centres completed a questionnaire every time they assessed multiple sclerosis relapses. The questionnaire requested a guided description of the relapse's clinical characteristics and an indication of the prescribed therapy, supported with up to 3 out of 20 suggested reasons. Over 3 months, 368 questionnaires were collected. Median percentage (%) of 21 relapses resulting in a prescription was 88.9%. Corticosteroids represented the most frequent prescription. A short-course of high-dose intravenous methylprednisolone was the most used corticosteroid (73.7%). Treatment was administrated mainly in day case unit (80.0%) and at home (13.6%). A tapered therapy was prescribed to 28.8% of patients. Neurologists' therapeutic decisions were driven mainly by relapse severity (45.3%) and symptom evolution (24.2%). Our study confirms the therapeutic attitude of multiple sclerosis specialists in treating relapses with high-dose intravenous corticosteroids in a day hospital setting, with a tapering in a proportion of cases. The main reasons for prescription are relapse severity and symptom evolution.

  12. Predictors of Relapse after Inpatient Opioid Detoxification during 1-Year Follow-Up

    PubMed Central

    2016-01-01

    Introduction. Relapse rate after opioid detoxification is very high. We studied the possibility that predetoxification patient characteristics might predict relapse at follow-up and thus conducted this 1-year follow-up study to assess the predictors of relapse after inpatient opioid detoxification. Materials and Methods. We conducted this study in our tertiary care institute in India over two-year time period (1 Jan 2014 to 31 Dec 2015). Out of 581 patients admitted, 466 patients were considered for study. Results and Discussion. No significant difference was found between relapsed and nonrelapsed patients regarding sociodemographic profile; however substance abuse pattern and forensic history showed significant differences. Relapsed patients abused greater amount and used injections more commonly, as compared to nonrelapsed group. Longer duration of abuse was also a significant risk factor. Patients with past attempt of opioid detoxification and family history (parental or first degree) of alcohol abuse had decreased possibility of maintaining remission during 1-year follow-up. Relapsed patients were found to abuse their spouse or parents. Conclusion. Our study compared profiles of relapsed and nonrelapsed patients after inpatient detoxification and concluded predictors of relapse during 1-year follow-up period. Early identification of predictors of relapse and hence high risk patients might be helpful in designing more effective and focused treatment plan. PMID:27722007

  13. Increased network centrality as markers of relapse risk in nicotine-dependent individuals treated with varenicline.

    PubMed

    Shen, Zhujing; Huang, Peiyu; Wang, Chao; Qian, Wei; Yang, Yihong; Zhang, Minming

    2017-04-03

    Identifying smokers at high risk of relapse could improve the effectiveness of cessation therapies. Although altered regional brain function in smokers has been reported, whether the whole-brain functional organization differs smokers with relapse vulnerability from others remains unclear. Thus, the goal of this study is to investigate the baseline functional connectivity differences between relapsers and quitters. Using resting-state fMRI, we acquired images from 57 smokers prior to quitting attempts. After 12-week treatment with varenicline, smokers were divided into relapsers (n=36) and quitters (n=21) (quitter: continuously abstinent for weeks 9-12). The smoking cessation outcomes were cross-validated by self-reports and expired carbon monoxide. We then used eigenvector centrality (EC) mapping to identify the functional connectivity differences between relapsers and quitters. When compared to quitters, increased EC in the right dorsolateral prefrontal cortex (DLPFC), left middle temporal gyrus (MTG) and cerebellum anterior lobe was observed in relapsers. In addition, a logistic regression analysis of EC data (with DLPFC, MTG and cerebellum included) predicted relapse with 80.7% accuracy. These findings suggest that the DLPFC, MTG and cerebellum may be important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment and improve smoking cessation outcomes.

  14. Towards an understanding of the biology and targeted treatment of paediatric relapsed acute lymphoblastic leukaemia.

    PubMed

    Irving, Julie A E

    2016-03-01

    Acute lymphoblastic leukaemia is the most common childhood cancer and for those children who relapse, prognosis is poor and new therapeutic strategies are needed. Recurrent pathways implicated in relapse include RAS, JAK STAT, cell cycle, epigenetic regulation, B cell development, glucocorticoid response, nucleotide metabolism and DNA repair. Targeting these pathways is a rational therapeutic strategy and may deliver novel, targeted therapies into the clinic. Relapse often stems from a minor clone present at diagnosis and thus analysis of persisting leukaemia during upfront therapy may allow targeted drug intervention to prevent relapse.

  15. N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse.

    PubMed

    Hacohen, Yael; Deiva, Kumaran; Pettingill, Phillipa; Waters, Patrick; Siddiqui, Ata; Chretien, Pascale; Menson, Esse; Lin, Jean-Pierre; Tardieu, Marc; Vincent, Angela; Lim, Ming J

    2014-01-01

    Herpes simplex virus encephalitis (HSVE) is a devastating condition that relapses, often with a chorea in children, despite adequate antiviral treatment. At relapse, evidence of viral replication is frequently absent, suggesting that the relapse may be immune-mediated. Seven children who had a neurological relapse following their initial encephalitis, identified from 20 cases of pediatric HSVE, were studied. Serum and/or cerebrospinal fluid (CSF) were tested for N-methyl-D-aspartate receptor (NMDAR) and other antibodies previously reported in central nervous system autoimmunity. Five of the 7 relapsing children had choreoathetosis; 2 of these were NMDAR antibody-positive, 2 were negative (1 with HSV-positive CSF), and 1 was not available for testing. An additional patient, who relapsed with cognitive regression but with no movement disorder, was also NMDAR antibody-positive. In 2 of the NMDAR antibody-positive patients who were treated at relapse and in 1 who was treated only after 10 years of having a relapsing encephalopathy, a beneficial response was observed. Neurological relapses after HSVE may frequently be immune-mediated, particularly in children with chorea. NMDAR antibodies are common, and immunotherapy may be beneficial.

  16. The Histological Slides and Drawings of Cajal

    PubMed Central

    Garcia-Lopez, Pablo; Garcia-Marin, Virginia; Freire, Miguel

    2009-01-01

    Ramón y Cajal's studies in the field of neuroscience provoked a radical change in the course of its history. For this reason he is considered as the father of modern neuroscience. Some of his original preparations are housed at the Cajal Museum (Cajal Institute, CSIC, Madrid, Spain). In this article, we catalogue and analyse more than 4,500 of Cajal's histological preparations, the same preparations he used during his scientific career. Furthermore, we catalogued Cajal's original correspondence, both manuscripts and personal letters, drawings and plates. This is the first time anyone has compiled an account of Cajal's enormous scientific production, offering some curious insights into his work and his legacy. PMID:20339483

  17. Rheumatoid neuropathy: a histological and electrophysiological study

    PubMed Central

    Weller, R. O.; Bruckner, F. E.; Chamberlain, M. Anne

    1970-01-01

    Peripheral nerves in five patients with rheumatoid neuropathy were examined electrophysiologically and by sural nerve biopsy. There was close correlation between the clinical severity of the disease and the degree of nerve damage found histologically and by EMG. Group 1 patients with a mild distal sensory neuropathy showed varying degrees of axonal degeneration in the large myelinated fibres and some segmental demyelination. Group 2 patients with a severe, rapidly progressive sensori-motor neuropathy had extensive loss of myelinated fibres. In one case all the large fibres had degenerated. The second case had lost both large and small myelinated fibres together with many of the non-myelinated axons. The major nerve damage in both groups appeared to be axonal degeneration but some segmental demyelination was detected. Occlusive vascular disease in the vasa nervorum was considered to be the major cause of the nerve damage. Images PMID:4320255

  18. Hair follicle changes following intense pulsed light axillary hair reduction: histometrical, histological and immunohistochemical evaluation.

    PubMed

    El-Domyati, Moetaz; Hosam, Wael; Moftah, Noha H; Abdel Raouf, Hamza; Saad, Selwet M

    2017-04-01

    Intense pulsed light (IPL) has been used for years in hair reduction; however, no previous studies discussed quantitative histological and immunohistochemical changes of hair follicles after IPL. Accordingly, this study aims to objectively quantify histological and immunohistochemical changes of hair follicles after IPL hair reduction. Right axillae of 21 volunteers were subjected to 6 IPL sessions using Quanta system IPL and evaluated at 1 week and 1 month after last session (i.e., 3 and 4 months from the start of treatment, respectively) in comparison to baseline and left control axillae. Using hair count, histological and immunohistochemical assessment of vertical and serial transverse sections coupled with computerized morphometric analysis, determination of hair reduction percentage, measurement of hair shaft (HS) diameter, calculation of percentage of hair follicle types and quantitative evaluation of PCNA, Ki67 and P53 markers were performed. After IPL, there was significant decrease of hair count, HS diameter, percentage of terminal anagen follicles, terminal/vellus (T/V) ratio, anagen/telogen (A/T) ratio and expression of PCNA and Ki67; however, significant increase of percentage of terminal telogen and total vellus follicles with vellus-like type and P53 expression was identified. So, reduction of hair number and thickness occurred after IPL by induction of telogenesis and miniaturization through decreased hair follicle proliferation and increase in DNA damage that could favor apoptosis.

  19. Positive impact of integrating histology and physiology teaching at a medical school in China.

    PubMed

    Sherer, Renslow; Wan, Yu; Dong, Hongmei; Cooper, Brian; Morgan, Ivy; Peng, Biwen; Liu, Jun; Wang, Lin; Xu, David

    2014-12-01

    To modernize its stagnant, traditional curriculum and pedagogy, the Medical School of Wuhan University in China adopted (with modifications) the University of Chicago's medical curriculum model. The reform effort in basic sciences was integrating histology and physiology into one course, increasing the two subjects' connection to clinical medicine, and applying new pedagogies and assessment methods. This study assessed the results of the reform by comparing the attitudes and academic achievements of students in the reform curriculum (n = 41) and their traditional curriculum peers (n = 182). An attitude survey was conducted to obtain students' views of their respective histology and physiology instruction. Survey items covered lectures, laboratory teaching, case analyses and small-group case discussions, assessment of students, and overall quality of the courses and instruction. A knowledge test consisting of questions from three sources was given to measure students' mastery of topics that they had learned. Results showed that reform curriculum students were rather satisfied with their course and new teaching methods in most cases. When these students' attitudes were compared with those of their traditional curriculum peers, several significant differences favoring the reform were identified regarding physiology teaching. No other significant difference was found for physiology or histology teaching. Reform curriculum students outperformed their peers on four of five subcategories of the knowledge test questions. These findings support the benefits of integration and state-of-the-art teaching methods. Our study may offer lessons to medical schools in China and other countries whose medical education is in need of change.

  20. The histological assessment of cutaneous vasculitis.

    PubMed

    Carlson, J Andrew

    2010-01-01

    Vasculitis is defined as inflammation directed at vessels, which compromises or destroys the vessel wall leading to haemorrhagic and/or ischaemic events. Skin biopsy is the gold standard for the diagnosis of cutaneous vasculitis, whose manifestations include urticaria, infiltrative erythema, petechiae, purpura, purpuric papules, haemorrhagic vesicles and bullae, nodules, livedo racemosa, deep (punched out) ulcers and digital gangrene. These varied morphologies are a direct reflection of size of the vessels and extent of the vascular bed affected, ranging from a vasculitis affecting few superficial, small vessels in petechial eruptions to extensive pan-dermal small vessel vasculitis in haemorrhagic bullae to muscular vessel vasculitis in lower extremity nodules with livedo racemosa. Skin biopsy, extending to subcutis and taken from the earliest, most symptomatic, reddish or purpuric lesion is crucial for obtaining a high-yielding diagnostic sample. Based on histology, vasculitis can be classified on the size of vessels affected and the dominant immune cell mediating the inflammation (e.g. neutrophilic, granulomatous, lymphocytic, or eosinophilic). Disruption of small vessels by inflammatory cells, deposition of fibrin within the lumen and/or vessel wall coupled with nuclear debris allows for the confident recognition of small vessel, mostly neutrophilic vasculitis (also known as leukocytoclastic vasculitis). In contrast, muscular vessel vasculitis can be identified solely by infiltration of its wall by inflammatory cells. Extravasation of red blood cells (purpura) and necrosis are supportive, but not diagnostic of vasculitis as they are also seen in haemorrhagic and/or vaso-occlusive disorders (pseudovasculitis). Vasculitic foci associated with extravascular granulomas (palisaded neutrophilic and granulomatous dermatitis), tissue eosinophilia, or tissue neutrophilia signal the risk for, or co-existence of systemic disease. This essential histological information

  1. Monoamine-containing fiber plexuses in the spinal cord of guinea pigs during paralysis, recovery and relapse stages of chronic relapsing experimental allergic encephalomyelitis.

    PubMed

    White, S R; Vyas, D; Bieger, D; Samathanam, G

    1989-05-01

    Immunohistochemical techniques were used to examine the morphology and distribution of monoamine- and substance P-containing fibers in the spinal cords of guinea pigs in acute paralytic, remission and relapse stages of chronic relapsing experimental allergic encephalomyelitis. During the initial paralytic attack, focal regions of axonal distortion appeared in the white matter of the cervical and thoracic cord; and axon terminal depletion in the gray matter of the caudal spinal cord was pronounced. This neuropathology persisted throughout remission and was exacerbated during relapse of paralysis. These results suggest that axonal damage is an important component of the pathophysiology of this autoimmune disease.

  2. Fingolimod after natalizumab and the risk of short-term relapse

    PubMed Central

    Li, Vivien; Kalincik, Tomas; Izquierdo, Guillermo; Hodgkinson, Suzanne; Alroughani, Raed; Lechner-Scott, Jeannette; Lugaresi, Alessandra; Duquette, Pierre; Girard, Marc; Barnett, Michael; Grand'Maison, Francois; Trojano, Maria; Slee, Mark; Giuliani, Giorgio; Shaw, Cameron; Boz, Cavit; Spitaleri, Daniele L.A.; Verheul, Freek; Haartsen, Jodi; Liew, Danny; Butzkueven, Helmut

    2014-01-01

    Objective: To determine early risk of relapse after switch from natalizumab to fingolimod; to compare the switch experience to that in patients switching from interferon-β/glatiramer acetate (IFN-β/GA) and those previously treatment naive; and to determine predictors of time to first relapse on fingolimod. Methods: Data were obtained from the MSBase Registry. Relapse rates (RRs) for each patient group were compared using adjusted negative binomial regression. Survival analyses coupled with adjusted Cox regression were used to model predictors of time to first relapse on fingolimod. Results: A total of 536 patients (natalizumab-fingolimod [n = 89]; IFN-β/GA-fingolimod [n = 350]; naive-fingolimod [n = 97]) were followed up for a median 10 months. In the natalizumab-fingolimod group, there was a small increase in RR on fingolimod (annualized RR [ARR] 0.38) relative to natalizumab (ARR 0.26; p = 0.002). RRs were generally low across all patient groups in the first 9 months on fingolimod (RR 0.001–0.13). However, 30% of patients with disease activity on natalizumab relapsed within the first 6 months on fingolimod. Independent predictors of time to first relapse on fingolimod were the number of relapses in the prior 6 months (hazard ratio [HR] 1.59 per relapse; p = 0.002) and a gap in treatment of 2–4 months compared to no gap (HR 2.10; p = 0.041). Conclusions: RRs after switch to fingolimod were low in all patient groups. The strongest predictor of relapse on fingolimod was prior relapse activity. Based on our data, we recommend a maximum 2-month treatment gap for switches to fingolimod to decrease the hazard of relapse. Classification of evidence: This study provides Class IV evidence that RRs are not higher in patients with multiple sclerosis switching to fingolimod from natalizumab compared to those patients switching to fingolimod from other therapies. PMID:24610329

  3. [Relapse prevention group therapy for paedophiles: French adaptation].

    PubMed

    Smith, J; Petibon, C

    2005-01-01

    Psychotherapy for sex offenders has only very recently started to develop in France. The French law on compulsory treatment for sex offenders was voted in 1998, and many mental health practitioners are not trained to treat such patients yet. In our ambulatory forensic consultation, sex offenders have been treated since 1992 and group psychotherapy has been offered to them since 1994. Our first therapeutic models were the North-American behavioural-cognitive therapy and Pithers' relapse prevention model. Behavioural-cognitive theory describes paedophilia as an acquired sexual preference maintained by positive reinforcement. Pithers (1990) considered that relapse only occurs in high-risk situations, and that high-risk situations always come after offence precursors. In North America, relapse prevention consists in helping paedophiles spot their high-risk situations and offence precursors, and enhance their skills to cope with such situations or to prevent them. Therapy programs were developed according to these models, aiming to help offenders develop such skills, ie empathy, social skills, cognitive restructuring, self-esteem, etc. Trying to apply these therapy programs in France, our team quickly realised that we would have to adapt them to French culture. On the one hand, behavioural-cognitive theory did not seem satisfactory enough in explaining paedophilic behaviour and paedophilic preference. On the other hand, behavioural-cognitive therapy made patients into children too much and increased resistance. Therapy based on programs seemed too rigid for French patients and therapists, and we often felt we were working on an issue that would have been much more accurate to work on a few sessions earlier, when this issue was spontaneously brought up by a patient. We believe change occurs all the more as issues are worked on at the right moment for the patient. Moreover, on a cultural point of view, we also realised the use of programs in psychotherapy was difficult to

  4. Nrf2 activation attenuates both orthodontic tooth movement and relapse.

    PubMed

    Kanzaki, H; Shinohara, F; Itohiya-Kasuya, K; Ishikawa, M; Nakamura, Y

    2015-06-01

    During orthodontic tooth movement, osteoclasts resorb the alveolar bone at the compress side of periodontium. Reactive oxygen species (ROS) works as intracellular signaling molecules of RANKL during osteoclastogenesis, although ROS has cytotoxicity against cells such as lipid oxidation. To deal with oxidative stress, cells have a defense system that is scavenging ROS by augmented antioxidative stress enzymes via transcriptional regulation with nuclear factor E2-related factor 2 (Nrf2). Previously, we reported that augmented antioxidative stress enzymes by Nrf2-gene transfer inhibited bone destruction. In the present study, we examined the effects of Nrf2 activation on osteoclastogenesis and, thereby, orthodontic tooth movement and orthodontic relapse. Mouse macrophage cell line RAW264.7 cells were used as osteoclast progenitor cells and stimulated with recombinant RANKL (100 ng/mL) with or without Nrf2 activator sulforaphane (SFN) and epigallocatechin gallate (EGCG) or ROS scavenger catechin. Osteoclastogenesis, resorption activity, and osteoclast marker gene expression were examined. Intracellular ROS was analyzed by flow cytometry. Maxillary first molars of C57BL6 male mice were moved palatally with 0.012-inch NiTi wire (100-mN force); SFN or EGCG was injected into the palatal gingiva once a week; and phosphate buffered saline was injected on the contralateral side. Tooth movement was monitored using a stone model with precise impression, and the amount of the tooth movement was compared among groups. SFN and EGCG significantly, but catechin weakly, inhibited RANKL-mediated osteoclastogenesis in vitro. Western blot analysis revealed that SFN and EGCG augmented the nuclear translocation of Nrf2 and the expression of anti-oxidative stress enzymes such as HO-1, although catechin did not. SFN and EGCG significantly, but catechin weakly, attenuated the intracellular ROS. Finally, animal experiment revealed that both SFN and EGCG successfully inhibited the orthodontic

  5. [Systemic proliferative angioendotheliomatosis: a cutaneous manifestation of malignant B-cell lymphomas. Histologic and immunohistologic studies of two cases].

    PubMed

    Kutzner, H; Englert, W; Hellenbroich, D; Embacher, G; Kutzner, U; Schröder, J

    1991-06-01

    Angioendotheliomatosis proliferans systemisata (AEPS) is a rare disease entity characterized by a predominantly intravascular proliferation of tumour cells. Two forms of AEPS are differentiated: a very rare, benign and self-limiting form, which is endothelial in origin, and a more common, malignant form, which is an angiotropic intravascular malignant B-cell lymphoma. Histological and immunohistological investigations of the malignant form of AEPS are presented: In a 69-year-old woman cutaneous lesions appeared 5 months before the diagnosis of B-immunoblastic lymphoma. In a 57-year-old woman lesions were observed simultaneously with the relapse of a high-grade malignant B-cell lymphoma. Immunohistological identification of the proliferating cell type made diagnosis of intravascular B-cell lymphoma possible in paraffin-embedded biopsies.

  6. When machine vision meets histology: A comparative evaluation of model architecture for classification of histology sections☆

    PubMed Central

    Zhong, Cheng; Han, Ju; Borowsky, Alexander; Parvin, Bahram; Wang, Yunfu; Chang, Hang

    2016-01-01

    Classification of histology sections in large cohorts, in terms of distinct regions of microanatomy (e.g., stromal) and histopathology (e.g., tumor, necrosis), enables the quantification of tumor composition, and the construction of predictive models of genomics and clinical outcome. To tackle the large technical variations and biological heterogeneities, which are intrinsic in large cohorts, emerging systems utilize either prior knowledge from pathologists or unsupervised feature learning for invariant representation of the underlying properties in the data. However, to a large degree, the architecture for tissue histology classification remains unexplored and requires urgent systematical investigation. This paper is the first attempt to provide insights into three fundamental questions in tissue histology classification: I. Is unsupervised feature learning preferable to human engineered features? II. Does cellular saliency help? III. Does the sparse feature encoder contribute to recognition? We show that (a) in I, both Cellular Morphometric Feature and features from unsupervised feature learning lead to superior performance when compared to SIFT and [Color, Texture]; (b) in II, cellular saliency incorporation impairs the performance for systems built upon pixel-/patch-level features; and (c) in III, the effect of the sparse feature encoder is correlated with the robustness of features, and the performance can be consistently improved by the multi-stage extension of systems built upon both Cellular Morphmetric Feature and features from unsupervised feature learning. These insights are validated with two cohorts of Glioblastoma Multiforme (GBM) and Kidney Clear Cell Carcinoma (KIRC). PMID:27644083

  7. I-131 metaiodobenzylguanidine: diagnostic use in neuroblastoma patients in relapse

    SciTech Connect

    Heyman, S.; Evans, A.E.; D'Angio, G.J.

    1988-01-01

    Metaiodobenzylguanidine (MIBG) has been used for the detection and treatment of neuroectodermal tumors, including neuroblastoma. We report our experience with /sup 131/I-MIBG used diagnostically in neuroblastoma patients with relapse. Thirty-eight studies were performed in 26 patients. There were 24 children (range 3 months-14 years) and two adults. While the study was found to be both sensitive and specific for the presence of disease, there are instances of discordance. False-negative studies were found with a markedly anaplastic tumor and with two mature ganglioneuromas. A bone lesion was negative with /sup 131/I-MIBG, but positive on bone scan. A biopsy confirmed the presence of neuroblastoma. Caution should be exercised when scanning pretreated patients, and perhaps with newly diagnosed patients as well.

  8. Fear extinction and relapse: state of the art.

    PubMed

    Vervliet, Bram; Craske, Michelle G; Hermans, Dirk

    2013-01-01

    Exposure-based treatments for clinical anxiety generally are very effective, but relapse is not uncommon. Likewise, laboratory studies have shown that conditioned fears are easy to extinguish, but they recover easily. This analogy is striking, and numerous fear extinction studies have been published that highlight the processes responsible for the extinction and return of acquired fears. This review examines and integrates the most important results from animal and human work. Overall, the results suggest that fear extinction is relatively easy to "learn" but difficult to "remember." It follows that treatments will benefit from an enhanced focus on the long-term retrieval of fear extinction. We review the available studies on the prevention of return of fear and the prospects of weakening fear memories forever. We show that the behavioral principles outlined in learning theory provide a continuous inspiration for preclinical (neurobiological) and clinical research on the extinction and return of fear.

