Science.gov

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. 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.

  3. 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.

  4. 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.

  5. Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing's sarcoma patients.

    PubMed

    Schlegel, P; Feuchtinger, T; Nitschke-Gérard, C; Seidel, U J Eva; Lang, A-M; Kyzirakos, C; Teltschik, H-M; Ebinger, M; Schumm, M; Koscielniak, E; Handgretinger, R; Lang, P

    2015-06-01

    Natural killer (NK) cell activity has been shown to have potential activity against Ewing's sarcoma (EWS) especially in tumors with low HLA I expression and high NKG2D expression. Two patients with metastatic relapsed and primary metastatic stage IV EWS who had received two courses of high dose chemotherapy with autologous stem cell rescue were transplanted from a haploidentical parental stem cell donor. Patients are alive in ongoing CR for 10.2 and 3.4 years now. Post transplant local second and first relapses were treated successfully in both patients. In vivo IL-2 stimulation not only increased the number and activity of effector cells in one patient but was also associated with severe GvHD. In vitro studies demonstrated high NK cell activity against K562 and relevant activity against EWS cell line A673 post transplant. NK activity was enhanced by cytokine prestimulation as well as by EWS targeting anti-GD2 Ab. Haploidentical hematopoietic stem cell transplantation (HSCT) might contribute to long-term survival by NK cell-mediated effect exerted by donor-derived NK cells. Local tumor recurrence was manageable in both high-risk patients indicating systemic immune control preventing subsequent metastasizing. The efficacy of haploidentical HSCT, cytokine application and tumor targeting antibodies for the use of Ab-dependent cellular cytotoxicity needs evaluation in clinical trials. PMID:26039213

  6. 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.

  7. 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.

  8. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial.

    PubMed

    Pettengell, Ruth; Sebban, Catherine; Zinzani, Pier Luigi; Derigs, Hans Gunter; Kravchenko, Sergey; Singer, Jack W; Theocharous, Panteli; Wang, Lixia; Pavlyuk, Mariya; Makhloufi, Kahina M; Coiffier, Bertrand

    2016-09-01

    This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28-d cycles of 85 mg/m(2) pixantrone dimaleate (equivalent to 50 mg/m(2) in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line. Median number of cycles was 4 (range, 2-6) with pixantrone and 3 (2-6) with comparator. In 3rd or 4th line, pixantrone was associated with higher complete response (CR) (23·1% vs. 5·1% comparator, P = 0·047) and overall response rate (ORR, 43·6% vs. 12·8%, P = 0·005). In 3rd or 4th line with previous rituximab (20 pixantrone, 18 comparator), pixantrone produced better ORR (45·0% vs. 11·1%, P = 0·033), CR (30·0% vs. 5·6%, P = 0·093) and progression-free survival (median 5·4 vs. 2·8 months, hazard ratio 0·52, 95% confidence interval 0·26-1·04) than the comparator. Similar results were found in patients without previous rituximab. There were no unexpected safety issues. Pixantrone monotherapy is more effective than comparator in relapsed or refractory aggressive B-cell NHL in the 3rd or 4th line setting, independently of previous rituximab. PMID:27118109

  9. 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. PMID:25981509

  10. Extinction, Relapse, and Behavioral Momentum

    PubMed Central

    Podlesnik, Christopher A.; Shahan, Timothy A.

    2010-01-01

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

  11. 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. PMID:20152889

  12. Preventing Relapse to Cigarette Smoking by Behavioral Skill Training.

    ERIC Educational Resources Information Center

    Hall, Sharon M.; And Others

    1984-01-01

    Crossed two relapse prevention conditions (skills training-vs-discussion control) with two levels of aversive smoking in volunteer subjects (N=123). Results indicated that relapse-prevention skill training did prevent relapse among cigarette smokers. Lighter smokers were more favorably influenced. (LLL)

  13. Find favorable reactions faster

    SciTech Connect

    Yaws, C.L.; Chiang, P.Y. )

    1988-11-01

    Now, equations are given to identify whether the reactions are thermodynamically favorable. The method uses Gibbs free energy of formation for the reactants and products. The equation for any 700 major organic compounds is given as temperature coefficients. Then the reaction can be tested at various temperature levels beyond the standard 298/sup 0/K conditions imposed by many other data tabulations. Data for the water and hydrogen chloride are also included. Gibbs free energy of formation of ideal gas (..delta..G/sub f/, jkoule/g-mol) is calculated from the tabulated coefficients (A, B, C) and the temperature (T, /sup 0/K) using the following equation: (1) ..delta..G/sub f/ = A + BT + CT/sup 2/. Chemical equilibrium for a reaction is associated with the change in Gibbs free energy (..delta..G/sub r/) calculated as follows: (2) ..delta..G/sub r/ = ..delta..G/sub f/, products - ..delta..G/sub f/, reactants. If the change in Gibbs free energy is negative, the thermodynamics for the reaction are favorable. On the other hand, if the change in Gibbs free energy is highly positive, the thermodynamics for the reaction are not favorable and may be feasible only under special circumstances.

  14. 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

  15. [Relapse: causes and consequences].

    PubMed

    Thomas, P

    2013-09-01

    Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. PMID:24084426

  16. Hypofractionated Radiotherapy for Favorable Risk Prostate Cancer

    SciTech Connect

    Rene, Nicholas; Faria, Sergio; Cury, Fabio; David, Marc; Duclos, Marie; Shenouda, George; Souhami, Luis

    2010-07-01

    Purpose: Since the recognition that prostate cancer probably has a low {alpha}/{beta} ratio, hypofractionated radiotherapy has become an attractive treatment option for localized prostate cancer. However, there is little experience with the use of hypofractionation delivering a high biologically equivalent dose. We report our experience with high-dose hypofractionated radiotherapy. Material and Methods: A total of 129 patients with favorable risk prostate cancer were treated with three-dimensional conformal radiotherapy treatment plans to the dose of 66 Gy in 22 fractions, prescribed at the isocenter. Planning target volume consisted of the prostate plus a uniform 7-mm margin, including the rectal margin. No patient received hormonal therapy. Toxicity was prospectively graded by the Common Toxicity Criteria version3. Biochemical relapse was defined as postradiotherapy nadir prostate-specific antigen + 2 ng/mL. Results: With a median follow-up of 51 months, the 5-year actuarial biochemical control rate is 98%. The only 3 cases with biochemical failure did not have a clinical local relapse. More than 50% of patients did not develop acute toxicity. For late toxicity, the worst crude rate of Grade {>=}2 genitourinary (GU) and gastrointestinal (GI) toxicity seen at any time during follow-up were 32% and 25%, respectively. There was no Grade 4 or 5 toxicity. At the last follow-up, persistent Grade {>=}2 late GU and GI toxicity were 2% and 1.5%, respectively. Conclusions: This hypofractionated regimen provides excellent biochemical control in favorable risk prostate cancer with an acceptable rate of late toxicity. Further studies exploring this hypofractionation regimen are warranted.

  17. Insomnia, alcoholism and relapse.

    PubMed

    Brower, Kirk J

    2003-12-01

    Insomnia and alcoholism are significantly associated in community surveys and patient samples. Insomnia occurs in 36-72% of alcoholic patients and may last for weeks to months after initiating abstinence from alcohol. Some correlates of insomnia in alcoholic patients are identical to those observed in non-alcoholic insomniacs, including anxiety and depression, tobacco smoking, and the use of alcohol to aid sleep. Other studies suggest that as the severity of alcoholism increases, so does the likelihood of insomnia in alcoholic patients. In the sleep laboratory, alcoholic patients who complain of insomnia have disrupted sleep continuity when compared to alcoholic patients without insomnia complaints. Recently sober alcoholics are also more likely than non-alcoholics to have sleep-disordered breathing and increased periodic leg movements, which might contribute to insomnia in some alcoholic patients. The co-occurrence of insomnia and alcoholism is clinically significant because alcoholism can exacerbate the adverse consequences of insomnia (e.g. mood changes and performance decrements) and because insomnia among patients entering treatment for alcoholism has been significantly associated with subsequent alcoholic relapse. Baseline polysomnographic correlates of subsequent relapse include prolonged sleep latency, decreased sleep efficiency and total sleep time, increased rapid eye movement sleep pressure, and decreased slow wave sleep. Whether treatment of insomnia in alcoholic patients reduces relapse rates is unknown, but preliminary treatment guidelines that accommodate the special characteristics of alcoholic patients are provided, with a goal to reduce daytime impairment and psychological distress. PMID:15018094

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

    PubMed Central

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

    2013-01-01

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

  19. [Relapse prevention in drug addicts].

    PubMed

    Rácz, József

    2013-12-01

    The literature review deals with methods of relapse prevention. Relapse prevention is the key in the treatment of clients with drug addictions according to the transtheoretical model of change. If relapse prevention is more effective then not only the relapse would be prevented, but the client would leave the circulus vitiosus of relapses. Among psychotherapies cognitive behavioural methods are proven effective. Shorter forms of cognitive therapies are also available: for example, cognitive bias modification. Pharmacotherapy partly decreases craving of the clients or ceases the effects of psychoactive substances. Specific pharmacotherapeutic methods prevent relapses in a non-abstinent treatment design. Here the goal is not the abstinence in a short time, but the reduction of harms associated with drug use. In this way, a new target group of drug users can be involved in treatment. PMID:24380964

  20. Handling Gifts, Gratuities, and Favors.

    ERIC Educational Resources Information Center

    Eastmond, Nick; Jones, Mark

    1993-01-01

    The twelfth in a series of articles featuring the principles of the AECT (Association for Educational Communications and Technology) Code of Professional Ethics focuses on the acceptance by professors of gratuities, gifts, or favors that might impair or appear to impair professional judgment. (LRW)

  1. Three histologically distinct cancers of the uterine corpus: A case report and review of the literature

    PubMed Central

    MASUYAMA, HISASHI; HARAGA, JUNKO; NISHIDA, TAKASHI; OGAWA, CHIKAKO; KUSUMOTO, TOMOYUKI; NAKAMURA, KEIICHIRO; SEKI, NORIKO; YANAI, HIROYUKI; HIRAMATSU, YUJI

    2016-01-01

    Collision tumors, which are characterized by the coexistence of two or more completely distinct and independent tumors in the uterine corpus, are very rare. A collision tumor is mainly composed of two distinct tumor types, epithelial and mesenchymal. To the best of our knowledge, there has only been a single case in which a choriocarcinoma with an endometrial carcinoma were coexistent but histologically distinct. We herein report the first case of a collision tumor in a 52-year-old woman, with a history of two pregnancies and two deliveries. The collision tumor was composed of three histologically distinct neoplasms in the uterine corpus, namely an endometrioid carcinoma, an undifferentiated carcinoma and a choriocarcinoma. The patient underwent hysterectomy, bilateral adnexectomy and pelvic lymph node dissection, followed by six cycles of adjuvant chemotherapy with paclitaxel/carboplatin due to the high risk of endometrial cancer, and an additional five cycles of chemotherapy with methotrexate, as the β-human chorionic gonadotropin level was beyond the normal range. Following adjuvant chemotherapy, the tumor markers were within normal limits and no relapses of the cancer have been observed during 1 year of follow-up. Diagnosing a collision tumor prior to surgery is difficult if the neoplasms are in close proximity, or if one of the tumors predominates. Careful pathological examination is crucial for accurately diagnosing the neoplasms in a collision tumor and ensuring appropriate management and a favorable prognosis. PMID:27073663

  2. Clinico-Histologic Conferences: Histology and Disease

    ERIC Educational Resources Information Center

    Shaw, Phyllis A.; Friedman, Erica S.

    2012-01-01

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

  3. Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.

    PubMed

    Zhang, Na; Ouyang, Taohui; Kang, Huicong; Long, Wang; Thomas, Benjamin; Zhu, Suiqiang

    2015-09-01

    To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes. PMID:26026861

  4. [Relapse prevention in anorexia nervosa].

    PubMed

    Giel, Katrin; Leehr, Elisabeth; Becker, Sandra; Startup, Helen; Zipfel, Stephan; Schmidt, Ulrike

    2013-07-01

    Anorexia nervosa is characterised by high relapse rates and thus there is a need for strategies that reduce reoccurrence of illness. One way of achieving this is to integrate relapse prevention into treatment, but clearly this requires identification of risk and maintenance factors. The Maudsley Model of Anorexia Nervosa Treatment in Adults (MANTRA) by Schmidt & Treasure has 5 major treatment stages. These include an initial stage of motivation and dialogue about change, an individual relapse formulation, improvement of cognitive and socio-emotional skills, work on the patient's identity and eventually a final stage of ending and parting. These treatment stages are derived from a maintenance model of AN by Schmidt & Treasure and on evidence from recovered patients and part of their objective is to prevent relapse. PMID:23592490

  5. Progressive-Relapsing MS (PRMS)

    MedlinePlus

    ... the disease process in MS and in MRI technology. Individuals who were previously diagnosed with progressive-relapsing MS would now be ... The National MS Society is Here to Help Need More Information? We ...

  6. Histologic diagnosis of sodomy.

    PubMed

    Paparo, G P; Siegel, H

    1979-10-01

    A case of homicidal strangulation with sodomy is presented. Without the use of a simple routine histologic technique, the diagnosis of sodomy could not have been unequivocally substantiated. PMID:541642

  7. Histologic remission: the ultimate therapeutic goal in ulcerative colitis?

    PubMed

    Peyrin-Biroulet, Laurent; Bressenot, Aude; Kampman, Wendy

    2014-06-01

    Ulcerative colitis (UC) is a disease of the mucosal layer, and activity of the disease is assumed to be related to mucosal appearance. Mucosal healing has emerged as a major therapeutic goal in UC. Whether mucosal healing should be the ultimate therapeutic goal in these patients is unknown. Even when endoscopy suggests mucosal healing, evidence of histologic activity has been observed. Histologic healing requires complete recovery of the colonic mucosa, with absence of inflammation or structural changes. Histologic improvements have been linked with improved clinical outcomes, such as a reduced risk of relapse and need for surgery/hospitalization and a reduced risk of developing cancer. Hence, there is a rationale for aiming for histologic remission in UC. Numerous methods of classification of histologic activity in UC have been proposed, although only some of these are widely used. We review the current definitions of histologic remission, the range of scoring systems most commonly used, and the evidence of histologic improvement that is available from the latest therapies for UC. We also highlight questions that will require careful consideration if histologic remission is to become more widely used as an end point in clinical trials and a treatment goal in clinical practice. PMID:23911875

  8. Late relapsing childhood lymphoblastic leukemia.

    PubMed

    Vora, A; Frost, L; Goodeve, A; Wilson, G; Ireland, R M; Lilleyman, J; Eden, T; Peake, I; Richards, S

    1998-10-01

    Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can

  9. Relapse prevention for addictive behaviors

    PubMed Central

    2011-01-01

    The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change. PMID:21771314

  10. Prognosis of patients with core binding factor acute myeloid leukemia after first relapse

    PubMed Central

    Kurosawa, Saiko; Miyawaki, Shuichi; Yamaguchi, Takuhiro; Kanamori, Heiwa; Sakura, Toru; Moriuchi, Yukiyoshi; Sano, Fumiaki; Kobayashi, Takeshi; Yasumoto, Atsushi; Hatanaka, Kazuo; Yanada, Masamitsu; Nawa, Yuichiro; Takeuchi, Jin; Nakamura, Yukinori; Fujisawa, Shin; Shibayama, Hirohiko; Miura, Ikuo; Fukuda, Takahiro

    2013-01-01

    Core binding factor acute myeloid leukemia is known to have a favorable prognosis, however, there have been no detailed analyses on prognostic factors after first relapse. Using a nationwide database, we retrospectively analyzed core binding factor acute myeloid leukemia patients who relapsed after being treated with chemotherapy alone during their first complete remission. Of a total of 397 patients who were diagnosed with core binding factor acute myeloid leukemia, 208 experienced a first relapse, and analyses were performed in 139 patients for whom additional data were available. In the entire cohort, the overall survival rate after relapse was 48% at 3 years. By multivariate analysis, younger age at diagnosis, a longer interval before relapse, and inv(16) were shown to be independently associated with better survival after relapse. Although there was no significant difference in survival after relapse between patients who underwent allogeneic hematopoietic cell transplantation and those who did not in the overall series of relapsed patients, we found that transplantation significantly improved survival among patients who had t(8;21) (54% versus 26% at 3 years, P=0.002). In addition, among patients with t(8;21), those who had different cytogenetics at relapse had a significantly improved survival after transplantation, while those who had same cytogenetics did not. We showed that the prognosis differs significantly and optimal treatment strategies may vary between groups of patients with core binding factor acute myeloid leukemia with different cytogenetic profiles at relapse. These findings may help to guide therapeutic decisions after first relapse. PMID:23716553

  11. 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

  12. 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

  13. 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. PMID:20008242

  14. Preventing Relapse Following Smoking Cessation

    PubMed Central

    Collins, Susan E.; Witkiewitz, Katie; Kirouac, Megan; Marlatt, G. Alan

    2012-01-01

    Cigarette smoking is the leading cause of preventable deaths worldwide. Long-term smoking cessation can drastically reduce people’s risk for developing smoking-related disease. The research literature points to a need for clearer operationalization and differentiation between smoking cessation and relapse prevention interventions and outcomes. That said, extensive meta-analyses and research studies have indicated that there are various efficacious smoking interventions that can both support smoking cessation and relapse prevention efforts. Specifically, behavioral treatments, relapse prevention psychotherapy, pharmacologic interventions, motivational enhancement, smoking reduction to quit, brief advice, alternative intervention modes (telephone, Internet, computer), self-help, and tailored treatments can help prepare smokers for longer-term abstinence. Although these methods vary on reach, they are relatively efficacious, particularly in combined formats. PMID:26550097

  15. Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet.

    PubMed

    Lengfelder, E; Lo-Coco, F; Ades, L; Montesinos, P; Grimwade, D; Kishore, B; Ramadan, S M; Pagoni, M; Breccia, M; Huerta, A J G; Nloga, A M; González-Sanmiguel, J D; Schmidt, A; Lambert, J-F; Lehmann, S; Di Bona, E; Cassinat, B; Hofmann, W-K; Görlich, D; Sauerland, M-C; Fenaux, P; Sanz, M

    2015-05-01

    In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively. PMID:25627637

  16. 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. PMID:26948349

  17. Survival After Relapse of Medulloblastoma.

    PubMed

    Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

    2016-05-01

    Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations. PMID:26907655

  18. Borrelia hispanica Relapsing Fever, Morocco

    PubMed Central

    Sarih, M’hammed; Garnier, Martine; Boudebouch, Najma; Bouattour, Ali; Rihani, Abdelaziz; Hassar, Mohammed; Gern, Lise; Postic, Danièle

    2009-01-01

    We found that 20.5% of patients with an unexplained fever in northwestern Morocco had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA gene identified Borrelia hispanica. The noncoding intergenic spacer sequence domain showed high sensitivity and good resolution for this species. PMID:19861058

  19. Borrelia hispanica relapsing fever, Morocco.

    PubMed

    Sarih, M'hammed; Garnier, Martine; Boudebouch, Najma; Bouattour, Ali; Rihani, Abdelaziz; Hassar, Mohammed; Gern, Lise; Postic, Danièle; Cornet, Muriel

    2009-10-01

    We found that 20.5% of patients with an unexplained fever in northwestern Morocco had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA gene identified Borrelia hispanica. The noncoding intergenic spacer sequence domain showed high sensitivity and good resolution for this species. PMID:19861058

  20. 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…

  1. [Histological techniques in oncodermatology].

    PubMed

    Chaput, B; Le Guellec, S; Courtade-Saïdi, M; Gangloff, D; Meresse, T; Chavoin, J-P; Grolleau, J-L; Garrido, I

    2012-04-01

    The skin oncology or "oncodermatology" requires a surgical treatment in most cases. For some surgeons, the oncodermatology takes a very important part of their practice. In the course of diagnostic and therapeutic of skin lesions, the pathologist plays now an essential role. He will guide our surgery. The techniques used by this specialist are numerous. Therefore, the objective of this paper is to review the different histological methods used to improve our management of skin tumors. PMID:22463986

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

    PubMed Central

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

    2016-01-01

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

  3. Late Relapse of Testicular Germ Cell Tumors.

    PubMed

    O'Shaughnessy, Matthew J; Feldman, Darren R; Carver, Brett S; Sheinfeld, Joel

    2015-08-01

    Germ cell tumors of the testis have an overall survival rate greater than 90% as a result of a successful multidisciplinary approach to management. Late relapse affects a subset of patients however, and tends to be chemorefractory and the overall prognosis is poor. Surgery is the mainstay in management of late relapse but salvage chemotherapy can be successful. In this review, the clinical presentation and detection of late relapse, clinical outcomes, and predictors of survival in late relapse and the importance of a multidisciplinary treatment approach for successful management of late relapse are discussed. PMID:26216823

  4. Animal models of fear relapse.

    PubMed

    Goode, Travis D; Maren, Stephen

    2014-01-01

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

  5. 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.