  9. Relapse of Biphenotypic Acute Leukemia as a Breast Mass

    PubMed Central

    2016-01-01

    In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia. PMID:28053635

  10. POLG mutations associated with remitting/relapsing neurological events.

    PubMed

    Degos, Bertrand; Laforêt, Pascal; Jardel, Claude; Sedel, Frédéric; Jossay-Winter, Murielle; Romero, Norma B; Lyon-Caen, Olivier; Tourbah, Ayman

    2014-01-01

    Recent experimental data underline the relationship between mitochondria and immune function. Clinical reports of patients presenting with mitochondrial dysfunction associated with dysimmune responses in the central nervous system reinforce this new concept. We describe the first case of a woman presenting with symptoms related to a novel compound heterozygous mutation of the mitochondrial polymerase γ (POLG) gene, associated with neurological events suggestive of a demyelinating process. Clinical examination revealed bilateral ptosis, progressive external ophthalmoplegia and axonal sensitive polyneuropathy suggestive of a mitochondrial disease. In line with this, muscle biopsy showed ragged red fibers, and sequencing of POLG revealed two heterozygous mutations. In addition, the patient exhibited relapsing neurological symptoms, and cerebral and spinal MRI mimicking multiple sclerosis. This patient stresses the relationship between mitochondrial dysfunction and inflammation. Recent studies suggest that targeting mitochondrial dysfunction could provide benefits in treating some inflammatory diseases.

  11. A Case of Relapsing Polyarthritis Associated With Hidradenitis Suppurativa

    PubMed Central

    Adiga, Avinash; Pixley, John

    2016-01-01

    Hidradenitis suppurativa (HS) is a chronic, inflammatory follicular skin disease with recurrent skin nodules, sinus tracts, and scarring. We observed a case of HS associated with relapsing polyarthritis. On presentation the patient had a flare of polyarthritis with an increase in the number and size of pustular nodules. He has had similar episodes 1 to 2 times yearly subsiding with antibiotic treatment. Radiographs revealed erosions and demineralization. Symptoms improved following institution of anti-inflammatory and antibiotic therapy. HS is associated with several inflammatory conditions, and dysregulation in innate immunity may play an important role in etiopathogenesis. Spondyloarthritis/sacroiliitis is the most common joint manifestation in HS and mechanism(s) underlying arthropathy is unknown. Treatment of arthritis in HS is anecdotal. PMID:27896279

  12. Can orthodontic relapse be blamed on the temporomandibular joint?

    PubMed Central

    Wolford, Larry M

    2014-01-01

    There are many temporomandibular joint (TMJ) conditions that can cause orthodontic treatment instability and relapse. These conditions are often associated with dentofacial deformities, malocclusion, TMJ pain, headaches, myofascial pain, TMJ and jaw functional impairment, ear symptoms, etc., Many of these TMJ conditions can cause progressive and continuous changes in the occlusion and jaw relationships. Patients with these conditions may benefit from corrective orthodontic and surgical intervention. The difficulty for many clinicians may lie in identifying the presence of a TMJ condition, diagnosing the specific TMJ pathology, and selecting the proper treatment for that condition. This paper will discuss the most common TMJ pathologies that can adversely affect orthodontic stability and outcomes as well as present the treatment considerations to correct the specific TMJ conditions and associated jaw deformities to provide stable and predictable treatment results. PMID:25426452

  13. Application of Neurolinguistic Programming for Treatment and Relapse Prevention of Addictive Behaviors.

    ERIC Educational Resources Information Center

    Sandhu, Daya Singh

    The dilemma of relapse exists for a number of addictive behaviors, and mental health authorities agree that keeping addictive behaviors off permanently is much more difficult than treating the behaviors initially. Several relapse prevention models have been posited and environmental, physiological, behavioral, cognitive, and affective factors have…

  14. Predictors of Relapse for American Indian Women after Substance Abuse Treatment

    ERIC Educational Resources Information Center

    Chong, Jenny; Lopez, Darlene

    2008-01-01

    The objective of this study was to describe the predictors of substance use relapse of American Indian (AI) women up to one year following substance abuse treatment. Relapse is defined as any use of alcohol or drugs in the past 30 days at the follow-up points. Data were collected from AI women in a 45-day residential substance abuse treatment…

  15. Ecological Relevance of Memory Tests and the Prediction of Relapse in Alcoholics.

    ERIC Educational Resources Information Center

    Sussman, Steve; And Others

    Recent research suggests that alcoholic inpatients' performance on neuropsychological tests is predictive of their drinking status following discharge from alcohol rehabilitation programs, although no single test itself has been predictive of relapse. This study seeks to develop a ecologically relevant memory test that would predict relapse and…

  16. Enhanced Gamma Interferon Responses of Mouse Spleen Cells following Immunotherapy for Tuberculosis Relapse

    PubMed Central

    Gil, Olga; Vilaplana, Cristina; Guirado, Evelyn; Díaz, Jorge; Cáceres, Neus; Singh, Mahavir; Cardona, Pere-Joan

    2008-01-01

    Gamma interferon responses of spleen cells in mice were examined during postchemotherapy relapse of intraperitoneally induced latent tuberculous infection. The mycobacterial extract RUTI, which prevented the relapse, significantly enhanced the immune responses to secreted and structural recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was mediated by activated T cells. PMID:18827194

  17. Smoking Cessation and Relapse Prevention among Undergraduate Students: A Pilot Demonstration Project.

    ERIC Educational Resources Information Center

    Ramsay, Jim; Hoffmann, Anne

    2004-01-01

    The prevalence of college students' tobacco use is widely recognized, but successful cessation and relapse-prevention programs for these smokers have drawn little attention. The authors, who explored the feasibility of training peers to lead cessation and relapse-prevention programs for undergraduates, found a quit rate of 88.2%, suggesting that…

  18. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia.

    PubMed

    Ma, Xiaotu; Edmonson, Michael; Yergeau, Donald; Muzny, Donna M; Hampton, Oliver A; Rusch, Michael; Song, Guangchun; Easton, John; Harvey, Richard C; Wheeler, David A; Ma, Jing; Doddapaneni, HarshaVardhan; Vadodaria, Bhavin; Wu, Gang; Nagahawatte, Panduka; Carroll, William L; Chen, I-Ming; Gastier-Foster, Julie M; Relling, Mary V; Smith, Malcolm A; Devidas, Meenakshi; Guidry Auvil, Jaime M; Downing, James R; Loh, Mignon L; Willman, Cheryl L; Gerhard, Daniela S; Mullighan, Charles G; Hunger, Stephen P; Zhang, Jinghui

    2015-03-19

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden. Six pathways were frequently mutated, with NT5C2, CREBBP, WHSC1, TP53, USH2A, NRAS and IKZF1 mutations enriched at relapse. Half of the leukaemias had multiple subclonal mutations in a pathway or gene at diagnosis, but mostly with only one, usually minor clone, surviving therapy to acquire additional mutations and become the relapse founder clone. Relapse-specific mutations in NT5C2 were found in nine cases, with mutations in four cases being in descendants of the relapse founder clone. These results provide important insights into the genetic basis of treatment failure in ALL and have implications for the early detection of mutations driving relapse.

  19. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia

    PubMed Central

    Ma, Xiaotu; Edmonson, Michael; Yergeau, Donald; Muzny, Donna M.; Hampton, Oliver A.; Rusch, Michael; Song, Guangchun; Easton, John; Harvey, Richard C.; Wheeler, David A.; Ma, Jing; Doddapaneni, HarshaVardhan; Vadodaria, Bhavin; Wu, Gang; Nagahawatte, Panduka; Carroll, William L.; Chen, I-Ming; Gastier-Foster, Julie M.; Relling, Mary V.; Smith, Malcolm A.; Devidas, Meenakshi; Auvil, Jaime M. Guidry; Downing, James R.; Loh, Mignon L.; Willman, Cheryl L.; Gerhard, Daniela S.; Mullighan, Charles G.; Hunger, Stephen P.; Zhang, Jinghui

    2015-01-01

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden. Six pathways were frequently mutated, with NT5C2, CREBBP, WHSC1, TP53, USH2A, NRAS and IKZF1 mutations enriched at relapse. Half of the leukaemias had multiple subclonal mutations in a pathway or gene at diagnosis, but mostly with only one, usually minor clone, surviving therapy to acquire additional mutations and become the relapse founder clone. Relapse-specific mutations in NT5C2 were found in nine cases, with mutations in four cases being in descendants of the relapse founder clone. These results provide important insights into the genetic basis of treatment failure in ALL and have implications for the early detection of mutations driving relapse. PMID:25790293

  20. Depression, Craving, and Substance Use Following a Randomized Trial of Mindfulness-Based Relapse Prevention

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Bowen, Sarah

    2010-01-01

    Objective: A strong relation between negative affect and craving has been demonstrated in laboratory and clinical studies, with depressive symptomatology showing particularly strong links to craving and substance abuse relapse. Mindfulness-based relapse prevention (MBRP), shown to be efficacious for reduction of substance use, uses…

  1. Relapse and Recurrence Prevention in the Treatment for Adolescents with Depression Study

    ERIC Educational Resources Information Center

    Simons, Anne D.; Rohde, Paul; Kennard, Betsy D.; Robins, Michele

    2005-01-01

    Relapse and recurrence in adolescent depression are important problems. Much less is known about relapse prevention compared to the acute treatment of depression in adolescents. Based on previous research, theoretical predictions, and clinical experience, the Treatment for Adolescents With Depression Study (TADS) protocol was designed to determine…

  2. Self-Modelling as a Relapse Intervention Following Speech-Restructuring Treatment for Stuttering

    ERIC Educational Resources Information Center

    Cream, Angela; O'Brian, Sue; Onslow, Mark; Packman, Ann; Menzies, Ross

    2009-01-01

    Background: Speech restructuring is an efficacious method for the alleviation of stuttered speech. However, post-treatment relapse is common. Aims: To investigate whether the use of video self-modelling using restructured stutter-free speech reduces stuttering in adults who had learnt a speech-restructuring technique and subsequently relapsed.…

  3. Factors associated with relapse in schizophrenia despite adherence to long-acting injectable antipsychotic therapy.

    PubMed

    Alphs, Larry; Nasrallah, Henry A; Bossie, Cynthia A; Fu, Dong-Jing; Gopal, Srihari; Hough, David; Turkoz, Ibrahim

    2016-07-01

    Many patients with schizophrenia will relapse despite uninterrupted antipsychotic (AP) long-acting therapy (LAT). This exploratory analysis examined variables associated with relapse despite ensured adherence to LAT. This was a post-hoc exploratory analysis of a 1-year study of risperidone long-acting injection in patients with stable schizophrenia or schizoaffective disorder (NCT00297388; N=323). Patients were discontinued from previous oral APs and randomly assigned to biweekly intramuscular injections of risperidone long-acting injectable 50 (n=163) or 25 mg (n=161) for 52 weeks. Cox proportional hazards regression models examined variables putatively associated with relapse. A total of 59/323 (18.3%) patients relapsed over 12 months despite continuous AP LAT. Variables associated with the risk of relapse included illness duration (6.0% increase each year; P=0.0003) and country (Canada vs. USA, 4.7-fold risk increase; P=0.0008). When illness duration was further categorized as ≤5, 6-10, and >10 years, patients with an illness duration of >10 versus ≤5 years were at greatest risk of relapse (>10 vs. ≤5 years associated with a 4.4-fold increase in the risk of relapse; P=0.0181). Findings suggest that patients with more chronic illness have a greater risk of relapse despite ensured treatment adherence, supporting the need for early intervention to prevent the deleterious effects of chronicity.

  4. Decreased dopamine activity predicts relapse in methamphetamine abusers

    SciTech Connect

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  5. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia

    PubMed Central

    Byrd, John C; Harrington, Bonnie; O’Brien, Susan; Jones, Jeffrey A; Schuh, Anna; Devereux, Steve; Chaves, Jorge; Wierda, William G; Awan, Farrukh T; Brown, Jennifer R; Hillmen, Peter; Stephens, Deborah M; Ghia, Paolo; Barrientos, Jacqueline C; Pagel, John M; Woyach, Jennifer; Johnson, Dave; Huang, Jane; Wang, Xiaolin; Lannutti, Brian J; Covey, Todd; Fardis, Maria; McGreivy, Jesse; Hamdy, Ahmed; Rothbaum, Wayne; Izumi, Raquel; Diacovo, Thomas G; Johnson, Amy J; Furman, Richard R

    2016-01-01

    Background Irreversible inhibition of Bruton tyrosine kinase (Btk) by ibrutinib represents a significant therapeutic advance for chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromise its therapeutic index. Acalabrutinib (ACP-196) is a more selective irreversible Btk inhibitor specifically designed to improve upon the safety and efficacy of first generation Btk inhibitors. Methods Sixty-one patients with relapsed CLL were treated in a phase 1–2 multicenter study designed to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of oral acalabrutinib. Patients were continuously treated with acalabrutinib 100 to 400 mg once daily in the dose-escalation portion of the study, and 100 mg twice daily in the expansion portion. Results Patient demographics include a median age of 62 years; median of 3 prior therapies; 31% del(17)(p13.1) and 75% unmutated immunoglobulin heavy chain variable genes. No dose-limiting toxicities occurred. The most common adverse events observed were headache (43%), diarrhea (39%) and increased weight (26%). Most adverse events were Grade 1–2. At a median follow-up of 14.3 months, the best overall response rate was 95%, including 85% partial response, 10% partial response with lymphocytosis and 5% stable disease. In patients with del(17)(p13.1), the best overall response was 100%. No cases of Richter’s transformation and only 1 CLL progression have occurred. Conclusions Acalabrutinib is a highly selective Btk inhibitor that provides effective and well tolerated treatment for patients with relapsed CLL, including those with del(17)(p13.1). PMID:26641137

  6. Mindfulness-based relapse prevention for substance craving.

    PubMed

    Witkiewitz, Katie; Bowen, Sarah; Douglas, Haley; Hsu, Sharon H

    2013-02-01

    Craving, defined as the subjective experience of an urge or desire to use substances, has been identified in clinical, laboratory, and preclinical studies as a significant predictor of substance use, substance use disorder, and relapse following treatment for a substance use disorder. Various models of craving have been proposed from biological, cognitive, and/or affective perspectives, and, collectively, these models of craving have informed the research and treatment of addictive behaviors. In this article we discuss craving from a mindfulness perspective, and specifically how mindfulness-based relapse prevention (MBRP) may be effective in reducing substance craving. We present secondary analyses of data from a randomized controlled trial that examined MBRP as an aftercare treatment for substance use disorders. In the primary analyses of the data from this trial, Bowen and colleagues (2009) found that individuals who received MBRP reported significantly lower levels of craving following treatment, in comparison to a treatment-as-usual control group, which mediated subsequent substance use outcomes. In the current study, we extend these findings to examine potential mechanisms by which MBRP might be associated with lower levels of craving. Results indicated that a latent factor representing scores on measures of acceptance, awareness, and nonjudgment significantly mediated the relation between receiving MBRP and self-reported levels of craving immediately following treatment. The mediation findings are consistent with the goals of MBRP and highlight the importance of interventions that increase acceptance and awareness, and help clients foster a nonjudgmental attitude toward their experience. Attending to these processes may target both the experience of and response to craving.

  7. Resistance to extinction and relapse in combined stimulus contexts.

    PubMed

    Podlesnik, Christopher A; Bai, John Y H; Elliffe, Douglas

    2012-09-01

    Reinforcing an alternative response in the same context as a target response reduces the rate of occurrence but increases the persistence of that target response. Applied researchers who use such techniques to decrease the rate of a target problem behavior risk inadvertently increasing the persistence of the same problem behavior. Behavioral momentum theory asserts that the increased persistence is a function of the alternative reinforcement enhancing the Pavlovian relation between the target stimulus context and reinforcement. A method showing promise for reducing the persistence-enhancing effects of alternative reinforcement is to train the alternative response in a separate stimulus context before combining with the target stimulus in extinction. The present study replicated previous findings using pigeons by showing that combining an "alternative" richer VI schedule (96 reinforcers/hr) with a "target" leaner VI schedule (24 reinforcers/hr) reduced resistance to extinction of target responding compared with concurrent training of the alternative and target responses (totaling 120 reinforcers/hr). We also found less relapse with a reinstatement procedure following extinction with separate-context training, supporting previous findings that training conditions similarly influence both resistance to extinction and relapse. Finally, combining the alternative stimulus context was less disruptive to target responding previously trained in the concurrent schedule, relative to combining with the target response trained alone. Overall, the present findings suggest the technique of combining stimulus contexts associated with alternative responses with those associated with target responses disrupts target responding. Furthermore, the effectiveness of this disruption is a function of training context of reinforcement for target responding, consistent with assertions of behavioral momentum theory.

  8. RESISTANCE TO EXTINCTION AND RELAPSE IN COMBINED STIMULUS CONTEXTS

    PubMed Central

    Podlesnik, Christopher A; Bai, John Y. H; Elliffe, Douglas

    2012-01-01

    Reinforcing an alternative response in the same context as a target response reduces the rate of occurrence but increases the persistence of that target response. Applied researchers who use such techniques to decrease the rate of a target problem behavior risk inadvertently increasing the persistence of the same problem behavior. Behavioral momentum theory asserts that the increased persistence is a function of the alternative reinforcement enhancing the Pavlovian relation between the target stimulus context and reinforcement. A method showing promise for reducing the persistence-enhancing effects of alternative reinforcement is to train the alternative response in a separate stimulus context before combining with the target stimulus in extinction. The present study replicated previous findings using pigeons by showing that combining an “alternative” richer VI schedule (96 reinforcers/hr) with a “target” leaner VI schedule (24 reinforcers/hr) reduced resistance to extinction of target responding compared with concurrent training of the alternative and target responses (totaling 120 reinforcers/hr). We also found less relapse with a reinstatement procedure following extinction with separate-context training, supporting previous findings that training conditions similarly influence both resistance to extinction and relapse. Finally, combining the alternative stimulus context was less disruptive to target responding previously trained in the concurrent schedule, relative to combining with the target response trained alone. Overall, the present findings suggest the technique of combining stimulus contexts associated with alternative responses with those associated with target responses disrupts target responding. Furthermore, the effectiveness of this disruption is a function of training context of reinforcement for target responding, consistent with assertions of behavioral momentum theory. PMID:23008521

  9. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia

    PubMed Central

    Cheson, Bruce D.; Pagel, John M.; Hillmen, Peter; Barrientos, Jacqueline C.; Zelenetz, Andrew D.; Kipps, Thomas J.; Flinn, Ian; Ghia, Paolo; Eradat, Herbert; Ervin, Thomas; Lamanna, Nicole; Coiffier, Bertrand; Pettitt, Andrew R.; Ma, Shuo; Stilgenbauer, Stephan; Cramer, Paula; Aiello, Maria; Johnson, Dave M.; Miller, Langdon L.; Li, Daniel; Jahn, Thomas M.; Dansey, Roger D.; Hallek, Michael; O’Brien, Susan M.

    2014-01-01

    BACKGROUND Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemo-therapy. Effective therapies with acceptable side-effect profiles are needed for this patient population. METHODS In this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta iso-form of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. The primary end point was progression-free survival. At the first prespecified interim analysis, the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy. RESULTS The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death in the idelalisib group, 0.15; P<0.001). Patients receiving idelalisib versus those receiving placebo had improved rates of overall response (81% vs. 13%; odds ratio, 29.92; P<0.001) and overall survival at 12 months (92% vs. 80%; hazard ratio for death, 0.28; P = 0.02). Serious adverse events occurred in 40% of the patients receiving idelalisib and rituximab and in 35% of those receiving placebo and rituximab. CONCLUSIONS The combination of idelalisib and rituximab, as compared with placebo and rituximab, significantly improved progression-free survival, response rate, and overall survival among patients with relapsed CLL who were less able to undergo chemo-therapy. (Funded by Gilead; ClinicalTrials.gov number, NCT01539512.) PMID:24450857

  10. Hypogammaglobulinemia after heart transplantation: use of intravenous immunoglobulin replacement therapy in relapsing CMV disease.

    PubMed

    Sarmiento, E; Fernàndez-Yáñez, J; Muñoz, P; Palomo, J; Rodríguez-Molina, J J; Bermejo, J; Catalan, P; Bouza, E; Fernández-Cruz, E; Carbone, J

    2005-01-01

    Secondary hypogammaglobulinemia after heart transplantation may follow immunosuppressive therapy with the resultant increased risk of infections, including cytomegalovirus (CMV) disease. There is limited information on the use of intravenous immunoglobulin replacement therapy (IVIG) in heart-transplanted patients with hypogammaglobulinemia and CMV disease. We present data on five consecutive heart-transplanted patients with relapsing CMV disease, four of whom developed gastrointestinal disease. The immunosuppressive regimen included prednisone, cyclosporine A, azathioprine, mycophenolate mofetil, tacrolimus and antithymocyte globulin (ATG). Evaluation revealed CMV antigenemia. All the patients had been treated with intravenous ganciclovir. In addition, hyperimmune CMV immunoglobulin was administered in three patients. Significantly reduced levels of immunoglobulin G (IgG) were observed in the patients as compared with 15 heart-transplanted individuals without CMV disease [mean IgG levels: 323+/-18 and 639+/-63 mg/dl, respectively (p=0.003)]. IVIG [FLEBOGAMMA], 200-400 mg/kg every 21 days with the goal of maintaining normal serum IgG levels, was added for the treatment of CMV disease. Selected batches with the highest anti-CMV titers were set apart for the treatment of the patients. IVIG treatment, in combination with antiviral therapy, proved able to control CMV disease. There was a favorable clinical response and the patients became free of gastrointestinal symptoms. Detection of CMV antigens was negative after treatment. During IVIG therapy no immediate or delayed adverse effects were observed. Even if our survey was limited to five cases, the results suggest that addition of IVIG to antiviral chemotherapy might improve outcome in heart-transplanted patients with hypogammaglobulinemia and CMV disease.

  11. Fatigue favors in vitro Th1 and Th17-like cell expansion and reduces corticoid sensitivity in MS patients.

    PubMed

    Alvarenga-Filho, Hélcio; Salles, Marisa; Hygino, Joana; Ferreira, Thais B; Sacramento, Priscila M; Monteiro, Clarice; Vasconcelos, Claudia Cristina F; Alvarenga, Regina Maria Papais; Bento, Cleonice A M

    2017-02-15

    Fatigue is a common "ghost" symptom in patients with multiple sclerosis (MS), an autoimmune disease mediated by T cells that target myelin antigens of the central nervous system. As fatigue has been associated with inflammatory states, its occurrence may negatively impact MS progression. The aim of this study was to evaluate the impact of fatigue on the cytokine profile of patients with relapsing-remitting (RR) MS. For our study, blood were collected from MS patients in clinical remission phase with (n=15) and without (n=15) fatigue. Cytokines were detected by ELISA in the plasma and supernatant collected from anti-CD3/anti-CD28-activated T cells or LPS-stimulated monocytes. In some wells, different doses of hydrocortisone (HC) were added at the beginning of the culture. Here, peripheral levels of IL-6 and TNF-α, as well as in vitro production of cytokines related to Th17 (IL-6, IL-17, IL-22, and GM-CSF) or Th1 (IFN-γ) phenotypes, were elevated in fatigued patients and their levels were associated with fatigue severity. The same phenomenon was observed between the production of IL-6, TNF-α, IL-1β, and IL-23 by monocytes and fatigue. Moreover, HC was less efficient in inhibiting in vitro inflammatory cytokine production in patients with fatigue, mainly those produced by both CD8(+) T cells and monocytes. Our data, although preliminary, suggests that the occurrence of fatigue, by favoring the in vitro production of Th1/Th17-related cytokines and corticoid resistance, may negatively impact the course of MS.