  6. Endocannabinoid regulation of relapse mechanisms.

    PubMed

    Fattore, Liana; Fadda, Paola; Fratta, Walter

    2007-11-01

    Addiction involves a complex neuropharmacologic behavioural cycle, in which positive reinforcement exerted by the drug and the negative state of withdrawal drive the user to extremes to obtain the drug. Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviours. Several types of anticraving medication are available nowadays, such as naltrexone for the treatment of alcoholism, bupropion for nicotine, methadone or buprenorphine for heroin. This review focuses on recent behavioural data providing a rationale for an endocannabinoid mechanism underlying reinstatement of compulsive drug seeking. Studies supporting the contention that reinstatement of extinguished drug self-administration behaviour may be generated by cannabinoid CB1 receptor agonists and attenuated, if not blocked, by CB1 receptor antagonists, are here reviewed. In support to these findings, conditioned place preference studies substantiate the involvement of the endocannabinoid system in recidivism mechanisms by demonstrating that motivation to relapse can be triggered by CB1 receptor activation while blockade of such receptors may prevent reinstatement of place conditioning induced by either drug primings or drug-associated cues. Finally, biochemical studies evaluating changes in endocannabinoid levels, CB1 receptor density and CB1 mRNA expression during re-exposure to drug following extinction are also examined. Taken together, the evidence available has important implications in the understanding and treatment of relapsing episodes in patients undergoing detoxification. PMID:17936008

  7. Why do patients with ulcerative colitis relapse?

    PubMed

    Riley, S A; Mani, V; Goodman, M J; Lucas, S

    1990-02-01

    To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis. PMID:2311975

  8. Cows' milk protein-sensitive enteropathy. Combined clinical and histological criteria for diagnosis.

    PubMed Central

    Iyngkaran, N; Robinson, M J; Prathap, K; Sumithran, E; Yadav, M

    1978-01-01

    Cows' milk protein enteropathy is recognised as a significant cause of persistent diarrhoea and malabsorption in young infants, but there are as yet no generally accepted diagnostic criteria. A combined clinical and histological approach to the diagnosis of cows' milk protein-sensitive enteropathy has been used in 15 patients, and the following set of criteria are proposed. (1) Clinical disease (diarrhoea with or without vomiting) while receiving cows' milk protein. (2) Clinical improvement on a diet free of cows' milk protein. (3) Normal or mildly abnormal histology of jejunal mucosa when taken 6-8 weeks after symptoms subside. (4) Histological relapse, with or without clinical relapse, after re-exposure to cows' milk protein. Images Fig. 1 Fig. 2 PMID:564668

  9. Lymphoma relapse presenting as neurolymphomatosis

    PubMed Central

    Pham, My; Awad, Mohammed

    2016-01-01

    Neurolymphomatosis (NL) is a rare neurological manifestation of lymphoma characterized by malignant lymphoma cells infiltrating cranial or peripheral nerve, or their roots. We present the first reported Australian case of a patient whose initial presentation of relapsed mantle cell lymphoma was NL. Our case highlights that clinical and imaging findings of NL often mimic other neuropathies, and hence presents unique challenges that may lead to delayed diagnosis and management. We emphasize the importance of considering NL in the differential diagnosis and combining imaging with other diagnostic modalities such as lumbar puncture (LP) to aid in the diagnosis of NL particularly where there is acute neurological deterioration. PMID:26889293

  10. Comparison of two locus of control scales in predicting relapse in an alcoholic population.

    PubMed

    Johnson, E E; Nora, R M; Tan, B; Bustos, N

    1991-02-01

    A 3-mo. follow-up was made of 64 male veterans who were discharged from a 21-day Alcohol Detoxification Treatment Program at the Veterans Affairs Medical Center at Lyons, NJ. Scores on the Rotter I-E and Alcohol Responsibility Scales were significantly correlated with tendencies toward a more external direction among the 13% who relapsed, significant on the I-E scale and nonsignificant on the Alcohol Responsibility Scale. When tests were compared as possible predictor variables of alcoholic relapse, the difference in favor of the I-E scale was statistically nonsignificant. PMID:2038534

  11. Severe alcoholic relapse after liver transplantation: What consequences on the graft? A study based on liver biopsies analysis.

    PubMed

    Erard-Poinsot, Domitille; Guillaud, Olivier; Hervieu, Valérie; Thimonier, Elsa; Vallin, Mélanie; Chambon-Augoyard, Christine; Boillot, Olivier; Scoazec, Jean-Yves; Dumortier, Jérôme

    2016-06-01

    Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT), but up to 20% of patients experience severe alcoholic relapse. The aims of this study were to evaluate the impact of severe alcoholic relapse on the graft (based on histological examination) and to identify predictive factors associated with recurrent alcoholic cirrhosis (RAC). From 1990 to 2010, 369 patients underwent LT for ALD at Edouard Herriot Hospital (Lyon, France) and survived more than 1 year. All patients who presented severe alcoholic relapse and histological follow-up were included. Liver biopsies were performed at 1 and 5 years and at every 5 years after LT, and when clinically indicated. The median follow-up after LT was 11 years (range, 3-18 years). Severe alcoholic relapse was observed in 73 (20%) of the 369 patients, from whom 56 patients with histological evaluation were included. RAC was diagnosed in 18 (32%) of the 56 patients included, which represents 5% of the 369 patients transplanted for ALD. The median delay between LT and RAC was 6 years (range, 3-10 years) and 4.5 years (range, 2-8 years) after severe alcoholic relapse. The median cumulated years of alcohol use before RAC was 3.5 years (range, 2-7 years). The cumulative risk for F4 fibrosis was 15% at 3 years, 32% at 5 years, and 54% at 10 years after severe alcoholic relapse. A young age at LT (≤50 years old) and an early onset of heavy drinking (within the first 3 years after LT) were associated with RAC. In conclusion, severe alcoholic relapse usually occurs in the first years after LT and is responsible for accelerated severe graft injury. Liver Transplantation 22 773-784 2016 AASLD. PMID:26929100

  12. 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.

  13. 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…

  14. Adjuvant steroids and relapse of typhoid fever.

    PubMed

    Cooles, P

    1986-10-01

    In a retrospective study, relapse after non-severe acute typhoid fever was highly significantly related to the use of adjuvant steroid in the initial illness. The steroid was given late and in small doses when compared with other studies. Caution should be observed when using steroids in this way as relapse though often mild may be a severe illness. PMID:3795323

  15. Relapse Crises and Coping among Dieters.

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; And Others

    1989-01-01

    Examined situational antecedents of dieting relapse crises and dieters'attempts to cope with temptations to overeat among obese type II diabetics (N=57). Found three categories of relapse crises: mealtime, low-arousal, and emotional upset situations. Found upset situations most frequently produced negative outcome while strong cognitive and…

  16. 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…

  17. Favorable response of reticular erythematous mucinosis to ultraviolet B irradiation using a 308-nm excimer lamp.

    PubMed

    Miyoshi, Ken; Miyajima, Osamu; Yokogawa, Maki; Sano, Shigetoshi

    2010-02-01

    Abstract Reticular erythematous mucinosis (REM) is a rare chronic mucinosis. Histologically, the presence of mucin in the upper dermis is the most specific feature. A 73-year-old woman presented to our outpatient clinic with a 4-year history of netlike macular erythema with slight edema on her left arm. She was diagnosed as having REM on the basis of the clinical picture and histological findings. She was treated with ultraviolet B irradiation using the VTRAC Excimer Lamp system with favorable response. This is the first reported case that was treated with a 308-nm excimer lamp. PMID:20175851

  18. Relapsing polychondritis: A clinical update.

    PubMed

    Longo, Lucia; Greco, Antonio; Rea, Andrea; Lo Vasco, Vincenza Rita; De Virgilio, Armando; De Vincentiis, Marco

    2016-06-01

    Relapsing polychondritis (RP) is a rare connective tissue disease in which recurrent bouts of inflammation, involve the cartilage of the ears, nose, larynx, tracheobronchial tree and cardiovascular system. RP is generally observed in the fourth and fifth decades of life and occurs with equal frequency in both sexes. The cause of RP is still unknown. It is considered an immune-mediated disease, as there is an overlap between well documented RP with other rheumatic and autoimmune diseases. There is a significant association of RP with the antigen HLA-DR4. RP includes loss of basophilic staining of cartilage matrix perichondral accompanied by inflammation of the cartilage. Cells are present perivascular mononuclear and polymorphonuclear cells infiltrated. The chondrocytes become vacuolated and necrotic and are replaced by fibrous tissue. Common symptoms are often absent in the early stages of the disease in almost half the cases, resulting in delay in diagnosis. The development of chondrite allows the diagnosis of RP in patients initially evaluated for joint abnormalities, ocular, cutaneous, or audio-vestibular. Diagnostic criteria for RP are based on characteristic clinical manifestations. According to Damiani and Levine, the diagnosis can be considered final when one or more of the clinical features are present in conjunction with biopsy confirmation. The course of symptoms for patients with relapsing polychondritis is often unpredictable. Patients with mild signs of acute inflammation are usually treated with non-steroidal anti-inflammatory drugs and small doses of prednisone. Patients with severe manifestations, such as airway compromise may require high doses of prednisone or even intravenous pulse methyl-prednisone. PMID:26876384

  19. Modelling intervention effects after cancer relapses

    PubMed Central

    González, Juan R.; Peña, Edsel A.; Slate, Elizabeth H.

    2014-01-01

    Summary This article addresses the problem of incorporating information regarding the effects of treatments or interventions into models for repeated cancer relapses. In contrast to many existing models, our approach permits the impact of interventions to differ after each relapse. We adopt the general model for recurrent events proposed by Peña and Hollander, in which the effect of interventions is represented by an effective age process acting on the baseline hazard rate function. To accommodate the situation of cancer relapse, we propose an effective age function that encodes three possible therapeutic responses: complete remission, partial remission, and null response. The proposed model also incorporates the effect of covariates, the impact of previous relapses, and heterogeneity among individuals. We use our model to analyse the times to relapse for 63 patients with a particular subtype of indolent lymphoma and compare the results to those obtained using existing methods. PMID:16320269

  20. Relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents - a report from the United Kingdom's Children's Cancer and Leukaemia Study Group.

    PubMed

    Shankar, Ananth G; Kirkwood, Amy A; Depani, Sarita; Bianchi, Eleonora; Hayward, Janis; Ramsay, Alan D; Hall, Georgina W

    2016-05-01

    There is a paucity of data on the treatment outcome in children with relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma (nLPHL). This retrospective report evaluates the treatment outcome in a national cohort of children with relapsed or poorly responsive nLPHL. A total of 37 patients, 22 with relapsed and 15 with poorly responding disease, are the subjects of this report. Of the 22 patients with relapsed nLPHL, 11 had relapsed after primary excision biopsy, 10 after chemotherapy and 1 after chemotherapy and involved field radiotherapy. The majority had localized disease at relapse. The median time to relapse was 8 months after chemotherapy and 11 months after excision biopsy. Seven of the 15 patients with poorly responding nLPHL had variant histology. Three patients with initial poor response did not receive any further treatment and have had no disease progression. Transformation to diffuse large B cell lymphoma, in addition to evolution from typical to variant nLPHL occurred in one patient each. Thirty-four patients have been successfully re-treated with second chemotherapy or radiotherapy. Multiple relapses were uncommon but treatable. Relapse or poorly responsive nLPHL is fully salvageable with either additional chemotherapy and or radiotherapy. PMID:26996288

  1. Relapse of pemphigus vulgaris after topical application of ingenol mebutate.

    PubMed

    Russo, I; Ferrazzi, A; Alaibac, M

    2016-08-01

    Ingenol mebutate is a recently approved topical agent for the treatment of actinic keratosis. Its most common adverse effects are transient local skin reactions. We report a 63-year-old white man who presented with a red-brownish crusted plaque involving the dorsum of his nose and an eroded area on his lower lip, which appeared soon after topical application of ingenol mebutate gel. Clinical, histological and immunopathological features were consistent with a diagnosis of pemphigus vulgaris (PV). To our knowledge, this is the first report of relapse of PV after topical application of ingenol mebutate gel. The temporal relationship between the application of the drug and the outbreak of PV supports the involvement of this agent in triggering the disease. It is plausible that ingenol mebutate may have induced the disease by its action on the production of proinflammatory cytokines. PMID:27381839

  2. A Case of Relapsing Polychondritis Initiating with Unexplained Fever

    PubMed Central

    Hirayama, Kosuke; Iwanaga, Nozomi; Izumi, Yasumori; Yoshimura, Satoshi; Kurohama, Kazuhiro; Yamashita, Mai; Takahata, Taichi; Oku, Ryuta; Ito, Masahiro; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    Relapsing polychondritis (RP) is a rare autoimmune disease affecting the multiple organ system. Here, we describe a case of RP initially presenting with high fever. The patient was referred to our hospital for further examination of fever of unknown origin (FUO). On admission, the patient reported dry cough in addition to fever. On physical examination, her red, swollen ears were noted, attributed on histology to inflammation with auricular perichondritis. She was diagnosed with RP and treated with oral prednisone (50 mg/day); her fever and auricular inflammation resolved. The patient no longer reported cough and body temperature returned to normal and the elevated levels of C-reactive protein (CRP) were normalized. In this case, identification of the origin of fever was a challenge because of unspecific symptoms; however, awareness of the systemic manifestations of RP may lead to the prompt diagnosis and therapeutic intervention. PMID:26981127

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

    SciTech Connect

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

    2007-06-01

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

  4. 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

  5. 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…

  6. Trait impulsive choice predicts resistance to extinction and propensity to relapse to cocaine seeking: a bidirectional investigation.

    PubMed

    Broos, Nienke; Diergaarde, Leontien; Schoffelmeer, Anton Nm; Pattij, Tommy; De Vries, Taco J

    2012-05-01

    Despite the strong association between impulsivity and addiction in humans, it is still a matter of debate whether impulsive choice predisposes to, or results from, drug dependence. Furthermore, it is unknown whether treating impulsivity can protect against relapse propensity. Therefore, this study explored the bidirectional relationship between impulsive choice and cocaine taking and seeking in rat behavioral models. In experiment 1, to determine whether impulsive choice predisposes to cocaine taking or seeking, rats were selected based on trait impulsivity in a delayed reward task and subsequently compared on various stages of cocaine self-administration (SA). To examine the consequence of cocaine intake on impulsive choice, impulsivity was monitored once a week throughout various stages of cocaine SA. To determine whether treating impulsive choice can protect against relapse propensity, in experiment 2, impulsive choice was manipulated by pharmacological interventions and cocaine-associated contextual cues. Trait impulsive choice as determined in experiment 1 predicted high extinction resistance and enhanced propensity to context-induced relapse in the cocaine SA model, whereas cocaine intake did not alter impulsive choice. Furthermore, acute changes in impulsive choice were not related to rates of context-induced relapse. Taken together, the current data indicate that trait impulsive choice predicts persistent cocaine seeking during extinction and enhanced propensity to relapse, whereas acute manipulations of impulsive choice had no favorable outcomes on relapse measures. These observations suggest that trait impulsivity can be used as a predictive factor for addiction liability, but treating this impulsivity does not necessarily protect against relapse. PMID:22318198

  7. Allogeneic hemopoietic stem cell transplants for patients with relapsed acute leukemia: long-term outcome.

    PubMed

    Bacigalupo, A; Lamparelli, T; Gualandi, F; Occhini, D; Bregante, S; Raiola, A M; Ibatici, A; di Grazia, C; Dominietto, A; Piaggio, G; Podesta, M; Bruno, B; Lombardi, A; Frassoni, F; Viscoli, C; Sacchi, N; Van Lint, M T

    2007-03-01

    We assessed the long-term outcome of patients with relapsed acute myeloid (n=86) or acute lymphoid leukemia (n=66), undergoing an allogeneic hemopoietic stem cell transplantation in our unit. The median blast count in the marrow was 30%. Conditioning regimen included total body irradiation (TBI) (10-12 Gy) in 115 patients. The donor was a matched donor (n=132) or a family mismatched donor (n=20). Twenty-two patients (15%) survive disease free, with a median follow-up of 14 years: 18 are off medications. The cumulative incidence of transplant related mortality is 40% and the cumulative incidence of relapse related death (RRD) is 45%. In multivariate analysis of survival, favorable predictors were chronic graft-versus-host disease (GvHD) (P=0.0003), donor other than family mismatched (P=0.02), donor age less than 34 years (P=0.02) and blast count less than 30% (P=0.07). Patients with all four favorable predictors had a 54% survival. In multivariate analysis of relapse, protective variables were the use of TBI (P=0.005) and cGvHD (P=0.01). This study confirms that a fraction of relapsed leukemias is cured with an allogeneic transplant: selection of patients with a blast count <30%, identification of young, human leukocyte antigen-matched donors and the use of total body radiation may significantly improve the outcome. PMID:17277788

  8. Improving reporting of multiple sclerosis relapse.

    PubMed

    Roberts, Megan; Lush, Tessa; Pohorely, John

    Many people with multiple sclerosis do not report a relapse. When it is reported, it is not always recorded in their notes. This can mean patients do not always have the most appropriate treatment. This article reviews some of the reasons why relapse reports are lacking and how the problem could be addressed. As a result, the decision was made to develop an app that patients could use to record their symptoms and wellbeing over time, to help identify and record relapses. Information could then be passed to their health professional via email, if desired. PMID:26775329

  9. Management of relapsed ovarian cancer: a review.

    PubMed

    Giornelli, Gonzalo H

    2016-01-01

    Around 70 % of ovarian cancer patients relapse after primary cytoreductive surgery and standard first-line chemotherapy. The biology of relapse remains unclear, but cancer stem cells seem to play an important role. There are still some areas of controversy on how to manage these relapses and or progressions that occur almost unavoidably in the course of this disease with shorter intervals between them as the natural history of this disease develops. The goal of treatments investigated in this neoplasm has shifted to maintenance therapy, trying to extend the progression free intervals in a disease that is becoming more and more protracted. PMID:27516935

  10. Preferences and attitudes toward approaches to depression relapse/recurrence prevention among pregnant women.

    PubMed

    Dimidjian, Sona; Goodman, Sherryl H

    2014-03-01

    Patient preferences are increasingly recognized as important in clinical research and the delivery of evidence based practice in psychology. Although the prevention of depressive relapse/recurrence among perinatal women is an important public health goal, little is known about pregnant women's preferences and attitudes toward relapse/recurrence prevention interventions. Such information is important given low rates of care seeking among this population, and the potential for a relapse/recurrence prevention to avert negative outcomes among both vulnerable women and their offspring. Pregnant women seeking routine prenatal care in obstetric clinics (n = 200) were surveyed to assess their preferences for and attitudes about psychotherapy and pharmacological approaches to relapse/recurrence prevention. Women preferred psychotherapy (mindfulness based cognitive therapy and interpersonal therapy) more so than pharmacotherapy and reported significantly more favorable perceptions of the psychotherapy as compared to pharmacotherapy approaches to depression relapse/recurrence prevention. Results suggest also that depression history is important to consider in evaluating women's preferences and attitudes. Clinical and research implications of these findings are discussed. PMID:24440577

  11. Long-Term Survival And Late Relapse In 2-Year Survivors Of Autologous Hematopoietic Cell Transplantation For Hodgkin And Non-Hodgkin Lymphoma

    PubMed Central

    Majhail, Navneet S.; Bajorunaite, Ruta; Lazarus, Hillard M.; Wang, Zhiwei; Klein, John P.; Zhang, Mei-Jie; Rizzo, J. Douglas

    2009-01-01

    Summary This study described long-term outcomes of autologous hematopoietic-cell transplantation (HCT) for advanced Hodgkin (HL) and non-Hodgkin lymphoma (NHL). The study included recipients of autologous HCT for HL (N=407) and NHL (N=960) from 1990–98 who were in continuous complete remission for at least 2 years post-HCT. Median follow-up was 104 months for HL and 107 months for NHL. Overall survival at 10-years was 77% (72–82%) for HL, 78% (73–82%) for diffuse large-cell NHL, 77% (71–83%) for follicular NHL, 85% (75–93%) for lymphoblastic/Burkitt NHL, 52% (37–67%) for mantle-cell NHL and 77% (67–85%) for other NHL. On multivariate analysis, mantle-cell NHL had the highest relative-risk for late mortality (2.87 (1.70–4.87)), while the risks of death for other histologies were comparable. Relapse was the most common cause of death. Relative mortality compared to age, race and gender adjusted normal population remained significantly elevated and was 14.8 (6.3–23.3) for HL and 5.9 (3.6–8.2) for NHL at 10-years post-HCT. Recipients of autologous HCT for HL and NHL who remain in remission for at least 2-years have favorable subsequent long-term survival but remain at risk for late relapse. Compared to the general population, mortality rates continue to remain elevated at 10-years post-transplantation. PMID:19573079

  12. Late relapses in acute promyelocytic leukaemia.

    PubMed

    Latagliata, Roberto; Carmosino, Ida; Breccia, Massimo; Minni, Antonio; Testi, Anna; Iorio, Nicol; Lo-Coco, Francesco; Avvisati, Giuseppe; Petti, Maria Concetta; Mandelli, Franco; Cimino, Giuseppe

    2007-01-01

    From January 1988 to December 1997, among 53 acute promyelocytic leukaemia patients in 1st complete remission (CR) after 5 years from diagnosis, we observed 5 late relapses (9.4%) after 60, 61, 71, 101 and 155 months from diagnosis; 3 of those late relapses (7.7%) occurred among 39 patients previously treated with all-trans-retinoic acid. An involvement of the mastoid occurred in 3/5 patients (60%), compared with 2/32 patients (6.3%) at an early relapse (p < 0.02). As to the treatment of the late relapse, 1 patient received all-trans-retinoic acid alone followed by allogeneic transplantation and 4 patients were treated according to the GIMEMA 0191 protocol. All patients achieved a 2nd CR and are still alive: 4 in the 2nd molecular CR after 6, 33, 34 and 115 months; 1 relapsed after 15 months and is now in the 3rd CR. In conclusion, a late relapse occurred in a sizeable fraction of acute promyelocytic leukaemia patients: the high rate of ear involvement might be explained considering the ear as a 'disease sanctuary'. PMID:17135723

  13. 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)

  14. Idelalisib-associated Colitis: Histologic Findings in 14 Patients.

    PubMed

    Weidner, Anna-Sophie; Panarelli, Nicole C; Geyer, Julia T; Bhavsar, Erica B; Furman, Richard R; Leonard, John P; Jessurun, Jose; Yantiss, Rhonda K

    2015-12-01

    Idelalisib is an inhibitor of the PI3Kδ isoform approved for treatment of patients with relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Many patients develop gastrointestinal symptoms during idelalisib therapy; however, the pathologic effects of this drug have not been characterized. We identified 50 patients who received at least 3 months of idelalisib therapy. Clinical findings and symptoms were noted for each patient, and endoscopic findings were recorded for those who underwent colonoscopic examination. Hematoxylin and eosin-stained sections from colonic biopsy samples were evaluated for histologic patterns of injury. Twenty-three (46%) patients experienced diarrhea during treatment with idelalisib, including 8 with severe symptoms (≥7 stools/d above baseline and/or requiring hospitalization). Fourteen patients underwent colonoscopic examination with mucosal biopsy. Twelve (86%) of these had colitis characterized by intraepithelial lymphocytosis, crypt cell apoptosis, and neutrophilic infiltration of crypt epithelium. Eleven patients had symptoms severe enough to warrant drug withdrawal, including 9 who were also treated with corticosteroids. Idelalisib commonly causes diarrheal symptoms in patients undergoing therapy for B-cell neoplasia, which may be severe in nearly 20% of patients. Characteristic histologic features include the combination of intraepithelial lymphocytosis and crypt cell apoptosis, often accompanied by neutrophils. Discontinuation of the drug results in symptomatic improvement and resolution of histologic changes. PMID:26448188

  15. Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse.