  12. Are histologic studies of adenotonsillectomy really necessary?

    PubMed

    Rebechi, Giseli; Pontes, Thiago Euênio; Braga, Elias Lobo; Matos, Willian Maduel; Rebechi, Fernando; Matsuyama, Cícero

    2013-10-01

    Introduction In most ear, nose, and throat services, it is routine to send the material extracted from tonsillectomy for histologic study to research malignancy, to analyze suspect material, or to provide medical-legal documentation. Recent studies have shown that this routine analysis is dispensable. Objective To evaluate the actual need and perform a cost-benefit analysis of routine histopathologic examination in tonsillectomy with no signs or symptoms of malignancy. Methods A retrospective observational study evaluated the charts of patients undergoing adenotonsillectomy, tonsillectomy, or adenoidectomy from January 2008 to September 2009 at the Institute of Otorhinolaryngology CEMA-SP. Costs of this test for the public health system were analyzed and the literature reviewed. Results We studied 281 patients between 2 and 22 years of age; 142 (50.5%) were male and 139 (49.5%) were female. Of the surgeries, 201 were adenotonsillectomies (71.5%), 41 were tonsillectomies (14.5%), and 39 were adenoidectomies (14%). The most common indication for surgery was recurrent infection (63.3%). None of study patients had clinical suspicion of malignancy. The tests showed a cost of R$20.03 per tonsil analyzed. Conclusion Routine histopathologic examination in patients undergoing adenotonsillectomy with no signs or symptoms of malignancy is dispensable and increases the cost of the surgeries.

  13. Two neutrophilic dermatoses captured simultaneously on histology

    PubMed Central

    Wlodek, Christina; Bhatt, Nidhi; Kennedy, Cameron

    2016-01-01

    A number of neutrophilic dermatoses are associated with malignancies and their treatment. These rarely occur together in the same patient. A Caucasian 72-year-old male was treated for acute myeloid leukemia (AML) with chemotherapy including daunorubicin and cytarabine. Within 48 hours of commencing treatment, he developed pyrexia and, two days later, disseminated non-tender pink plaques on the limbs and trunk. A skin biopsy showed a dermal interstitial infiltrate of lymphocytes, histiocytoid cells and predominantly neutrophils. This extended into the subcutis, where a neutrophilic lobular panniculitis was seen. These findings are consistent with Sweet’s syndrome. In addition, a neutrophilic and lymphocytic infiltrate was also present around eccrine coils and lower ducts. The eccrine epithelium showed squamous metaplasia with dyskeratosis and sloughing into the lumen. These latter findings are consistent with neutrophilic eccrine hidradenitis (NEH). These two histologically distinct entities form part of the neutrophilic dermatoses that have been described in oncology patients with reports of concurrent or sequential occurrence of various neutrophilic dermatoses in the same patient. Ours, however, is only the second reported case of simultaneously captured Sweet’s and NEH in the setting of AML. The most likely explanation is that of an epiphenomenon, whereby the neutrophilic infiltrate extended around the sweat glands in the context of the neutrophilic dermatosis. PMID:27648385

  14. Are Histologic Studies of Adenotonsillectomy Really Necessary?

    PubMed Central

    Rebechi, Giseli; Pontes, Thiago Euênio; Braga, Elias Lobo; Matos, Willian Maduel; Rebechi, Fernando; Matsuyama, Cícero

    2013-01-01

    Introduction In most ear, nose, and throat services, it is routine to send the material extracted from tonsillectomy for histologic study to research malignancy, to analyze suspect material, or to provide medical-legal documentation. Recent studies have shown that this routine analysis is dispensable. Objective To evaluate the actual need and perform a cost–benefit analysis of routine histopathologic examination in tonsillectomy with no signs or symptoms of malignancy. Methods A retrospective observational study evaluated the charts of patients undergoing adenotonsillectomy, tonsillectomy, or adenoidectomy from January 2008 to September 2009 at the Institute of Otorhinolaryngology CEMA-SP. Costs of this test for the public health system were analyzed and the literature reviewed. Results We studied 281 patients between 2 and 22 years of age; 142 (50.5%) were male and 139 (49.5%) were female. Of the surgeries, 201 were adenotonsillectomies (71.5%), 41 were tonsillectomies (14.5%), and 39 were adenoidectomies (14%). The most common indication for surgery was recurrent infection (63.3%). None of study patients had clinical suspicion of malignancy. The tests showed a cost of R$20.03 per tonsil analyzed. Conclusion Routine histopathologic examination in patients undergoing adenotonsillectomy with no signs or symptoms of malignancy is dispensable and increases the cost of the surgeries. PMID:25992042

  15. Chronic viral hepatitis: the histology report.

    PubMed

    Guido, Maria; Mangia, Alessandra; Faa, Gavino

    2011-03-01

    In chronic viral hepatitis, the role of liver biopsy as a diagnostic test has seen a decline, paralleled by its increasing importance for prognostic purposes. Nowadays, the main indication for liver biopsy in chronic viral hepatitis is to assess the severity of the disease, in terms of both necro-inflammation (grade) and fibrosis (stage), which is important for prognosis and therapeutic management. Several scoring systems have been proposed for grading and staging chronic viral hepatitis and there is no a general consensus on the best system to be used in the daily practice. All scoring systems have their drawbacks and all may be affected by sampling and observer variability. Whatever the system used, a histological score is a reductive approach since damage in chronic viral hepatitis is a complex biological process. Thus, scoring systems are not intended to replace the detailed, descriptive, pathology report. In fact, lesions other than those scored for grading and staging may have clinical relevance and should be assessed and reported. This paper aims to provide a systematic approach to the interpretation of liver biopsies obtained in cases of chronic viral hepatitis, with the hope of helping general pathologists in their diagnostic practice.

  16. Anatomy and Histology of an Epicanthal Fold.

    PubMed

    Park, Jae Woo; Hwang, Kun

    2016-06-01

    The aim of this study is to elucidate the precise anatomical and histological detail of the epicanthal fold.Thirty-two hemifaces of 16 Korean adult cadavers were used in this study (30 hemifaces with an epicanthal fold, 2 without an epicanthal fold). In 2 patients who had an epicanthoplasty, the epicanthal folds were sampled.In a dissection, the periorbital skin and subcutaneous tissues were removed and the epicanthal fold was observed in relation to each part of the orbicularis oculi muscle. Specimens including the epicanthal fold were embeddedin in paraffin, sectioned at 10 um, and stained with Hematoxylin-Eosin. The horizontal section in the level of the paplebral fissure was made and the prepared slides were observed under a light microscope.In the specimens without an epicanthal fold, no connection between the upper preseptal muscle and the lower preseptal muscle was found. In the specimens with an epicanthal fold, a connection of the upper preseptal muscle to the lower preseptal muscle was observed. It was present in all 15 hemifaces (100%). There was no connection between the pretarsal muscles. In a horizontal section, the epicanthal fold was composed of 3 compartments: an outer skin lining, a core structure, and an innerskin lining. The core structure was mainly composed of muscular fibers and fibrotic tissue and they were intermingled.Surgeons should be aware of the anatomical details of an epicanthal fold. In removing or reconstructing an epicanthal fold, the fibromuscular core band should also be removed or reconstructed.

  17. Comparative anatomy and histology of xenarthran osteoderms.

    PubMed

    Hill, Robert V

    2006-12-01

    Reconstruction of soft tissues in fossil vertebrates is an enduring challenge for paleontologists. Because inferences must be based on evidence from hard tissues (typically bones or teeth), even the most complete fossils provide only limited information about certain organ systems. Osteoderms ("dermal armor") are integumentary bones with high fossilization potential that hold information about the anatomy of the skin in many extant and fossil amniotes. Their importance for functional morphology and phylogenetic research has recently been recognized, but studies have focused largely upon reptiles, in which osteoderms are most common. Among mammals, osteoderms occur only in members of the clade Xenarthra, which includes armadillos and their extinct relatives: glyptodonts, pampatheres, and, more distantly, ground sloths. Here, I present new information on the comparative morphology and histology of osteoderms and their associated soft tissues in 11 extant and fossil xenarthrans. Extinct mylodontid sloths possessed simple, isolated ossicles, the presence of which is likely plesiomorphic for Xenarthra. More highly derived osteoderms of glyptodonts, pampatheres, and armadillos feature complex articulations and surface ornamentation. Osteoderms of modern armadillos are physically associated with a variety of soft tissues, including nerve, muscle, gland, and connective tissue. In some cases, similar osteological features may be caused by two or more different tissue types, rendering soft-tissue inferences for fossil osteoderms equivocal. Certain osteological structures, however, are consistently associated with specific soft-tissue complexes and therefore represent a relatively robust foundation upon which to base soft-tissue reconstructions of extinct xenarthrans.

  18. Histology of the central nervous system.

    PubMed

    Garman, Robert H

    2011-01-01

    The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cytoplasmic processes is helpful in determining that certain patterns of treatment-related neuropil vacuolation (as well as some artifacts) represent swelling of these processes. On the other hand, vacuoles with different distribution patterns may represent alterations of the myelin sheath. Because brains are typically undersampled for microscopic evaluation, many pathologists are unfamiliar with the circumventricuar organs (CVOs) that represent normal brain structures but are often mistaken for lesions. Therefore, the six CVOs found in the brain are also illustrated in this article.

  19. Automatic morphometry of nerve histological sections.

    PubMed

    Romero, E; Cuisenaire, O; Denef, J F; Delbeke, J; Macq, B; Veraart, C

    2000-04-15

    A method for the automatic segmentation, recognition and measurement of neuronal myelinated fibers in nerve histological sections is presented. In this method, the fiber parameters i.e. perimeter, area, position of the fiber and myelin sheath thickness are automatically computed. Obliquity of the sections may be taken into account. First, the image is thresholded to provide a coarse classification between myelin and non-myelin pixels. Next, the resulting binary image is further simplified using connected morphological operators. By applying semantic rules to the zonal graph axon candidates are identified. Those are either isolated or still connected. Then, separation of connected fibers is performed by evaluating myelin sheath thickness around each candidate area with an Euclidean distance transformation. Finally, properties of each detected fiber are computed and false positives are removed. The accuracy of the method is assessed by evaluating missed detection, false positive ratio and comparing the results to the manual procedure with sampling. In the evaluated nerve surface, a 0.9% of false positives was found, along with 6.36% of missed detections. The resulting histograms show strong correlation with those obtained by manual measure. The noise introduced by this method is significantly lower than the intrinsic sampling variability. This automatic method constitutes an original tool for morphometrical analysis.

  20. Assessment of neuroactive steroids in cerebrospinal fluid comparing acute relapse and stable disease in relapsing-remitting multiple sclerosis.

    PubMed

    Orefice, Ns; Carotenuto, A; Mangone, G; Bues, B; Rehm, R; Cerillo, I; Saccà, F; Calignano, A; Orefice, G

    2016-05-01

    Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological

  1. Exploring the factors influencing relapse and recovery among drug and alcohol addicted women.

    PubMed

    Snow, D; Anderson, C

    2000-07-01

    1. Both women who were in treatment for relapse to and in sustained recovery from drugs and alcohol had multiple co-occurring addictions such as relationship, spending, food, and shopping that complicated the recovery process. 2. Depression is a major trigger for relapse in women with alcohol and drug problems. Recognition and treatment of depression is critical to achieve successful outcomes of treatment for these women, and teaching them to monitor their mood changes and seek help will improve the chances of preventing relapse. 3. Subjects in neither the relapse nor recovery sample recognized the significant influence of current violent partnerships or the ending of a violent relationship on their relapse or recovery.

  2. Assessment of Relapse Following Intraoral Vertical Ramus Osteotomy Mandibular Setback and Short-term Immobilization

    PubMed Central

    Talesh, Koroush Taheri; Motamedi, Mohammad Hosein Kalantar; Sazavar, Mahdi; Yazdani, Javad

    2010-01-01

    Aim: Relapse is an important issue of concern following operations for mandibular setback. Decreasing the immobilization (IMF) period may play a role in this regard. Usual IMF period ranges from 1 to 2 months. We aimed to assess relapse following a 1-week IMF period. Materials and methods: This study aimed to assess 40 purely prognathic patients who had undergone Vertical Ramus osteotomy for mandibular setback. After the release of IMF, guiding elastics were used to direct the mandible to maximal intercuspation for 3 weeks. Relapse was measured from cephalometric radiographs preoperatively and 1 year postoperatively. Results: The mean skeletal horizontal relapse after 1 year in 40 treated patients was 0.6 mm. Conclusion: The mean skeletal horizontal relapse after 1 year was similar to figures reported for this operation with longer fixation. PMID:20694038

  3. Unilateral Migratory Relapsing Orbital Myositis While on Immunosuppressant Therapy: An Uncommon Entity.

    PubMed

    Singh, Swati; Mittal, Ruchi; Padhan, Prasanta; Tripathy, Devjyoti

    A young healthy female presented with acute onset left ocular pain, restricted ocular motility, and binocular diplopia. CT imaging showed left lateral rectus myositis that resolved with oral corticosteroids. Two sequential relapses occurred subsequently involving the superior rectus-levator complex followed by the medial rectus. Biopsy revealed orbital inflammatory disease with lymphocytic vasculitis. Detailed systemic work up was normal. The second relapse was seen while on long-term oral methotrexate although initial disease remission had been achieved with the same drug. A changeover to oral azathioprine was able to achieve disease remission after the second relapse. All relapses involved the same side and the contralateral orbit was not affected. This report presents the curious phenomenon of unilateral migratory relapsing orbital myositis of unknown cause that recurred even while on immunosuppressant therapy. It highlights the unpredictable nature of this uncommon entity and the challenges faced in managing such cases.

  4. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

    SciTech Connect

    Barkati, Maroie; Williams, Scott G.; Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat; Dyk, Sylvia van; See, Andrew; Duchesne, Gillian M.

    2012-04-01

    Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

  5. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder

    PubMed Central

    Kessler, Remi A.; Mealy, Maureen A.

    2016-01-01

    Objective: The purpose of this study was to review cases of neuromyelitis optica spectrum disorder (NMOSD) relapses and pseudorelapses to identify early features that differentiate between them at onset of symptoms. Methods: This was a retrospective analysis of 74 hospitalizations of patients with NMOSD who were admitted to the Johns Hopkins Hospital for workup and treatment of a presumed relapse. Standard workup included MRI and blood and urine testing for metabolic and infectious etiologies. The gold standard for a relapse was defined as new or worsening symptoms and a change in neurologic examination correlating with a new or enhancing MRI lesion. A pseudorelapse was a clinical exacerbation with similar symptoms and signs but the MRI was negative, and workup identified an alternative cause for the symptoms that, when treated, resulted in the improvement of neurologic symptoms. Factors considered to be early predictors of relapses vs pseudorelapses were analyzed using the Fisher test. Results: Among 74 NMOSD hospitalizations for presumed relapse, 57 were confirmed relapses while 17 had a negative MRI and an identifiable cause of pseudorelapse. The most common causes of pseudorelapse were infection, pain, and dysautonomia. The only early predictor that reliably differentiated relapse from pseudorelapse among this NMOSD patient population was vision loss (p = 0.039). Race, sex, presentations of weakness, numbness, and bowel/bladder dysfunction, white blood cell count, and urinary tract infection were not different among patients with relapses vs pseudorelapses. Conclusions: Vision loss in NMOSD is strongly suggestive of a true relapse vs a pseudorelapse. Pseudorelapses localized to the spinal cord in patients with previous myelitis presented similarly to true relapses and could only be ruled out by a negative MRI. PMID:27508210

  6. Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

    SciTech Connect

    Kriz, Jan; Reinartz, Gabriele; Dietlein, Markus; Kobe, Carsten; Kuhnert, Georg; Haverkamp, Heinz; Haverkamp, Uwe; Engenhart-Cabillic, Rita; Herfarth, Klaus; Lukas, Peter; Schmidberger, Heinz; Staar, Susanne; Hegerfeld, Kira; Baues, Christian; Engert, Andreas; Eich, Hans Theodor

    2015-05-01

    Purpose: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. Methods and Materials: All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluated all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. Results: A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. Conclusions: The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses.

  7. The alcohol deprivation effect model for studying relapse behavior: a comparison between rats and mice.

    PubMed

    Vengeliene, Valentina; Bilbao, Ainhoa; Spanagel, Rainer

    2014-05-01

    Understanding the psychological mechanisms and underlying neurobiology of relapse behavior is essential for improving the treatment of addiction. Because the neurobiology of relapse behavior cannot be well studied in patients, we must rely on appropriate animal models. The alcohol deprivation effect (ADE) is a phenomenon in laboratory animals that models a relapse-like drinking situation, providing excellent face and predictive validity. In rodents, relapse-like behavior is largely influenced by the genetic make-up of an animal. It is not clear which other factors are responsible for variability of this behavior, but there seems to be no correlation between levels of baseline alcohol intake and the occurrence, duration, and robustness of the ADE. Rats that undergo long-term alcohol drinking for several months with repeated deprivation phases develop a compulsive drinking behavior during a relapse situation, characterized by insensitivity to taste adulteration with quinine, a loss of circadian drinking patterns during relapse-like drinking, and a shift toward drinking highly concentrated alcohol solutions to rapidly increase blood alcohol concentrations and achieve intoxication. Some mouse strains also exhibit an ADE, but this is usually of shorter duration than in rats. However, compulsive drinking in mice during a relapse situation has yet to be demonstrated. We extend our review section with original data showing that during long-term alcohol consumption, mice show a decline in alcohol intake, and the ADE fades with repeated deprivation phases. Furthermore, anti-relapse compounds that produce reliable effects on the ADE in rats produce paradoxical effects in mice. We conclude that the rat provides a better model system to study alcohol relapse and putative anti-relapse compounds.

  8. FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma.

    PubMed

    Perez-Balaguer, Ariadna; Ortiz-Martínez, Fernando; García-Martínez, Araceli; Pomares-Navarro, Critina; Lerma, Enrique; Peiró, Gloria

    2015-09-01

    The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10% (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher's test). Patients whose tumors expressed FOXA2 had increased relapses (59 vs. 79%, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95% = 1.45-7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like tumors, and is associated with increase relapses.

  9. Could magnetic resonance provide in vivo histology?

    PubMed

    Dominietto, Marco; Rudin, Markus

    2014-01-13

    THE DIAGNOSIS OF A SUSPECTED TUMOR LESION FACES TWO BASIC PROBLEMS: detection and identification of the specific type of tumor. Radiological techniques are commonly used for the detection and localization of solid tumors. Prerequisite is a high intrinsic or enhanced contrast between normal and neoplastic tissue. Identification of the tumor type is still based on histological analysis. The result depends critically on the sampling sites, which given the inherent heterogeneity of tumors, constitutes a major limitation. Non-invasive in vivo imaging might overcome this limitation providing comprehensive three-dimensional morphological, physiological, and metabolic information as well as the possibility for longitudinal studies. In this context, magnetic resonance based techniques are quite attractive since offer at the same time high spatial resolution, unique soft tissue contrast, good temporal resolution to study dynamic processes and high chemical specificity. The goal of this paper is to review the role of magnetic resonance techniques in characterizing tumor tissue in vivo both at morphological and physiological levels. The first part of this review covers methods, which provide information on specific aspects of tumor phenotypes, considered as indicators of malignancy. These comprise measurements of the inflammatory status, neo-vascular physiology, acidosis, tumor oxygenation, and metabolism together with tissue morphology. Even if the spatial resolution is not sufficient to characterize the tumor phenotype at a cellular level, this multiparametric information might potentially be used for classification of tumors. The second part discusses mathematical tools, which allow characterizing tissue based on the acquired three-dimensional data set. In particular, methods addressing tumor heterogeneity will be highlighted. Finally, we address the potential and limitation of using MRI as a tool to provide in vivo tissue characterization.

  10. Image-based histologic grade estimation using stochastic geometry analysis

    NASA Astrophysics Data System (ADS)

    Petushi, Sokol; Zhang, Jasper; Milutinovic, Aladin; Breen, David E.; Garcia, Fernando U.

    2011-03-01

    Background: Low reproducibility of histologic grading of breast carcinoma due to its subjectivity has traditionally diminished the prognostic value of histologic breast cancer grading. The objective of this study is to assess the effectiveness and reproducibility of grading breast carcinomas with automated computer-based image processing that utilizes stochastic geometry shape analysis. Methods: We used histology images stained with Hematoxylin & Eosin (H&E) from invasive mammary carcinoma, no special type cases as a source domain and study environment. We developed a customized hybrid semi-automated segmentation algorithm to cluster the raw image data and reduce the image domain complexity to a binary representation with the foreground representing regions of high density of malignant cells. A second algorithm was developed to apply stochastic geometry and texture analysis measurements to the segmented images and to produce shape distributions, transforming the original color images into a histogram representation that captures their distinguishing properties between various histological grades. Results: Computational results were compared against known histological grades assigned by the pathologist. The Earth Mover's Distance (EMD) similarity metric and the K-Nearest Neighbors (KNN) classification algorithm provided correlations between the high-dimensional set of shape distributions and a priori known histological grades. Conclusion: Computational pattern analysis of histology shows promise as an effective software tool in breast cancer histological grading.

  11. Promoting Rapid Learning in the Histology Laboratory by Integrating Technology

    ERIC Educational Resources Information Center

    Shields, Vonnie

    2008-01-01

    This paper describes the results of incorporating technology in the histology laboratory by using high-resolution video-imaging equipment (VIE). The study sought to determine if (1) the VIE would allow students to more easily and rapidly find histological structures over more conventional methods, and (2) if they could find the structures with the…

  12. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial

    PubMed Central

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-01-01

    Background Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. Design and Methods This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1–4, prednisone at a dose of 1.5 mg/kg also on days 1–4 and thalidomide at a dose of 50–100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1–4 and 1.6, 3.2, or 4.8 g on days 5–35. Results Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3–4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. Conclusions This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1–4 followed by 4.8 g p.o. on days 5–35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs (ClinicalTrials.gov Identifier: NCT00406978). PMID:20053869

  13. Esophageal granular cell tumor: Clinical, endoscopic and histological features of 19 cases

    PubMed Central

    ZHANG, MING; SUN, ZE-QUN; ZOU, XIAO-PING

    2014-01-01

    Esophageal granular cell tumors (GCTs) are rare and often misdiagnosed. To demonstrate their clinicopathological features, the present study reports 19 cases and reviews the literature. There were 11 female and eight male esophageal GCT patients with a median age of 42.0 years. All the tumors were solitary. The majority of patient indications for endoscopy (89.5%) were non-specific and endoscopic therapy was performed in 17 cases with a relapse in one case after a 12-month follow-up. The endoscopic appearance of esophageal GCT was variable and the majority of tumors (80.0%) were located in the middle and lower esophageal segments. The size of the tumors ranged from 0.4 to 2 cm in diameter and the surface was white-gray, pink or yellow. Nine patients underwent an endoscopic ultrasound exam, eight of which demonstrated hypoechoic echostructures with a smooth margin and intracavity growth features. One case was derived from the muscularis propria layer with an irregular margin and intra- and extra-cavity growth features. The histological features could mimic other tumors and immunohistochemical stains are usually positive for S-100, periodic acid-Schiff, neuron-specific enolase and nestin. Three cases indicated pleomorphism and Ki-67 was locally positive. Esophageal GCTs are rare and endoscopic ultrasound features are variable. Immunohistochemical staining may aid in the diagnosis. PMID:25013469

  14. Neurolymphomatosis as a late relapse of non-Hodgkin's lymphoma detected by 18F-FDG PET/CT: a case report.

    PubMed

    Kajáry, K; Molnár, Z; Mikó, I; Barsi, P; Lengyel, Z; Szakáll, S

    2014-01-01

    Neurolymphomatosis is a rare condition defined as an infiltration of nerves, nerve roots or nervous plexuses by haematological malignancy. Its diagnosis may sometimes be difficult with conventional imaging techniques. This paper aims to emphasize the importance of this entity and the role of (18)F-FDG PET/CT in this indication. We present the case of a 53-year-old male who complained of sharp pain in his right hip and right leg paresthesia after 2 years of complete remission from Non-Hodgkin's lymphoma. Physical examination and CT scan were negative and the lumbar MRI showed protrusion of L5-S1 disc. Physiotherapy, nonsteroid antiinflammatory drugs and steroids were inefficient. PET/CT was performed four months after the onset of the symptoms, revealing focal FDG uptake in the right S1 nerve root and linear FDG uptake along the right sacral plexus suggesting relapse. This was confirmed by histology.

  15. Survival of AML patients relapsing after allogeneic hematopoietic cell transplantation: a CIBMTR study

    PubMed Central

    Bejanyan, Nelli; Weisdorf, Daniel J.; Logan, Brent R.; Wang, Hai-Lin; Devine, Steven M.; de Lima, Marcos; Bunjes, Donald W.; Zhang, Mei-Jie

    2015-01-01

    Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990–2010) during first or second complete remission (CR) to identify factors associated with longer post-relapse survival. Median time of post HCT relapse was 7 months (mo; range, 1–177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy (CT) alone (n=660), donor lymphocyte infusion (DLI)±CT (n=202; %), or 2nd alloHCT±CT ±DLI (n=369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 mo (range, <1–193). Survival for all patients was 23% at 1 year post-relapse; however, 3-yr overall survival correlated with time from HCT to relapse (4% for relapse during 1–6 mo period, 12% during 6 mo-2 yr, 26% during 2–3 yr, and 38% for ≥3 yr). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (RR 0.55 for 6 mo-2 yr, RR 0.39 for 2–3 yr, and RR 0.28 for ≥3 yr; p<0.0001) and a 1st HCT using reduced-intensity conditioning (RR=0.77; 95% CI 0.66–0.88, p=0.0002). In contrast, inferior survival was associated with age >40 yr (RR=1.42, 95% CI 1.24–1.64; p<0.0001), active GVHD at relapse (RR=1.25, 95% CI 1.13–1.39; p<0.0001), adverse cytogenetics (RR=1.37, 95% CI 1.09–1.71; p=0.0062), mismatched URD (RR=1.61, 95% CI 1.22–2.13; p=0.0008), and use of cord blood for 1st HCT (RR=1.23, 95% CI 1.06–1.42; p=0.0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 mo after their initial alloHCT had better survival and may benefit from intensive therapy such as 2nd alloHCT±DLI. PMID:25460355

  16. Protective Effects on Central Nervous System by Acidic Polysaccharide of Panax ginseng in Relapse-Remitting Experimental Autoimmune Encephalomyelitis-Induced SJL/J Mice.

    PubMed

    Bing, So Jin; Ha, Danbee; Hwang, Insun; Park, Eunjin; Ahn, Ginnae; Song, Jie-Young; Jee, Youngheun

    2016-01-01

    Bearing pathologic and clinical similarities to human multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) is used as a murine model to test potential therapeutic agents for MS. Recently, we reported the protective effects of an acidic polysaccharide of Panax ginseng (APG) in C57BL/6 strain-dependent EAE, a model of primary progressive MS. In this study, we extend our previous findings on the therapeutic capacity of APG in relapsing-remitting EAE (rr-EAE), the animal model to closely mimic recurrent inflammatory demyelination lesions of relapsing-remitting MS. Treatments with APG led to a significant reduction of clinical symptoms and the relapse rate of EAE than vehicle treatments. Consistent with this, histological examination revealed that APG markedly modulated the infiltration of CD4[Formula: see text] T cells and CD11b[Formula: see text] macrophages into the spinal cord and the APG-treated CNS was devoid of demyelination and axonal damages. In addition, APG decreased the proliferation of peripheral PLP-reactive T cells and the production of pro-inflammatory factors such as IFN-[Formula: see text], IL-17 and TNF-[Formula: see text]. The fact that APG can induce clinically beneficial effects to distinct types of EAE furthers our understanding on the basis of its immunosuppression in EAE and, possibly, in MS. Our results suggest that APG may serve as a new therapeutic agent for MS as well as other human autoimmune diseases, and warrants continued evaluation for its translation into therapeutic application.

  17. Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation

    PubMed Central

    Kunz, Joachim B.; Rausch, Tobias; Bandapalli, Obul R.; Eilers, Juliane; Pechanska, Paulina; Schuessele, Stephanie; Assenov, Yassen; Stütz, Adrian M.; Kirschner-Schwabe, Renate; Hof, Jana; Eckert, Cornelia; von Stackelberg, Arend; Schrappe, Martin; Stanulla, Martin; Koehler, Rolf; Avigad, Smadar; Elitzur, Sarah; Handgretinger, Rupert; Benes, Vladimir; Weischenfeldt, Joachim; Korbel, Jan O.; Muckenthaler, Martina U.; Kulozik, Andreas E.

    2015-01-01

    Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by resistance against chemotherapy and is frequently fatal. We aimed at understanding the molecular mechanisms resulting in relapse of T-cell acute lymphoblastic leukemia and analyzed 13 patients at first diagnosis, remission and relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex ligation dependent probe amplification and DNA methylation array. Compared to primary T-cell acute lymphoblastic leukemia, in relapse the number of single nucleotide variants and small insertions and deletions approximately doubled from 11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that were selected for in relapse. The mutational pattern defined two types of relapses. While both are characterized by selection of subclones and acquisition of novel mutations, ‘type 1’ relapse derives from the primary leukemia whereas ‘type 2’ relapse originates from a common pre-leukemic ancestor. Relapse-specific changes included activation of the nucleotidase NT5C2 resulting in resistance to chemotherapy and mutations of epigenetic modulators, exemplified by SUZ12, WHSC1 and SMARCA4. While mutations present in primary leukemia and in relapse were enriched for known drivers of leukemia, relapse-specific changes revealed an association with general cancer-promoting mechanisms. This study thus identifies mechanisms that drive progression of pediatric T-cell acute lymphoblastic leukemia to relapse and may explain the characteristic treatment resistance of this condition. PMID:26294725

  18. Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.

    PubMed

    Kunz, Joachim B; Rausch, Tobias; Bandapalli, Obul R; Eilers, Juliane; Pechanska, Paulina; Schuessele, Stephanie; Assenov, Yassen; Stütz, Adrian M; Kirschner-Schwabe, Renate; Hof, Jana; Eckert, Cornelia; von Stackelberg, Arend; Schrappe, Martin; Stanulla, Martin; Koehler, Rolf; Avigad, Smadar; Elitzur, Sarah; Handgretinger, Rupert; Benes, Vladimir; Weischenfeldt, Joachim; Korbel, Jan O; Muckenthaler, Martina U; Kulozik, Andreas E

    2015-11-01

    Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by resistance against chemotherapy and is frequently fatal. We aimed at understanding the molecular mechanisms resulting in relapse of T-cell acute lymphoblastic leukemia and analyzed 13 patients at first diagnosis, remission and relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex ligation dependent probe amplification and DNA methylation array. Compared to primary T-cell acute lymphoblastic leukemia, in relapse the number of single nucleotide variants and small insertions and deletions approximately doubled from 11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that were selected for in relapse. The mutational pattern defined two types of relapses. While both are characterized by selection of subclones and acquisition of novel mutations, 'type 1' relapse derives from the primary leukemia whereas 'type 2' relapse originates from a common pre-leukemic ancestor. Relapse-specific changes included activation of the nucleotidase NT5C2 resulting in resistance to chemotherapy and mutations of epigenetic modulators, exemplified by SUZ12, WHSC1 and SMARCA4. While mutations present in primary leukemia and in relapse were enriched for known drivers of leukemia, relapse-specific changes revealed an association with general cancer-promoting mechanisms. This study thus identifies mechanisms that drive progression of pediatric T-cell acute lymphoblastic leukemia to relapse and may explain the characteristic treatment resistance of this condition.

  19. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

    Cancer.gov

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  20. Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection

    PubMed Central

    Li, Jinqing; Liao, Yuan; Ding, Tong; Wang, Bo; Yu, Xingjuan; Chu, Yifan; Xu, Jing; Zheng, Limin

    2016-01-01

    Interleukin-25 (IL-25) is a recently identified member of the proinflammatory IL-17 cytokine family; however, its role in human tumors remains largely unknown. The aim of this study was to investigate the cellular source and clinical significance of IL-25 in gastric cancer (GC) in situ. The results demonstrated that macrophages (Mφs) were the primary IL-25-expressing cells (IL-25+) in GC in situ. Moreover, IL-25+ cells were highly enriched in the intra-tumoral (IT) region of GC tissues (p < 0.001). The production of IL-25 in Mφs exposed to culture supernatant from gastric cancer cell line SGC7901 in vitro was induced by transforming growth factor-β1, and their density in the IT region was positively associated with those of other effector immune cells, namely, CD4+ T cells, CD8+ T cells and CD103+T cells (p < 0.01). This suggested that macrophages might produce IL-25 to create an antitumor micromilieu in GC tissues. The level of IL-25+IT cells was positively associated with histological grade (p < 0.001) and found to be an independent predictor of favorable survival (p = 0.024) in patients with GC after radical resection. These findings suggest that IL-25+IT cells may be a novel therapeutic target in those patients. PMID:26840565

  1. Cost-effectiveness analysis of antipsychotics in reducing schizophrenia relapses

    PubMed Central

    2012-01-01

    Background Schizophrenia is a severe form of mental illness which is associated with significant and long-lasting health, social and financial burdens. The aim of this project is to assess the efficiency of the antipsychotics used in Spain in reducing schizophrenia relapses under the Spanish Health System perspective. Material and methods A decision-analytic model was developed to explore the relative cost-effectiveness of five antipsychotic medications, amisulpride, aripiprazole, olanzapine, paliperidone Extended-Release (ER) and risperidone, compared to haloperidol, over a 1-year treatment period among people living in Spain with schizophrenia. The transition probabilities for assessed therapies were obtained from the systemic review and meta-analysis performed by National Institute for Health and Clinical Excellence (NICE). Results Paliperidone ER was the option that yielded more quality-adjusted life years (QALYs) gained per patient (0.7573). In addition, paliperidone ER was the least costly strategy (€3,062), followed by risperidone (€3,194), haloperidol (€3,322), olanzapine (€3,893), amisulpride (€4,247) and aripiprazole (€4,712). In the incremental cost-effectiveness (ICE) analysis of the assessed antipsychotics compared to haloperidol, paliperidone ER and risperidone were dominant options. ICE ratios for other medications were €23,621/QALY gained, €91,584/QALY gained and €94,558/QALY gained for olanzapine, amisulpride and aripiprazole, respectively. Deterministic sensitivity analysis showed that risperidone is always dominant when compared to haloperidol. Paliperidone ER is also dominant apart from the exception of the scenario with a 20% decrease in the probability of relapses. Conclusions Our findings may be of interest to clinicians and others interested in outcomes and cost of mental health services among patients with schizophrenia. Paliperidone ER and risperidone were shown to be dominant therapies compared to haloperidol in Spain

  2. Antagonist Models for Relapse Prevention and Reducing HIV Risk.

    PubMed

    Woody, George E; Krupitsky, Evgeny; Zvartau, Edwin

    2016-09-01

    Naltrexone is an antagonist that binds tightly to μ-opioid receptors and blocks the subjective and analgesic effects of opioids. It does not produce physiologic dependence and precipitates withdrawal if administered to an opioid dependent person, thus starting it must begin with detoxification. It was first available in the mid-1970s as a 50 mg tablet that blocked opioids for 24-36 h if taken daily, or every 2-3 days at higher doses - for example: 100 mg Monday and Wednesday, 150 mg on Friday. From a pharmacological perspective it worked very well and was hoped to be an effective treatment but results were disappointing due to low patient interest and high dropout followed by relapse. Interest in it waned but rose again in the late 1990's when injecting opioid use and the rapid spread of HIV in the Russian Federation converged with an international interest in reducing the spread of HIV. One result was a series of meetings sponsored by the U.S. National Institute on Drug Abuse (NIDA) and Pavlov State Medical University in St. Petersburg, Russian Federation, on ways to reduce the spread of HIV in that country. Addiction treatment was a clear priority and discussions showed that naltrexone could have a role since agonist treatment is against Russian law but naltrexone is approved and the government funds over 25,000 beds for detoxification, which is the first step in starting naltrexone treatment. These meetings were followed by NIDA studies that showed better compliance to oral naltrexone than in prior U.S. studies with the expected reductions in HIV injecting risk for those that stayed in treatment. These events and findings provided a background and identified an infrastructure for the study that led to FDA approval of extended release injectable naltrexone for preventing relapse to opioid dependence. This paper will briefly review findings from these studies and end with comments on the potential role of extended release naltrexone as a meaningful addition

  3. TNF-α increases in the CSF of children with acute lymphoblastic leukemia before CNS relapse.

    PubMed

    Jaime-Pérez, José Carlos; Gamboa-Alonso, Carmen Magdalena; Jiménez-Castillo, Raúl Alberto; López-Silva, Leslie Jazmín; Pinzón-Uresti, Mónica Andrea; Gómez-De León, Andrés; Gómez-Almaguer, David

    2017-03-01

    There is scarce information regarding the concentration of cytokines in cerebrospinal fluid (CSF) of children with acute lymphoblastic leukemia (ALL) and their clinical association with CNS status. A prospective analysis of 40 patients <18years with newly diagnosed ALL was performed. Human cytokine magnetic bead panel assay values of IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, TNF-α in CSF at diagnosis, end of induction to remission, and 6months after diagnosis were determined. IL-6 and MCP-1 values showed a significant increment at the end of induction. From the whole group 4 (10.0%), patients relapsed to the CNS at a median of 11.48months. A significantly higher value of TNF-α at third determination in these CNS-relapsed patients was documented, 7.48 vs. 2.86pg/mL in 36 children without relapse (p=0.024). TNF-α concentration increased at a median 5.48months before CNS relapse. By receiver-operating characteristic curve (ROC) analysis, the best cut-off point of TNF-α concentration that better predicted CNS relapse was ≥1.79pg/mL. In conclusion an increase in TNF-α concentration on CSF preceded CNS relapse in children with ALL. An increase in MCP-1 and IL-6 was not associated to CNS relapse and appears to result from an inflammatory response after IT injection of chemotherapy.

  4. Distinctive clinical course and pattern of relapse in adolescents with medulloblastoma

    SciTech Connect

    Tabori, Uri . E-mail: uri.tabori@sickkids.ca; Sung, Lillian; Laperriere, Normand; Crooks, Bruce; Wilson, Beverly

    2006-02-01

    Purpose: To report the clinical course of adolescents with medulloblastoma, with specific emphasis on prognosis and pattern of relapse. Methods and Materials: We retrospectively studied the clinical course and outcomes of children aged 10-20 years with medulloblastoma, treated at centers throughout Canada between 1986 and 2003. To better assess time to relapse, a cohort of patients aged 3-20 years at diagnosis was generated. Results: A total of 72 adolescents were analyzed. Five-year overall survival and event-free survival rates were 78.3% {+-} 5.4% and 68.0% {+-} 6.2%, respectively. Late relapses occurred at a median of 3.0 years (range, 0.3-6.8 years). In univariate analysis, conventional risk stratification and the addition of chemotherapy to craniospinal radiation did not have prognostic significance. Female patients had improved overall survival (p = 0.007). Time to relapse increased with age in a linear fashion. After relapse, patients faired poorly regardless of treatment modality. Patients who did not receive chemotherapy initially had improved progression-free survival at relapse (p 0.05). Conclusions: Our study suggests that adolescents with medulloblastoma might have a unique prognosis and pattern of relapse, dissimilar to those in younger children. They might benefit from different risk stratifications and prolonged follow-up. These issues should be addressed in future prospective trials.

  5. Cocaine dependent individuals with attenuated striatal activation during reinforcement learning are more susceptible to relapse.

    PubMed

    Stewart, Jennifer L; Connolly, Colm G; May, April C; Tapert, Susan F; Wittmann, Marc; Paulus, Martin P

    2014-08-30

    Cocaine-dependent individuals show altered brain activation during decision making. It is unclear, however, whether these activation differences are related to relapse vulnerability. This study tested the hypothesis that brain-activation patterns during reinforcement learning are linked to relapse 1 year later in individuals entering treatment for cocaine dependence. Subjects performed a Paper-Scissors-Rock task during functional magnetic resonance imaging (fMRI). A year later, we examined whether subjects had remained abstinent (n=15) or relapsed (n=15). Although the groups did not differ on demographic characteristics, behavioral performance, or lifetime substance use, abstinent patients reported greater motivation to win than relapsed patients. The fMRI results indicated that compared with abstinent individuals, relapsed users exhibited lower activation in (1) bilateral inferior frontal gyrus and striatum during decision making more generally; and (2) bilateral middle frontal gyrus and anterior insula during reward contingency learning in particular. Moreover, whereas abstinent patients exhibited greater left middle frontal and striatal activation to wins than losses, relapsed users did not demonstrate modulation in these regions as a function of outcome valence. Thus, individuals at high risk for relapse relative to those who are able to abstain allocate fewer neural resources to action-outcome contingency formation and decision making, as well as having less motivation to win on a laboratory-based task.

  6. Cocaine dependent individuals with attenuated striatal activation during reinforcement learning are more susceptible to relapse

    PubMed Central

    Stewart, Jennifer L.; Connolly, Colm G.; May, April C.; Tapert, Susan F.; Wittmann, Marc; Paulus, Martin P.

    2014-01-01

    Cocaine-dependent individuals show altered brain activation during decision making. It is unclear, however, whether these activation differences are related to relapse vulnerability. This study tested the hypothesis that brain-activation patterns during reinforcement learning are linked to relapse 1 year later in individuals entering treatment for cocaine dependence. Subjects performed a Paper-Scissors-Rock task during functional magnetic resonance imaging (fMRI). A year later, we examined whether subjects had remained abstinent (n=15) or relapsed (n=15). Although the groups did not differ on demographic characteristics, behavioral performance, or lifetime substance use, abstinent patients reported greater motivation to win than relapsed patients. The fMRI results indicated that compared with abstinent individuals, relapsed users exhibited lower activation in (1) bilateral inferior frontal gyrus and striatum during decision making more generally; and (2) bilateral middle frontal gyrus and anterior insula during reward contingency learning in particular. Moreover, whereas abstinent patients exhibited greater left middle frontal and striatal activation to wins than losses, relapsed users did not demonstrate modulation in these regions as a function of outcome valence. Thus, individuals at high risk for relapse relative to those who are able to abstain allocate fewer neural resources to action-outcome contingency formation and decision making, as well as having less motivation to win on a laboratory-based task. PMID:24862388

  7. Qualitative investigation of targets for and barriers to interventions to prevent psychosis relapse

    PubMed Central

    2014-01-01

    Background Early signs based relapse prevention interventions for psychosis show promise. In order to examine how they might be improved we sought to better understand the early relapse process, service users’ abilities to identify early signs, and any potential facilitators and barriers to early signs interventions. Methods Data from in-depth interviews with a convenience sample of service users with psychosis varying in gender, age, duration of mental health problems, and time since last relapse were analysed using a thematic approach. Interview transcripts were coded inductively and relationships between emerging themes were examined by the research team to provide a thorough synthesis of the data. Results Three central themes emerged from the analysis: 1) recognising risk factors (how risk factors were identified and linked to relapse, and reactions to such risk factors); 2) identifying early signs (issues related to both recognising and recalling signs of relapse); 3) reacting to deterioration (participants’ thoughts and feelings in response to early signs, including help seeking and its challenges). Conclusions There was considerable variation in the attention participants had paid to pre-relapse signs, the ease with which they were able to recall them, and their reactions to them. For many, there were substantial barriers to help seeking from services. A family or friend confidant was an important means of assistance, although the supportive presence of significant others was not always available. Based on these results, a number of recommendations about facilitating service users’ recognition of early signs and targeting potential accelerants of relapse are made. PMID:25030092

  8. Progressive intraparenchymal lung nodules dissemination in a heavy smoker and seropositive rheumatoid arthritis suspected of tuberculosis relapse.

    PubMed

    Arghir, Oana Cristina; Niţu, Mimi; Trenchea, Mihaela; Ciobotaru, Camelia

    2013-01-01

    Anthony Caplan first described rheumatoid lung nodules associated with pneumoconiosis in coal-miners (Caplan, 1953). Intraparenchymal lung nodules were later described in rheumatoid arthritis (RA) patients who were never exposed to coal dust and/or without pneumoconiosis. Rheumatoid lung nodules are usually detected in unselected patients: 0.2% in chest radiography and 4% in high-resolution computed tomography (Nannini et al., 2008). Patients could be reluctant to perform surgical lung biopsy for an accurate histopathological diagnosis. We present a peculiar association between a seropositive RA and a presumptive active tuberculosis (TB) disease in a 59-year-old male patient, ex-smoker with a previously healed pulmonary TB disease. The purpose of this report is to describe an unusual case of a presumptive relapse of the nodular TB disease, which progressed to an extensive nodular bilateral dissemination under anti-tuberculosis therapy, mimicking a metastatic carcinoma. The diagnosis of rheumatoid necrobiotic lung nodules was confirmed after open biopsy left pulmonary was performed. Formalin-fixed paraffin-embedded pulmonary rheumatoid nodules were processed for histology and stained with Masson's trichrome. Central structure of the removed pulmonary nodules is typical of a rheumatoid nodule with central necrosis surrounded by a palisade of macrophages. The accumulation of anthracotic pigment was noticed inside the pulmonary nodules in a RA patient without professional exposure to coal or mineral dust. This rare entity is an appearance of the rheumatoid nodules lung syndrome and anthracosis in a heavy tobacco former smoker.

  9. "Time" and "Newsweek" Favor John F. Kennedy, Criticize Robert and Edward Kennedy.

    ERIC Educational Resources Information Center

    Fedler, Fred; And Others

    1983-01-01

    Finds that the percentage of favorable, neutral, and unfavorable statements about the three Kennedy brothers in two national news magazines was similar and that both magazines published proportionately more favorable statements about John Kennedy than about either of his brothers. (FL)

  10. 45 CFR 73.735-503 - Criminal provisions relating to gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-503 Criminal provisions relating to gifts, entertainment, and favors. (a) The law provides criminal penalties for whoever... 45 Public Welfare 1 2010-10-01 2010-10-01 false Criminal provisions relating to...

  11. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  12. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  13. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  14. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity, favor... between the employee and his or her parents, spouse or children, if it is clear that the relationship is the motivating factor. (b) Loans from banks or other financial institutions may be accepted...

  15. High frequency of p53/MDM2/p14ARF pathway abnormalities in relapsed neuroblastoma

    PubMed Central

    Carr-Wilkinson, Jane; O' Toole, Kieran; Wood, Katrina M.; Challen, Christine C.; Baker, Angela G.; Board, Julian R.; Evans, Laura; Cole, Michael; Cheung, Nai-Kong V.; Boos, Joachim; Köhler, Gabriele; Leuschner, Ivo; Pearson, Andrew D.J.; Lunec, John; Tweddle, Deborah A.