    PubMed

    Wang, Eunice S; Sait, Sheila N J; Gold, David; Mashtare, Terry; Starostik, Petr; Ford, Laurie Ann; Wetzler, Meir; Nowak, Norma J; Deeb, George

    2010-10-15

    Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia (AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant karyotype (AK) AML. To determine the etiology of relapsed AK AML cells, we evaluated cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic NK AML and relapsed AK AML at our institute. AK AML karyotype was diverse, involving no favorable and largely (8 of 17) complex cytogenetics. Despite clear cytogenetic differences, immunophenotype and NPM1/FLT3 gene mutation status did not change between presentation and relapse in 83% (10 of 12) and 94% (15 of 16) cases, respectively. High-resolution array-based comparative genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples from the same patient confirmed cytogenetic aberrations only in the relapse sample. Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic aberrations undetected by conventional cytogenetics in any case. These results favor evolution of NK AML leukemia cells with acquisition of novel genetic changes as the most common etiology of AK AML relapse as opposed to secondary leukemogenesis. Additional studies are needed to confirm whether AK AML cells represent selection of rare preexisting clones below aCGH detection and to further characterize the molecular lesions found at time of AK AML relapse. PMID:20875872

  16. Appearance Normalization of Histology Slides

    PubMed Central

    Niethammer, Marc; Borland, David; Marron, J. S.; Woosley, John; Thomas, Nancy E.

    2011-01-01

    This paper presents a method for automatic color and intensity normalization of digitized histology slides stained with two different agents. In comparison to previous approaches, prior information on the stain vectors is used in the estimation process, resulting in improved stability of the estimates. Due to the prevalence of hematoxylin and eosin staining for histology slides, the proposed method has significant practical utility. In particular, it can be used as a first step to standardize appearances across slides, that is very effective at countering effects due to differing stain amounts and protocols, and to slide fading. The approach is validated using synthetic experiments and 13 real datasets. PMID:25360444

  17. Temporal bone metastasis as a sign of relapsing chronic lymphocytic leukemia

    PubMed Central

    Aljafar, Hadeel M.; Alsuhibani, Sari S.; Alahmari, Mohammad S.; Alzahrani, Musaed A.

    2015-01-01

    Otologic manifestations in chronic lymphocytic leukemia (CLL) are common presentations. However, temporal bone metastasis is rarely described as a sign of relapsing CLL. A 65-year-old male diabetic patient known to have CLL on remission presented to the outpatient otolaryngology clinic with a one month history of progressive bilateral otalgia and right otorrhea, despite multiple courses of antibiotics. He was admitted with suspicion of malignant otitis externa. Left ear showed large hemorrhagic bullae on the posterior segment of tympanic membrane. Left sided facial paralysis developed on the third day of admission. Full recovery of facial paralysis is achieved by 10 days course of corticotherapy. Histological examination of middle ear tissue biopsy showed infiltration by monotonous small lymphoid cells, showing round nuclei, condensed chromatin suggestive of CLL. Although rare, unusual otologic manifestations should raise the suspicion of a temporal bone metastasis as a sign of relapsing CLL. PMID:26446337

  18. 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.

  19. 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. PMID:25434846

  20. Relapse prevention with intellectually disabled sexual offenders.

    PubMed

    Keeling, Jenny A; Rose, John L

    2005-10-01

    The adaptation of relapse prevention theory to sexual offending (W. D. Pithers, J. K. Marques, C. C. Gibat, & G. A. Marlatt, 1983) has represented an important movement in cognitive-behavioural treatment for sexual offenders. However, this model of relapse prevention has been criticised for its limited view and oversimplification of the relapse prevention process (R. K. Hanson, 2000; T. Ward & S. M. Hudson, 1996). As a result, T. Ward and S. M. Hudson (2000a) have developed a multiple pathway model of the relapse prevention process based on self-regulation theory. Although this model continues to be empirically validated on sexual offenders (J. A. Bickley & A. R. Beech, 2002; T. Ward, S. M. Hudson, & J. C. McCormick, 1999), there has been no empirical research regarding the application of this theory to intellectually disabled sexual offenders. This paper discusses whether the characteristics of offenders in each of the relapse offence pathways, as described by T. Ward and S. M. Hudson (2000a), may be similar to the characteristics of intellectually disabled sexual offenders. From a review of the literature, it appears that the intellectually disabled sexual offender may be most likely to offend via the approach-automatic pathway or the avoidant-passive pathway. The potential treatment implications of the self-regulation model for intellectually disabled sexual offenders is discussed, as well as the need for empirical evaluation with regards to the application of this model to the intellectually disabled sexual offender population. PMID:16341602

  1. Results of sustained long-term use of interferon beta-1a in a community-based cohort of patients with relapsing multiple sclerosis

    PubMed Central

    Cohan, Stanley; Chen, Chiayi; Baraban, Elizabeth; Stuchiner, Tamela; Grote, Lois; Rodriguez, Monica

    2015-01-01

    Background Few studies have evaluated long-term efficacy of interferon beta-1a in large community-based cohorts. Objective Evaluate time to relapse, relapse rate, and disability progression in patients treated with intramuscular interferon beta-1a. Methods A retrospective review of medical records from 2000–2010 was performed. Adult patients with relapsing-remitting MS or clinically isolated syndrome treated with interferon beta-1a were included. Primary outcomes were time to relapse, annualized relapse rate, and changes in Expanded Disability Status Scale score. Other outcomes included factors associated with time to first relapse, risk of having a relapse while receiving interferon beta-1a, and discontinuation of therapy. Results In total, 364 of 696 patients screened were enrolled, with a mean age of 51 ± 12.1 years, disease duration of 9.39 ± 7.02 years, and duration of therapy of 4.03 ± 2.56 years. Mean time to first on-therapy relapse was 5.58 ± 0.26 years, annualized relapse rate was 0.30 ± 0.55 years, and mean increase in sustained Expanded Disability Status Scale score was 0.018. Relapse risk was associated with higher baseline Expanded Disability Status Scale score, age at disease onset, and number of relapses in the 12 months prior to therapy initiation. Conclusions This study demonstrates favorable clinical outcomes observed in a large community-based cohort, and serves to emphasize the continued therapeutic importance of interferon beta-1a, despite the development of newer agents with greater convenience of use, but also more potential risk of serious morbidity.

  2. Anti-relapse medications: Preclinical models for drug addiction treatment

    PubMed Central

    Yahyavi-Firouz-Abadi, Noushin; See, Ronald E.

    2009-01-01

    Addiction is a chronic relapsing brain disease and treatment of relapse to drug-seeking is considered the most challenging part of treating addictive disorders. Relapse can be modeled in laboratory animals using reinstatement paradigms, whereby behavioral responding for a drug is extinguished and then reinstated by different trigger factors, such as environmental cues or stress. In this review, we first describe currently used animal models of relapse, different relapse triggering factors, and the validity of this model to assess relapse in humans. We further summarize the growing body of pharmacological interventions that have shown some promise in treating relapse to psychostimulant addiction. Moreover, we present an overview on the drugs tested in cocaine or methamphetamine addicts and examine the overlap of existing preclinical and clinical data. Finally, based on recent advances in our understanding of the neurobiology of relapse and published preclinical data, we highlight the most promising areas for future anti-relapse medication development. PMID:19683019

  3. Histological findings in human brucellosis

    PubMed Central

    Hunt, A. C.; Bothwell, P. W.

    1967-01-01

    The histological findings in 14 cases of brucellosis are described. Unusual findings include the occurrence of brucellosis in a patient with Hodgkin's disease and in another with lymphosarcoma. A patient with hepatic cirrhosis apparently due to brucellosis is included in the series. Images PMID:5632572

  4. Strongyloidiasis histologically mimicking eosinophilic folliculitis.

    PubMed

    Cannavò, Serafinella P; Guarneri, Fabrizio; Guarneri, Claudio

    2004-01-01

    The authors report an unusual case of strongyloidiasis in an Italian patient, who has always lived in Sicily. The patient presented with marked blood eosinophilia and an itching maculo-papular eruption, histologically simulating eosinophilic folliculitis. The clinical resolution was achieved after albendazol therapy. PMID:15319162

  5. Histological evolution of pleuroparenchymal fibroelastosis

    PubMed Central

    Hirota, Takako; Yoshida, Yuji; Kitasato, Yasuhiko; Yoshimi, Michihiro; Koga, Takaomi; Tsuruta, Nobuko; Minami, Masato; Harada, Taishi; Ishii, Hiroshi; Fujita, Masaki; Nabeshima, Kazuki; Nagata, Nobuhiko; Watanabe, Kentaro

    2015-01-01

    Aims To investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE). Methods and results We examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3–12 years. Conclusions Interstitial inflammation or acute lung injury may be an initial step in the development of PPFE. PMID:25234959

  6. Histologic Technician. Laboratory Occupations Cluster.

    ERIC Educational Resources Information Center

    Michigan State Univ., East Lansing. Coll. of Agriculture and Natural Resources Education Inst.

    This task-based curriculum guide for histologic technician is intended to help the teacher develop a classroom management system where students learn by doing. Introductory materials include a Dictionary of Occupational Titles job code and title sheet, a career ladder, a matrix relating duty/task numbers to job titles, and a task list. Each task…

  7. 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…

  8. An Interpersonal Model of Addiction Relapse

    PubMed Central

    Leach, David; Kranzler, Henry R.

    2012-01-01

    In this article, we review the literature on interpersonal stress and rejection sensitivity and examine how these factors increase the risk of relapse in individuals with alcohol or drug dependence. We begin by considering the constructs of social pain and social threat, examining their evolutionary origins and their neuroanatomical, neuropsychological and neurophysiological dimensions. Together, these perspectives provide insight into the role of interpersonal stress as a powerful and oftentimes destructive factor that affects individuals in recovery from substance dependence. We then review the empirical evidence showing that intrapersonal traits and interpersonal environments interact to increase an addict’s risk of relapse. We conclude by proposing that substance-dependent individuals with high trait rejection sensitivity and a critical interpersonal environment are particularly vulnerable to relapse to substance use. PMID:24489485

  9. Outcome of older patients with acute myeloid leukemia in first relapse.

    PubMed

    Sarkozy, Clémentine; Gardin, Claude; Gachard, Nathalie; Merabet, Fathia; Turlure, Pascal; Malfuson, Jean-Valère; Pautas, Cécile; Micol, Jean-Baptiste; Thomas, Xavier; Quesnel, Bruno; Celli-Lebras, Karine; Preudhomme, Claude; Terré, Christine; Fenaux, Pierre; Chevret, Sylvie; Castaigne, Sylvie; Dombret, Hervé

    2013-09-01

    To provide data for future drug evaluation, we analyzed the outcome of 393 patients aged 50 years or older (median, 64 years) with AML in first relapse after treatment in recent ALFA trials. Salvage options were retrospectively classified as follows: best supportive care (BSC), low-dose cytarabine (LDAC), gemtuzumab ozogamicin (GO), intensive chemotherapy (ICT), or ICT combined with GO. Second complete remission (CR2) rate was 31% and median post-relapse survival was 6.8 months (0, 17, 42.5, 53, and 80% and 3.2, 5.6, 8.9, 9, and 19.8 months in BSC, LDAC, GO, ICT, and ICT + GO subsets, respectively). Age, performance status, WBC, CR1 duration, and favorable AML karyotype, but not other cytogenetic or molecular features, influenced post-relapse outcome. Multivariate adjustment and propensity score matching showed that intensive salvage (ICT/ICT+GO/GO versus LDAC/BSC) was associated with longer post-relapse survival, at least in patients with CR1 duration ≥12 months (P = 0.001 and 0.0005, respectively). Of interest, GO appeared to be as effective as standard ICT, and ICT + GO combination more effective than standard ICT. In conclusion, older patients with CR1 duration ≥12 months appeared to benefit from intensive salvage and results observed with GO-containing salvage suggest that GO combination studies should be actively pursued in this setting. PMID:23749683

  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. Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

    PubMed

    Link, C S; Teipel, R; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Reinhardt, J; Oelschlägel, U; von Bonin, M; Middeke, J M; Muetherig, A; Trautmann-Grill, K; Platzbecker, U; Bornhäuser, M; Schetelig, J

    2016-06-01

    Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT. PMID:26752141

  12. 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.

  13. Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.

    PubMed Central

    Stewart, J

    2000-01-01

    Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain. PMID:10740986

  14. Efficacy of immune suppression tapering in treating relapse after reduced intensity allogeneic stem cell transplantation

    PubMed Central

    Kekre, Natasha; Kim, Haesook T.; Thanarajasingam, Gita; Armand, Philippe; Antin, Joseph H.; Cutler, Corey; Nikiforow, Sarah; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Soiffer, Robert J.

    2015-01-01

    For patients who relapse after allogeneic hematopoietic stem cell transplantation while still on immune suppression, there is anecdotal evidence that tapering the immune suppression may result in graft-versus-tumor activity. We reviewed the medical records of all patients with documented histological or radiographic disease recurrence within 1 year of stem cell transplantation while on immune suppression at our institution. The median time to relapse was 110 days (range, 18–311) after transplant. Among 123 patients with relapse treated with immune suppression tapering without chemotherapy, radiation, or donor lymphocyte infusion, 34 responded (33/101 reduced intensity conditioning transplant and 1/22 myeloablative conditioning transplant, 32.7% and 4.5% respectively; P=0.007). The median time to response after initiation of immune suppression tapering was 82 days (range, 16–189). Thirty-three patients (97.1%) had development or progression of acute or chronic graft-versus-host disease as a consequence of immune suppression tapering, at a median time of 39 days (range, 16–98). Six patients subsequently relapsed late after initial response to immune suppression tapering at a median time of 2 years (range, 0.9–3.8). The median overall survival from immune suppression tapering for responders was 5.1 years (range, 1.9-not estimable). When clinically feasible, immune suppression tapering alone in patients who relapse early after reduced intensity conditioning allogeneic stem cell transplantation can produce durable remissions, but is almost always associated with graft-versus-host disease. PMID:26088931

  15. Appearance normalization of histology slides.

    PubMed

    Vicory, Jared; Couture, Heather D; Thomas, Nancy E; Borland, David; Marron, J S; Woosley, John; Niethammer, Marc

    2015-07-01

    This paper presents a method for automatic color and intensity normalization of digitized histology slides stained with two different agents. In comparison to previous approaches, prior information on the stain vectors is used in the plane estimation process, resulting in improved stability of the estimates. Due to the prevalence of hematoxylin and eosin staining for histology slides, the proposed method has significant practical utility. In particular, it can be used as a first step to standardize appearance across slides and is effective at countering effects due to differing stain amounts and protocols and counteracting slide fading. The approach is validated against non-prior plane-fitting using synthetic experiments and 13 real datasets. Results of application of the method to adjustment of faded slides are given, and the effectiveness of the method in aiding statistical classification is shown. PMID:25863518

  16. 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…

  17. The School Counselor's Role in Relapse Prevention.

    ERIC Educational Resources Information Center

    Fisher, Gary L.; Harrison, Thomas C.

    1993-01-01

    Notes that most individuals who receive treatment for alcohol or other drug problems fail to maintain abstinence. Sees it as essential that school counselors be aware of relapse prevention strategies and use these strategies proactively when adolescents complete treatment. Discusses strategies, adapted from work using cognitive-behavioral…

  18. Noncirrhotic hyperammonemia causing relapsing altered mental status

    PubMed Central

    Khatiwada, Binod; Holbrook, Christopher; Ekeh, Ifeoma Sylvia; Uzoka, Chukwuemeka; Ikwu, Isaac; Upadhyay, Bishwas

    2015-01-01

    Hyperammonemia is a recognized cause of encephalopathy. However, it is commonly seen in patients with liver disease. The clinical entity of noncirrhotic hyperammonemia is now being increasingly recognized. We report a man who presented to our hospital with relapsing altered mental status later diagnosed as noncirrhotic hyperammonemia. PMID:26424945

  19. Immunotoxin Therapy for Relapsed Hairy Cell Leukemia

    Cancer.gov

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

  20. Hypopyon uveitis (without scleritis) a manifestation symptom of relapsing polychondritis.

    PubMed

    Genevois, Olivier; Calenda, E; Nasser, Z; Benzerroug, M; Gardea, E; Muraine, M

    2009-01-01

    We report an atypical ocular symptom, hypopyon uveitis without scleritis encountered in relapsing polychondritis. Relapsing polychondritis should be considered in the differential diagnosis of sterile hypopyon uveitis. PMID:20214060

  1. Smoking Linked to Higher Relapse Risk After Surgery for Crohn's

    MedlinePlus

    ... html Smoking Linked to Higher Relapse Risk After Surgery for Crohn's Research supports immediate drug treatment after bowel surgery for ... Crohn's disease patients will have relapses after bowel surgery, new research suggests. The study included 240 Crohn's disease patients ...

  2. [Explanation and forecast: relapse of juvenile offenders].

    PubMed

    Giebel, S M

    2006-01-01

    On the basis of n=82 juvenile offenders from a prison for juvenile offenders in Rheinland Pfalz the model of the logistic regression is compared with a procedure from the family of the neural nets in its efficiency to explain and predict "relapse" in form of a renewed imprisonment or prosecution /police search after dismissal. The group which can be examined is limited by the population of the prison for juvenile offenders and the explaining variables for "relapse" as "addicted to drugs" present non-metric scaling. For the explanation only probabilities for "relapse" can be indicated in this connection. By means of this probability it is possible to classify the individual case. The forecast is simulated by coincidental dividing of the data: the first part of the data is used for the explanation, the second for the forecast. With the comparison of the logistic regression with the neural nets, the superiority of neural nets in the explanation of "relapse" can be shown, since the neural nets are able to consider dependence between the explaining variables and according to that they offer a differentiated explanation. Their efficiency to predict "relapse" depends on the comparability of the distribution in the two coincidentally provided samples, the training data record for determining the explanation and the test case for the use of the explanation regarding the forecast. For optimal explanation and forecast neural nets are to be preferred to the logistic regression, since in the model with the better explanation also includes the potential for a usable better forecast. Moreover the model of the logistic regression is in fact a special case of the neural net, with a reduced complexity of the net. PMID:17124800

  3. Dimethyl fumarate in relapsing-remitting multiple sclerosis: rationale, mechanisms of action, pharmacokinetics, efficacy and safety.

    PubMed

    Dubey, Duvyanshu; Kieseier, Bernd C; Hartung, Hans P; Hemmer, Bernhard; Warnke, Clemens; Menge, Til; Miller-Little, William A; Stuve, Olaf

    2015-04-01

    Dimethyl fumarate (DMF), a fumaric acid ester, is a new orally available disease-modifying agent that was recently approved by the US FDA and the EMA for the management of relapsing forms of multiple sclerosis (MS). Fumaric acid has been used for the management of psoriasis, for more than 50 years. Because of the known anti-inflammatory properties of fumaric acid ester, DMF was brought into clinical development in MS. More recently, neuroprotective and myelin-protective mechanism actions have been proposed, making it a possible candidate for MS treatment. Two Phase III clinical trials (DEFINE, CONFIRM) have evaluated the safety and efficacy of DMF in patients with relapsing-remitting MS. Being an orally available agent with a favorable safety profile, it has become one of the most commonly prescribed disease-modifying agents in the USA and Europe. PMID:25800129

  4. The Role of Allogeneic Stem Cell Transplantation in Relapsed/Refractory Hodgkin's Lymphoma Patients

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Kröger, Nicolaus; Kazantsev, Ilya; Zabelina, Tatjana; Ayuk, Francis; Zander, Axel Rolf

    2011-01-01

    Despite the favorable prognosis of most patients with Hodgkin's Lymphoma (HL), 15–20% of patients remain refractory to chemoradiotherapy, and 20–40% experience relapses following autologous stem cell transplantation (SCT) being used as salvage approach in this situation. Long-term survival of only 20% was reported for patients who failed this option. As some authors suggested the presence of a graft versus HL effect, allogeneic SCT was introduced as a further option. Myeloablative strategies were reported to be able to achieve cure in some younger patients, but high nonrelapse mortality remains a problem. Reduced intensity conditioning, in turn, was found to be associated with high posttransplant relapse rates. As there is currently no standard in the management of HL patients who failed autologous SCT, we here review the literature on allogeneic stem cell transplantation in HL patients with a special focus on the outcomes and risk factors being reported in the largest studies. PMID:20981158

  5. [Relapse of Plasmodium falciparum malaria in a patient treated with artesunate].

    PubMed

    Vandenbos, F; Delaunay, P; Del Giudice, P; Counillon, E

    2006-05-01

    Chemoprophylaxis and the curative treatment of malaria are well documented in France. Nevertheless this data is still not accounted for by healthcare professionals and in the global population, and no longer approved treatments may be prescribed. The authors report the case of a 24-year-old female traveler having stayed in Africa where she was used to treat fever with artesunate. Soon after her return, she presented with uncomplicated Plasmodium falciparum malaria once again treated with artesunate. The evolution was initially favorable but a relapse occurred 3 weeks later. A conventional mefloquine treatment lead to a final cure. This observation confirms that artesunate monotherapy in malaria exposes to a risk of relapse. Artesunate should not be used as monotherapy in P. falciparum malaria. PMID:16697545

  6. Chinese youth favor one-child families.

    PubMed

    Yu, P

    1995-04-01

    with parents about having children or received information from parents about sexuality. 62% knew almost nothing about family planning. Only 16% of 12th grade students knew three or more methods. Sexual practices were not surveyed. More formally educated students and students with a modern outlook were most likely to have greater knowledge of sexual matters. The population education curriculum favored social aspects over reproductive content. PMID:12319246

  7. Antipsychotic withdrawal-induced relapse predicts future relapses in institutionalized adults with severe intellectual disability.

    PubMed

    Janowsky, David S; Barnhill, L Jarrett; Khalid, Abdul S; Davis, John M

    2008-08-01

    Severe intellectual and developmental disabilities are frequently associated with aggression toward self and others, destruction of property, and disruption. Antipsychotic medications are a mainstay of treatment of such behaviors. National and state guidelines suggest stopping these medications or decreasing their dosages when possible if patients have maintained stability. The current study evaluated the likelihood of future antipsychotic drug withdrawal-induced relapses in those individuals where such a relapse had occurred previously. Subjects were 57 institutionalized adults with severe or profound intellectual disability. Between 1990 and 2000, each had experienced an initial activation of maladaptive aggressive behaviors after an attempt at antipsychotic drug withdrawal and/or termination. Quarterly behavioral reports were evaluated to determine whether subsequent antipsychotic drug withdrawal attempts were also associated with future relapses. Initial relapse was followed by subsequent antipsychotic drug withdrawal attempts in 49 of the 57 individuals. Between 1990 and 2005, 28.6% of these 49 subjects had experienced 1, 38.7% had 2, 20.4% had 3, and 8.2% had 4 additional relapses. Two (4.1%) had not relapsed. Eight individuals remained on antipsychotic agents without a subsequent withdrawal attempt. By the end of 2005, only 4 (7%) of the 57 individuals had become antipsychotic drug free, 22.8% were receiving first-generation antipsychotic agents alone, 45.6% were receiving second-generation antipsychotic agents alone, and 24.6% were receiving a combination of first- and second-generation antipsychotic agents. Thus, if relapse occurs after an antipsychotic drug withdrawal attempt, subsequent attempts at withdrawal are also very likely to lead to further relapses. PMID:18626266

  8. The role of neuroadaptations in relapse to drug seeking.

    PubMed

    Shaham, Yavin; Hope, Bruce T

    2005-11-01

    One of the most difficult problems in treating addiction is not withdrawing addicts from drugs, but preventing relapse. Persistent neuroadaptations are thought to underlie aspects of addiction, including relapse. This commentary assesses the degree to which these neuroadaptations, primarily identified in preclinical studies on cocaine, induce relapse. PMID:16251983

  9. 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…

  10. Relapse Prevention Model of Behavioral Maintenance: Implications for Alcohol Education.

    ERIC Educational Resources Information Center

    Rose-Colley, Mary; Cinelli, Bethann

    1992-01-01

    Describes Relapse Prevention as therapeutic modality, based on Social Learning Theory, used to prevent relapse for individuals who have completed treatment for substance abuse behaviors. Outlines relapse prevention theory and suggests various components of model be incorporated into alcohol education curricula. Outlines teaching strategies to…

  11. 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.

  12. Histological aspects of cervical ripening.

    PubMed

    Ichijo, M; Shimizu, T; Sasai, Y

    1976-02-01

    There is a close relationship between the rate of the uterine cervix opening during parturition and the presence or absence of a completely ripened cervix. In order to learn the basic pattern of the ripening of cervix, histological and histochemical studies were performed on the human uterine cervix during pregnancy. It was noted that the collagen bundles disintegrated into fine fibers and also underwent quantitative changes during the ripening process of the cervix. During pregnancy, the number of connective tissue cells was increased, but that of mast cells was decreased. Acid mucopolysaccharides in the cervical ground substance were found to increase in late pregnancy. PMID:136067

  13. 22 CFR 1203.735-305 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Gifts, entertainment, and favors. 1203.735-305....735-305 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, a..., gratuity, loan, entertainment, or favor for the employee or another person, particularly one with whom...

  14. 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

  15. 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.

  16. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    PubMed Central

    Fullmer, Amber; O’Brien, Susan; Kantarjian, Hagop; Jabbour, Elias

    2015-01-01

    The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromosome–positive ALL has improved responses in relapsed patients without resistance to available tyrosine kinase inhibitors. Nelarabine demonstrates activity as monotherapy in T-cell ALL and is approved by the US Food and Drug Administration. Clofarabine, a second-generation purine analogue approved in pediatric leukemia, has shown activity in adult acute leukemias including ALL and acute myeloid leukemia. The role of pegaspargase in adult ALL requires further investigation. The benefit of matched related-donor allogeneic stem cell transplantation is significant for standard-risk ALL but not for high-risk ALL. Development of new drugs and agents tailored to subset-specific cytogenetic-molecular characteristics remains vital to success in treating adult ALL. PMID:20425428

  17. Treatment of relapsed and refractory Hodgkin Lymphoma.

    PubMed

    von Tresckow, Bastian; Moskowitz, Craig H

    2016-07-01

    Despite the high first-line cure rates in patients with Hodgkin Lymphoma (HL) still 10%-20% of patients suffer from relapsed or refractory disease. High-dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is standard of care for suitable patients with relapsed or refractory HL and allows for cure in approximately 50%. Due to the poor prognosis of high-risk patients even with HDCT and ASCT, consolidation strategies have been evaluated to improve the cure rates. For patients with recurrence after HDCT and ASCT, treatment is palliative in most cases. The anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) has been shown to induce high response rates in these patients; however, durable responses were reported in a small percentage of patients only. For carefully selected patients with multiple relapses, dose-reduced allogeneic transplant (RICallo) is a potentially curative option. The role of RICallo will have to be re-evaluated in the era of anti-programmed death-1 (PD1) antibodies. PMID:27496309

  18. Craving and relapse measurement in alcoholism.

    PubMed

    Potgieter, A S; Deckers, F; Geerlings, P

    1999-01-01

    This paper attempts to summarize the measurement of craving with four different craving instruments and to relate this to definitions and measurement of relapse. The definitions of relapse may vary between studies and researchers, but are usually well defined. Five commonly used methods to measure relapse are: (1) quantity/frequency of drinking; (2) cumulative duration of abstinence (CDA); (3) post-withdrawal abstinent period; (4) stable recovery period; (5) the time line follow-back method. The definition of craving is much less clear and is mostly described as an emotional-motivational state or as obsessive-compulsive behaviour. Four self-rating instruments are briefly discussed and compared: the Obsessive-Compulsive Drinking Scale, OCDS, the Lübeck Craving Scale, LCRR, the Alcohol Craving Questionnaire, ACQ-Now-SF-R, and ordinal scales (e.g. visual analogue, Likert, or verbal descriptive scales). These instruments measure different aspects or dimensions of craving over different periods. The different dimensions measured suggest that there is still a need to conceptualize a standard interpretation of the word craving. There is a need also to measure an emotional-motivational dimension, a cognitive-behavioural dimension, expectancies, and effects on positive and negative reinforcement with different instruments or with one multidimensional instrument. It is suggested that different patients are expected to have different craving profiles. PMID:10344785

  19. A Case of Relapsing-Remitting Neuroborreliosis? Challenges in the Differential Diagnosis of Recurrent Myelitis

    PubMed Central

    Albrecht, P.; Henke, N.; Lehmann, H.C.; Macht, S.; Hefter, H.; Goebels, N.; Mackenzie, C.; Rupprecht, T.A.; Fingerle, V.; Hartung, H.P.; Methner, A.

    2012-01-01

    We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case. PMID:22649342

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

    PubMed

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

    2015-01-01

    In this research, the possible neuropsychological predictors of relapse and dropout of group cognitive behavioral therapy (CBT) for methamphetamine (MA) users were explored. Participants were 42 MA users sentenced by the judicial system to take part in an out-patient relapse prevention program for MA abuse and dependence that employs a CBT model once a week over the course of 12 weeks. Baseline neuropsychological functions were evaluated with the Conners' Continuous Performance Test, Wisconsin Card Sorting Test, Iowa Gambling Task, and Barratt Impulsiveness Scale. All participants had to submit to urine drug tests every week. Of the 42 participants, 69.0% had a MA positive urine screening result at least once throughout the program (relapse), while 40.5% dropped out of the treatment program prior to its completion. Short duration of MA abstinence at baseline and poor attention predicted relapse. Predictors of dropout included being unmarried and having risky decision making. Findings may be helpful for clinicians, who can screen for the aforementioned risk factors and provide strategies for high-risk patients to help prevent relapse and dropout among MA users in treatment programs. PMID:26267045

  1. Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group.

    PubMed

    Sung, Lillian; Aplenc, Richard; Alonzo, Todd A; Gerbing, Robert B; Wang, Yi-Cheng; Meshinchi, Soheil; Gamis, Alan S

    2016-11-01

    Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five hundred and sixty-nine patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54-204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, p = 0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy. PMID:27312107

  2. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    PubMed Central

    Vidal, Fabien; Guerby, Paul; Luyckx, Mathieu; Haddad, Pascale; Stoeckle, Eberhard; Morice, Philippe; Leblanc, Eric; Lecuru, Fabrice; Daraï, Emile; Classe, Jean Marc; Pomel, Christophe; Filleron, Thomas; Ferron, Gwenael; Querleu, Denis; Rafii, Arash

    2016-01-01

    Objective Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. Study Design We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. Results The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). Conclusion ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. PMID:26820579

  3. 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. PMID:25997994

  4. New Findings on Biological Factors Predicting Addiction Relapse Vulnerability

    PubMed Central

    2013-01-01

    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. PMID:21792580

  5. Does internet-based prevention reduce the risk of relapse for anorexia nervosa?

    PubMed

    Fichter, Manfred M; Quadflieg, Norbert; Nisslmüller, Kerstin; Lindner, Susanne; Osen, Bernhard; Huber, Thomas; Wünsch-Leiteritz, Wally

    2012-03-01

    Technological advancements allow new approaches to psychotherapy via electronic media. The eating disorder literature currently contains no studies on internet intervention in anorexia nervosa (AN). This study presents a RCT on an internet-based relapse prevention program (RP) over nine months after inpatient treatment for AN. The sample comprised 258 women, randomized to the RP or treatment as usual (TAU). Expert- and self-ratings were evaluated by intent-to-treat analyses. Concerning age, age at onset and comorbidity, both groups were comparable at randomization. During the RP, the intervention group gained weight while the TAU group had minimal weight loss. RP completers gained significantly more body weight than patients in the TAU condition. Group-by-time comparisons for eating-related cognitions and behaviors and general psychopathology showed a significantly more favorable course in the RP program for "sexual anxieties" and "bulimic symptoms" (interview), and "maturity fears" and "social insecurity" (EDI-2). General psychopathology showed no significant group-by-time interaction. Important factors for successful relapse prevention were adherence to the intervention protocol and increased spontaneity. Considering the unfavorable course and chronicity of anorexia nervosa (AN), internet-based relapse prevention in AN following inpatient treatment appears a promising approach. Future internet-based programs may be further improved and enhanced. PMID:22317754

  6. Recent developments in animal models of drug relapse.

    PubMed

    Marchant, Nathan J; Li, Xuan; Shaham, Yavin

    2013-08-01

    Drug craving and relapse to drug use during abstinence are defining features of addiction. Evidence indicates that drug craving and relapse in humans are often provoked by acute exposure to the self-administered drug, drug-associated cues, or stress. During the last two decades, this clinical scenario has been primarily studied at the preclinical level using the classical reinstatement model. However, a single preclinical model cannot capture the complicated nature of human drug relapse. Therefore, more recently, we and others have developed several other models to study different facets of human drug relapse. In this review, we introduce and discuss recent findings from these other relapse models, including incubation of drug craving, reacquisition and resurgence models, and punishment-based and conflict-based relapse models. PMID:23374536

  7. The Alcohol Relapse Situation Appraisal Questionnaire: Development and Validation

    PubMed Central

    Martin, Rosemarie A.; MacKinnon, Selene M.; Johnson, Jennifer E.; Myers, Mark G.; Cook, Travis A. R.; Rohsenow, Damaris J.

    2011-01-01

    Background The role of cognitive appraisal of the threat of alcohol relapse has received little attention. A previous instrument, the Relapse Situation Appraisal Questionnaire (RSAQ), was developed to assess cocaine users’ primary appraisal of the threat of situations posing a high risk for cocaine relapse. The purpose of the present study was to modify the RSAQ in order to measure primary appraisal in situations involving a high risk for alcohol relapse. Methods The development and psychometric properties of this instrument, the Alcohol Relapse Situation Appraisal Questionnaire (A-RSAQ), were examined with two samples of abstinent adults with alcohol abuse or dependence. Factor structure and validity were examined in Study 1 (N=104). Confirmation of the factor structure and predictive validity were assessed in Study 2 (N=161). Results Results demonstrated construct, discriminant and predictive validity and reliability of the A-RSAQ. Discussion Results support the important role of primary appraisal of degree of risk in alcohol relapse situations. PMID:21237586

  8. Callosal Disconnection Syndrome Associated with Relapsing Polychondritis.

    PubMed

    Baba, Toru; Kanno, Shigenori; Shijo, Tomomi; Nishio, Yoshiyuki; Iizuka, Osamu; Kamimura, Naoto; Ishii, Tomonori; Mori, Etsuro

    2016-01-01

    Relapsing polychondritis (RP) is a rare inflammatory disorder of the cartilagenous structures, and it sometimes involves the central nervous system. Encephalitis associated with RP causes a wide variety of symptoms according to the affected sites. We herein report the first case of 72-year-old right-handed man who developed acute meningoencephalitis associated with RP involving the corpus callous. After immunosuppressive therapy, his symptoms dramatically improved, but difficulty in performing bimanual movements with occasional diagonistic dyspraxia in his right hand remained. Because callosal signs are easily missed, especially in acute settings, it would be useful to know that RP can sometimes cause callosal disconnection syndrome. PMID:27150878

  9. Relapsing Fever Borreliae: A Global Review.

    PubMed

    Cutler, Sally J

    2015-12-01

    Relapsing fever borreliae were notorious and feared infectious agents that earned their place in history through their devastating impact as causes of both epidemic and endemic infection. They are now considered more as an oddity, and their burden of infection is largely overshadowed by other infections such as malaria, which presents in a similar clinical way. Despite this, they remain the most common bacterial infection in some developing countries. Transmitted by soft ticks or lice, these fascinating spirochetes have evolved a myriad of mechanisms to survive within their diverse environments. PMID:26593261

  10. [Sporadic recurrent hypertrophic polyneuropathy. Clinical-histological contributions on differential diagnosis].

    PubMed

    Haferkamp, G; Regli, F

    1976-01-01

    The authors report about an own case of recurrent sporadic hypertrophic polyneuropathy and describe the clinical course and histologic picture with reference to the literature. The disease is characterized by recurrences of subacutely occurring polyradiculoneuropathy and sequent nearly complete remission. Clinical examination discloses preferentially symmetrically and distally occurring motor paresis while sensibility in most cases is less affected. The peripheral nerves may be enlarged after a few relapses and frequently painful to pressure during the bout. Excessive increase in CSF proteins is found only during the bout. Motor nerve conduction velocity is considerably reduced. Histological pictures typically present an onion bulb formation of the Schwann cells with marked proliferation of connective tissue. There frequently younger individuals are involved; the relation female to male is 3:1. Differentiation has to be made concerning hereditary and symptomatic forms of hypertrophic polyneuropathy. Etiological factors of the disease are discussed. PMID:185690

  11. 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

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

    PubMed

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

    2016-04-01

    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

  13. 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

  14. Relapsing and refractory ulcerative colitis in children.

    PubMed

    Turner, Dan

    2014-01-01

    Approximately half of the children with ulcerative colitis (UC) have refractory, relapsing or steroid-dependent disease. UC in children is more extensive than in adults, presents more often with severe attacks and carries a more aggressive disease course. Therefore, although a step-up approach is usually recommended in UC, aggressive therapy will often be indicated in children since steroid dependency should never be tolerated. It is vital to ensure that in every resistant case, the symptoms are truly related to the inflammatory disease activity and not to other conditions such as poor adherence to treatment, infections, adverse reactions to drugs, irritable bowel syndrome, lactose intolerance, celiac disease and bacterial overgrowth. The clinician should be ready to escalate therapy in a timely manner but only after ensuring optimization of current treatments. Optimization may include, among others, appropriate dosage, utilization of assays that determine thiopurine, calcineurin inhibitors and anti-tumor necrosis factor levels, introduction of combination therapy when indicated (enemas and immunomodulators) and a long enough time for treatment to become effective. Colectomy is always a valid option and should be discussed before major treatment escalations. Experimental therapies can be considered when all else fails and the family prefers to avoid colectomy. The management of refractory and relapsing disease is particularly challenging in children, and this review summarizes the available evidence to guide treatment decisions in this setup. PMID:24969290

  15. 36 CFR 905.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Gifts, entertainment, and favors. 905.735-202 Section 905.735-202 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION STANDARDS OF CONDUCT Conduct and Responsibilities of Employees § 905.735-202 Gifts, entertainment, and favors. Pursuant to...

  16. 18 CFR 706.202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Gifts, entertainment, and favors. 706.202 Section 706.202 Conservation of Power and Water Resources WATER RESOURCES COUNCIL EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Employees § 706.202 Gifts, entertainment, and favors. (a) Except as provided...

  17. 22 CFR 1203.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Gifts, entertainment, and favors. 1203.735-202 Section 1203.735-202 Foreign Relations UNITED STATES INTERNATIONAL DEVELOPMENT COOPERATION AGENCY EMPLOYEE RESPONSIBILITIES AND CONDUCT Ethical and Other Conduct and Responsibilities of Employees § 1203.735-202 Gifts, entertainment, and favors....

  18. 36 CFR 905.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., entertainment, and favors. Pursuant to paragraph (b) of 5 CFR 735.202, the following exceptions to the... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Gifts, entertainment, and favors. 905.735-202 Section 905.735-202 Parks, Forests, and Public Property PENNSYLVANIA...

  19. 12 CFR 560.110 - Most favored lender usury preemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Most favored lender usury preemption. 560.110 Section 560.110 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY LENDING AND INVESTMENT Lending and Investment Provisions Applicable to all Savings Associations § 560.110 Most favored lender usury preemption. (a)...

  20. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Gifts, entertainment....303 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section a..., entertainment, or favor for himself or another person, particularly one with whom he has family, business,...

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

    SciTech Connect

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

    2007-03-15

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

  2. 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

  3. Comparative histology of pineal calcification.

    PubMed

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

    1998-07-01

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

  4. Comparative Histology of Plasma Treated Tissue

    NASA Astrophysics Data System (ADS)

    Rick, Kyle

    2009-10-01

    Atmospheric plasmas applied in surgical settings have unique characteristics found in histological results from animal tissue studies. This is evident in both ex vivo bench tissue tests and in vivo fresh tissue. Examples of these histological features are presented as results of a comparative study between plasma treated, common medical argon coagulation, and electrosurgery.

  5. High dose chemotherapy with peripheral blood stem cells transplantation in patients with relapsed or refractory lymphomas preliminary reports.

    PubMed

    Chang, C S; Lin, S F; Huang, S M; Liu, T C; Chen, T P; Yeh, C J

    1997-03-01

    High dose chemotherapy with peripheral blood stem cells transplantation (PBSCT) has been used worldwide in the treatment of patients with various hematological malignancies and other solid tumors. It has just come into use as a salvage therapy in various malignancies in Taiwan in recent years. We report eight cases with relapsed or refractory lymphoma treated with high dose chemotherapy and PBSCT. Our results showed all cases but one achieved complete remission. The mean days of white cell recovery were 10 days to > 500/microliter (ranges, 8-16 days) and 12 days to > 1,000/microliter (ranges, 9-19 days). The mean days to platelet transfusion independent, i.e. platelet > 20,000/microliters, was 14 days. No specific side effect was noted except death in one case on D+9 during cytopenia state. Four patients relapsed and died during the follow-up after PBSCT. From our preliminary results we suggest that high dose chemotherapy with PBSCT could be used as a salvage therapy in patients with relapsed or refractory lymphomas with favorable and sustained hematological recovery. Most cases were tolerable with myeloablative chemotherapy and re-achieved remission, however, remission duration was still short and relapse remained the main problem to be overcome. The long term effects of high dose chemotherapy with PBSCT still need further study. PMID:9109301

  6. Why Koreans are More Likely to Favor "Apology," While Americans are More Likely to Favor "Thank You"

    ERIC Educational Resources Information Center

    Lee, Hye Eun; Park, Hee Sun

    2011-01-01

    Two studies investigated whether apologies or thanks are preferred in asking favors in the United States and Korea, and how this relates to perceptions of reduction in positive and negative face threats. In the first study (n = 224), participants composed an e-mail message where a favor was asked. In the second (n = 807), participants completed…

  7. Reproducibility of histologic classification of gastric cancer.

    PubMed Central

    Palli, D.; Bianchi, S.; Cipriani, F.; Duca, P.; Amorosi, A.; Avellini, C.; Russo, A.; Saragoni, A.; Todde, P.; Valdes, E.

    1991-01-01

    A panel review of histologic specimens was carried out as part of a multi-centre case-control study of gastric cancer (GC) and diet. Comparisons of diagnoses of 100 GCs by six pathologists revealed agreement in histologic classification for about 70-80% of the cancers. Concordance was somewhat higher when using the Lauren rather than the Ming or World Health Organization classification systems. Histologic types from reading biopsy tissue agreed with those derived from surgical specimens for 65-75% of the 100 tumours. Intra-observer agreement in histologic classification, assessed by repeat readings up to 3 years apart by one pathologist, was 95%. The findings indicate that, although overall concordance was good, it is important to standardise diagnoses in multi-centre epidemiologic studies of GC by histologic type. PMID:2039701

  8. Effective topical delivery systems for corticosteroids: dermatological and histological evaluations.

    PubMed

    Eroğlu, İpek; Azizoğlu, Erkan; Özyazıcı, Mine; Nenni, Merve; Gürer Orhan, Hande; Özbal, Seda; Tekmen, Işıl; Ertam, İlgen; Ünal, İdil; Özer, Özgen

    2016-06-01

    Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment. PMID:25259424

  9. 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…

  10. Relapse Prevention Needs More Emphasis on Interpersonal Factors

    ERIC Educational Resources Information Center

    Stanton, Mark

    2005-01-01

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

  11. 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

  12. Emphasis on Interpersonal Factors in a Dynamic Model of Relapse

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, G. Alan

    2005-01-01

    This article presents comments on "Relapse Prevention Needs More Emphasis on Interpersonal Factors" by Stanton which is a comment on the original article "Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao" by Katie Witkiewitz and G. Alan Marlatt. In the current comment the authors of the original article respond to…

  13. 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…

  14. 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…

  15. Power2: Relapse Management with Adolescents Who Stutter.

    ERIC Educational Resources Information Center

    Blood, Gordon W.