    2010-01-01

    Purpose: Most neuroblastomas initially respond to therapy but many relapse with chemoresistant disease. p53 mutations are rare in diagnostic neuroblastomas, but we have previously reported inactivation of the p53/MDM2/p14ARF pathway in 9/17 (53%) neuroblastoma cell lines established at relapse. Hypothesis: Inactivation of the p53/MDM2/p14ARF pathway develops during treatment and contributes to neuroblastoma relapse. Methods: Eighty-four neuroblastomas were studied from 41 patients with relapsed neuroblastoma including 38 paired neuroblastomas at different stages of therapy. p53 mutations were detected by automated sequencing, p14ARF methylation and deletion by methylation-specific PCR and duplex PCR respectively, and MDM2 amplification by fluorescent in-situ hybridisation. Results: Abnormalities in the p53 pathway were identified in 20/41(49%) cases. Downstream defects due to inactivating missense p53 mutations were identified in 6/41 (15%) cases, 5 following chemotherapy and/or at relapse and 1 at diagnosis, post chemotherapy and relapse. The presence of a p53 mutation was independently prognostic for overall survival (hazard ratio 3.4, 95% confidence interval 1.2, 9.9; p = 0.02). Upstream defects were present in 35% cases: MDM2 amplification in 3 cases, all at diagnosis & relapse and p14ARF inactivation in 12/41 (29%) cases: 3 had p14ARF methylation, 2 after chemotherapy, and 9 had homozygous deletions, 8 at diagnosis and relapse. Conclusions: These results show that a high proportion of neuroblastomas which relapse have an abnormality in the p53 pathway. The majority have upstream defects suggesting that agents which reactivate wild-type p53 would be beneficial, in contrast to those with downstream defects where p53 independent therapies are indicated. PMID:20145180

  16. Clinical characteristics and prognostic factors for relapse in patients with polymyalgia rheumatica (PMR).

    PubMed

    Lee, Jung Hwa; Choi, Sang Tae; Kim, Jin Su; Yoon, Bo Young; Kwok, Seung-Ki; Kim, Hyun-Sook; Kim, Yun Sung; Song, Jung-Soo; Lee, Sang-Heon; Kim, Hae-Rim

    2013-06-01

    Polymyalgia rheumatica (PMR) is a common inflammatory disease of the elderly in western countries, but the prevalence is apparently different between races and countries. Until now, an epidemiologic study of PMR is limited in Korea. We retrospectively evaluated the clinical data of 78 patients with PMR who were treated in 5 tertiary hospitals, and analyzed initial laboratory data, symptoms, therapeutic responses, and prognostic factors for relapse 1 year after treatments. Sixty percent of patients had pain in both shoulder and hip girdles with 10.6 weeks of duration, 75.9 ± 32.7 mm/h of erythrocyte sedimentation rate (ESR), and 6.2 ± 6.4 mg/dl of C-reactive protein. The rate of relapse and remission at 1 year was 38.4 and 2.5 %, respectively. The rate of overall relapse was 46.1 %, and the relapse occurred mostly in a year, especially between 6 and 12 months after diagnosis. There were more female in relapse group (88.9 %, p = 0.037), and cumulative steroid dose of 1 year was significantly higher in relapse group (5.5 ± 2.7 vs. 4.4 ± 2.5 g, p = 0.018). Independent risk factors for relapse were initial CRP ≥ 2.5 mg/dl (OR 6.296, p = 0.047) and the use of hydroxychloroquine (OR 6.798, p = 0.035). Initial dosage or tapering speed of steroid did not influence on prognosis. In Korean patients with PMR, baseline clinical characteristics and relapse rate were similar to previous studies, but our patients accompanied no giant cell arteritis and showed lower remission rate as well as delayed therapeutic response and later occurrence of relapse. More aggressive management would be needed according to the clinical status of patients.

  17. Ceftriaxone attenuates cocaine relapse after abstinence through modulation of nucleus accumbens AMPA subunit expression.

    PubMed

    LaCrosse, Amber L; Hill, Kristine; Knackstedt, Lori A

    2016-02-01

    Using the extinction-reinstatement model of cocaine relapse, we and others have demonstrated that the antibiotic ceftriaxone attenuates cue- and cocaine-primed reinstatement of cocaine-seeking. Reinstatement is contingent on the release of glutamate in the nucleus accumbens core (NAc) and manipulations that reduce glutamate efflux or block post-synaptic glutamate receptors attenuate reinstatement. We have demonstrated that the mechanism of action by which ceftriaxone attenuates reinstatement involves increased NAc GLT-1 expression and a reduction in NAc glutamate efflux during reinstatement. Here we investigated the effects of ceftriaxone (100 and 200 mg/kg) on context-primed relapse following abstinence without extinction training and examined the effects of ceftriaxone on GluA1, GluA2 and GLT-1 expression. We conducted microdialysis during relapse to determine if an increase in NAc glutamate accompanies relapse after abstinence and whether ceftriaxone blunts glutamate efflux. We found that both doses of ceftriaxone attenuated relapse. While relapse was accompanied by an increase in NAc glutamate, ceftriaxone (200 mg/kg) was unable to significantly reduce NAc glutamate efflux during relapse despite its ability to upregulate GLT-1. GluA1 was reduced in the NAc by both doses of ceftriaxone while GluA2 expression was unchanged, indicating that ceftriaxone altered AMPA subunit composition following cocaine. Finally, GLT-1 was not altered in the PFC by ceftriaxone. These results indicate that it is possible to attenuate context-primed relapse to cocaine-seeking through modification of post-synaptic receptor properties without attenuating glutamate efflux during relapse. Furthermore, increasing NAc GLT-1 protein expression is not sufficient to attenuate glutamate efflux.

  18. Prevention of Schizophrenia Relapse with Extended Release Quetiapine Fumarate Dosed Once Daily

    PubMed Central

    Trivedi, Jitendra; Malyarov, Sergiy; Brecher, Martin; Svensson, Ola; Miller, Frank; Persson, Inger; Meulien, Didier

    2007-01-01

    Introduction: This long-term, randomized, double-blind, placebo-controlled study examined the efficacy of extended release quetiapine fumarate (quetiapine XR) in preventing psychotic relapse in schizophrenia. Methods: Three hundred twenty-seven clinically stable patients with schizophrenia were switched to open-label quetiapine XR (300mg on Day 1, 600mg on Day 2, followed by flexible dosing [400–800mg/day]) for a 16-week stabilization phase. Thereafter, patients who were clinically stable for four months were randomized to flexible doses of quetiapine XR (400–800mg/day) or placebo. Primary endpoint was time to first schizophrenia relapse after randomization. Secondary endpoints included risk of relapse at six months. Interim analyses were planned after 45 and 60 relapses and final analysis after 90 relapses. Maximal treatment time was one year. Results: The study was terminated after the first interim analysis showed a significant difference between randomized treatment groups. Time to relapse was significantly longer in quetiapine XR-treated patients versus placebo (hazard ratio 0.16 [95% confidence interval 0.08, 0.34]; p=0.001). Fewer quetiapine XR-treated patients relapsed versus those receiving placebo (10.7% vs. 41.4%, respectively). Estimated risk of relapse at six months was significantly lower with quetiapine XR (14.3%) compared with placebo (68.2%; p=0.0001). The incidence of treatment-related adverse events (AEs) was similar between quetiapine XR and placebo groups (18% and 21% of patients, respectively) and only one percent of patients in each group withdrew because of AEs. Conclusion: Once-daily quetiapine XR (400–800mg/day) was effective in preventing relapse in patients with clinically stable schizophrenia. Quetiapine XR was well tolerated during longer-term use. PMID:20428302

  19. Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.

    PubMed

    Edgar, Contessa E; Terrell, Deirdra R; Vesely, Sara K; Wren, Jonathan D; Dozmorov, Igor M; Niewold, Timothy B; Brown, Michael; Zhou, Fang; Frank, Mark Barton; Merrill, Joan T; Kremer Hovinga, Johanna A; Lämmle, Bernhard; James, Judith A; George, James N; Farris, A Darise

    2015-01-01

    Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and

  20. [Disciplinar thematic integration in medicine: a proposal from histology and embryology].

    PubMed

    Bassan, N D; D'Ottavio, A E

    2013-01-01

    This paper intends to clarify a concept with multiple meanings and a complex reality. It starts providing varied histological and embryological examples apt to contribute the stimulation of teacher and student imaginations in favor of a crucial skill, as thematic integration is, into the present and changing curricula in Medicine in particular and Health Sciences in general. In this sense, it offers linear and branched sequences as well as consolidation graphics which focusing in both disciplines may also include other basic ones, key for clinic diagnosis, among the competences to be developed. After registering some preliminary results revealing the need of its continuous and progressive training along the complete medical career, its own integrative value and the integrative one for their teachers due to its natural link with other basic ones is outlined, its relevance for undergraduate is reaffirmed and possible future variations for them are previewed, considering the present exponential growth of science and technology.

  1. Gender differences in trauma history and symptoms as predictors of relapse to alcohol and drug use.

    PubMed

    Heffner, Jaimee L; Blom, Thomas J; Anthenelli, Robert M

    2011-01-01

    The objective of this study was to determine whether there are gender-specific associations between trauma exposure and alcohol or drug relapse in alcohol-dependent adults. Participants were 51 men (n = 24) and women (n = 27) with alcohol dependence, 22 (43.1%) of whom relapsed during study participation. Severity of childhood trauma; number of lifetime events evoking fear, helplessness, or horror; and current trauma symptoms all predicted relapse in women, but not in men. These findings highlight the importance of assessing trauma history and providing treatment of trauma-related symptoms for individuals with alcohol and drug dependence, and for women in particular.

  2. Lymphocyte subsets as biomarkers of therapeutic response in Fingolimod treated Relapsing Multiple Sclerosis patients.

    PubMed

    Paolicelli, D; Manni, A; D'Onghia, M; Direnzo, V; Iaffaldano, P; Zoccolella, S; Di Lecce, V; Tortorella, C; Specchia, G; Trojano, M

    2017-02-15

    We investigated, lymphocyte count (LC) and lymphocyte subpopulations (LS) in a real life setting of Fingolimod (FTY) treated Relapsing MS (RMS) patients. Peripheral blood counts with LS, relapses and MRI scans were recorded in a cohort of 119 FTY patients, during one year of treatment. Simple and multivariate logistic regression models, were performed. ROC analysis identified cut-off values of LS predicting a higher risk of relapses and of Gd+ lesions. We demonstrated a FTY-induced re-modulation of the immune system, suggesting that LS in RMS FTY treated patients can predict the clinical response to the drug.

  3. Molecular events in relapsed oral squamous cell carcinoma: Recurrence vs. secondary primary tumor.

    PubMed

    Gleber-Netto, Frederico O; Braakhuis, Boudewijn J M; Triantafyllou, Asterios; Takes, Robert P; Kelner, Natalie; Rodrigo, Juan P; Strojan, Primož; Vander Poorten, Vincent; Rapidis, Alexander D; Rinaldo, Alessandra; Brakenhoff, Ruud H; Ferlito, Alfio; Kowalski, Luiz P

    2015-08-01

    Relapses have a great impact on both the morbidity and mortality rates of oral squamous cell carcinoma (OSCC) patients. Current classification criteria are imprecise and need improvements. Recent advances in understanding of OSCC relapses on a molecular level provide new possibilities to better classify true recurrences and second primary tumors. This review discusses the limitations of the current OSCC relapse classification method and presents possible alternatives to improve this classification based on molecular techniques. Moreover, these molecular techniques add to the further understanding of these lesions and may provide tools for clinical management.

  4. Primary breast lymphoma sequentially relapsed in the peripheral and central nervous system.

    PubMed

    Tang, Tzung-Chih; Chang, Hung; Chuang, Wen-Yu

    2012-09-01

    Primary breast lymphoma (PBL) is an uncommon extranodal type of lymphoma, exhibiting more aggressive behavior and poorer prognosis. Patients with PBL have a higher incidence to relapse in central nervous system (CNS), which is always leading to a dismal outcome even treating with high intensity chemotherapy plus radiotherapy. Lymphoma involving the peripheral nervous system (PNS), either primarily or secondarily, is also rare. But no PBL with PNS relapse has been reported before. Herein, we reported a case of PBL who presented with subsequent relapse in two discrete sites of the PNS followed by the CNS.

  5. Dental students' evaluations of an interactive histology software.

    PubMed

    Rosas, Cristian; Rubí, Rafael; Donoso, Manuel; Uribe, Sergio

    2012-11-01

    This study assessed dental students' evaluations of a new Interactive Histology Software (IHS) developed by the authors and compared students' assessment of the extent to which this new software, as well as other histology teaching methods, supported their learning. The IHS is a computer-based tool for histology learning that presents high-resolution images of histology basics as well as specific oral histologies at different magnifications and with text labels. Survey data were collected from 204 first-year dental students at the Universidad Austral de Chile. The survey consisted of questions for the respondents to evaluate the characteristics of the IHS and the contribution of various teaching methods to their histology learning. The response rate was 85 percent. Student evaluations were positive for the design, usability, and theoretical-practical integration of the IHS, and the students reported they would recommend the method to future students. The students continued to value traditional teaching methods for histological lab work and did not think this new technology would replace traditional methods. With respect to the contribution of each teaching method to students' learning, no statistically significant differences (p>0.05) were found for an evaluation of IHS, light microscopy, and slide presentations. However, these student assessments were significantly more positive than the evaluations of other digital or printed materials. Overall, the students evaluated the IHS very positively in terms of method quality and contribution to their learning; they also evaluated use of light microscopy and teacher slide presentations positively.

  6. Locally relapsed and metastatic uterine leiomyoma: A case report

    PubMed Central

    Londero, Ambrogio P; Perego, Patrizia; Mangioni, Costantino; Lellé, Ralph J; Londero, Franco; Marchesoni, Diego

    2008-01-01

    Introduction Benign metastasising leiomyoma refers to a type of lesion characterised by leiomyomatous alterations without any indication of malignancy. It presents as either a singular nodule or multiple nodules of proliferating smooth muscle cells and is generally found in the lungs of women who have undergone a hysterectomy. The purpose of this case report is to contribute to the knowledge of this rare disease by presenting evidence and experience of a patient case. In particular, this report seeks to investigate the therapeutic approaches in order to understand whether a standard of care can be prescribed and whether the use of prophylaxis therapy with progesterone as a follow-up to surgery serves as a reasonable treatment in certain cases diagnosed as benign metastasising leiomyoma. Case presentation We present the case of a 52-year-old Caucasian woman who developed a pelvic relapse and a pulmonary localisation of benign metastasising leiomyoma following a hysterectomy for myomatous uterus. Conclusion Our literature review revealed a single case of the use of chemoprophylaxis as treatment of a benign metastasising leiomyoma. The role of chemoprophylaxis in preventing future recurrences remains unclear. The use of progesterone as an adjuvant therapy for benign metastasising leiomyoma could simply be palliative, with associated psychological benefits, or it could be of therapeutic significance. PMID:18811931

  7. Relapsing-Remitting Multiple Sclerosis Patients' Experience with Natalizumab

    PubMed Central

    Miller, Colleen E.; Jezewski, Mary Ann

    2012-01-01

    This phenomenological investigation was undertaken to gain a better understanding of multiple sclerosis (MS) patients' experience with natalizumab (Tysabri; Biogen Idec Inc, Cambridge, MA) treatment and its impact on their quality of life (QOL). Twenty MS patients who were receiving natalizumab treatment were recruited by the physicians, nurse practitioners, nurses, and social worker of the William C. Baird Multiple Sclerosis Center in Buffalo, New York, between March 2009 and November 2009. Patients were invited to participate if they had relapsing-remitting MS, had received at least six treatments of natalizumab, and could articulate their experience. An interviewer obtained informed consent, gathered basic demographic information, and then tape-recorded the participants' accounts of their experience with natalizumab. The audio-recorded interviews were transcribed and de-identified before being submitted to the investigators for analysis. The Atlas.ti qualitative data analysis program (Scolari, Berlin, Germany) was used to manage the data. Patients found natalizumab easy to tolerate and effective; moreover, they described improvement in their QOL. Patients must weigh the benefits of control of their MS against the increased risk of developing progressive multifocal leukoencephalopathy with natalizumab treatment. Information from this study will be used to educate professionals involved in MS patient care as well as patients and families considering treatment with natalizumab. PMID:24453731

  8. Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma.

    PubMed

    Hoy, Sheridan M

    2016-04-01

    Carfilzomib (Kyprolis®) is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome (the proteolytic core particle within the 26S proteasome), inducing growth arrest and apoptosis. This intravenous drug is approved in the EU and the USA as combination therapy with oral lenalidomide and intravenous or oral dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In the multinational, phase III ASPIRE study in this patient population, carfilzomib triple combination therapy significantly prolonged progression-free survival (PFS), reflecting a clinically relevant gain in PFS of 8.7 months, compared with lenalidomide plus dexamethasone. Improvements in overall response rate and patients' global health status were also observed with carfilzomib triple combination therapy. A significant improvement in overall survival (OS) is yet to be demonstrated, with the prespecified stopping boundary not crossed at the time of the prespecified interim analysis, although OS data were not mature by the cut-off date. Carfilzomib triple combination therapy had a manageable tolerability profile. The incidences of the most frequently reported grade 3 or higher adverse events of special interest (with the exception of neutropenia, anaemia and thrombocytopenia) were low in both the carfilzomib triple combination therapy and lenalidomide plus dexamethasone groups. Although final OS data are awaited, current evidence suggests carfilzomib in combination with lenalidomide and dexamethasone is a welcome addition to the treatment options currently available for patients with relapsed multiple myeloma.

  9. The atlas of mouse development eHistology resource.

    PubMed

    Graham, Elizabeth; Moss, Julie; Burton, Nick; Roochun, Yogmatee; Armit, Chris; Richardson, Lorna; Baldock, Richard

    2015-06-01

    The Atlas of Mouse Development by Professor Mathew Kaufman is an essential text for understanding mouse developmental anatomy. This definitive and authoritative atlas is still in production and is essential for any biologist working with the mouse embryo, although the last revision dates back to 1994. Here, we announce the eHistology online resource that provides free access to high-resolution colour images digitized from the original histological sections (www.emouseatlas.org/emap/eHistology/index.php) used by Kaufman for the Atlas. The images are provided with the original annotations and plate numbering of the paper atlas and enable viewing the material to cellular resolution.

  10. Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers

    PubMed Central

    Zaja, Francesco; De Luca, Stefano; Vitolo, Umberto; Orsucci, Lorella; Levis, Alessandro; Salvi, Flavia; Rusconi, Chiara; Ravelli, Erika; Tucci, Alessandra; Bottelli, Chiara; Balzarotti, Monica; Brusamolino, Ercole; Bonfichi, Maurizio; Pileri, Stefano A.; Sabattini, Elena; Volpetti, Stefano; Monagheddu, Chiara; Vacca, Angelo; Ria, Roberto; Fanin, Renato

    2012-01-01

    Background Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone. Design and Methods In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1–21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months. Results The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35–68%) and 8 of 33 patients (24%; 95% CI, 13–41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5–19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%). Conclusions These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. (clinicaltrials.gov identifier: NCT00786851). PMID:22058200

  11. [Experience in irradiating with helium-neon lasers to treat patients with relapsing aphthous stomatitis].

    PubMed

    Prikuls, V F

    2000-01-01

    Seventy-five patients with relapsing aphthous stomatitis (41 with the fibrinous form, 25 with glandular form, and 9 with necrotic form) were treated using He-Ne laser and a photosensitizer. A good therapeutic effect was attained.

  12. Helping Adults to Stay Physically Fit: Preventing Relapse Following Aerobic Exercise Training.

    ERIC Educational Resources Information Center

    Goodrick, G. Ken; And Others

    1984-01-01

    Long-term adherence to an aerobic exercise regime is a major problem among exercise program graduates. This article discusses the steps involved in developing relapse prevention treatment strategies for aerobic exercise programs. (JMK)

  13. Mindfulness predicts relapse/recurrence in major depressive disorder after mindfulness-based cognitive therapy.

    PubMed

    Michalak, Johannes; Heidenreich, Thomas; Meibert, Petra; Schulte, Dietmar

    2008-08-01

    Empirical evidence for the effectiveness of mindfulness-based cognitive therapy (MBCT) is encouraging. However, data concerning the role of mindfulness in its relapse preventive effect are lacking. In our study, 25 formerly depressed patients received MBCT. Mindfulness was assessed before and immediately after MBCT using the Mindful Attention and Awareness Scale. Mindfulness significantly increased during MBCT, and posttreatment levels of mindfulness predicted the risk of relapse/recurrence to major depressive disorder in the 12-month follow-up period. Mindfulness predicted the risk of relapse/recurrence after controlling for numbers of previous episodes and residual depressive symptoms. The results provide preliminary evidence for the notion that mindfulness is an important factor in relapse prevention in major depression.

  14. Binary logistic regression modelling: Measuring the probability of relapse cases among drug addict

    NASA Astrophysics Data System (ADS)

    Ismail, Mohd Tahir; Alias, Siti Nor Shadila

    2014-07-01

    For many years Malaysia faced the drug addiction issues. The most serious case is relapse phenomenon among treated drug addict (drug addict who have under gone the rehabilitation programme at Narcotic Addiction Rehabilitation Centre, PUSPEN). Thus, the main objective of this study is to find the most significant factor that contributes to relapse to happen. The binary logistic regression analysis was employed to model the relationship between independent variables (predictors) and dependent variable. The dependent variable is the status of the drug addict either relapse, (Yes coded as 1) or not, (No coded as 0). Meanwhile the predictors involved are age, age at first taking drug, family history, education level, family crisis, community support and self motivation. The total of the sample is 200 which the data are provided by AADK (National Antidrug Agency). The finding of the study revealed that age and self motivation are statistically significant towards the relapse cases..

  15. Multiple Myeloma Relapse Following Autologous Stem Cell Transplant Presenting With Diffuse Pulmonary Nodules

    PubMed Central

    Sumrall, Bradley; Diethelm, Lisa; Brown, Archie

    2013-01-01

    Background Multiple myeloma is a common disease, accounting for about 10% of hematologic malignancies in the United States. For eligible patients, the treatment of choice includes induction therapy (usually involving newer biologic agents) followed by autologous stem cell transplant; however, this treatment is generally not considered curative, and relapses usually occur. However, extramedullary relapse is an uncommon presentation, and relapses that involve the lungs have only rarely been described. Case Report We report the case of a patient who underwent an autologous stem cell transplant for multiple myeloma and subsequently relapsed with diffuse pulmonary nodules. She then had a rapid clinical and serologic response following initiation of salvage therapy. Conclusion This case is remarkable for both the radiographic appearance of the pulmonary involvement, as well as the rapid resolution of these findings after 2 cycles of treatment with bortezomib, dexamethasone, and lenalidomide. PMID:24358007

  16. Partial relapse of Bell's palsy following superficial radiotherapy to a basal cell carcinoma in the temple.

    PubMed

    Brincat, S; Mantell, B S

    1986-07-01

    A patient who developed a partial relapse of Bell's palsy following superficial radiotherapy to a basal cell carcinoma in the temple is reported. Nerves injured by Bell's palsy may be more susceptible to radiation induced damage.

  17. Relapsing and progressive forms of multiple sclerosis – insights from pathology

    PubMed Central

    Dutta, Ranjan; Trapp, Bruce D.

    2014-01-01

    PURPOSE OF THIS REVIEW The predominant clinical disease course of multiple sclerosis (MS) starts with reversible episodes of neurological disability, which transforms into progressive neurological decline. This review provides insight into the pathological differences during relapsing and progressive phases of MS. RECENT FINDINGS The clinical course of MS is variable and the disease can be classified into relapsing and progressive phases. Pathological studies have been successful in distinguishing between these two forms of the disease and correlate with the clinical findings in terms of cellular responses, the inflammatory environment, and the location of lesions. SUMMARY Available therapies for MS patients, while effective during the relapsing phase, have little benefit for progressive MS patients. Development of therapies to benefit progressive MS patients will require a better understanding of the pathogenesis of progressive MS. This review discusses and compares the pathological findings in relapsing and progressive MS patients. PMID:24722325

  18. Isolated testicular relapse in boys with acute lymphoblastic leukaemia: treatment and outcome.

    PubMed Central

    Tiedemann, J; Chessells, J M; Sandland, R M

    1982-01-01

    In 22 boys among a group of 169 with acute lymphoblastic leukaemia the first relapse occurred in the testis. In 14 of these late isolated testicular relapse was detected on routine biopsy or became apparent after treatment was electively stopped. Eleven of these boys were treated with reinduction, irradiation of 2400 rads to both testicles, intrathecal methotrexate, and two years of chemotherapy; 10 remained well and were in second complete remission from two and a half to five and a half years later. It is concluded that boys with late isolated testicular relapse fare better than those with late marrow relapse and may have a change of long-term disease-free survival. Images p1616-a PMID:6814673

  19. FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases

    PubMed Central

    2011-01-01

    Background This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR. Methods The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m2x 3 days), C (1 gr/m2 day 1) and R (375 mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. Results Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection. Conclusions Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by 90Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS. PMID:21303501

  20. PREPARATION OF WHOLE SMALL FISH FOR HISTOLOGICAL EVALUATION

    EPA Science Inventory

    Toxicologic pathology, which is primarily concerned with chemically-induced structural changes in cells or tissues, depends on the proper histological processing of test specimens. In fishes, histopathological examination is widely recognized as a reliable method for disease diag...

  1. Correlation between optical coherence tomography images and histology of pigskin

    NASA Astrophysics Data System (ADS)

    Kuranov, Roman; Sapozhnikova, Veronika; Prough, Donald; Cicenaite, Inga; Esenaliev, Rinat

    2007-04-01

    Noninvasive imaging techniques such as optical coherence tomography (OCT) are being widely used for early diagnostics of a variety of pathologies. Traditional tissue preparation for histological evaluation alters the dimensions of histological images such that differences between the dimensions of histologic and OCT images can be as great as 2.5-fold. This discrepancy complicates quantitative interpretation of OCT images. Here we used a steel ring sewn to the pigskin to avoid tissue deformation due to excision and fixation and used a surgical suture as a fixed tissue marker. With these techniques, we achieved good correlation between OCT and histological images with differences of less than 10%. The resulting method significantly enhances the diagnostic capabilities of the OCT technique.

  2. OOGENESIS AND OVARIAN HISTOLOGY OF THE AMERICAN ALLIGATOR ALLIGATOR MISSISSIPPIENSIS

    EPA Science Inventory

    Although folliculogenesis and oogenesis have been observed in numerous reptiles, these phenomena have not been described in detail in a crocodilian. Oogenesis and histological features of the adult ovary of Alligator mississippiensis are described. Using a complex process, the ov...

  3. Clinical implications of rhinoceros reproductive tract anatomy and histology.

    PubMed

    Schaffer, N E; Foley, G L; Gill, S; Pope, C E

    2001-03-01

    Reproductive tracts or tissues from five male black rhinoceroses (Diceros bicornis), two male white rhinoceroses (Ceratotherium simum), two male one-horned Asian rhinoceroses (Rhinoceros unicornis), seven female black rhinoceroses, and six female white rhinoceroses from multiple institutions were examined to characterize their anatomy and histology. Some observations and measurements were obtained from in situ tracts of intact animals before or during necropsy. Formalin-fixed tissues were dissected and examined histologically. Retrospective reproductive data from each rhinoceros was obtained from the institutions of origin. Reproductive histology of these species was similar to that of other mammals. Male accessory gland structure varied among species, and the Asian rhinoceros epididymis was more loosely attached and had larger duct diameters than did the epididymides of the African species. Although histology was typically mammalian, rhinoceros reproductive morphology combined characteristics of several different mammals. Defining this unique morphology of rhinoceroses may help in understanding their reproductive physiology and will effect the development of appropriate reproductive techniques.

  4. Intramedullary reamings for the histological diagnosis of suspected pathological fractures.

    PubMed

    Hassan, K; Kalra, S; Moran, C

    2007-08-01

    The aim of this study was to evaluate how effective reamings taken at the time of surgery for fracture were in the diagnosis of malignancy. All histology reports over a five-year period were examined. Ninety cases, where reamings were taken, were identified and included. Reamings are commonly sent for histological diagnosis in orthopaedic practice. A definitive tissue diagnosis was established in 55 samples (60%). No diagnosis was established in 30 (33%), as the tissue sample was deemed inadequate, 17 of which were known to have a malignancy elsewhere. Five case reports were lost. The process by which the bone samples were obtained is believed to be very destructive, making histological diagnosis difficult and unreliable. Our study does not support the use of reamings for histology. An alternative technique should be used such as biopsy with the Harlow-Wood trephine.

  5. Predicting Time-to-Relapse in Breast Cancer Using Neural Networks

    DTIC Science & Technology

    1997-12-01

    AD GRANT NUMBER DÄMD17-94-J-4137 TITLE: Predicting Time-to-Relapse in Breast Cancer Using Neural Networks PRINCIPAL INVESTIGATOR: Jonathan D...Nov 97) 4. TITLE AND SUBTITLE Predicting Time-to-Relapse in Breast Cancer Using Neural Networks 6. AUTHOR(S) Buckley, Jonathan D., Ph.D. 5...Biomedical Laboratories. Date in TABLE OF CONTENTS STANDARD FORM 298 ii FOREWORD iii TABLE OF CONTENTS iv INTRODUCTION 1 Neural networks - a

  6. BRAIN MORPHOLOGY AT ENTRY INTO TREATMENT FOR ALCOHOL DEPENDENCE IS RELATED TO RELAPSE PROPENSITY

    PubMed Central

    Cardenas, VA; Durazzo, TC; Gazdzinski, S; Mon, A; Studholme, C; Meyerhoff, DJ

    2011-01-01

    Background We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers. Methods Individuals in alcohol dependence treatment (N=75) underwent magnetic resonance imaging approximately 6 ± 4 days after their last alcoholic drink, and 40 age-matched non-smoking light drinkers were studied as controls. At follow-up 7.8 ± 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and light drinkers. Results Compared to light drinkers, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex, and bilaterally in the thalamus and adjacent subcortical white matter (WM), and had larger volume in the left lateral orbitofrontal region. Compared to light drinkers, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared to future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities. Conclusion At entry into alcohol dependence treatment, the brain structure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry may confer greater risk for resumption of hazardous drinking after treatment and may contribute to the definition of a neurobiological relapse risk profile in alcohol dependence. PMID:21601177

  7. Intraventricularly injected Olig2-NSCs attenuate established relapsing-remitting EAE in mice.

    PubMed

    Sher, Falak; Amor, Sandra; Gerritsen, Wouter; Baker, David; Jackson, Samuel L; Boddeke, Erik; Copray, Sjef

    2012-01-01

    In multiple sclerosis (MS), a chronic inflammatory relapsing demyelinating disease, failure to control or repair damage leads to progressive neurological dysfunction and neurodegeneration. Implantation of neural stem cells (NSCs) has been shown to promote repair and functional recovery in the acute experimental autoimmune encephalomyelitis (EAE) animal model for MS; the major therapeutic mechanism of these NSCs appeared to be immune regulation. In the present study, we examined the efficacy of intraventricularly injected NSCs in chronic relapsing experimental autoimmune encephalomyelitis (CREAE), the animal disease model that is widely accepted to mimic most closely recurrent inflammatory demyelination lesions as observed in relapsing-remitting MS. In addition, we assessed whether priming these NSCs to become oligodendrocyte precursor cells (OPCs) by transient overexpression of Olig2 would further promote functional recovery, for example, by contributing to actual remyelination. Upon injection at the onset of the acute phase or the relapse phase of CREAE, NSCs as well as Olig2-NSCs directly migrated toward active lesions in the spinal cord as visualized by in vivo bioluminescence and biofluorescence imaging, and once in the spinal cord, the majority of Olig2-NSCs, in contrast to NSCs, differentiated into OPCs. The survival of Olig2-NSCs was significantly higher than that of injected control NSCs, which remained undifferentiated. Nevertheless, both Olig2-NSCs and NSC significantly reduced the clinical signs of acute and relapsing disease and, in case of Olig2-NSCs, even completely abrogated relapsing disease when administered early after onset of acute disease. We provide the first evidence that NSCs and in particular NSC-derived OPCs (Olig2-NSCs) ameliorate established chronic relapsing EAE in mice. Our experimental data in established neurological disease in mice indicate that such therapy may be effective in relapsing-remitting MS preventing chronic progressive

  8. Patterns and Timing of Initial Relapse in Patients Subsequently Undergoing Transplantation for Hodgkin's Lymphoma

    SciTech Connect

    Dhakal, Sughosh; Biswas, Tithi; Liesveld, Jane L.; Friedberg, Jonathan W.; Phillips, Gordon L.; Constine, Louis S.

    2009-09-01

    Purpose: To evaluate the patterns and timing of initial recurrence in patients with Hodgkin's lymphoma (HL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplantation to enhance our understanding of the natural history of this disease and its modern treatment strategies and to direct approaches to disease surveillance. Methods and Materials: The records of 69 patients with HL who had undergone high-dose chemotherapy with autologous stem cell transplantation in our center between May 1992 and June 2006 were analyzed. The initial diagnosis had been made between April 1982 and January 2005 at a median patient age of 33 years (range, 19-65). The patients were segregated according to the initial stage (Stage I-II vs. III-IV). Results: Early-stage HL patients developed a relapse at a median of 2.1 years (range, 0.5-10.3), with 91% of relapses at the initial disease site, 71% of which (65% overall) were only in previously involved sites. Advanced-stage HL patients developed a relapse at a median of 1.5 years (range, 0.6-10.5), with 97% at the initial site, 71% of which (69% overall) were only in previously involved sites. Single-site relapses occurred in 47% of early- vs. 26% of advanced-stage patients, and extranodal relapses occurred in 12% of early- vs. 31% of advanced-stage patients. Conclusions: Almost all patients with HL who develop relapse and subsequently undergo high-dose chemotherapy with autologous stem cell transplantation initially developed recurrence in previously involved disease sites. Early-stage HL relapses often occurred in single sites, and advanced-stage disease relapses were more likely in multiple and extranodal sites. The interval to recurrence was brief, suggesting that the frequency of screening should be the greatest in the early post-therapy years.

  9. The Effect of Paternal Age on Relapse in First-Episode Schizophrenia

    PubMed Central

    Hui, Christy L M; Chiu, Cindy P Y; Li, Yuet-Keung; Law, Chi-Wing; Chang, Wing-Chung; Chan, Sherry K W; Lee, Edwin H M; Sham, Pak; Chen, Eric Y H

    2015-01-01

    Objective: Multiple etiological and prognostic factors have been implied in schizophrenia and its outcome. Advanced paternal age has been reported as a risk factor in schizophrenia. Whether this may affect schizophrenia outcome was not previously studied. We hypothesized that advanced paternal age may have a negative effect on the outcome of relapse in schizophrenia. Method: We interviewed 191 patients with first-episode schizophrenia and their relatives for parental ages, sociodemographic factors at birth, birth rank, family history of psychotic disorders, and obstetric complications. The outcome measure was the presence of relapse at the end of the first year of treatment. Results: In the 1-year follow-up period, 42 (22%) patients experienced 1 or more relapses. The mean paternal age was 34.62 years (SD 7.69). Patients who relapsed had significantly higher paternal age, poorer medication adherence, were female, and were hospitalized at onset, compared with patients who did not relapse. A multivariate regression analysis showed that advanced paternal age (OR 1.05, 95% CI 1.01 to 1.10), medication nonadherence (OR 2.37, 95% CI 1.12 to 4.99), and female sex (OR 2.44, 95% CI 1.14 to 5.24) independently contributed to a higher risk of relapse. Analysis between different paternal age groups found a significantly higher relapse rate with paternal age over 40. Conclusions: Advanced paternal age is found to be modestly but significantly related to more relapses, and such an effect is the strongest at a cut-off of paternal age of 40 years or older. The effect is less likely to be mediated through less effective parental supervision or nonadherence to medication. Other possible biological mechanisms need further explorations. PMID:26454556

  10. Craving, withdrawal, and smoking urges on days immediately prior to smoking relapse.

    PubMed

    Allen, Sharon S; Bade, Tracy; Hatsukami, Dorothy; Center, Bruce

    2008-01-01

    Rates of smoking relapse remain high, despite the wide availability of cessation aids. Presumably factors such as craving, withdrawal symptoms, and smoking urges are key contributors to relapse, but empirical support for this presumption is not conclusive and is complicated by the high variability in symptoms across individuals and time, as well as by the lack of an absolute symptom threshold for response. Data were analyzed from 137 female smokers, aged 18-40 years, who completed 30 days of a protocol for a longitudinal smoking cessation trial. Subjects were assigned a quit date and followed regardless of subsequent smoking status. At baseline, subjects completed written measures of nicotine craving, withdrawal symptoms, and smoking urges. They also completed these measures daily for 30 days, beginning on their quit date, Scores were standardized within subjects and graphed to identify temporal symptom patterns. A total of 26 women quit smoking and 111 relapsed (at least one cigarette puff). The intensity of subjects' craving, withdrawal, and smoking urges Factors 1 and 2 peaked on the day of relapse by an average of 1.4, 1.1, 1.2, and 1.1 standard deviations, respectively, with symptoms rising during the previous 2-5 days and dropping precipitously over the 2 days subsequent to relapse. Additionally, women who relapsed had higher absolute (unstandardized) symptom scores on their quit day than those who were abstinent for 30 days. These findings imply that escalation of withdrawal symptoms, craving, and smoking urges during a quit attempt may contribute to smoking relapse. Frequent symptom monitoring might be clinically important for relapse prevention.

  11. Paroxysmal dysarthria-ataxia in remitting-relapsing Bickerstaff's-like encephalitis.

    PubMed

    Piffer, Silvio; Turri, Giulia; Acler, Michele; Richelli, Silvia; Cerini, Roberto; Fiaschi, Antonio; Monaco, Salvatore; Bonetti, Bruno

    2014-06-15

    Paroxysmal dysarthria-ataxia is a rare neurological condition due to ephaptic transmission, generally appearing in multiple sclerosis patients characterized by stereotyped attacks of slurred speech usually accompanied by ataxia, appearing many times a day. Here we describe a patient with an unusual remitting-relapsing form of Bickerstaff's-like brainstem encephalitis who manifested PDA after a relapse with the involvement of a peculiar region below the red nuclei and benefited from lamotrigine.

  12. [Modern methods of comprehensive management of patients with varicose disease relapsing after surgical interventions].

    PubMed

    Gavrilenko, A V; Vakhrat'ian, P E

    2012-01-01

    Despite progress achieved by Russian phlebology in diagnosis and treatment of lower-limb varicose disease, the latter remains the most commonly encountered pathology of the vascular bed. Treatment for varicose disease includes a series of unsolved as yet problems, the main of which being a relapse of varicose disease after surgical interventions. The authors share herein their experience gained in using comprehensive methods while managing varicose disease relapses, also describing the technique of the procedures performed and analysing certain technical variants thereof.

  13. Retraining the addicted brain: a review of hypothesized neurobiological mechanisms of mindfulness-based relapse prevention.

    PubMed

    Witkiewitz, Katie; Lustyk, M Kathleen B; Bowen, Sarah

    2013-06-01

    Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse.

  14. Radiologic and histologic presentation of male mammary myofibroblastoma.

    PubMed

    Omar, Lena A; Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A; Sharma, Pooja B

    2016-07-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors.

  15. Radiological versus histological diagnosis in UIP and NSIP: survival implications

    PubMed Central

    Flaherty, K; Thwaite, E; Kazerooni, E; Gross, B; Toews, G; Colby, T; Travis, W; Mumford, J; Murray, S; Flint, A; Lynch, J; Martinez, F

    2003-01-01

    Background: High resolution computed tomography (HRCT) has an important diagnostic role in idiopathic interstitial pneumonia (IIP). We hypothesised that the HRCT appearance would have an impact on survival in patients with IIP. Methods: HRCT scans from patients with histological usual interstitial pneumonia (UIP; n=73) or histological non-specific interstitial pneumonia (NSIP; n=23) were characterised as definite UIP, probable UIP, indeterminate, probable NSIP, or definite NSIP. Cox regression analysis examined the relationships between histopathological and radiological diagnoses and mortality, controlling for patient age, sex, and smoking status. Results: All 27 patients with definite or probable UIP on HRCT had histological UIP; 18 of 44 patients with probable or definite NSIP on HRCT had histological NSIP. Patients with HRCT diagnosed definite or probable UIP had a shorter survival than those with indeterminate CT (hazards ratio (HR) 2.43, 95% CI 1.06 to 5.58; median survival 2.08 v 5.76 years) or HRCT diagnosed definite or probable NSIP (HR 3.47, 95% CI 1.58 to 7.63; median survival 2.08 v 5.81 years). Patients with histological UIP with no HRCT diagnosis of probable or definite UIP fared better than patients with histological UIP and an HRCT diagnosis of definite or probable UIP (HR 0.49, 95% CI 0.25 to 0.98; median survival 5.76 v 2.08 years) and worse than those with a histological diagnosis of NSIP (HR 5.42, 95% CI 1.25 to 23.5; median survival 5.76 v >9 years). Conclusions: Patients with a typical HRCT appearance of UIP experience the highest mortality. A surgical lung biopsy is indicated for patients without an HRCT appearance of UIP to differentiate between histological UIP and NSIP. PMID:12554898

  16. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma.

    PubMed

    Palumbo, Antonio; Ambrosini, Maria Teresa; Benevolo, Giulia; Pregno, Patrizia; Pescosta, Norbert; Callea, Vincenzo; Cangialosi, Clotilde; Caravita, Tommaso; Morabito, Fortunato; Musto, Pellegrino; Bringhen, Sara; Falco, Patrizia; Avonto, Ilaria; Cavallo, Federica; Boccadoro, Mario

    2007-04-01

    In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.

  17. Large Linear Plasmids of Borrelia Species That Cause Relapsing Fever

    PubMed Central

    Porcella, Stephen F.; Raffel, Sandra J.; Schwan, Tom G.; Barbour, Alan G.

    2013-01-01

    Borrelia species of relapsing fever (RF) and Lyme disease (LD) lineages have linear chromosomes and both linear and circular plasmids. Unique to RF species, and little characterized to date, are large linear plasmids of ∼160 kb, or ∼10% of the genome. By a combination of Sanger and next-generation methods, we determined the sequences of large linear plasmids of two New World species: Borrelia hermsii, to completion of its 174-kb length, and B. turicatae, partially to 114 kb of its 150 kb. These sequences were then compared to corresponding sequences of the Old World species B. duttonii and B. recurrentis and to plasmid sequences of LD Borrelia species. The large plasmids were largely colinear, except for their left ends, about 27 kb of which was inverted in New World species. Approximately 60% of the B. hermsii lp174 plasmid sequence was repetitive for 6 types of sequence, and half of its open reading frames encoded hypothetical proteins not discernibly similar to proteins in the database. The central ∼25 kb of all 4 linear plasmids was syntenic for orthologous genes for plasmid maintenance or partitioning in Borrelia species. Of all the sequenced linear and circular plasmids in Borrelia species, the large plasmid's putative partition/replication genes were most similar to those of the 54-kb linear plasmids of LD species. Further evidence for shared ancestry was the observation that two of the hypothetical proteins were predicted to be structurally similar to the LD species' CspA proteins, which are encoded on the 54-kb plasmids. PMID:23749977

  18. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis

    PubMed Central

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

    2016-01-01

    Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS. PMID:26727514

  19. Large linear plasmids of Borrelia species that cause relapsing fever.

    PubMed

    Miller, Shelley Campeau; Porcella, Stephen F; Raffel, Sandra J; Schwan, Tom G; Barbour, Alan G

    2013-08-01

    Borrelia species of relapsing fever (RF) and Lyme disease (LD) lineages have linear chromosomes and both linear and circular plasmids. Unique to RF species, and little characterized to date, are large linear plasmids of ∼160 kb, or ∼10% of the genome. By a combination of Sanger and next-generation methods, we determined the sequences of large linear plasmids of two New World species: Borrelia hermsii, to completion of its 174-kb length, and B. turicatae, partially to 114 kb of its 150 kb. These sequences were then compared to corresponding sequences of the Old World species B. duttonii and B. recurrentis and to plasmid sequences of LD Borrelia species. The large plasmids were largely colinear, except for their left ends, about 27 kb of which was inverted in New World species. Approximately 60% of the B. hermsii lp174 plasmid sequence was repetitive for 6 types of sequence, and half of its open reading frames encoded hypothetical proteins not discernibly similar to proteins in the database. The central ∼25 kb of all 4 linear plasmids was syntenic for orthologous genes for plasmid maintenance or partitioning in Borrelia species. Of all the sequenced linear and circular plasmids in Borrelia species, the large plasmid's putative partition/replication genes were most similar to those of the 54-kb linear plasmids of LD species. Further evidence for shared ancestry was the observation that two of the hypothetical proteins were predicted to be structurally similar to the LD species' CspA proteins, which are encoded on the 54-kb plasmids.

  20. Antibiotic prophylaxis in children with relapsing urinary tract infections: review.

    PubMed

    Mangiarotti, P; Pizzini, C; Fanos, V

    2000-04-01

    Recurrent urinary tract infections (UTIs) are observed in 30-50% of children after the first UTI. Of these, approximately 90% occur within 3 months of the initial episode. The basic aim of antibiotic prophylaxis in children with malformative uropathy and/or recurrent UTIs, is to reduce the frequency of UTIs. The bacteria most frequently responsible for UTI are gram-negative organisms, with Escherichia coli accounting for 80% of urinary tract pathogens. In children with recurrent UTIs and in those treated with antibiotic prophylaxis there is a greater incidence of UTI due to Proteus spp., Klebsiella spp. and Enterobacter spp., whereas Pseudomonas spp., Serratia spp. and Candida spp. are more frequent in children with urogenital abnormalities and/or undergoing invasive instrumental investigations. Several factors are involved in the pathogenesis of UTI, the main ones being circumcision, periurethral flora, micturition disorders, bowel disorders, local factors and hygienic measures. Several factors facilitate UTI relapse: malformative uropathies, particularly of the obstructive type; vesico-ureteric reflux (VUR); previous repeated episodes of cystitis and/or pyelonephritis (3 or more episodes a year), even in the absence of urinary tract abnormalities; a frequently catheterized neurogenic bladder; kidney transplant. The precise mechanism of action of low-dose antibiotics is not yet fully known. The characteristics of the ideal prophylactic agent are presented in this review, as well as indications, dosages, side effects, clinical data of all molecules. While inappropriate use of antibiotic prophylaxis encourages the emergence of microbial resistance, its proper use may be of great value in clinical practice, by reducing the frequency and clinical expression of UTIs and, in some cases such as VUR, significantly helping to resolve the underlying pathology.