    1995-01-01

    This article describes a cognitive-behavioral treatment package for relapse management in adolescents who stutter. The package includes game-based training techniques in problem solving, communication skills, and assertiveness; coping responses for stuttering episodes; and realistic expectations for fluency and relapse. Follow-up results with…

  16. Effects of Nicotine Fading and Relapse Prevention on Smoking Cessation.

    ERIC Educational Resources Information Center

    Brown, Richard A.; And Others

    1984-01-01

    Conducted a pilot study which combined nicotine-fading and relapse prevention with smokers (N=30) and compared this program to conditions where subjects (N=46) received nicotine-fading or relapse prevention only. Results showed no difference among groups in abstinence or rate at any follow-up point. (LLL)

  17. Relapsing Polychondritis: Inflamed Joints and Ears

    PubMed Central

    Melikoğlu, Meltem Alkan; Şenel, Kazım

    2015-01-01

    Background: Relapsing polychondritis (RP) is an episodic and progressive inflammatory disease of the cartilaginous structures, including elastic cartilage of the ear and nose, hyaline cartilage of the peripheral joints, fibrocartilage at axial sites, and cartilage of the tracheo-bronchial tree. The spectrum of its presentations may vary from intermittent mild episodes of chondritis to occasional organ involvement or even life-threatening manifestations. Case Report: We presented a 64 year-old male patient with bilaterally knee arthritis and discoloration of pinna. Conclusion: There is lack of awareness about this disease due to its rarity. With this case presentation, our goal was to draw attention to this disease, which could be delayed for the diagnosis. PMID:25759785

  18. Graves’ Ophthalmopathy Misdiagnosed as Relapsing Conjunctivitis

    PubMed Central

    Chatziralli, Irini P.; Kanonidou, Evgenia; Keryttopoulos, Petros; Papadopoulou, Dionyssia; Papazisis, Leonidas

    2010-01-01

    A 59-year-old female patient presented at the outpatients’ Department of Ophthalmology with epiphora, eyelid swelling, and a foreign body feeling in the right eye. The symptoms were present for 4 months, and the patient was treated as suffering from relapsing conjunctivitis. The slit lamp examination revealed keratitis due to exposure, related with the deficient closure of the eyelids. There was a 2 mm difference in the readings with the Hertel exophthalmometry examination between the eyes. Her medical history was clear, and she was referred for computed tomography of the orbits and brain and biochemical examinations (FT3, FT4, and TSH) to investigate the presence of an intraorbital mass. FT3 was significantly increased and TSH was accordingly low, indicating the diagnosis of Graves’ disease, which presented without other signs and symptoms apart from ophthalmopathy. Computed tomography scan excluded the diagnosis of an intraorbital mass. Therefore, it is important not to underestimate the ocular manifestations of systemic diseases. PMID:21060773

  19. Mathematical Models of Tuberculosis Reactivation and Relapse

    PubMed Central

    Wallis, Robert S.

    2016-01-01

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

  20. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

    Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit

  1. 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

  2. Studies on the Plasmodium vivax relapse pattern in Delhi, India.

    PubMed

    Adak, T; Sharma, V P; Orlov, V S

    1998-07-01

    A five-year epidemiologic study of patients attending a malaria clinic in Delhi was conducted to find the relapse rate of infections with Plasmodium vivax, its seasonal correlation between the primary infection and subsequent relapses, the duration of the incubation period, and the patterns of relapse. By our definition, the relapse rate ranged from 23% to 44% depending on the duration of follow-up. The relapse pattern observed in the study clearly suggests the existence of both tropical and temperate zone types of P. vivax in the population characterized by distinct incubation periods and the possible existence of P. vivax subpopulations characterized by primary long incubation periods. The implication of different incubating forms of P. vivax on the epidemiology and control of malaria is also discussed. PMID:9684649

  3. 11 CFR 7.20 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of Special Commission Employees § 7.20 Gifts, entertainment, and favors. Except as provided at 11 CFR..., shall not receive or solicit from a person having business with the Commission anything of value such...

  4. 36 CFR 905.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., entertainment, and favors. Pursuant to paragraph (b) of 5 CFR 735.202, the following exceptions to the... advertising or promotional materials, such as pens, pencils, note pads, calendars and other items of...

  5. 36 CFR 905.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., entertainment, and favors. Pursuant to paragraph (b) of 5 CFR 735.202, the following exceptions to the... of value under circumstances which arise from an obvious family or personal relationship(s) (such...

  6. 36 CFR 905.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., entertainment, and favors. Pursuant to paragraph (b) of 5 CFR 735.202, the following exceptions to the... of value under circumstances which arise from an obvious family or personal relationship(s) (such...

  7. 22 CFR 1203.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., entertainment, loan, or any other thing of monetary value, from a person who: (1) Has, or is seeking to obtain... apply to: (1) Gifts, gratuities, favors, entertainments, loans, or any other thing of monetary...

  8. 22 CFR 1203.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., entertainment, loan, or any other thing of monetary value, from a person who: (1) Has, or is seeking to obtain... apply to: (1) Gifts, gratuities, favors, entertainments, loans, or any other thing of monetary...

  9. 22 CFR 1203.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., entertainment, loan, or any other thing of monetary value, from a person who: (1) Has, or is seeking to obtain... apply to: (1) Gifts, gratuities, favors, entertainments, loans, or any other thing of monetary...

  10. 22 CFR 1203.735-202 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., entertainment, loan, or any other thing of monetary value, from a person who: (1) Has, or is seeking to obtain... apply to: (1) Gifts, gratuities, favors, entertainments, loans, or any other thing of monetary...

  11. Multidisciplinary approach to breast angiosarcoma in an elderly patient: Repeated local relapses and significant objective responses.

    PubMed

    Mocerino, Carmela; Iannaci, Giuseppe; Sapere, Patrizia; Luise, Rossella; Canonico, Silvestro; Gambardella, Antonio

    2016-09-01

    Angiosarcomas are malignant tumors of endovascular origin, which may be divided into primary and secondary forms. Secondary breast angiosarcomas are an increasing problem, especially in patients treated with breast-conserving surgery followed by radiotherapy.We report a case of radiation-induced angiosarcoma of the breast in a 77-year-old woman who presented with a suspect lesion in her left breast. Excisional biopsy and subsequent immunohistochemical staining of the specimen was performed. Histological report was diagnostic for low-intermediate grade angiosarcoma. The tumor cells were diffusely positive for CD31 and CD34. We performed surgical resection with mastectomy.A multidisciplinary approach with bleomycin-based electrochemotherapy, radiation treatment, and chemotherapy with pegylated liposomal doxorubicin has been most useful to control subsequent local relapses. To date, the patient is under close observation and is performing well. No recurrence has been demonstrated after ending of chemotherapy. PMID:26872968

  12. 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

  13. High expression of SOX30 is associated with favorable survival in human lung adenocarcinoma

    PubMed Central

    Han, Fei; Liu, Wenbin; Xiao, Hualiang; Dong, Yan; Sun, Lei; Mao, Chengyi; Yin, Li; Jiang, Xiao; Ao, Lin; Cui, Zhihong; Cao, Jia; Liu, Jinyi

    2015-01-01

    In our previous study, we had identified SOX30 as a novel tumor suppressor that acts through direct regulation of p53 transcription in human lung cancer. Here, we sought to determine the clinical relevance of SOX30 expression in a series of surgically-resected non-small cell lung cancer (NSCLC) patients. Analysis of SOX30 expression and clinico-pathologic features reveal a significant correlation of SOX30 expression with histological type (n = 220, P = 0.008) and clinical stage (n = 220, P = 0.024). Kaplan-Meier analysis indicates an association of high SOX30 expression with better prognosis in NSCLC patients (n = 220, P = 0.007). Via multivariate Cox-regression analysis, SOX30 expression is revealed to be an independent prognostic factor for overall survival (OS) of NSCLC patients (n = 220, P = 0.014, hazard ratio (HR) = 0.816). In particular, SOX30 is a favorable and independent prognostic factor in one main subtype of NSCLC, lung adenocarcinoma (ADC) patients (n = 150, P = 0.000, HR = 0.405), but not in another main subtype of NSCLC, squamous cell carcinoma patients. Furthermore, high expression of SOX30 represents a favorable and independent factor for the prognosis of ADC patients at clinical stage II (P = 0.013), with positive lymph node (P = 0.003), at histological grade 2 (P = 0.000) or grade 3 (P = 0.025). In summary, SOX30 expression represents an important prognostic factor for survival time in ADC patients. PMID:26330328

  14. Irinotecan and capecitabine combination chemotherapy in a patient with triple-negative breast cancer relapsed after adjuvant chemotherapy with anthracycline and taxane.

    PubMed

    Lee, Anna; Go, Se-Il; Lee, Won Sup; Lee, Un Seok; Kim, Moon Jin; Kang, Myoung Hee; Lee, Gyeong-Won; Kim, Hoon-Gu; Kang, Jung Hun; Jeon, Kyung-Nyeo; Cho, Jae Min; Lee, Jeong-Hee

    2015-01-01

    The most effective regimen for taxane- and anthracycline-refractory triple-negative breast cancer (TNBC) has not yet been established. Capecitabine was approved by the US Food and Drug Administration for the treatment of advanced breast cancer and has shown efficacy in advanced breast cancer refractory to anthracyclines and taxanes. Irinotecan has synergism with 5-fluorouracil and shows efficacy in advanced breast cancer. Here we report on a patient with TNBC who relapsed with widespread bone and lung metastases shortly after adjuvant anthracycline followed by taxane chemotherapy. She achieved a metabolic complete response with irinotecan and capecitabine combination therapy and had 10 months' progression-free survival and 22 months' overall survival. She relapsed with and died of brain metastasis without any definite signs of progression of the lung and bone lesions she had had before the irinotecan and capecitabine combination therapy. To validate this favorable result, larger clinical trials are warranted in patients with metastatic or relapsed TNBC. PMID:25702650

  15. Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients

    PubMed Central

    2016-01-01

    Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile. PMID:27366017

  16. Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients.

    PubMed

    Lee, Seung-Shin; Jung, Sung-Hoon; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Cho, Min-Seok; Jung, Seung-Yeon; Lee, Je-Jung; Kim, Hyeoung-Joon; Yang, Deok-Hwan

    2016-07-01

    Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile. PMID:27366017

  17. 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

  18. Plasma HHV8 DNA predicts relapse in individuals with HIV-associated multicentric Castleman disease.

    PubMed

    Stebbing, Justin; Adams, Caroline; Sanitt, Adam; Mletzko, Salvinia; Nelson, Mark; Gazzard, Brian; Newsom-Davis, Tom; Bower, Mark

    2011-07-14

    HIV-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder caused by infection with human herpesvirus-8. The disease follows a relapsing and remitting clinical course, with marked systemic symptoms during an active attack, which can prove fatal. Its incidence is rising, and new data indicate the utility of the anti-CD20 monoclonal antibody rituximab at inducing remissions in both first- and second-line settings, although biomarkers associated with relapse have not been previously identified. In 52 individuals with a histologic diagnosis of HIV-MCD, we performed univariate and multivariate analyses to predict factors associated with an HIV-MCD attack. Although a younger age (< 50 years) was associated with an attack, the strongest association was observed with plasma levels of human herpesvirus-8 DNA. Rising levels predicted an attack (hazard ratio = 2.9; 95% confidence interval, 1.3-6.7), and maintenance therapy with rituximab should be considered in these individuals. PMID:21511959

  19. GALNT2 suppresses malignant phenotypes through IGF-1 receptor and predicts favorable prognosis in neuroblastoma

    PubMed Central

    Jeng, Yung-Ming; Lu, Meng-Yao; Yang, Yung-Li; Jou, Shiann-Tarng; Lin, Dong-Tsamn; Chang, Hsiu-Hao; Lin, Kai-Hsin; Hsu, Wen-Ming; Huang, Min-Chuan

    2014-01-01

    Aberrant expression of the simple mucin-type carbohydrate antigens such as Tn antigen is associated with malignant transformation and cancer progression. N-acetylgalactosaminyltransferase 2 (GALNT2), one of the enzymes that mediate the initial step of mucin-type O-glycosylation, is responsible for forming Tn antigen. GALNT2 is expressed differentially in nervous tissues during mouse embryogenesis; however, the role of GALNT2 in neuroblastoma (NB) remains unclear. Here we showed that increased GALNT2 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as younger age at diagnosis, early clinical stage, primary tumor originated from the extra-adrenal site, favorable INPC histology, and MYCN non-amplification. Multivariate analysis showed that GALNT2 expression is an independent prognostic factor for better survival for NB patients. GALNT2 overexpression suppressed IGF-1-induced cell growth, migration, and invasion of NB cells, whereas GALNT2 knockdown enhanced these NB phenotypes. Mechanistic investigations demonstrated that GALNT2 overexpression modified O-glycans on IGF-1R, which suppressed IGF-1-triggered IGF-1R dimerization and subsequent downstream signaling events. Conversely, these properties were reversed by GALNT2 knockdown in NB cells. Our findings suggest that GALNT2 regulates malignant phenotypes of NB cells through the IGF-1R signaling pathway, suggesting a critical role for GALNT2 in the pathogenesis of NB. PMID:25362349

  20. GALNT2 suppresses malignant phenotypes through IGF-1 receptor and predicts favorable prognosis in neuroblastoma.

    PubMed

    Ho, Wan-Ling; Chou, Chih-Hsing; Jeng, Yung-Ming; Lu, Meng-Yao; Yang, Yung-Li; Jou, Shiann-Tarng; Lin, Dong-Tsamn; Chang, Hsiu-Hao; Lin, Kai-Hsin; Hsu, Wen-Ming; Huang, Min-Chuan

    2014-12-15

    Aberrant expression of the simple mucin-type carbohydrate antigens such as Tn antigen is associated with malignant transformation and cancer progression. N-acetylgalactosaminyltransferase 2 (GALNT2), one of the enzymes that mediate the initial step of mucin-type O-glycosylation, is responsible for forming Tn antigen. GALNT2 is expressed differentially in nervous tissues during mouse embryogenesis; however, the role of GALNT2 in neuroblastoma (NB) remains unclear. Here we showed that increased GALNT2 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as younger age at diagnosis, early clinical stage, primary tumor originated from the extra-adrenal site, favorable INPC histology, and MYCN non-amplification. Multivariate analysis showed that GALNT2 expression is an independent prognostic factor for better survival for NB patients. GALNT2 overexpression suppressed IGF-1-induced cell growth, migration, and invasion of NB cells, whereas GALNT2 knockdown enhanced these NB phenotypes. Mechanistic investigations demonstrated that GALNT2 overexpression modified O-glycans on IGF-1R, which suppressed IGF-1-triggered IGF-1R dimerization and subsequent downstream signaling events. Conversely, these properties were reversed by GALNT2 knockdown in NB cells. Our findings suggest that GALNT2 regulates malignant phenotypes of NB cells through the IGF-1R signaling pathway, suggesting a critical role for GALNT2 in the pathogenesis of NB. PMID:25362349

  1. The Impact of Histologic Variants on FSGS Outcomes

    PubMed Central

    Meliambro, Kristin; Campbell, Kirk N.

    2014-01-01

    Focal segmental glomerulosclerosis (FSGS) is the most common glomerular disease leading to end-stage renal disease. The clinical course is highly variable with disparate responses to therapeutic intervention and rates of progression. Histologic variant subtype has been commonly used as a prognostic and therapeutic guide in the clinical management of FSGS. The tip lesion is widely considered to portend the most favorable prognosis and to be the most responsive to steroid therapy. Conversely, the collapsing lesion, more prevalent in patients of African descent, is associated with steroid resistance and higher risk of disease progression. In the 10 years since the Columbia classification system for FSGS was published, some retrospective and one prospective study explored the impact of histologic variants at the time of biopsy on FSGS outcomes. The results largely validate its clinical predictive value with respect to treatment response, though its utility in cases recurring after kidney transplantation is still unknown. Sampling and interpretation errors are additional sources of caution. More research is needed to fully define reproducible prognostic and therapeutic markers for this polymorphic disorder.

  2. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-10

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  3. [Metal implant sensitivity: clinical and histological presentation].

    PubMed

    Hartmann, D; Letulé, V; Schneider, J J; Flaig, M J

    2016-05-01

    Metal implant sensitivity (intolerance) can cause pain, reduced mobility, loosening of the implant and skin rashes. Knowledge of differential diagnoses, histology and appropriate diagnostics are essential for proper diagnosis. To outline typical clinical signs and histology in metal-implant-associated skin lesions we present three exemplary patients from our implant allergy outpatient department and give an overview of the current literature regarding metal implant sensitivity. In patients with a negative patch test the lymphocyte transformation test may reveal metal sensitization. Even "pure" titanium alloys may contain traces of nickel. The histology of implant-associated skin reactions goes from teleangiectatic postimplantation erythema to eczema and vasculitis. Based on the synopsis of history, clinical picture, allergological testing and histology, metal implant sensitivity can be diagnosed more precisely. PMID:27090521

  4. 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

  5. Why do homosexual men relapse into unsafe sex? Predictors of resumption of unprotected anogenital intercourse with casual partners.

    PubMed

    de Wit, J B; van Griensven, G J; Kok, G; Sandfort, T G

    1993-08-01

    The objective was to assess predictors of relapse into unprotected anogenital intercourse with casual partners among homosexual men in Amsterdam, The Netherlands. In the period 1984-91 1103 predominantly white, well-educated, homosexual men participated in the study. 340 participants were HIV-antibody-positive, and 763 men were HIV-antibody-seronegative. Self-reported data on sexual behavior were obtained at 12 semi-annual intervals. Mean age of the participants at wave 12 was 41.2 years, and participants had been homosexually active for an average of 23.2 years, Participants were categorized according to sexual behavior in waves 11 and 12, the interval in which an increase in unprotected anogenital intercourse with casual partners was observed. Participants who reported unprotected anogenital intercourse with casual partners at wave 12, but not at wave 11, were considered to have relapsed into unsafe sex (n=47). Men who did not report unprotected anogenital intercourse at wave 11 or at wave 12 were considered to have maintained a behavior change (n=197). Possible predictors of relapse into unprotected anogenital intercourse with casual partners included a large number of variables assessed from wave 9 up to wave 12. Bivariate relations between outcome measure and predictors were first assessed. Significant variables were entered in a multivariate logistic regression analysis. 4 variables were multivariately reacted to maintenance of safer sex behaviors versus relapse into unprotected anogenital intercourse with casual partners. The relationships found indicated that relapse was more likely to occur among participants who had less intention to avoid unprotected anal sex with casual partners (odds ratio (OR) 3.75), were less convinced that they can use condoms with casual sex partners (OR 3.54), had a less favorable attitude towards the use of condoms (OR 3.2), and were not involved in a primary relationship PMID:8397949

  6. 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.

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

    PubMed

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

    2016-01-01

    Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values <0.05). On multivariate analysis, CEBPA (dm) (p = 0.007, OR 39.593) was an independent risk factor for achievement of complete remission (CR). With a median follow-up of 40.1 months, CEBPA (dm) showed a favorable overall survival (OS), event-free survival (EFS), and lower relapse incidence (RI) in comparison with CEBPA (wild) (all p values <0.005). Comparison of clinical outcome analyses (consolidation chemotherapy vs. allogeneic hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML. PMID:26537612

  8. 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.

  9. 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…

  10. Clinical characteristics and outcome of isolated extramedullary relapse in acute leukemia after allogeneic stem cell transplantation: a single-center analysis.

    PubMed

    Shi, Ji-Min; Meng, Xiao-Jian; Luo, Yi; Tan, Ya-Min; Zhu, Xiao-Li; Zheng, Gao-Feng; He, Jing-Song; Zheng, Wei-Yan; Xie, Wan-Zhuo; Li, Li; Ye, Xiu-Jin; Zhang, Jie; Cai, Zhen; Lin, Mao-Fang; Huang, He

    2013-04-01

    Isolated extramedullary relapse (EMR) of acute leukemia (AL) is a rare occurrence. However, it appears to be more common after allogeneic stem cell transplantation (allo-SCT). To characterize what has been observed in isolated EMR, we investigated 287 consecutive AL patients (144 acute myeloid leukemia; 138 acute lymphocytic leukemia; 5 acute mixed-lineage leukemia) who underwent allo-SCT. Twelve cases experienced relapse at extramedullary sites without concomitant involvement of the bone marrow (BM). The onset to relapse after allo-SCT was longer in extramedullary sites than in the BM (median, 10 months versus 5.5 months). EMR sites varied widely and included the central nervous system, skin, bone, pelvis and breasts. Univariate analysis demonstrated that cytogenetic abnormalities were correlated significantly with the onset of isolated EMR (P=0.001). The prognosis for patients who develop EMR remained poor but was relatively better than that after BM relapse (overall survival, 10 versus 18 months). Compared with local or single therapy, patients treated with systemic treatment in combination with local treatment could yield a favorable prognosis. In conclusion, we observed a significant number of isolated cases of EMR in AL patients after allo-SCT, cytogenetic abnormalities were correlated significantly with the onset of isolated EMR. We found that intensive approaches combining local and systemic therapy could produce favorable responses which may cure a proportion of these patients. PMID:23347901

  11. [A case of relapsing polychondritis with oculobulbar symptoms and successful treatment of respiratory failure with BiPAP].

    PubMed

    Ishikawa, S; Yamazaki, M; Takei, Y; Miyazaki, A; Hanyu, N

    1999-10-01

    A 66-year-old man developed diplopia, ptosis, dysphagia, and acute respiratory failure. The initial diagnosis was myasthenia gravis and prednisolone had been administrated for three years. Because of recurrent upper respiratory infections, prednisolone was tapered off. Two months later, auricular chondritis, arthritis, and conjunctivitis appeared. He was diagnosed as having relapsing polychondritis on the basis of histological findings of the ear lobe biopsy. Reinstituted prednisolone had the effect on the auricular chondritis, arthritis, and conjunctivitis, but no effect on dysphagia, hoarseness, and respiratory failure caused by the deformity of the pharynx and airway. Tracheal collapse usually causes rapid death, so early tracheostomy and the use of endotracheal prostheses have been recommended in patients with airway obstruction from relapsing polychondritis, but such surgical management can only partially open up the large airways and has no effect on smaller airways. In this case tracheostomy and endoluminal stent placement have helped improve the patient's respiratory failure, but have had little effect on its aggravation at night in the supine position. The use of BiPAP after surgical management can be an effective treatment for airway involvement in relapsing polychondritis probably because it keeps the narrowed airways from collapsing, especially at night. PMID:10655766

  12. CEBPA single mutation can be a possible favorable prognostic indicator in NPM1 and FLT3-ITD wild-type acute myeloid leukemia patients with intermediate cytogenetic risk.

    PubMed

    Park, Sang Hyuk; Chi, Hyun-Sook; Cho, Young-Uk; Jang, Seongsoo; Park, Chan-Jeoung

    2013-11-01

    The aim of this study was to evaluate the prognostic impact of CEBPA single mutation in acute myeloid leukemia (AML) patients with intermediate cytogenetic risk. CEBPA single and double mutations were detected in 11 (9.7%) and 17 (15.1%) of 113 NPM1 wild-type patients, but no CEBPA mutations were detected in a group of 44 NPM1 mutated patients. Among patients with NPM1/FLT3-ITD wild-type, those with CEBPA double mutations (P=0.013 and 0.007 for overall survival and relapse-free survival, respectively) or a single mutation (P=0.039 and 0.020 for overall survival and relapse-free survival, respectively) demonstrated a favorable prognosis compared with CEBPA wild-type patients. Subsequent multivariate analysis confirmed the favorable prognostic impact of CEBPA single and double mutations. Despite the low statistical power of this study due to the small number of patients, our preliminary data suggest that CEBPA single mutation may be associated with favorable clinical outcomes in NPM1/FLT3-ITD wild-type AML patients with intermediate cytogenetic risk. PMID:24054719

  13. Conservatism in least favorable response analysis and testing

    SciTech Connect

    Paez, T L

    1980-01-01

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

  14. 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

  15. Tyrosinemia type 1: metastatic hepatoblastoma with a favorable outcome.

    PubMed

    Nobili, Valerio; Jenkner, Alessandro; Francalanci, Paola; Castellano, Aurora; Holme, Elisabeth; Callea, Francesco; Dionisi-Vici, Carlo

    2010-07-01

    The clinical course of tyrosinemia type 1 is characterized by acute liver failure in infancy or chronic liver dysfunction and renal Fanconi syndrome in late-presenting cases. Dietary treatment may improve liver function but does not prevent the development of hepatocellular carcinoma (HCC) in late childhood. A new treatment strategy that uses 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which prevents the production of toxic/carcinogenic metabolites, has dramatically changed the outcome of the disease by reducing the occurrence of liver cancer, especially in patients who start this treatment before the age of 2 years. We report here the case of a patient with a diagnosis of tyrosinemia type 1 at 5 months of age who was treated with NTBC and dietary restriction and in whom a liver neoplasm with lung metastases, histologically determined to be HCC, was found at the age of 15 months. A conservative approach that consisted of chemotherapy and partial hepatectomy resulted in a 12-year disease-free period. The excellent postchemotherapy course, in sharp contrast to the expected course of HCC, led to histologic reevaluation with reclassification of the neoplasm as hepatoblastoma. A diagnosis of hepatoblastoma would no longer be a mandate for a liver transplant for patients with tyrosinemia type 1 undergoing NTBC treatment. We encourage clinicians to perform more accurate evaluation of liver histology, because a neoplastic mass in a child with tyrosinemia type 1 is not the same as HCC. PMID:20547648

  16. Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

    Cancer.gov

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

  17. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

    PubMed Central

    Jona, Adam; Younes, Anas

    2011-01-01

    The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival is less than 3 years. With no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patients population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL. PMID:20828898

  18. Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma).

    PubMed

    Mantovani, Lucia; Zauli, Stefania; Sarno, Oriele; Querzoli, Patrizia; Corazza, Monica; Virgili, Annarosa

    2013-06-01

    A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed. As retreatment with oral methylprednisolone induced glucose intolerance and high arterial pressure, sulfa drugs were initially employed with a transitory recovery of the skin lesion. A successive prolonged course with minocycline induced a new complete resolution. To date, at six months' follow-up, the patient is relapse-free. This case confirms that sulfa drugs and minocycline may also be considered alternative therapies in PM. PM is a variety of PG characterized by specific morphological features, a higher tendency to relapse, and poor responsiveness to treatment. PMID:23330662

  19. 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.

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

    PubMed

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

    2015-06-01

    Glatiramer acetate (GA) is approved for relapsing-remitting multiple sclerosis in 57 countries worldwide, with more than 2 million patient-years of exposure and over 20 years of continuous clinical use without new safety concerns. GA has an overall favorable risk-benefit profile: 30% reduced annual relapse rate and decreased brain lesion activity. In clinically definite MS or clinically isolated syndrome, GA slows brain atrophy, which may be related to its unique anti-inflammatory and neuroprotective mechanisms of action. Early treatment with GA delays the onset of clinically definite MS more effectively than late treatment in clinically isolated syndrome. GA is not associated with immunosuppression, autoimmune disease, infections or development of neutralizing antibodies. A new three-times-weekly formulation of GA is available to potentially reduce the incidence of injection-related side effects. Other safety advantages of GA include its pregnancy rating (Category B) and limited uncontrolled data suggesting that tolerability is similar in children with MS. PMID:25924547

  1. A controlled field trial of group versus individual cognitive-behavioural training for relapse prevention.

    PubMed

    Graham, K; Annis, H M; Brett, P J; Venesoen, P

    1996-08-01

    Results are presented of a randomized field trial comparing two aftercare regimes, namely individual versus group delivery of a structured relapse prevention approach. Two addictions treatment programs (one a 12-Step 26-day residential program, the other an evening group counselling program) implemented structured relapse prevention in either group or individual format as part of the first three months of aftercare. Process measures (e.g. attendance, client satisfaction) indicated that both group and individual formats were delivered very successfully at both sites. Follow-up rate at 12 months across both programs was 74%, and drinking and drug use at the 12-month follow-up was substantially less than use at entry into treatment. However, there were no significant differences in outcomes between individual and group delivery on any of the alcohol or drug use measures. Only one psychosocial outcome measure (social support from friends at 12-month follow-up) showed a significant difference for format and it favored the group format. These findings suggest some important directions for future research. PMID:8828241

  2. Tick-borne relapsing fever in a premature infant.

    PubMed

    Brasseur, D

    1985-09-01

    Relapsing fever is caused by the Borrelia species of spirochetes. Louse-born epidemics of the disease may occur but the endemic disease is usually transmitted to humans by the bite of an infected tick (Ornithodorus). Transplacental infection was suggested more than 75 years ago (1) but has been rarely documented (2). We describe a case of neonatal relapsing fever where maternal infection was the probable cause of the premature delivery and infection in the infant. PMID:2415056

  3. Recrudescence and relapse of meningococcal meningitis and septicaemia.

    PubMed

    Nielsen, P E; Thelle, T; Tvede, M

    1995-03-01

    Three cases of recrudescence and relapse of Neisseria meningitidis group B meningitis and septicaemia are reported. The recrudescence and relapses could not be explained by infectious foci, increased bacterial penicillin resistance or immunological defects. As a supplement to antibiotic treatment, all three patients received corticosteroids for the initial 2 days of treatment, and this may have contributed to the unusual course of the disease in our patient. PMID:7780262

  4. Histological types of polypoid cutaneous melanoma II.

    PubMed

    Knezević, Fabijan; Duancić, Vjekoslav; Sitić, Sanda; Horvat-Knezević, Anica; Benković, Vesna; Ramić, Snjezana; Kostović, Kresimir; Ramljak, Vesna; Vrdoljak, Danko Velemir; Stanec, Mladen; Bozović, Angelina

    2007-12-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type. PMID:18217457

  5. [Gastritis from a histological point of view].

    PubMed

    Vieth, M; Stolte, M

    2006-06-01

    Since the rediscovery of spiral-shaped gastric bacteria in 1983 by Warren and Marshal numerous detailed facts have enlarged our knowledge base for a better understanding of gastritis. The WHO classified Helicobacter as a class 1 carcinogen. Helicobacter plays a role in many diseases of the upper GI tract (gastric and duodenal ulcer, MALT lymphoma, and gastric cancer). Knowledge of the interaction between bacterium and host led to an improvement of the diagnosis of gastritis. Unfortunately endoscopy, histology, and patient's symptoms do not correlate with each other. Therefore, gastritis is a purely histological diagnosis. A histological diagnosis always needs to be accompanied by an etiological cause of the inflammation. Only when this information is given a clinical consequence can be drawn from a histological diagnosis. In Germany the so-called ABCD scheme of gastritis is widely used (A: autoimmune gastritis, B: bacterial gastritis, C: chemical reactive gastritis, D: other forms of gastritis). At least two antrum and two corpus biopsies (matrix diagnostics) are necessary to reach representative tissue with an acceptable probability. If less than these four (minimal standard) biopsies are taken, the histological diagnosis will remain uncertain. PMID:16612608

  6. Comprehensive histological evaluation of bone implants.

    PubMed

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

    2014-01-01

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

  7. Comprehensive histological evaluation of bone implants

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Banks, Michael A.

    1998-01-01

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

  9. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Gifts, entertainment, and favors. 706.303 Section 706.303 Conservation of Power and Water Resources WATER RESOURCES COUNCIL EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Special Government Employees §...

  10. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Gifts, entertainment, and favors. 706.303 Section 706.303 Conservation of Power and Water Resources WATER RESOURCES COUNCIL EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Special Government Employees §...

  11. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Gifts, entertainment, and favors. 706.303 Section 706.303 Conservation of Power and Water Resources WATER RESOURCES COUNCIL EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Special Government Employees §...

  12. 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...

  13. 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…

  14. 18 CFR 706.303 - Gifts, entertainment, and favors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Gifts, entertainment, and favors. 706.303 Section 706.303 Conservation of Power and Water Resources WATER RESOURCES COUNCIL EMPLOYEE RESPONSIBILITIES AND CONDUCT Conduct and Responsibilities of Special Government Employees §...

  15. Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis.

    PubMed

    Perrin, C; Lacour, J P; Castanet, J; Michiels, J F

    2001-08-01

    The interstitial granulomatous drug reaction (IGDR) is a novel drug-associated entity, characterized by violaceous plaques with a predilection for skin fold areas. Light microscopically, it resembles the incipient diffuse interstitial phase of granuloma annulare. Differentiating light microscopic features include the absence of complete collagen necrobiosis, the presence of interface dermatitis, and variable lymphoid atypia. The lack of vasculitis rules out the extravascular necrotizing granuloma (Winkelmann granuloma) associated with systemic disease. The differential diagnosis with interstitial granulomatous dermatitis with arthritis as defined by Ackerman et al. has not been studied until now. Our aim was to determine the histologic criteria allowing us to differentiate IGDR without interface dermatitis and lymphoid atypia from interstitial granulomatous dermatitis. We report three patients with IGDR triggered, in two cases by respectively angiotensin convertin enzyme (ACE) inhibitors and furosemide, and in one case by the association of an ACE inhibitor, furosemide, and fluindione. Histologic examination showed a histological pattern of interstitial granulomatous dermatitis. We found a dense, diffuse histiocytic infiltrate distributed interstitially and in palisaded array within the reticular dermis. Eosinophils and some neutrophils were scattered throughout the infiltrate. In some tiny foci, enveloped by histiocytes, thick collagen bundles associated with basophilic nuclear debris or "flame figures" were seen. Vasculitis, interface dermatitis, or lymphoid atypia were absent. Our study allowed us to expand the histological spectrum of IGDR including a histological pattern similar to interstitial granulomatous dermatitis. The lack of degenerated collagen could be a subtle clue in favor of interstitial granulomatous dermatitis triggered by a drug. PMID:11481519

  16. Relapse and rehospitalization: comparing oral and depot antipsychotics.

    PubMed

    Schooler, Nina R

    2003-01-01

    A review of studies that compared conventional oral and depot antipsychotic medications highlighted the following points. Mirror-image studies in which patients served as their own controls provided evidence of substantial benefit for depot injectable medications. The randomized clinical trials did not, in general, support the findings of significant decrease in relapse rates between these 2 routes of administration. Across the studies reviewed, the 1-year relapse rate for long-acting depot medication was 27% compared with 42% for patients who received oral medication. The 27% risk of relapse in patients who received guaranteed depot medication suggests that relapse is not always driven by noncompliance. In the only study that lasted for 2 years, the risk of relapse decreased substantially in the depot-treated patients, suggesting that risk of noncompliance may be a more important factor in relapse over extended periods of time. A recent formal meta-analytic review of depot medications concluded that this route of administration resulted in clinical advantages in terms of global outcome. PMID:14680414

  17. Modeling Relapsing Disease Dynamics in a Host-Vector Community

    PubMed Central

    Stone, Emily F.

    2016-01-01

    Vector-borne diseases represent a threat to human and wildlife populations and mathematical models provide a means to understand and control epidemics involved in complex host-vector systems. The disease model studied here is a host-vector system with a relapsing class of host individuals, used to investigate tick-borne relapsing fever (TBRF). Equilibrium analysis is performed for models with increasing numbers of relapses and multiple hosts and the disease reproduction number, R0, is generalized to establish relationships with parameters that would result in the elimination of the disease. We show that host relapses in a single competent host-vector system is needed to maintain an endemic state. We show that the addition of an incompetent second host with no relapses increases the number of relapses needed for maintaining the pathogen in the first competent host system. Further, coupling of the system with hosts of differing competencies will always reduce R0, making it more difficult for the system to reach an endemic state. PMID:26910884

  18. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations.

    PubMed

    Eleveld, Thomas F; Oldridge, Derek A; Bernard, Virginie; Koster, Jan; Daage, Leo Colmet; Diskin, Sharon J; Schild, Linda; Bentahar, Nadia Bessoltane; Bellini, Angela; Chicard, Mathieu; Lapouble, Eve; Combaret, Valérie; Legoix-Né, Patricia; Michon, Jean; Pugh, Trevor J; Hart, Lori S; Rader, JulieAnn; Attiyeh, Edward F; Wei, Jun S; Zhang, Shile; Naranjo, Arlene; Gastier-Foster, Julie M; Hogarty, Michael D; Asgharzadeh, Shahab; Smith, Malcolm A; Guidry Auvil, Jaime M; Watkins, Thomas B K; Zwijnenburg, Danny A; Ebus, Marli E; van Sluis, Peter; Hakkert, Anne; van Wezel, Esther; van der Schoot, C Ellen; Westerhout, Ellen M; Schulte, Johannes H; Tytgat, Godelieve A; Dolman, M Emmy M; Janoueix-Lerosey, Isabelle; Gerhard, Daniela S; Caron, Huib N; Delattre, Olivier; Khan, Javed; Versteeg, Rogier; Schleiermacher, Gudrun; Molenaar, Jan J; Maris, John M

    2015-08-01

    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. Seven of these events were detected only in the relapse tumor, whereas the others showed clonal enrichment. In neuroblastoma cell lines, we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18; 61%), and these lesions predicted sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastomas and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease. PMID:26121087

  19. The reinstatement model and relapse prevention: a clinical perspective

    PubMed Central

    Preston, Kenzie L

    2005-01-01

    Objectives This commentary assesses the degree to which the reinstatement model is homologous to the human experience of relapse. Results A review of the literature suggests that the relationship is less clear than is often assumed, largely due to a lack of prospective data on the precipitants and process of relapse (especially relapse to heroin or cocaine abuse). However, reinstatement does not need to resemble relapse to have immediate clinical value; predictive validity as a medication screen would be sufficient. Whether the model has predictive validity is unknown, because, to date, very few clinical trials have tested medications that are effective in the reinstatement model, and even fewer have used designs comparable to those of reinstatement experiments. A clinical trial comparable to a reinstatement experiment would enroll participants who are already abstinent, and its main outcome measure would be propensity to undergo a specific type of relapse (e.g., relapse induced by stress or cues). Conclusions Until clinical and preclinical work are more comparable, criticisms of the reinstatement model’s presumed shortcomings are premature. PMID:12721778

  20. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations

    PubMed Central

    Eleveld, Thomas F.; Oldridge, Derek A.; Bernard, Virginie; Koster, Jan; Daage, Leo Colmet; Diskin, Sharon J.; Schild, Linda; Bentahar, Nadia Bessoltane; Bellini, Angela; Chicard, Mathieu; Lapouble, Eve; Combaret, Valérie; Legoix-Né, Patricia; Michon, Jean; Pugh, Trevor J.; Hart, Lori S.; Rader, JulieAnn; Attiyeh, Edward F.; Wei, Jun S.; Zhang, Shile; Naranjo, Arlene; Gastier-Foster, Julie M.; Hogarty, Michael D.; Asgharzadeh, Shahab; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Watkins, Thomas B. K.; Zwijnenburg, Danny A.; Ebus, Marli E.; van Sluis, Peter; Hakkert, Anne; van Wezel, Esther; van der Schoot, C. Ellen; Westerhout, Ellen M.; Schulte, Johannes H.; Tytgat, Godelieve A.; Dolman, M. Emmy M.; Janoueix-Lerosey, Isabelle; Gerhard, Daniela S.; Caron, Huib N.; Delattre, Olivier; Khan, Javed; Versteeg, Rogier; Schleiermacher, Gudrun; Molenaar, Jan J.; Maris, John M.

    2016-01-01

    The majority of neuroblastoma patients have tumors that initially respond to chemotherapy, but a large proportion of patients will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole genome sequencing of 23 paired diagnostic and relapsed 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 signaling pathway. Seven events were detected only in the relapse tumor while the others showed clonal enrichment. In neuroblastoma cell lines we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18, 61%) and these lesions predicted for sensitivity to MEK inhibition in vitro and in vivo. Our findings provide the rationale for genetic characterization of relapse neuroblastoma and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease. PMID:26121087

  1. Aggressive chemotherapy for acute leukemia relapsed after transplantation.

    PubMed

    Sica, S; Salutari, P; Di Mario, A; D'Onofrio, G; Etuk, B; Leone, G

    1994-09-01

    Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36). Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival. PMID:7858490

  2. Modeling Relapsing Disease Dynamics in a Host-Vector Community.

    PubMed

    Johnson, Tammi L; Landguth, Erin L; Stone, Emily F

    2016-02-01

    Vector-borne diseases represent a threat to human and wildlife populations and mathematical models provide a means to understand and control epidemics involved in complex host-vector systems. The disease model studied here is a host-vector system with a relapsing class of host individuals, used to investigate tick-borne relapsing fever (TBRF). Equilibrium analysis is performed for models with increasing numbers of relapses and multiple hosts and the disease reproduction number, R0, is generalized to establish relationships with parameters that would result in the elimination of the disease. We show that host relapses in a single competent host-vector system is needed to maintain an endemic state. We show that the addition of an incompetent second host with no relapses increases the number of relapses needed for maintaining the pathogen in the first competent host system. Further, coupling of the system with hosts of differing competencies will always reduce R0, making it more difficult for the system to reach an endemic state. PMID:26910884

  3. Adoptive transfer of murine relapsing experimental allergic encephalomyelitis.

    PubMed

    Lublin, F D

    1985-02-01

    Relapsing experimental allergic encephalomyelitis (EAE), an autoimmune disorder resembling multiple sclerosis, has been produced by inoculating SJL/J mice with spinal cord or myelin basic protein in appropriate adjuvants. To determine whether initially sensitized lymphocytes or the persistence of antigen depots in the animal were responsible for the relapsing episodes of inflammatory demyelination, adoptive transfer studies were undertaken utilizing lymphocytes from relapsing EAE-immunized donors transferred directly or after in vitro culture. In direct-transfer studies donor lymphocytes produced clinical and pathological signs of relapsing EAE in 3 of 7 recipients of lymph node lymphocytes and 1 of 5 recipients of splenic lymphocytes. In vitro culture of lymphocytes in myelin basic protein or T cell growth factor prior to transfer increased both the incidence of disease and the number of animals having relapses, and allowed transfer with fewer lymphocytes. Because all animals had delayed onset of disease, this study demonstrates that the ability to develop relapsing inflammatory demyelination is transferable with lymphocytes and does not require the presence of antigen. PMID:3977301

  4. The International Histological Classification of Tumours*

    PubMed Central

    Sobin, L. H.

    1981-01-01

    This article reviews the development of the WHO project on the histological classification of tumours, which has included the establishment of several collaborating centres and has involved more than 300 pathologists in over 50 countries. The project has resulted in the publication, over the last 14 years, of 25 volumes in the first series of the International Histological Classification of Tumours (IHCT), each giving a classification of tumours specific to a certain site. The classifications are based primarily on the microscopic characteristics of the tumours and are concerned with morphologically identifiable cell types and histological patterns as seen by means of light microscopy and conventional staining techniques. The article also describes the relationship between IHCT and other classification and coding systems and assesses possible future developments that may result from new approaches to diagnosis. PMID:6978190

  5. Appendicitis in Dar es Salaam, histological pattern.

    PubMed

    Mbembati, N A; Lema, L E; Mwakyoma, H A; Ussiri, E V

    1996-03-01

    Histology of 378 appendicectomy specimens submitted to the Histopathology Department of Muhimbili Medical Centre from its surgical wards over a 10 year period (1985 to 1994) were reviewed. There were 185 cases (48.9 pc) of acute appendicitis, 101 cases (26.7 pc) of chronic appendicitis, 74 (19.6 pc) normal appendices and 13 cases (3.5 pc) schistosomal appendicitis. There were two cases of tuberculous appendicitis and two cases of mucocele of the appendix. Apart from the high frequency of chronic appendicitis the histological findings in this study compare well with findings reported from other studies. PMID:8653771

  6. 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. PMID:25559290

  7. A long survivor with local relapse of hilar cholangiocarcinoma after R1 surgery treated with chemoradiotherapy: a case report and literature review.