  1. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

    PubMed

    Laubach, J; Garderet, L; Mahindra, A; Gahrton, G; Caers, J; Sezer, O; Voorhees, P; Leleu, X; Johnsen, H E; Streetly, M; Jurczyszyn, A; Ludwig, H; Mellqvist, U-H; Chng, W-J; Pilarski, L; Einsele, H; Hou, J; Turesson, I; Zamagni, E; Chim, C S; Mazumder, A; Westin, J; Lu, J; Reiman, T; Kristinsson, S; Joshua, D; Roussel, M; O'Gorman, P; Terpos, E; McCarthy, P; Dimopoulos, M; Moreau, P; Orlowski, R Z; Miguel, J S; Anderson, K C; Palumbo, A; Kumar, S; Rajkumar, V; Durie, B; Richardson, P G

    2016-05-01

    The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

  2. [Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

    PubMed

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

    Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary.

  3. Does providing extended relapse prevention bibliotherapy to problem gamblers improve outcome?

    PubMed

    Hodgins, David C; Currie, Shawn R; el-Guebaly, Nady; Diskin, Katherine M

    2007-03-01

    Relapse rates among pathological gamblers are high with as many as 75% of gamblers returning to gambling shortly after a serious attempt to quit. The present study focused on providing a low cost, easy to access relapse prevention program to such individuals. Based on information collected in our ongoing study of the process of relapse, a series of relapse prevention booklets were developed and evaluated. Individuals who had recently quit gambling (N = 169) were recruited (through media announcements) and randomly assigned to a single mailing condition in which they received one booklet summarizing all of the relapse prevention information or a repeated mailing condition in which they received the summary booklet plus 7 additional booklets mailed to them at regular intervals over the course of a year period. Gambling involvement over the course of the 12-month follow-up period, confirmed by family or friends, was compared between the two groups. Results indicated that participants receiving the repeated mailings were more likely to meet their goal, but they did not differ from participants receiving the single mailing in frequency of gambling or extent of gambling losses. The results of this project suggest that providing extended relapse prevention bibliotherapy to problem gamblers does not improve outcome. However, providing the overview booklet may be a low cost, easy to access alternative for individuals who have quit gambling.

  4. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer.

    PubMed

    Garcia-Murillas, Isaac; Schiavon, Gaia; Weigelt, Britta; Ng, Charlotte; Hrebien, Sarah; Cutts, Rosalind J; Cheang, Maggie; Osin, Peter; Nerurkar, Ashutosh; Kozarewa, Iwanka; Garrido, Javier Armisen; Dowsett, Mitch; Reis-Filho, Jorge S; Smith, Ian E; Turner, Nicholas C

    2015-08-26

    The identification of early-stage breast cancer patients at high risk of relapse would allow tailoring of adjuvant therapy approaches. We assessed whether analysis of circulating tumor DNA (ctDNA) in plasma can be used to monitor for minimal residual disease (MRD) in breast cancer. In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment-either at a single postsurgical time point or with serial follow-up plasma samples-predicted metastatic relapse with high accuracy [hazard ratio, 25.1 (confidence interval, 4.08 to 130.5; log-rank P < 0.0001) or 12.0 (confidence interval, 3.36 to 43.07; log-rank P < 0.0001), respectively]. Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse. We further demonstrated that targeted capture sequencing analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. Mutation tracking can therefore identify early breast cancer patients at high risk of relapse. Subsequent adjuvant therapeutic interventions could be tailored to the genetic events present in the MRD, a therapeutic approach that could in part combat the challenge posed by intratumor genetic heterogeneity.

  5. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL.

    PubMed

    Li, Benshang; Li, Hui; Bai, Yun; Kirschner-Schwabe, Renate; Yang, Jun J; Chen, Yao; Lu, Gang; Tzoneva, Gannie; Ma, Xiaotu; Wu, Tongmin; Li, Wenjing; Lu, Haisong; Ding, Lixia; Liang, Huanhuan; Huang, Xiaohang; Yang, Minjun; Jin, Lei; Kang, Hui; Chen, Shuting; Du, Alicia; Shen, Shuhong; Ding, Jianping; Chen, Hongzhuan; Chen, Jing; von Stackelberg, Arend; Gu, Longjun; Zhang, Jinghui; Ferrando, Adolfo; Tang, Jingyan; Wang, Shengyue; Zhou, Bin-Bing S

    2015-06-01

    Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes a rate-limiting purine biosynthesis enzyme, in 24/358 (6.7%) relapsed childhood B cell ALL (B-ALL) cases. All individuals who harbored PRPS1 mutations relapsed early during treatment, and mutated ALL clones expanded exponentially before clinical relapse. Our functional analyses of PRPS1 mutants uncovered a new chemotherapy-resistance mechanism involving reduced feedback inhibition of de novo purine biosynthesis and competitive inhibition of thiopurine activation. Notably, the de novo purine synthesis inhibitor lometrexol effectively abrogated PRPS1 mutant-driven drug resistance. These results highlight the importance of constitutive activation of the de novo purine synthesis pathway in thiopurine resistance, and they offer therapeutic strategies for the treatment of relapsed and thiopurine-resistant ALL.

  6. Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

    PubMed

    Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

    2015-07-02

    Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease.

  7. Stimulus-reinforcer relations established during training determine resistance to extinction and relapse via reinstatement.

    PubMed

    Bai, John Y H; Jonas Chan, C K; Elliffe, Douglas; Podlesnik, Christopher A

    2016-11-01

    The baseline rate of a reinforced target response decreases with the availability of response-independent sources of alternative reinforcement; however, resistance to disruption and relapse increases. Because many behavioral treatments for problem behavior include response-dependent reinforcement of alternative behavior, the present study assessed whether response-dependent alternative reinforcement also decreases baseline response rates but increases resistance to extinction and relapse. We reinforced target responding at equal rates across two components of a multiple schedule with pigeons. We compared resistance to extinction and relapse via reinstatement of (1) a target response trained concurrently with a reinforced alternative response in one component with (2) a target response trained either concurrently or in separate components from the alternative response across conditions. Target response rates trained alone in baseline were higher but resistance to extinction and relapse via reinstatement tests were greater after training concurrently with the alternative response. In another assessment, training target and alternative responding together, but separating them during extinction and reinstatement tests, produced equal resistance to extinction and relapse. Together, these findings are consistent with behavioral momentum theory-operant response-reinforcer relations determined baseline response rates but Pavlovian stimulus-reinforcer relations established during training determined resistance to extinction and relapse. These findings imply that reinforcing alternative behavior to treat problem behavior could initially reduce rates but increase persistence.

  8. The future of therapy for relapsed/refractory multiple myeloma: emerging agents and novel treatment strategies.

    PubMed

    Moreau, Philippe

    2012-07-01

    Treatment of relapsed or refractory multiple myeloma (MM) continues to present a therapeutic challenge. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor (PI) bortezomib, have dramatically improved clinical outcomes for patients with newly diagnosed and relapsed/refractory MM. However, nearly all patients will eventually relapse or become refractory to these drugs. Numerous agents are currently in development for the treatment of relapsed/refractory MM. Those farthest along in clinical development include new IMiDs (pomalidomide), new PIs (eg, carfilzomib, MLN9708, and marizomib), histone deacetylase inhibitors (eg, panobinostat and vorinostat), monoclonal antibodies (eg, elotuzumab, siltuximab, and BT062), and signal transduction modulators (eg, perifosine). These emerging agents with diverse mechanisms of action have demonstrated promising anti-tumor activity in patients with relapsed/refractory MM, and rationally designed combinations with established agents are being investigated in the clinic. These new agents are creating opportunities to target multiple pathways, overcome resistance, and improve clinical outcomes, particularly for those patients who are refractory to approved novel agents. This article describes emerging antimyeloma agents in mid-stage to late-stage clinical development, and highlights the novel treatment approaches and combination strategies being evaluated in the relapsed/refractory setting.

  9. Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia.

    PubMed

    Kawedia, Jitesh D; Liu, Chengcheng; Pei, Deqing; Cheng, Cheng; Fernandez, Christian A; Howard, Scott C; Campana, Dario; Panetta, John C; Bowman, W Paul; Evans, William E; Pui, Ching-Hon; Relling, Mary V

    2012-02-16

    We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti-asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10(-8)) in patients whose sera was positive (17.7 ± 18.6 L/h per m(2)) versus nega-tive (10.6 ± 5.99 L/h per m(2)) for anti-asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti-asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti-asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse.

  10. Longitudinal Investigation of Smoking Initiation and Relapse Among Younger and Older US Military Personnel

    PubMed Central

    Trone, Daniel W.; Peterson, Arthur V.; Jacobson, Isabel G.; Littman, Alyson J.; Maynard, Charles; Seelig, Amber D.; Crum-Cianflone, Nancy F.; Bricker, Jonathan B.

    2015-01-01

    Objectives. We examined whether military service, including deployment and combat experience, were related to smoking initiation and relapse. Methods. We included older (panel 1) and younger (panel 2) participants in the Millennium Cohort Study. Never smokers were followed for 3 to 6 years for smoking initiation, and former smokers were followed for relapse. Complementary log-log regression models estimated the relative risk (RR) of initiation and relapse by military exposure while adjusting for demographic, health, and lifestyle factors. Results. Deployment with combat experience predicted higher initiation rate (panel 1: RR = 1.44; 95% confidence interval [CI] = 1.28, 1.62; panel 2: RR = 1.26; 95% CI = 1.04, 1.54) and relapse rate (panel 1 only: RR = 1.48; 95% CI = 1.36, 1.62). Depending on the panel, previous mental health disorders, life stressors, and other military and nonmilitary characteristics independently predicted initiation and relapse. Conclusions. Deployment with combat experience and previous mental disorder may identify military service members in need of intervention to prevent smoking initiation and relapse. PMID:25880953

  11. Tiotropium bromide inhibits relapsing allergic asthma in BALB/c mice.

    PubMed

    Bosnjak, Berislav; Tilp, Cornelia; Tomsic, Christopher; Dekan, Gerhard; Pieper, Michael P; Erb, Klaus J; Epstein, Michelle M

    2014-02-01

    Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway remodeling and lung damage. We tested the efficacy of tiotropium bromide, a selective long-acting, muscarinic receptor antagonist as an adjunct therapy in relapses of allergic asthma in mice. We compared the effectiveness of local intranasal administration of tiotropium and dexamethasone in acute and relapsing allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent bronchodilator, we tested higher doses to determine effectiveness on inflammation and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during disease initiation and 88% at relapse compared to vehicle alone. Both drugs were comparable in their capacity to suppress airway and parenchymal inflammation and mucus hypersecretion, though tiotropium was better than dexamethasone at reducing mucus secretion during disease relapse. Despite treatment with either drug, serum antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study indicates that tiotropium at higher doses than required for bronchodilation, effectively suppresses inflammation and mucus hypersecretion in the lungs and airways of mice during the initiation and relapse of asthma. Tiotropium is currently not approved for use in asthma. Clinical studies have to demonstrate the efficacy of tiotropium in this respiratory disease.

  12. Baclofen as relapse prevention in the treatment of gamma-hydroxybutyrate dependence: a case series.

    PubMed

    Kamal, Rama M; Loonen, Anton J M; Dijkstra, Boukje A G; De Jong, Cornelis A J

    2015-06-01

    In the last decade, gamma-hydroxybutyrate (GHB) abuse and dependence have increased. It has been reported that GHB dependence has a high rate of relapse, serious complications of intoxication, and a potentially life-threatening withdrawal syndrome. Nevertheless, in clinical practice, there is no known medical treatment to support GHB relapse prevention. We describe a case series of patients who were supported through an off-label treatment with baclofen to avoid a relapse into GHB abuse, for a period of 12 weeks. Nine of 11 patients did not relapse while taking a dose ranging from 30 to 60 mg per day, one patient relapsed after 5 weeks, and one stopped after 7 weeks. Baclofen was well tolerated; patients reported mild side effects such as fatigue, nausea, dry mouth, excessive sweating, and depressive feelings. Although systematic evidence is still lacking, our practice-based experience suggests that treatment with baclofen to assist abstinence might be effective in patients with GHB dependence. Further systematic controlled studies are necessary to establish the exact efficacy and safety of baclofen as relapse prevention for GHB-dependent patients.

  13. Histology of a Harris line in a human distal tibia.

    PubMed

    Miszkiewicz, Justyna J

    2015-07-01

    Identification and diagnosis of Harris lines (HLs) is usually achieved using radiography. To date, histological methods have been mainly implemented in research exploring the underlying processes of HL deposition using longitudinal sections taken from animal bone. Here, a new insight into HL formation is provided following transverse histological sectioning in a human specimen. A distinct HL was identified macroscopically, and from a radiograph, in a left distal tibia taken from an adult human male. Transverse sections were taken through the HL, and also from trabeculae immediately superior and inferior to the HL. Thin sections were produced following standard histological procedures. Micrographs were captured using a digital microscope camera. Trabeculae immediately superior and inferior to the HL displayed no indication of abnormal growth, exhibiting abundant osteocyte lacunae and a lamellar structure. However, the micro-anatomy of the HL was characterised by the following three main features: (1) non-lamellar appearance, (2) a complete lack of osteocyte lacunae, and (3) presence of irregularly distributed tubular structures. These three histological features indicate a specific process of bone deposition, implying that trapping of osteoblasts may not take place during HL formation. Pictorial and descriptive records of HL histology are provided, aiding current understanding about the nature of HL, its identification from histology, and serving as a reference point for future comparative research.

  14. Renal cell carcinoma: histological classification and correlation with imaging findings.

    PubMed

    Muglia, Valdair F; Prando, Adilson

    2015-01-01

    Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes.

  15. 15 CFR Supplement No. 3 to Part 740 - License Exception ENC Favorable Treatment Countries

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Treatment Countries No. Supplement No. 3 to Part 740 Commerce and Foreign Trade Regulations Relating to... Favorable Treatment Countries Austria Australia Belgium Bulgaria Canada Cyprus Czech Republic Estonia... Turkey United Kingdom...

  16. Preliminary Evaluation of a Sitafloxacin-Containing Regimen for Relapsed or Refractory Pulmonary Mycobacterium avium Complex Disease

    PubMed Central

    Fujita, Kohei; Fujita, Masaki; Ito, Yutaka; Hirai, Toyohiro; Mio, Tadashi; Watanabe, Kentaro; Mishima, Michiaki

    2016-01-01

    Although sitafloxacin (STFX) is known to have a favorable minimum inhibitory concentration for Mycobacterium avium, few studies have evaluated the clinical efficacy of an STFX-containing regimen for pulmonary M avium complex (MAC) disease. To evaluate the clinical efficacy of STFX-containing regimens for relapsed or refractory pulmonary MAC disease, we retrospectively reviewed 18 patients with pulmonary MAC disease who received STFX for at least 4 weeks for pulmonary MAC disease between January 2008 and February 2016. Of 18 patients, 10 (55.6%) showed improved radiological characteristics and 8 (44.4%) showed negative sputum cultures at 6 months. Regarding the clinical symptoms, improvements were observed in decreasing order in sputum production (77.8%), cough (72.2%), and malaise (55.6%). Common adverse events included nausea or vomiting (38.9%), followed by loose stool or diarrhea (27.8%) and sleepiness (11.1%). Although this study contained a small number of subjects, we describe a STFX-containing regimen that was effective in achieving sputum culture negative conversions and had an acceptable adverse events profile. PMID:27704005

  17. Clinical Presentation, Convalescence, and Relapse of Rocky Mountain Spotted Fever in Dogs Experimentally Infected via Tick Bite

    PubMed Central

    Levin, Michael L.; Killmaster, Lindsay F.; Zemtsova, Galina E.; Ritter, Jana M.; Langham, Gregory

    2014-01-01

    Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by R. rickettsii in North and South America. Domestic dogs are susceptible to infection and canine RMSF can be fatal without appropriate treatment. Although clinical signs of R. rickettsii infection in dogs have been described, published reports usually include descriptions of either advanced clinical cases or experimental infections caused by needle-inoculation of cultured pathogen rather than by tick bite. The natural progression of a tick-borne R. rickettsii infection has not been studied in sufficient detail. Here, we provide a detailed description of clinical, hematological, molecular, and serological dynamics of RMSF in domestic dogs from the day of experimental exposure to infected ticks through recovery. Presented data indicate that neither the height/duration of fever nor detection of rickettsial DNA in dogs' blood by PCR are good indicators for clinical prognosis. Only the apex and subsequent subsidence of neutrophilia seem to mark the beginning of recovery and allow predicting a favorable outcome in Rickettsia-infected dogs, even despite the continuing persistence of mucosal petechiae and skin rash. On the other hand the appropriate (doxycycline) antibiotic therapy of sufficient duration is crucial in prevention of RMSF relapses in dogs. PMID:25542001

  18. Clinical presentation, convalescence, and relapse of rocky mountain spotted fever in dogs experimentally infected via tick bite.

    PubMed

    Levin, Michael L; Killmaster, Lindsay F; Zemtsova, Galina E; Ritter, Jana M; Langham, Gregory

    2014-01-01

    Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by R. rickettsii in North and South America. Domestic dogs are susceptible to infection and canine RMSF can be fatal without appropriate treatment. Although clinical signs of R. rickettsii infection in dogs have been described, published reports usually include descriptions of either advanced clinical cases or experimental infections caused by needle-inoculation of cultured pathogen rather than by tick bite. The natural progression of a tick-borne R. rickettsii infection has not been studied in sufficient detail. Here, we provide a detailed description of clinical, hematological, molecular, and serological dynamics of RMSF in domestic dogs from the day of experimental exposure to infected ticks through recovery. Presented data indicate that neither the height/duration of fever nor detection of rickettsial DNA in dogs' blood by PCR are good indicators for clinical prognosis. Only the apex and subsequent subsidence of neutrophilia seem to mark the beginning of recovery and allow predicting a favorable outcome in Rickettsia-infected dogs, even despite the continuing persistence of mucosal petechiae and skin rash. On the other hand the appropriate (doxycycline) antibiotic therapy of sufficient duration is crucial in prevention of RMSF relapses in dogs.

  19. The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

    PubMed Central

    Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael N.; Gibson, Brenda; Tamminga, Rienk; Abrahamsson, Jonas; Ha, Shau-Yin; Hasle, Henrik; Maschan, Alexey; Bertrand, Yves; Leverger, Guy; von Neuhoff, Christine; Razzouk, Bassem; Rizzari, Carmelo; Smisek, Petr; Smith, Owen P.; Stark, Batia; Reinhardt, Dirk; Kaspers, Gertjan L.

    2014-01-01

    The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ≤5%, 6–10%, 11–20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ≥12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677. PMID:24763401

  20. Remission, Relapse, and Persistence of Vulvodynia: A Longitudinal Population-Based Study

    PubMed Central

    Harlow, Sioban D.; Plegue, Melissa A.; Sen, Ananda

    2016-01-01

    Abstract Background: Vulvodynia has been considered to be a chronic disorder. We sought to estimate the probability of and risk factors for remission, relapse, and persistence among women screening positive for vulvodynia. Methods: Survey-based assessment in a longitudinal population-based study of women (the Woman to Woman Health Study) who screened positive for vulvodynia and completed at least four follow-up surveys. Outcome measures included remission without relapse, relapse (after remission), and persistence of a positive vulvodynia screen. Multinomial regression was used to assess factors associated with outcomes. Results: Of 441 women screening positive for vulvodynia during the study, 239 completed 4 additional surveys. Of these, 23 (9.6%) had consistently positive vulvodynia screens, 121 (50.6%) remitted without relapse, and 95 (39.7%) relapsed following remission. Overall, factors associated with both relapse and persistence (compared with remission alone) included increased severity of pain ever (p < 0.001) or after intercourse (p = 0.03), longer duration of symptoms (p ≤ 0.001), and screening positive for fibromyalgia (p < 0.001). Factors associated with persistence (but not relapse) included more severe symptoms with intercourse (p = 0.001) and pain with oral sex (p = 0.003) or partner touch (p = 0.04). Factors associated with relapse (but not persistence) included having provoked pain (p = 0.001) or screening positive for interstitial cystitis (p = 0.05) at first positive vulvodynia screen. Demographic characteristics, age at pain onset, and whether vulvodynia was primary or secondary did not predict outcome. Conclusion: Remission of vulvodynia symptoms is common with approximately half of remitters experiencing a relapse within 6–30 months. Persistence without remission is the exception rather than the rule. Pain history and comorbid conditions were associated with the more severe outcomes of relapse and

  1. KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia.

    PubMed

    Malinowska-Ozdowy, K; Frech, C; Schönegger, A; Eckert, C; Cazzaniga, G; Stanulla, M; zur Stadt, U; Mecklenbräuker, A; Schuster, M; Kneidinger, D; von Stackelberg, A; Locatelli, F; Schrappe, M; Horstmann, M A; Attarbaschi, A; Bock, C; Mann, G; Haas, O A; Panzer-Grümayer, R

    2015-08-01

    High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone.

  2. Diagnostic criteria for selenium toxicosis in aquatic birds: histologic lesions

    USGS Publications Warehouse

    Green, D.E.; Albers, P.H.

    1997-01-01

    Chronic selenium toxicosis was induced in 1-year-old male mallard ducks (Anas platyrhynchos) by feeding selenium, as seleno-DL-methionine, in amounts of 0, 10, 20, 40, and 80 parts per million (ppm) to five groups of 21 ducks each for 16 wk during March to July 1988. All mallards in the 80 ppm group, three in the 40 ppm group, and one in the 20 ppm group died. Histologic lesions in mallards that died of selenosis were hepatocellular vacuolar degeneration progressing to centrolobular and panlobular necrosis, nephrosis, apoptosis of pancreatic exocrine cells, hypermaturity and avascularity of contour feathers of the head with atrophy of feather follicles, lymphocytic necrosis and atrophy of lymphoid organs (spleen, gut-associated lymphoid tissue, and lumbar lymph nodes), and severe atrophy and degeneration of fat. Histologic lesions in surviving mallards in the 40 ppm group, which had tissue residues of selenium comparable to mallards that died, were fewer and much milder than mallards that died; lesions consisted of atrophy of lymphoid tissue, hyalinogranular swelling of hepatocytes, atrophy of seminiferous tubules, and senescence of feathers. No significant histologic lesions were detected in euthanized mallards in the 0, 10 and 20 ppm groups. Based on tissue residues and histologic findings, primarily in the liver, there was a threshold of selenium accumulation above which pathophysiologic changes were rapid and fatal. Pathognomonic histologic lesions of fatal and nonfatal selenosis were not detected. Criteria for diagnosis of fatal selenosis in aquatic birds include consistent histologic lesions in the liver, kidneys, and organs of the immune system. Although histologic changes were present in cases of chronic non-fatal selenosis, these were inconsistent. Consistent features of fatal and non-fatal chronic selenosis were marked weight loss and elevated concentrations of selenium in organs.

  3. Histology-directed MALDI mass spectrometry for the diagnostic pathology

    NASA Astrophysics Data System (ADS)

    Kim, Hark Kyun; Kim, In-Hoo

    2012-10-01

    With the advent of targeted agents, it has become clinically important to distinguish histologic types of non-small cell lung cancers (NSCLCs) using biopsy samples. We investigated whether direct tissue matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis on lipid may classify histology of NSCLCs. Twentyone pairs of frozen, resected NSCLCs were analyzed using histology-directed, MALDI MS. 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Squamous cell carcinomas and adenocarcinomas, two major histologic types of NSCLC, were found to have different lipid profiles. Discriminatory lipids correctly classified the histology of 80.4% of independent NSCLC surgical tissue samples (41 out of 51) in validation set, suggesting that lipid profiles can classify NSCLCs according to the histologic type. We also found that protein and lipid MALDI MS profiles can classify 30 breast cancers according to the intrinsic subtypes. Immunohistochemistry-defined, luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by cross validation P values < 0.01. Discriminatory proteins and lipids classified tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in 100 random test sets. Potential advantages of this label-free approach may include small tissue requirement, relatively rapid procedure, and low reagent cost. Day-today variation of this technology is also acceptable, with the Pearson correlation of 0.95. Taken together, these results suggest the possible clinical utility of histology-directed, lipid and protein MALDI MS.