    PubMed

    Okabe, Hirohisa; Chikamoto, Akira; Maruno, Masataka; Hashimoto, Daisuke; Imai, Katsunori; Taki, Katsunobu; Arima, Kota; Ishiko, Takatoshi; Uchiyama, Hideaki; Ikegami, Toru; Harimoto, Norifumi; Itoh, Shinji; Yoshizumi, Tomoharu; Beppu, Toru; Baba, Hideo; Maehara, Yoshihiko

    2016-12-01

    The treatment outcome of extrahepatic cholangiocarcinoma remains insufficient because it is difficult to obtain accurate diagnosis of tumor spreading and effective treatment agent is quite limited in spite of substantial current efforts, all of which have been unsuccessful except for gemcitabine plus cisplatin. The patient was a 60-year-old female who had developed hilar cholangiocarcinoma and underwent extrahepatic bile duct resection. Although it was conceivable that it would be the R1 resection, the patient wanted to receive limited resection to avoid postoperative complication mainly because she was depressed. In histology, interstitial spreading of tumor was appreciated at the surgical margin of bile duct. The patient did not accept to receive the additional treatment after the surgery and hardly visited the hospital to take the periodical test for monitoring the residual cancer cells. As expected, the local relapse of tumor was appreciated 1 year after the R1 surgery. She chose radiotherapy and agreed with subsequent S-1 treatment for 26 months. Consequently, elevated CA19-9 was decreased, and local relapse has been successfully controlled for more than 7 years after the relapse of tumor. Here, we report quite a rare case in terms of long survivor after chemoradiotherapy on locally relapsed unresectable hilar cholangiocarcinoma. PMID:27376654

  8. 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.

  9. Factorization Tests with Cabibbo-Favored Hadronic B Decays

    NASA Astrophysics Data System (ADS)

    Kass, Richard; Honscheid, K.; Pedlar, T.; von Toerne, E.; Wilksen, T.

    2002-04-01

    Based on a data sample of 9.7 million Υ(4s)arrow B barB decays recorded with CLEO II and II.V we present new measurements of cabibbo-favored, hadronic B meson decays. Precise measurements of these decays provide tests of the factorization hypothesis and allow us to examine the theoretical models which are used to constrain the unitarity triangle. Isospin relations in B arrow D(*) π decays permit the investigation of final state interactions.

  10. Psammomatous Melanotic Schwannoma: A Challenging Histological Diagnosis

    PubMed Central

    Merat, Rastine; Szalay-Quinodoz, Ildiko; Laffitte, Emmanuel; Kaya, Gürkan

    2015-01-01

    Psammomatous melanotic schwannoma (PMS) is a rare pigmented tumor that can be part of the Carney complex. Here, we describe the case of a 35-year-old female patient presenting an isolated subcutaneous PMS. Histopathological analysis could not formally exclude the malignant nature of the tumor. The challenging histological diagnosis and consequently the management of the patient are described. PMID:27047937

  11. 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…

  12. Wilms Tumor 1 rs16754 predicts favorable clinical outcomes for acute myeloid leukemia patients in South Chinese population.

    PubMed

    Zhang, Dao-Yu; Yan, Han; Cao, Shan; Zhang, Wei; Li, Xiao-Lin; Zeng, Hui; Chen, Xiao-Ping

    2015-06-01

    The single nucleotide polymorphism (SNP) rs16754 in WT1 shows a clinical implication in Caucasus population. However, the results were not reproducible in different population cohorts. We evaluated the clinical significance of rs16754 for 205 de novo acute myeloid leukemia (AML) patients in South Chinese population, 188 healthy volunteers were recruited as healthy controls. WT1 mRNA expression was investigated in 81 pretreatment bone marrow specimens. WT1(GA/AA) patients showed better overall survival (OS, P=0.006) and relapse-free survival (RFS, P=0.025) as compared with WT1(GG) patients, and the favorable clinical outcomes were most prominent in older patients with superior OS (P=0.001) and RFS (P=0.003). In multivariable analysis, rs16754 was still associated with favorable OS (HR=1.533, P=0.042). The WT1(GG) patients showed significantly higher WT1 mRNA expression than the WT1(GA/AA) patients (P=0.01). In summary, WT1 rs16754 may serve as an independent biomarker in AML patients from South Chinese. PMID:25841655

  13. 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

  14. 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

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

    PubMed

    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

    2016-08-01

    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

  16. Relapse prevention. An overview of Marlatt's cognitive-behavioral model.

    PubMed

    Larimer, M E; Palmer, R S; Marlatt, G A

    1999-01-01

    Relapse prevention (RP) is an important component of alcoholism treatment. The RP model proposed by Marlatt and Gordon suggests that both immediate determinants (e.g., high-risk situations, coping skills, outcome expectancies, and the abstinence violation effect) and covert antecedents (e.g., lifestyle factors and urges and cravings) can contribute to relapse. The RP model also incorporates numerous specific and global intervention strategies that allow therapist and client to address each step of the relapse process. Specific interventions include identifying specific high-risk situations for each client and enhancing the client's skills for coping with those situations, increasing the client's self-efficacy, eliminating myths regarding alcohol's effects, managing lapses, and restructuring the client's perceptions of the relapse process. Global strategies comprise balancing the client's lifestyle and helping him or her develop positive addictions, employing stimulus control techniques and urge-management techniques, and developing relapse road maps. Several studies have provided theoretical and practical support for the RP model. PMID:10890810

  17. Dimethyl Fumarate: A Review in Relapsing-Remitting MS.

    PubMed

    Deeks, Emma D

    2016-02-01

    Dimethyl fumarate (Tecfidera(®)) is an oral disease-modifying agent indicated for the twice-daily treatment of relapsing forms of multiple sclerosis (MS) and relapsing-remitting MS (RRMS). It displays immunomodulating and neuroprotective properties, both of which may contribute to its efficacy in these settings. In two phase III trials of 2 years' duration (DEFINE and CONFIRM), twice-daily dimethyl fumarate reduced clinical relapse (both the proportion of patients with MS relapse and the annualized relapse rate), as well as MRI measures of disease activity, versus placebo in adults with RRMS; the drug also reduced disability progression relative to placebo in one of the two studies (DEFINE). Dimethyl fumarate had an acceptable tolerability profile in these trials, with the most common tolerability issues being flushing and gastrointestinal events, which appear to be largely manageable. In the DEFINE and CONFIRM extension (ENDORSE), a minimum of 5 years of treatment with the drug was associated with continued benefit and no new/worsening tolerability signals. Although additional active comparator data are needed, dimethyl fumarate is an effective twice-daily treatment option for use in adults with RRMS, with the convenience of oral administration and an acceptable long-term tolerability profile. PMID:26689201

  18. Multiple myeloma: from front-line to relapsed therapies.

    PubMed

    Moreau, Philippe; Touzeau, Cyrille

    2015-01-01

    Recent developments in the treatment of multiple myeloma (MM) have led to improvements in response rates and to increased survival. A major advance in the last decade has been the introduction of the novel agents thalidomide, bortezomib, and lenalidomide as part of front-line treatment in both the transplant and nontransplant settings. However, disease relapse is inevitable for the majority of patients and myeloma typically recurs more aggressively with each relapse, eventually leading to the development of treatment-refractory disease. Several phase II and III trials have demonstrated the efficacy of recently approved agents in the setting of relapsed and relapsed and refractory MM, including pomalidomide and carfilzomib. Ixazomib, an oral proteasome inhibitor, and multiple other novel classes of agents are being investigated. These include monoclonal antibodies and histone deacetylase inhibitors, which may further add to the therapeutic armamentarium for this malignancy. Therefore, in a disease characterized by multiple relapses, the optimal sequencing of the different effective options is an important consideration in attempting to prolong survival. PMID:25993216

  19. Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment

    PubMed Central

    Cliff, Jacqueline M.; Cho, Jang-Eun; Lee, Ji-Sook; Ronacher, Katharina; King, Elizabeth C.; van Helden, Paul; Walzl, Gerhard; Dockrell, Hazel M.

    2016-01-01

    Background. Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years. Methods. Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays. Results. At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell-mediated killing. Results were confirmed by real-time quantitative reverse-transcription polymerase chain reaction analysis in a wider patient cohort. Conclusions. These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development. PMID:26351358

  20. Tubular Carcinoma of the Breast: A Single Institution's Experience of a Favorable Prognosis.

    PubMed

    Boyan, William; Shea, Brian; Farr, Michael; Kohli, Manpreet; Ginalis, Ernest

    2016-06-01

    Tubular carcinoma is a subtype of invasive breast cancer that comprises 1 to 4 per cent of invasive breast cancers. Prior studies show nearly 100 per cent 15 year survival rate for tubular carcinoma compared to the 89.2 per cent five year survival of all breast cancers. These encouraging statistics beg the question should tubular cancers be treated as other invasive cancers, or can some patients be spared an invasive procedure or the side effects of adjuvant therapy? Fifty-seven cases of tubular carcinoma over 16 years were analyzed. All relevant aspects of the patient's history, treatment, and outcomes were documented. The aim was compare treatment outcomes of tubular breast cancer outcomes to that of all invasive breast cancers. Of the 57 patients, local recurrence was seen in two patients (3.5%) only one of which recurred as a tubular carcinoma (1.75%). There were no cancer-related mortalities. A look into our institution's data supported the notion that tubular carcinoma of the breast is a less aggressive histological type. Of our 57 cases, only two recurrences (3.5%) were noted and there were no cancer-related mortalities. Interestingly only one patient (1.75%) recurred as tubular carcinoma. Without controlling for adjuvant therapy, recommendations cannot be made for a less aggressive treatment plan at this point. Future randomized controlled trials may lead to a less aggressive treatment plan for this favorable subtype. On the basis of this study and others like it, physicians can give evidenced-based favorable prognosis with a diagnosis of tubular carcinoma of the breast. PMID:27305881

  1. Drugs in development for relapsing multiple sclerosis.

    PubMed

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

    2013-05-01

    drugs in development, and it is likely that BG-12 will be licensed this year. This has been licensed for psoriasis so there are good safety data in humans that may also hold true in MS; however, its three times daily dosage will probably impact on patient compliance. Laquinimod has lower efficacy than BG-12 but appears safe and could find a place as a first-line agent. Teriflunomide has just been licensed by the US FDA and may challenge the current injectable first-line therapies as it has a similar efficacy but the advantage of being taken orally. However, risk of teratogenicity may caution against its use in some women of child-bearing potential. This review will examine drugs that have been recently approved as well as those that are in late phase 2 or 3 development as treatment for relapsing MS, highlighting their mechanism of action as well as the clinical trial and safety data before discussing their potential for success in an increasingly florid and complex DMT armamentarium. PMID:23609782

  2. 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

  3. Orbital Relapsing Polychondritis: A Unique Presentation, Complication, and Treatment.

    PubMed

    Moore, Grant H; Rootman, Daniel B; Roybal, C Nathaniel; Goldberg, Robert A

    2016-01-01

    An 87-year-old man with a history of relapsing polychondritis presented to the emergency department after 4 days of worsening left periorbital swelling and erythema. On examination, he demonstrated clinical features consistent with orbital cellulitis and was treated with a trial of intravenous antibiotics. His condition did not improve over the next 36 hours and intravenous methylprednisolone was initiated. This led to rapid improvement in orbital symptoms and signs, and a diagnosis of specific orbital inflammation secondary to relapsing polychondritis was made. The patient was discharged on a tapering dose of prednisone. As a steroid-sparing measure, adalimumab was initiated; however, the patient developed Sweet Syndrome. Adalimumab was subsequently discontinued, steroid dose was increased, and anakinra treatment was initiated. This therapeutic course led to significant clinical improvement. Since initiating anakinra, the patient has had no recurrences of Sweet Syndrome. Anakinra may be a useful adjunct therapy for ophthalmic manifestations of relapsing polychondritis. PMID:25072220

  4. Neuropsychological and neurological outcome after relapse of lymphoblastic leukaemia.

    PubMed

    Christie, D; Battin, M; Leiper, A D; Chessells, J; Vargha-Khadem, F; Neville, B G

    1994-04-01

    Fourteen children who relapsed after initial remission of leukaemia were studied. Six received a second course of cranial radiotherapy, while the remaining eight children were given total body irradiation before bone marrow transplantation. The postirradiation somnolence syndrome was common after cranial radiotherapy. All children had mild/soft neurological signs, mostly of coordination. None had a major motor disability. All but the youngest child had cataracts; two children required an operation for these. All children were growth hormone deficient. Verbal IQ, attention, and concentration were selectively reduced (with respect to normative levels). The time between the two treatments, age at relapse, and higher doses of radiotherapy all correlated with cognitive outcome, with girls showing greater impairments than boys. Only two children were performing at age appropriate levels on measures of academic achievement. It is concluded that neurological and neuropsychological morbidity is significantly increased by the current treatments prescribed after the relapse of leukaemia. PMID:7514391

  5. Current strategies for treatment of relapsed/refractory multiple myeloma.

    PubMed

    Laubach, Jacob P; Voorhees, Peter M; Hassoun, Hani; Jakubowiak, Andrzej; Lonial, Sagar; Richardson, Paul G

    2014-02-01

    In spite of significant advances in the management of multiple myeloma (MM), the disease remains incurable and nearly all patients ultimately relapse and require salvage chemotherapy. As such, relapsed and relapsed-refractory MM remains a critical area of research pertaining to biological mechanisms of progression and chemotherapy resistance, as well as to the development of new pharmacologic agents and immunologic approaches for the disease. The immunomodulatory agents and proteasome inhibitors represent the cornerstone of treatment in this setting, with combination regimens incorporating these drugs demonstrating encouraging rates and duration of response, including the newer agents, pomalidomide and carfilzomib. In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat. PMID:24471924

  6. Counseling Women on Smoking Relapse Prevention During Postpartum.

    PubMed

    Feeney, Ann; Britton, Geraldine

    2016-01-01

    Many women who quit smoking after learning they are pregnant revert back to smoking after birth of their baby. The high rate of recidivism suggests that women need education about risk of relapse and effective strategies to remain smoke free even before they are discharged from the hospital. Despite evidence that smoking cessation and relapse prevention counseling is effective during early postpartum, many nurses do not provide their patients with this important information, perhaps because they feel inadequately prepared to do so. Helping Women Stop Smoking in Pregnancy and Beyond is an education program designed to help perinatal nurses inform women of negative risks of smoking and offer women strategies to avoid the high probability of resuming smoking after birth. It includes evidence-based interventions that can be used by nurses to provide effective smoking relapse prevention counseling to women during postpartum. PMID:27537087

  7. [Rapidly evolving diabetic mononeuritis multiplex. Favorable outcome after immunosuppressive treatment].

    PubMed

    Awada, A; Dehoux, E; al Jumah, M; al Ayafi, H

    2001-11-01

    A 61 year-old man with type 2 diabetes mellitus presented with an extremely rapid and aggressive mononeuritis multiplex. Four months after onset, he had severe postural hypotension and at least 6 cranial nerves and 4 somatic nerves were involved. Extensive work-up failed to discover any etiology for the neuropathy apart from diabetes. Treatment with corticosteroids, i.v. immunoglobulins and cyclosporin was followed by progressive but sustained improvement. This case and few other published ones suggest that some particularly aggressive forms of diabetic neuropathy have an immune mechanism and may be treated favorably with immunosuppressor drugs. PMID:11924012

  8. Hodgkin's lymphoma: biology and treatment strategies for primary, refractory, and relapsed disease.

    PubMed

    Diehl, Volker; Stein, Harald; Hummel, Michael; Zollinger, Raphael; Connors, Joseph M

    2003-01-01

    Hodgkin's lymphomas belong to the most curable tumor diseases in adults. About 80% of patients in all anatomical stages and of all histological subtypes can be cured with modern treatment strategies. In spite of the great clinical progress, the pathogenesis of this peculiar lymphoproliferative entity has not been elucidated completely up until now. In Section I Drs. Stein, Hummel, and Zollinger describe the different pro-proliferative and antiapoptotic pathways and molecules involved in the transformation of the germinal center B-lymphocyte to the malignant Hodgkin-Reed-Sternberg cell. They use a comprehensive gene expression profiling (Affymetrix gene chip U133A) on B- and T-Hodgkin cell lines and state that the cell of origin is not the dominant determinant of the Hodgkin cell phenotype, but the transforming event. H-RS cells lack specific functional markers (B-T-cell receptors) and physiologically should undergo apoptosis. Why they do not is unclear and a matter of intensive ongoing research. In Section II Dr. Diehl summarizes the commonly used primary treatment strategies adapted to prognostic strata in early, intermediate and advanced anatomical stages using increasing intensities of chemotherapy (two, four, eight courses of chemotherapy such as ABVD) and additive radiation with decreased doses and field size. ABVD is without doubt the gold standard for early and intermediate stages, but its role as the standard regimen for advanced stages is challenged by recent data with time- and dose-intensified regimens such as the escalated BEACOPP, demonstrating superiority over COPP/ABVD (equivalent to ABVD) for FFTF and OS in all risk strata according to the International Prognostic Score. In Section III, Dr. Connors states that fortunately there is a considerably decreased need for salvage strategies in Hodgkin's lymphomas since primary treatment results in a more than 80% tumor control. Nevertheless, a significant number of patients experience either a tumor

  9. A focus group study of predictors of relapse in electronic gaming machine problem gambling, part 1: factors that 'push' towards 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 problem gambling. In this paper the authors describe part one of a two part, linked relapse process: the 'push' towards relapse. In this two-part process, factors interact sequentially and simultaneously within the problem gambler to produce a series of mental and behavioural events that ends with relapse when the 'push' overcomes 'pull' (part one); or as described in part two, continued abstinence when 'pull' overcomes 'push'. In the second paper, the authors describe how interacting factors 'pull' the problem gambler away from relapse. This study used four focus groups comprising thirty participants who were gamblers, gamblers' significant others, therapists and counsellors. The groups were recorded, recordings were then transcribed and analysed using thematic, textual analysis. With the large number of variables considered to be related to relapse in problem gamblers, five key factors emerged that 'push' the gambler towards relapse. These were urge, erroneous cognitions about the outcomes of gambling, negative affect, dysfunctional relationships and environmental gambling triggers. Two theories emerged: (1) each relapse episode comprised a sequence of mental and behavioural events, which evolves over time and was modified by factors that 'push' this sequence towards relapse and (2) a number of gamblers develop an altered state of consciousness during relapse described as the 'zone' which prolongs the relapse. PMID:21901457

  10. Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors.

    PubMed

    Rössle, Matthias; Cathomas, Gieri; Bonapace, Laura; Sachs, Melanie; Dehler, Silvia; Storz, Martina; Huber, Gerhard; Moch, Holger; Junt, Tobias; Mertz, Kirsten D

    2016-08-01

    The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities-for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33-negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics. PMID:26912475

  11. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

    PubMed Central

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-01

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

  12. Impact of hiatal hernia on histological pattern of non-erosive reflux disease

    PubMed Central

    2005-01-01

    Background Hiatus hernia (HH) has major pathophysiological effects favoring gastroesophageal reflux and hence contributing to esophageal mucosa injury, especially in patients with severe gastroesophageal disease. However, prospective studies investigating the impact of HH on the esophageal mucosa in non-erosive reflux disease (NERD) are lacking. This study evaluated the association between the presence of (HH) and the histological findings in symptomatic patients with NERD. Methods Fifty consecutive patients with gastroesophageal reflux disease (GERD) were enrolled. After conventional endoscopy, Lugol solution was applied and biopsy specimens were obtained. Histological parameters including basal zone hyperplasia, papillary length and cellular infiltration were evaluated. The chi-square test with Yates' correlation was used for comparing discrete parameters between groups. However, Fisher's exact probability test was used where the expected frequencies were lower than 5. Wilcoxon's test for unpaired samples was preferred in cases of semi-quantitative parameters. Results The presence of HH along with more severe findings (0.01

    histological patterns were similar between erosive reflux disease and NERD in the presence of HH. Conclusion The presence of HH is correlated with more severe endoscopy findings, and predisposes for severe histological abnormality in cases of NERD. PMID:15638947

  13. 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.

  14. 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

  15. Porcine deltacoronavirus: histological lesions and genetic characterization.

    PubMed

    Wang, Leyi; Hayes, Jeff; Sarver, Craig; Byrum, Beverly; Zhang, Yan

    2016-01-01

    First identified in 2012 in a surveillance study in Hong Kong, porcine deltacoronavirus (PDCoV) is a proposed member of the genus Deltacoronavirus of the family Coronaviridae. In February of 2014, PDCoV was detected in pigs with clinical diarrheal symptoms for the first time in the USA. Since then, it has been detected in more than 20 states in the USA and in other countries, including Canada, South Korea, and mainland China. So far, histological lesions in the intestines of pigs naturally infected with PDCoV under field conditions have not been reported. In this report, we describe the characteristic histological lesions in the small intestine that were associated with PDCoV infection, as evidenced by detection of viral nucleic acid by RT-PCR. In addition, we performed genomic analysis to determine the genetic relationship of all PDCoV strains from the four countries. We found that PDCoV mainly caused histological lesions in the small intestines of naturally infected piglets. Sequence analysis demonstrated that the PDCoV strains of different countries are closely related and shared high nucleotide sequence similarity; however, deletion patterns in the spike and 3' untranslated regions are different among the strains from mainland China, Hong Kong, the USA, and South Korea. Our study highlights the fact that continual surveillance is needed to trace the evolution of this virus. PMID:26475155

  16. The histological nature of epulides in dogs.

    PubMed

    Verstraete, F J; Ligthelm, A J; Weber, A

    1992-02-01

    The histological characteristics of a series of 154 oral tumours with the clinical appearance of epulides in 129 dogs were reviewed. Diagnoses were based on current criteria in human oral pathology and compared with the original diagnoses. The histological findings suggested that the majority of epulides in the dog can be classified as focal fibrous hyperplasia (43.5 per cent), peripheral ameloblastoma (17.5 per cent), peripheral odontogenic fibroma (WHO type) (16.9 per cent) and pyogenic granuloma (1.95 per cent). In addition, a number of other odontogenic tumours (1.95 per cent) and non-odontogenic tumours (18.2 per cent) such as fibrosarcoma and squamous cell carcinoma, which are not traditionally associated with the clinical appearance of an epulis, were diagnosed. Of 74 lesions that were previously diagnosed as fibromatous and ossifying epulides, 50 (68 per cent) were reclassified as focal fibrous hyperplasia and 21 (28 per cent) as peripheral odontogenic fibroma (WHO type). The majority of lesions (76 per cent), which were originally classified as acanthomatous epulis, were found to be peripheral ameloblastoma. In addition, three squamous cell carcinomas, two rare odontogenic tumours and two cases of focal fibrous hyperplasia were diagnosed in this classification. It was concluded that, as in man, the term epulis is a clinically descriptive term and that the renal nature of these lesions should be determined histologically. PMID:1597534

  17. 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

  18. Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis

    PubMed Central

    O’Connor, Paul; Wolinsky, Jerry S; Confavreux, Christian; Kappos, Ludwig; Olsson, Tomas P; Truffinet, Philippe; Wang, Lin; D’Castro, Laura; Comi, Giancarlo; Freedman, Mark S

    2012-01-01

    Background: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups. Methods: RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. Subgroup analyses were performed for ARR and disability progression by baseline demographics (gender, race, age), disease characteristics (Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis (MS) subtype), MRI parameters (gadolinium-enhancing lesions, total lesion volume) and prior use of MS drugs. A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups, utilizing a treatment-by-subgroup interaction test for each factor separately. Results: Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance. Conclusion: The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO. PMID:22723573

  19. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma

    PubMed Central

    Xie, Wanling; Jagannath, Sundar; Jakubowiak, Andrzej; Lonial, Sagar; Raje, Noopur S.; Alsina, Melissa; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Mazumder, Amitabha; Vesole, David H.; Kaufman, Jonathan L.; Colson, Kathleen; McKenney, Mary; Lunde, Laura E.; Feather, John; Maglio, Michelle E.; Warren, Diane; Francis, Dixil; Hideshima, Teru; Knight, Robert; Esseltine, Dixie-Lee; Mitsiades, Constantine S.; Weller, Edie; Anderson, Kenneth C.