  4. TET2 exon 2 skipping is an independent favorable prognostic factor for cytogenetically normal acute myelogenous leukemia (AML): TET2 exon 2 skipping in AML.

    PubMed

    Mohamed, Aminetou Mint; Balsat, Marie; Koering, Catherine; Maucort-Boulch, Delphine; Boissel, Nicolas; Payen-Gay, Lea; Cheok, Meyling; Mortada, Hussein; Auboeuf, Didier; Pinatel, Christiane; El-Hamri, Mohamed; Tigaud, Isabelle; Hayette, Sandrine; Dumontet, Charles; Cros, Emeline; Flandrin-Gresta, Pascale; Nibourel, Olivier; Preudhomme, Claude; Thomas, Xavier; Nicolini, Franck-Emmanuel; Solly, Françoise; Guyotat, Denis; Campos, Lydia; Michallet, Mauricette; Ceraulo, Antony; Mortreux, Franck; Wattel, Eric

    2017-01-16

    In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n=99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S(high) patients were found to be younger than TET2(low) patients without a difference in the rate of complete remission. However, TET2E2S(high) patients exhibited a significantly lower CIR (p<10(-4)). TET2E2S and FLT3-ITD, but not age or NPM1 mutation status were independent prognostic factors for DFS and event-free survival (EFS), while TET2E2S was the sole prognostic factor that we identified for overall survival (OS). In both the intermediate-1 and favorable ELN genetic categories, TET2E2S remained significantly associated with prolonged survival. There was no correlation between TET2E2S status and outcomes in 34 additional AML patients who were unfit for IC. Therefore our results suggest that assessments of TET2 exon 2 splicing status might improve risk stratification in CN-AML patients treated with IC.

  5. A nationwide study of the epidemiology of relapsing polychondritis

    PubMed Central

    Horváth, Anna; Páll, Nóra; Molnár, Katalin; Kováts, Tamás; Surján, György; Vicsek, Tamás; Pollner, Péter

    2016-01-01

    Objective Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease that attacks mainly cartilaginous structures or causes serious damage in proteoglycan-rich structures (the eyes, heart, blood vessels, inner ear). This study shows results regarding the epidemiology, progression, and associations of this highly variable disease by collecting all cases from a 124-million-person-year Central European nationwide cohort. Methods We used the Hungarian Health Care Database to identify all persons with possible RP infection. We followed patients who had International Classification of Diseases 10th edition code M94.1 at least once in their inpatient or outpatient records between January 1, 2002 and December 31, 2013 in Hungary. We classified these patients into disease severity groups by their drug consumption patterns between January 1, 2010 and December 31, 2013. We analyzed the regional distribution of RP incidences as well. Overall maps of comorbidity are presented with network layouts. Results We identified 256 patients with RP among cumulatively 11.5 million registered inhabitants. We classified these patients into four severity classes as “extremely mild” (n=144), “mild” (n=22), “moderate” (n=41), and “severe” (n=4). Two additional groups were defined for patients without available drug data as “suspected only” (n=23) and “confirmed but unknown treatment” (n=22). The age and sex distributions of patients were similar to worldwide statistics. Indeed, the overall survival was good (95% confidence interval for 5 years was 83.6%–92.9% and for 10 years was 75.0%–88.3% which corresponds to the overall survival of the general population in Hungary), and the associations with other autoimmune disorders were high (56%) in Hungary. Almost any disease can occur with RP; however, the symptoms of chromosomal abnormalities are only incidental. Spondylosis can be a sign of the activation of RP, while Sjögren syndrome is the most frequent

  6. A relapsing fever group spirochete transmitted by Ixodes scapularis ticks.

    PubMed

    Scoles, G A; Papero, M; Beati, L; Fish, D

    2001-01-01

    A species of Borrelia spirochetes previously unknown from North America has been found to be transmitted by Ixodes scapularis ticks. Infected ticks are positive for Borrelia spp. by DFA test but negative for Borrelia burgdorferi by polymerase chain reaction (PCR) using species-specific primers for 16S rDNA, outer surface protein A, outer surface protein C, and flagellin genes. A 1,347-bp portion of 16S rDNA was amplified from a pool of infected nymphs, sequenced, and compared with the homologous fragment from 26 other species of Borrelia. The analysis showed 4.6% pairwise difference from B. burgdorferi, with the closest relative being Borrelia miyamotoi (99.3% similarity) reported from Ixodes persulcatus in Japan. Phylogenetic analysis showed the unknown Borrelia to cluster with relapsing fever group spirochetes rather than with Lyme disease spirochetes. A 764-bp fragment of the flagellin gene was also compared with the homologous fragment from 24 other Borrelia species. The flagellin sequence of B. burgdorferi was 19.5% different from the unknown Borrelia and showed 98.6% similarity with B. miyamotoi. A pair of PCR primers specifically designed to amplify a 219-bp fragment of the flagellin gene from this spirochete was used to survey field-collected I. scapularis nymphs from five northeastern states (Connecticut, Rhode Island, New York, New Jersey, and Maryland). Positive results were obtained in 1.9-2.5% of 712 nymphs sampled from four states but in none of 162 ticks collected from Maryland. Transovarial transmission was demonstrated by PCR of larval progeny from infected females with filial infection rates ranging from 6% to 73%. Transstadial passage occurred from larvae through adults. Vertebrate infection was demonstrated by feeding infected nymphs on Peromyscus leucopus mice and recovering the organism from uninfected xenodiagnostic larvae fed 7-21 days later. Considering the frequency of contact between I. scapularis and humans, further work is needed to

  7. The use of the reinstatement model to study relapse to palatable food seeking during dieting.

    PubMed

    Calu, Donna J; Chen, Yu-Wei; Kawa, Alex B; Nair, Sunila G; Shaham, Yavin

    2014-01-01

    Excessive consumption of unhealthy foods is a major public health problem. While many people attempt to control their food intake through dieting, many relapse to unhealthy eating habits within a few months. We have begun to study this clinical condition in rats by adapting the reinstatement model, which has been used extensively to study relapse to drug seeking. In our adaptation of the relapse model, reinstatement of palatable food seeking by exposure to food-pellet priming, food-associated cues, or stress is assessed in food-restricted (to mimic dieting) rats after operant food-pellet self-administration training and subsequent extinction of the food-reinforced responding. In this review, we first outline the clinical problem and discuss a recent study in which we assessed the predictive validity of the reinstatement model for studying relapse to food seeking during dieting by using the anorexigenic drug fenfluramine. Next, we summarize results from our initial studies on the role of several stress- and feeding-related peptides (corticotropin-releasing factor, hypocretin, melanin-concentrating hormone, peptide YY3-36) in reinstatement of palatable food seeking. We then present results from our studies on the role of dopamine and medial prefrontal cortex in stress-induced reinstatement of food seeking. We conclude by discussing potential clinical implications. We offer two main conclusions: (1) the food reinstatement model is a simple, reliable, and valid model to study mechanisms of relapse to palatable food seeking during dieting, and to identify medications to prevent this relapse; (2) mechanisms of relapse to food seeking are often dissociable from mechanisms of ongoing food intake. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  8. 3D analysis of condylar remodelling and skeletal relapse following bilateral sagittal split advancement osteotomies.

    PubMed

    Xi, Tong; Schreurs, Ruud; van Loon, Bram; de Koning, Martien; Bergé, Stefaan; Hoppenreijs, Theo; Maal, Thomas

    2015-05-01

    A major concern in mandibular advancement surgery using bilateral sagittal split osteotomies (BSSO) is potential postoperative relapse. Although the role of postoperative changes in condylar morphology on skeletal relapse was reported in previous studies, no study so far has objectified the precise changes of the condylar volume. The aim of the present study was to quantify the postoperative volume changes of condyles and its role on skeletal stability following BSSO mandibular advancement surgery. A total of 56 patients with mandibular hypoplasia who underwent BSSO advancement surgery were prospectively enrolled into the study. A cone beam computed tomography (CBCT) scan was acquired preoperatively, at 1 week postoperatively and at 1 year postoperatively. After the segmentation of the facial skeleton and condyles, three-dimensional cephalometry and condylar volume analysis were performed. The mean mandibular advancement was 4.6 mm, and the mean postoperative relapse was 0.71 mm. Of 112 condyles, 55% showed a postoperative decrease in condylar volume, with a mean reduction of 105 mm(3) (6.1% of the original condylar volume). The magnitude of condylar remodelling (CR) was significantly correlated with skeletal relapse (p = 0.003). Patients with a CR greater than 17% of the original condylar volume exhibited relapse as seen in progressive condylar resorption. Female patients with a high mandibular angle who exhibited postoperative CR were particularly at risk for postoperative relapse. Gender, preoperative condylar volume, and downward displacement of pogonion at surgery were prognostic factors for CR (r(2) = 21%). It could be concluded that the condylar volume can be applied as a useful 3D radiographic parameter for the diagnosis and follow-up of postoperative skeletal relapse and progressive condylar resorption.

  9. Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

    PubMed

    Garbusow, Maria; Schad, Daniel J; Sebold, Miriam; Friedel, Eva; Bernhardt, Nadine; Koch, Stefan P; Steinacher, Bruno; Kathmann, Norbert; Geurts, Dirk E M; Sommer, Christian; Müller, Dirk K; Nebe, Stephan; Paul, Sören; Wittchen, Hans-Ulrich; Zimmermann, Ulrich S; Walter, Henrik; Smolka, Michael N; Sterzer, Philipp; Rapp, Michael A; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas

    2016-05-01

    In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.

  10. Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia.

    PubMed

    Sutanto, Inge; Tjahjono, Bagus; Basri, Hasan; Taylor, W Robert; Putri, Fauziah A; Meilia, Rizka A; Setiabudy, Rianto; Nurleila, Siti; Ekawati, Lenny L; Elyazar, Iqbal; Farrar, Jeremy; Sudoyo, Herawati; Baird, J Kevin

    2013-03-01

    Radical cure of Plasmodium vivax infection applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse. Chloroquine and primaquine have been used for 60 years in this manner. Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine. However, the safety and efficacy of primaquine against relapse when combined with other drugs have not been demonstrated. This randomized, open-label, and relapse-controlled trial estimated the efficacy of primaquine against relapse when administered with quinine or dihydroartemisinin-piperaquine for treatment of the acute infection. Among 650 soldiers who had returned to their malaria-free base in Java, Indonesia, after 12 months in malarious Papua, Indonesia, 143 with acute P. vivax malaria were eligible for study. One hundred sixteen enrolled subjects were randomized to these treatments: artesunate (200-mg dose followed by 100 mg/day for 6 days), quinine (1.8 g/day for 7 days) plus concurrent primaquine (30 mg/day for 14 days), or dihydroartemisinin (120 mg) plus piperaquine (960 mg) daily for 3 days followed 25 days later by primaquine (30 mg/day for 14 days). Follow-up was for 12 months. One hundred thirteen subjects were analyzable. Relapse occurred in 32 of 41 (78%) subjects administered artesunate alone (2.71 attacks/person-year), 7 of 36 (19%) administered quinine plus primaquine (0.23 attack/person-year), and 2 of 36 (6%) administered dihydroartemisinin-piperaquine plus primaquine (0.06 attack/person-year). The efficacy of primaquine against relapse was 92% (95% confidence interval [CI] = 81% to 96%) for quinine plus primaquine and 98% (95% CI = 91% to 99%) for dihydroartemisinin-piperaquine plus primaquine. Antirelapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by P. vivax acquired in Papua, Indonesia.

  11. Whole Neuraxis Irradiation to Address Central Nervous System Relapse in High-Risk Neuroblastoma

    SciTech Connect

    Croog, Victoria J.; Kramer, Kim; Cheung, Nai-Kong V.; Kushner, Brian H.; Modak, Shakeel; Souweidane, Mark M.; Wolden, Suzanne L.

    2010-11-01

    Background: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). Methods: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); one patient in the non-CSI cohort received IO-RIT. Results: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. Conclusions: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.

  12. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse

    PubMed Central

    Nagata, Yasunobu; Kanojia, Deepika; Mayakonda, Anand; Yoshida, Kenichi; Haridas Keloth, Sreya; Zang, Zhi Jiang; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ding, Ling-Wen; Alpermann, Tamara; Sun, Qiao-Yang; Lin, De-Chen; Chien, Wenwen; Madan, Vikas; Liu, Li-Zhen; Tan, Kar-Tong; Sampath, Abhishek; Venkatesan, Subhashree; Inokuchi, Koiti; Wakita, Satoshi; Yamaguchi, Hiroki; Chng, Wee Joo; Kham, Shirley-Kow Yin; Yeoh, Allen Eng-Juh; Sanada, Masashi; Schiller, Joanna; Kreuzer, Karl-Anton; Kornblau, Steven M.; Kantarjian, Hagop M.; Haferlach, Torsten; Lill, Michael; Kuo, Ming-Chung; Shih, Lee-Yung; Blau, Igor-Wolfgang; Blau, Olga; Yang, Henry; Ogawa, Seishi; Koeffler, H. Phillip

    2015-01-01

    Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone. PMID:26438511

  13. Laboratory Diagnosis of Tick-Borne African Relapsing Fevers: Latest Developments

    PubMed Central

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

    In Africa, relapsing fevers caused by ectoparasite-borne Borrelia species are transmitted by ticks, with the exception of Borrelia recurrentis, which is a louse-borne spirochete. These tropical diseases are responsible for mild to deadly spirochetemia. Cultured Borrelia crocidurae, Borrelia duttonii, and Borrelia hispanica circulate alongside at least six species that have not yet been cultured in vectors. Direct diagnosis is hindered by the use of non-specific laboratory tools. Indeed, microscopic observation of Borrelia spirochaeta in smears of peripheral blood taken from febrile patients lacks sensitivity and specificity. Although best visualized using dark-field microscopy, the organisms can also be detected using Wright–Giemsa or acridine orange stains. PCR-based detection of specific sequences in total DNA extracted from a specimen can be used to discriminate different relapsing fever Borreliae. In our laboratory, we developed a multiplex real-time PCR assay for the specific detection of B. duttonii/recurrentis and B. crocidurae: multispacer sequence typing accurately identified cultured relapsing fever borreliae and revealed diversity among them. Other molecular typing techniques, such as multilocus sequence analysis of tick-borne relapsing fever borreliae, showed the potential risk of human infection in Africa. Recent efforts to culture and sequence relapsing fever borreliae have provided new information for reassessment of the diversity of these bacteria. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has been reported as a means of identifying cultured borreliae and of identifying both vectors and vectorized pathogens such as detecting relapsing fever borreliae directly in ticks. The lack of a rapid diagnosis test restricts the management of such diseases. We produced monoclonal antibodies against B. crocidurae in order to develop cheap assays for the rapid detection of relapsing fever borreliae. In this paper, we

  14. Decision-making Processes as Predictors of Relapse and Subsequent Use in Stimulant Dependent Patients

    PubMed Central

    Adinoff, Bryon; Carmody, Thomas J.; Walker, Robrina; Donovan, Dennis M.; Brigham, Gregory S.; Winhusen, Theresa

    2016-01-01

    Background Decision-making processes have been posited to affect treatment outcome in addicted patients. Objective The present multi-site study assessed whether two measures of decision-making predicted relapse and subsequent use in stimulant-dependent patients. Methods 160 methamphetamine- or cocaine-dependent patients participating in a multi-site clinical trial evaluating a modified 12-step facilitation intervention for stimulant-dependent patients (STAGE-12) were assessed. Decision-making processes of risk and delay [Iowa Gambling Task (IGT)] and response reversal [Wisconsin Card Sorting Task (WCST)] were obtained shortly after treatment admission followed by assessment of stimulant use over the next six months. The relationships of the IGT and WCST (Perseverative Errors) with relapse (yes/no) and days of stimulant use during the 6-month period following post-randomization were evaluated. Results Performance on the IGT and WCST did not significantly predict relapse status or time to relapse. Unexpectedly, better performance on the IGT was associated with a fewer number of stimulant use days (p = 0.001). In contrast, worse performance on the WCST (more perseverative errors) was associated with a greater number of stimulant use days (p = 0.0003). The predictive effects of perseverative errors on subsequent use were confined to methamphetamine-dependent and Minority participants. Conclusions Decision-making processes, as measured in the current study, do not uniformly predict relapse or subsequent use. A decrease in the salience attribution of nondrug reinforcers may explain the positive relationship between IGT performance and post-relapse use. More comprehensive and global measures of impulsiveness may better assess relapse risk and use. PMID:26743586

  15. Relapse after Oral Terbinafine Therapy in Dermatophytosis: A Clinical and Mycological Study

    PubMed Central

    Majid, Imran; Sheikh, Gousia; Kanth, Farhath; Hakak, Rubeena

    2016-01-01

    Background: The incidence of recurrent tinea infections after oral terbinafine therapy is on the rise. Aim: This study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris. Materials and Methods: A total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study. The enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks. All clinically cured patients were then followed up for 12 weeks to look for any relapse/cure. Results: The common dermatophytes grown on culture were Trichophyton rubrum and Trichophyton tonsurans in 55% and 20% patients, respectively. At the end of 2-week oral terbinafine therapy, 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture (persisters) at this time. These culture positive patients included all the clinically positive cases. Rest of the patients (65/100) demonstrated both clinical and mycological cure at this time (cured). Over the 12-week follow-up, clinical relapse was seen in 22 more patients (relapse) among those who had shown clinical and mycological cure at the end of terbinafine therapy. Thus, only 43% patients could achieve a long-term clinical and mycological cure after 2 weeks of oral terbinafine treatment. Majority of the relapses (16/22) were seen after 8 weeks of completion of treatment. There was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured, persister, or relapse groups. Conclusions: Incomplete mycological cure as well as relapse is very common after standard (2-week) terbinafine therapy in our patients of tinea cruris/corporis. PMID:27688443

  16. Striatum and Insula Dysfunction during Reinforcement Learning Differentiates Abstinent and Relapsed Methamphetamine Dependent Individuals

    PubMed Central

    Stewart, Jennifer L.; Connolly, Colm G.; May, April C.; Tapert, Susan F.; Wittmann, Marc; Paulus, Martin P.

    2013-01-01

    Background and aims Individuals with methamphetamine dependence (MD) exhibit dysfunction in brain regions involved in goal maintenance and reward processing when compared with healthy individuals. We examined whether these characteristics also reflect relapse vulnerability within a sample of MD patients. Design Longitudinal, with functional magnetic resonance imaging (fMRI) and clinical interview data collected at baseline and relapse status collected at one-year follow up interview. Setting Keck Imaging Center, University of California San Diego, USA Participants MD patients (n=60) enrolled in an inpatient drug treatment program at baseline. MD participants remaining abstinent at one year follow-up (Abstinent MD group; n=42) were compared with MD participants who relapsed within this period (Relapsed MD group; n=18). Measurements Behavioral and neural responses to a reinforcement learning (Paper-Scissors-Rock) paradigm recorded during an fMRI session at time of treatment. Findings The Relapsed MD group exhibited greater bilateral inferior frontal gyrus (IFG) and right striatal activation than the Abstinent MD group during the learning of reward contingencies (Cohen’s d range: 0.60–0.83). In contrast, the Relapsed MD group displayed lower bilateral striatum, bilateral insula, left IFG, and left anterior cingulate activation than the Abstinent MD group (Cohen’s d range: 0.90–1.23) in response to winning, tying, and losing feedback. Conclusions Methamphetamine-dependent individuals who achieve abstinence and then relapse show greater inferior frontal gyrus activation during learning, and relatively attenuated striatal, insular, and frontal activation in response to feedback, compared with methamphetamine-dependent people who remain abstinent. PMID:24329936

  17. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia.

    PubMed

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients.

  18. Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals.

    PubMed

    Zakiniaeiz, Yasmin; Scheinost, Dustin; Seo, Dongju; Sinha, Rajita; Constable, R Todd

    2017-01-01

    Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome). Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC) participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.

  19. Mandibular histology and growth of the nonmammaliaform cynodont Tritylodon

    PubMed Central

    Jasinoski, Sandra C; Chinsamy, Anusuya

    2012-01-01

    An investigation of bone microstructure of nonmammalian therapsids has revealed distinctive signals pertaining to their ontogenetic growth and biology. Until now, histological studies of the nonmammaliaform cynodonts have focused only on postcranial material. Through the examination of micro-computed tomography (micro-CT) scans and serial thin sections, the current study provides a novel perspective on the structure and growth of the mandible of Tritylodon, a derived herbivorous cynodont from southern Africa. By tracking histological features across the serial thin sections, trends in relocation and modelling are documented for the growing Tritylodon mandible. For example, during growth, localized changes in the cross-sectional shape of the mandible occurred. Localized deposits of new lamellar and fibrolamellar bone on the lateral edge indicate widening of the mandible during different episodes of growth. The presence of radial channels indicates the deepening of the mandible at its anterior and posterior ends. The relocation of the paired mental foramina suggests that the mandibular body lengthened mainly in the posterior direction. The medial movement of a posterior postcanine tooth during growth and eruption is recorded in the histology. This histological assessment also documents the presence of Sharpey’s fibres in the cellular cementum of the first incisor, providing novel and unequivocal evidence that it was attached to the Tritylodon jaw by a periodontal ligament. This is the first comprehensive study that uses histological analysis to document the growth dynamics of the mandible of a nonmammalian therapsid, thus providing a unique perspective of localized mandibular growth in a fossil animal.

  20. Atypical fibroxanthoma: a histological and immunohistochemical review of 171 cases.

    PubMed

    Beer, Trevor W; Drury, Paul; Heenan, Peter J

    2010-08-01

    The clinical and histological features of 171 atypical fibroxanthomas (AFX) from a single institution in Western Australia are outlined. This area experiences high levels of solar radiation, and all assessable biopsies showed solar elastosis. Patients were aged between 41 and 97 years (median age 74), with 76% of tumors occurring in men (male to female ratio approximately 3 to 1). Most tumors were small, with a median diameter of 10 mm and a range of 4-35 mm. Only 5% exceeded 20 mm in diameter. Most AFX were well-circumscribed dermal lesions, with limited invasion of subcutis in a minority. Histological variants identified included keloidal (n = 8), clear cell (n = 3), and granular cell (n = 3), plaque like (n = 4), and myxoid (n = 1). Bland cytological appearances (spindle cell nonpleomorphic AFX) were noted in 5 tumors, with osteoclast-like giant cells in 2. Features suggesting regression were present in 22 cases. Two cases recurred locally, none metastasized. No tumors expressed melanocytic or epithelial markers. Seventy-four percent of cases expressed smooth muscle actin, typically strongly and diffusely. No AFX stained with desmin. Only 1 of 50 cases was CD117 positive. In conclusion, AFX may show a wide range of histological appearances, and a panel of immunohistochemical markers is essential to make the correct diagnosis. Histological mimics, such as poorly differentiated squamous cell carcinoma, must be carefully excluded. Specific diagnosis is important because there seems to be a very low risk of recurrence or metastasis despite the frequently alarming histology.