    2014-01-01

    In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m2 (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomide-bortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with www.clinicaltrials.gov as #NCT00378209. PMID:24429336

  20. Relapse frequency in transitioning from natalizumab to dimethyl fumarate: assessment of risk factors.

    PubMed

    Zurawski, Jonathan; Flinn, Ashley; Sklover, Lindsay; Sloane, Jacob A

    2016-08-01

    Risk of relapse after natalizumab (NAT) cessation and switch to dimethyl fumarate (DMF) is unknown. The objective of this paper is to identify the risk and associated risk factors for relapse after switching from NAT to DMF in relapsing-remitting multiple sclerosis. Patients (n = 30) were treated with NAT for ≥12 months and then switched to DMF in a mean of 50 days. Patient age, annualized relapse rates (ARR), Expanded Disability Status Scale scores (EDSS), and lymphocyte counts were assessed. Overall, eight patients (27 %) had relapses after switching to DMF. Five patients (17 %) suffered severe relapses with multifocal clinical and radiological findings. New lesions by MRI (T2 hyperintense or enhancing) were observed in 35 % of patients. Relapses occurred at a mean of 3.5 months after NAT cessation. Patient age and elevated ARR prior to NAT use were significantly associated with risk of relapse after switch to DMF. Once on DMF for 4 months prior to relapse, lymphocyte count decreased more significantly in patients without relapses than those with relapses. Switching from NAT to DMF correlated with increased relapses. Young patient age, high ARR and stability of lymphocyte counts were risk factors for relapse after transition from NAT to DMF. PMID:27193310

  1. 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. PMID:27346066

  2. Reticulate evolution is favored in influenza niche switching.

    PubMed

    Ma, Eric J; Hill, Nichola J; Zabilansky, Justin; Yuan, Kyle; Runstadler, Jonathan A

    2016-05-10

    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

  3. 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.

  4. 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.

  5. New opioid prescribing guidelines favor non-opioid alternatives.

    PubMed

    2016-05-01

    Determined to make a dent in the growing problem of opioid addiction, the CDC has unveiled new guidelines for opioid prescribing for chronic pain. The recommendations urge providers to be more judicious in their prescribing, opting for opioids only after carefully weighing substantial risks and benefits. Public health authorities note the rampant use and misuse of opioids have "blurred the lines" between prescription opioids and illicit opioids. The new guidelines are designed to help frontline providers balance the need to manage their patients' chronic pain with the duty to curb dangerous prescribing practices. The recommendations are built around three principles: favor non-opioid alternatives for most cases of chronic pain, use the lowest effective dose when prescribing opioids, and exercise caution/monitor patients who are treated with opioids. PMID:27266000

  6. 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

  7. 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…

  8. Second autologous stem cell transplant for multiply relapsed Hodgkin's disease.

    PubMed

    Lin, T S; Avalos, B R; Penza, S L; Marcucci, G; Elder, P J; Copelan, E A

    2002-05-01

    Therapeutic options for patients with Hodgkin's disease who relapse after high-dose chemotherapy with autologous stem cell support are limited. Salvage chemotherapy is not curative, and allogeneic stem cell transplantation in this setting is associated with mortality rates of 40-65%. We report our institution's experience with second autologous transplants in this patient population. Five patients (median age 36) with relapsed Hodgkin's disease underwent a second autologous stem cell transplant at a median of 66 months after first transplant. Four patients received CBV, and one patient received BuCy as conditioning. Neutrophil and platelet engraftment occurred by days +10 and +16, respectively. All patients achieved a complete response, and no relapses have occurred after a median follow-up of 42 months. All four patients who received CBV developed interstitial pneumonitis, and two patients died of pulmonary complications 37 and 48 months following second transplant. Three patients remain alive and disease-free 41, 42 and 155 months after second transplant. These data indicate that second autologous transplantation should be considered for selected patients who relapse after a prolonged response to first autologous transplant. However, BCNU pneumonitis is the major toxicity in patients who have undergone previous mantle radiation and received busulfan with first transplant. PMID:12040474

  9. 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…

  10. Lord Byron's death: a case of late malarial relapse?

    PubMed

    Tsiamis, Costas; Piperaki, Evangelia Theophano; Kalantzis, George; Poulakou Rebelakou, Effie; Tompros, Nikolaos; Thalassinou, Eleni; Spilipoulou, Chara; Tsakris, Athanassios

    2015-09-01

    The study examines the pathological circumstances related to Byron's death, the primary issue being malaria. Lord Byron died during the Greek War of Independence against the Ottoman Empire, in Messolonghi on 19 April 1824. Byron's medical profile consists of recurrent onsets of fever, which gave rise to the issue of malaria relapses. According to Byron's letters he reported crises of fever in Greece (1810), Malta (1811), Italy (1817-1819) and England. Evidence from Byron's autopsy, specifically the absence of hepatosplenomegaly, does not support a hypothetical diagnosis of malaria. Nonetheless, the relapsing fevers cannot be ignored and the same applies to the possibility of malaria relapse or re-infection in line with the endemic nature of the Messolonghi area. Our research on the chronologies of Byron's reported fevers found that new attacks occurred at intervals of 540 days on average. Moreover, the most outstanding feature of Plasmodium vivax and Plasmodium ovale is their ability to form dormant forms of hypnozoites in the liver which, when reactivated (110-777 days), cause true relapses of clinical disease. Of course, an ex post facto diagnosis is under debate, because the diagnosis is not clinical but microscopic. Byron's example raises alarm over a current medical problem, i.e. the diagnosis of unexplained fevers, and the need for a detailed travel or immigration history, which will include malaria in the differential diagnosis. PMID:26397304

  11. 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…

  12. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

    PubMed Central

    Madan, V; Shyamsunder, P; Han, L; Mayakonda, A; Nagata, Y; Sundaresan, J; Kanojia, D; Yoshida, K; Ganesan, S; Hattori, N; Fulton, N; Tan, K-T; Alpermann, T; Kuo, M-C; Rostami, S; Matthews, J; Sanada, M; Liu, L-Z; Shiraishi, Y; Miyano, S; Chendamarai, E; Hou, H-A; Malnassy, G; Ma, T; Garg, M; Ding, L-W; Sun, Q-Y; Chien, W; Ikezoe, T; Lill, M; Biondi, A; Larson, R A; Powell, B L; Lübbert, M; Chng, W J; Tien, H-F; Heuser, M; Ganser, A; Koren-Michowitz, M; Kornblau, S M; Kantarjian, H M; Nowak, D; Hofmann, W-K; Yang, H; Stock, W; Ghavamzadeh, A; Alimoghaddam, K; Haferlach, T; Ogawa, S; Shih, L-Y; Mathews, V; Koeffler, H P

    2016-01-01

    Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential. PMID:27063598

  13. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

    PubMed

    Madan, V; Shyamsunder, P; Han, L; Mayakonda, A; Nagata, Y; Sundaresan, J; Kanojia, D; Yoshida, K; Ganesan, S; Hattori, N; Fulton, N; Tan, K-T; Alpermann, T; Kuo, M-C; Rostami, S; Matthews, J; Sanada, M; Liu, L-Z; Shiraishi, Y; Miyano, S; Chendamarai, E; Hou, H-A; Malnassy, G; Ma, T; Garg, M; Ding, L-W; Sun, Q-Y; Chien, W; Ikezoe, T; Lill, M; Biondi, A; Larson, R A; Powell, B L; Lübbert, M; Chng, W J; Tien, H-F; Heuser, M; Ganser, A; Koren-Michowitz, M; Kornblau, S M; Kantarjian, H M; Nowak, D; Hofmann, W-K; Yang, H; Stock, W; Ghavamzadeh, A; Alimoghaddam, K; Haferlach, T; Ogawa, S; Shih, L-Y; Mathews, V; Koeffler, H P

    2016-08-01

    Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential. PMID:27063598

  14. Does Extended Telephone Callback Counselling Prevent Smoking Relapse?

    ERIC Educational Resources Information Center

    Segan, C. J.; Borland, R.

    2011-01-01

    This randomized controlled trial tested whether extended callback counselling that proactively engaged ex-smokers with the task of embracing a smoke-free lifestyle (four to six calls delivered 1-3 months after quitting, i.e. when craving levels and perceived need for help had declined) could reduce relapse compared with a revised version of…

  15. 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…

  16. Quantification of Clonal Circulating Plasma cells in Relapsed Multiple Myeloma

    PubMed Central

    Gonsalves, Wilson I; Morice, William G; Rajkumar, S. Vincent; Gupta, Vinay; Timm, Michael M; Dispenzieri, Angela; Buadi, Francis K; Lacy, Martha Q; Singh, Preet P; Kapoor, Prashant; Gertz, Morie A; Kumar, Shaji K

    2014-01-01

    The presence of clonal circulating plasma cells (cPCs) remains a marker of high-risk disease in newly diagnosed multiple myeloma (MM) patients. However, its prognostic utility in MM patients with previously treated disease is unknown. We studied 647 consecutive patients with previously treated MM seen at the Mayo Clinic, Rochester who had their peripheral blood evaluated for cPCs by multi-parameter flow cytometry. Of these patients, 145 had actively relapsing disease while the remaining 502 had disease that was in a plateau and included 68 patients in complete remission (CR) and 434 patients with stable disease. Patients with actively relapsing disease were more likely to have clonal cPCs than those in a plateau (P < 0.001). None of the patients in CR had any clonal cPCs detected. Among patients whose disease was in a plateau, the presence of clonal cPCs predicted for a worse median survival (22 months vs. not reached; P=0.004). Among actively relapsing patients, the presence of ≥100 cPCs predicted for a worse survival after flow cytometry analysis (12 months vs. 33 months; P<0.001). Future studies are needed to determine the role of these findings in developing a risk-adapted treatment approach in MM patients with actively relapsing disease. PMID:25113422

  17. 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.

  18. A Protocol for Reducing Juvenile Recidivism through Relapse Prevention.

    ERIC Educational Resources Information Center

    Roget, Nancy A.; Fisher, Gary L.; Johnson, Michael L.

    1998-01-01

    The connection between alcohol and other drug use and juvenile crime activities is well established. The source of this connection and specific interventions with juvenile offenders involved in alcohol and drug use is unclear. Reviews existing literature and presents an adolescent-specific relapse-prevention protocol that provides a structure for…

  19. 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…

  20. 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…

  1. Schizophrenia relapse, patient considerations, and potential role of lurasidone.

    PubMed

    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

  2. [Relapsing fever: an almost forgotten disease in focus again].

    PubMed

    Wieser, Andreas; Löscher, Thomas; Schunk, Mirjam; Seilmaier, Michael; Balzer, Lukas; Margos, Gabriele; von Both, Ulrich; Schulzki, Thomas; Kopf, Sabine; Hoch, Martin; Sing, Andreas; Fingerle, Volker

    2016-07-01

    Introduction | Relapsing fevers, transmitted by arthropods, are rarely encountered in Germany, thus they are often not considered as differential diagnosis in febrile patients. In the last months, more than fourty cases of louse-borne relapsing fever were diagnosed in asylum seekers in Germany. Some of the patients had to be admitted to intensive care units, one patient died despite therapy. Pathogen, disease and diagnosis | The causative agents are spirochetes of the genus borrelia, which can reach high densities in patient blood. Depending on the vector and the region, different species are prevalent worldwide. For diagnosis, appropriate techniques include direct detection by microscopy or PCR from EDTA-blood. Ordering such tests should not be delayed when there is suspicion for relapsing fever. Besides, malaria can also be excluded with microscopy of blood smears. Therapy | First-line antibiotics include tetracyclines and penicillin, acquired resistance has not yet been observed. Frequently patients develop a Jarisch-Herxheimer reaction shortly after initiation of therapy, requiring hospitalization or intensive care treatment. Managing the treatment exclusively in an outpatient setting is not recommended. Especially in migrants with febrile illness, relapsing fever is an important differential diagnosis. PMID:27404930

  3. Modifiable factors influencing relapses and disability in multiple sclerosis.

    PubMed

    D'hooghe, M B; Nagels, G; Bissay, V; De Keyser, J

    2010-07-01

    A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetanus appear to be safe. Surgery, general and epidural anaesthesia, and physical trauma are not associated with an increased risk of relapses. Factors that have been associated with a reduced relapse rate are pregnancy, exclusive breastfeeding, sunlight exposure and higher vitamin D levels. A number of medications, including hormonal fertility treatment, seem to be able to trigger relapses. Factors that may worsen progression of disability include stressful life events, radiotherapy to the head, low levels of physical activity and low vitamin D levels. Strong evidence suggests that smoking promotes disease progression, both clinically and on brain magnetic resonance imaging. There is no evidence for an increased progression of disability following childbirth in women with multiple sclerosis. Moderate alcohol intake and exercise might have a neuroprotective effect, but this needs to be confirmed. PMID:20483884

  4. [Kikuchi-Fujimoto subacute necrotizing lymphadenitis: two histologic forms observed in the same patient].

    PubMed

    el Mezni, F; Mrad, K; el Mezni-Benzarti, A; Zermani, R; Ben Abdeladhim, A; Ben Jilani, S

    1998-11-01

    Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease is a rare self-limited condition of young adults usually misdiagnosed as malignant hematologic disease. The diagnosis depends on microscopic findings. Two histologic types are classically described, proliferative and necrotic types. This is a case report of 17 year-old girl who presented cervical lymphadenopathy. The first lymph node biopsy was in favor of malignant lymphoma. The second lymph node biopsy, done one month later, showed typical histiocytic necrotizing lymphadenitis. To our knowledge, this is the first time that the two forms of this disease are described in the same patient. PMID:9864579

  5. Favorable Geochemistry from Springs and Wells in COlorado

    DOE Data Explorer

    Zehner, Richard E.

    2012-02-01

    Citation Information: Originator: Geothermal Development Associates, Reno Nevada Originator: United States Geological Survey (USGS) Originator: Colorado Geological Survey Publication Date: 2012 Title: Favorable Geochemistry Edition: First Publication Information: Publication Place: Reno Nevada Publisher: Geothermal Development Associates, Reno, Nevada Description: This layer contains favorable geochemistry for high-temperature geothermal systems, as interpreted by Richard "Rick" Zehner. The data is compiled from the data obtained from the USGS. The original data set combines 15,622 samples collected in the State of Colorado from several sources including 1) the original Geotherm geochemical database, 2) USGS NWIS (National Water Information System), 3) Colorado Geological Survey geothermal sample data, and 4) original samples collected by R. Zehner at various sites during the 2011 field season. These samples are also available in a separate shapefile FlintWaterSamples.shp. Data from all samples were reportedly collected using standard water sampling protocols (filtering through 0.45 micron filter, etc.) Sample information was standardized to ppm (micrograms/liter) in spreadsheet columns. Commonly-used cation and silica geothermometer temperature estimates are included. Spatial Domain: Extent: Top: 4515595.841032 m Left: 149699.513964 m Right: 757959.309388 m Bottom: 4104156.435530 m Contact Information: Contact Organization: Geothermal Development Associates, Reno, Nevada Contact Person: Richard “Rick” Zehner Address: 3740 Barron Way City: Reno State: NV Postal Code: 89511 Country: USA Contact Telephone: 775-737-7806 Spatial Reference Information: Coordinate System: Universal Transverse Mercator (UTM) WGS’1984 Zone 13N False Easting: 500000.00000000 False Northing: 0.00000000 Central Meridian: -105.00000000 Scale Factor: 0.99960000 Latitude of Origin: 0.00000000 Linear Unit: Meter Datum: World Geodetic System 1984 (WGS ’1984) Prime Meridian: Greenwich

  6. High nevus counts confer a favorable prognosis in melanoma patients.

    PubMed

    Ribero, Simone; Davies, John R; Requena, Celia; Carrera, Cristina; Glass, Daniel; Rull, Ramon; Vidal-Sicart, Sergi; Vilalta, Antonio; Alos, Lucia; Soriano, Virtudes; Quaglino, Pietro; Traves, Victor; Newton-Bishop, Julia A; Nagore, Eduardo; Malvehy, Josep; Puig, Susana; Bataille, Veronique

    2015-10-01

    A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma-specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21-0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08-0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi. PMID:25809795

  7. Concurrent Alcohol and Tobacco Treatment: Effect on Daily Process Measures of Alcohol Relapse Risk

    PubMed Central

    Cooney, Ned L.; Litt, Mark D.; Sevarino, Kevin A.; Levy, Lucienne; Kranitz, Linda S.; Sackler, Helen; Cooney, Judith L.

    2014-01-01

    Objective The aim of this study was to compare the effects of alcohol treatment along with concurrent smoking treatment or delayed smoking treatment on process measures related to alcohol relapse risk. Method Alcohol dependent smokers (N = 151) who were enrolled in an intensive outpatient alcohol treatment program and were interested in smoking cessation were randomized to a concurrent smoking cessation (CSC) intervention or to a waiting list for delayed smoking cessation (DSC) intervention scheduled to begin three months later. Daily assessments of relapse process measures were obtained using an Interactive Voice Response (IVR) system for 12 weeks after the onset of smoking treatment in the CSC condition, and before beginning smoking treatment in the DSC condition. Smoking outcomes were assessed at 2 and 13 weeks after starting treatment. Results Seven-day CO-verified smoking abstinence in the CSC condition was 50.5% at 2 weeks and 19.0% at 13 weeks compared to 2.2% abstinence at two weeks and 0% abstinence at 13 weeks for those in the DSC condition. Drinking outcomes were not significantly different for CSC vs. DSC treatment conditions. On daily IVR assessments, CSC participants had significantly lower positive alcohol outcome expectancies relative to DSC participants. Multilevel modeling (MLM) analyses of within-person effects across the 12 weeks of daily monitoring showed that daily smoking abstinence was significantly associated with same day reports of lower alcohol consumption, lower urge to drink, lower negative affect, lower positive alcohol outcome expectancies, greater alcohol abstinence self-efficacy, greater alcohol abstinence readiness to change, and greater perceived self-control demands. Conclusions; Analyses of process measures provide support for recommending smoking intervention concurrent with intensive outpatient alcohol treatment. Public Health Significance Statement Study results support conveying a message to alcohol dependent smokers that

  8. Prediction of Risk Factors of Frequent Relapse Idiopathic Nephrotic Syndrome.

    PubMed

    Jahan, I; Hanif, M; Ali, M A; Hoque, M M

    2015-10-01

    This case control study was aimed to identify the predictive risk factors for frequent relapse idiopathic nephrotic syndrome (INS) and conducted in Sir Salimullah Medical College & Mitford Hospital, Dhaka and at Renal and Dialysis Unit of Dhaka Shishu Hospital and Bangladesh Institute of Child Health (BICH), Dhaka, from January 2006 to December 2006. We examined retrospectively the clinical course of fifty cases of frequent relapse nephrotic syndrome (FRNS) as cases and fifty cases of infrequent relapse nephrotic syndrome (IRNS) as control who met the predefined enrollment criteria, followed for at least one year after initial onset of disease. After enrollment following parameters were studied as predictors of frequent relapse: i) Socio-demographic variables: age, sex, socio-economic condition, number of living room ii) Disease related variables i.e. age of onset, duration of illness, frequency of relapse within the 1st year, regimen of initial steroid therapy, total cumulative dose of steroid for remission, day of remission after starting steroid, association with atopy and infection, concomitant upper respiratory illness iii) Biochemical and pathological variables (at the time of initial attack) i.e. Serum albumin, serum cholesterol, blood urea, 24 hours urinary protein, serum creatinine, complete blood count, urine RBC, urine pus cell, urine culture. The test statistics used to analyses the data were descriptive statistics, Chi-square probability test, Student's t-test and Binary logistic regression analysis for Odds ratio. Both univariate and multivariate logistic regression analysis revealed that age of onset (P<0.001, OR=0.9, 95% CI=0.85-0.95), poor socioeconomic status (P<0.034, OR=0.5.8, 95% CI=1.14-29.5) and low serum albumin level at the time of initial presentation (P<0.022, OR=0.8, 95% CI=0.65-0.97) were independent predictors of frequent relapse nephrotic syndrome. In conclusion, we demonstrated that age at onset, poor socioeconomic condition and low

  9. African Relapsing Fever Borreliae Genomospecies Revealed by Comparative Genomics

    PubMed Central

    Elbir, Haitham; Abi-Rached, Laurent; Pontarotti, Pierre; Yoosuf, Niyaz; Drancourt, Michel

    2014-01-01

    Background: Relapsing fever borreliae are vector-borne bacteria responsible for febrile infection in humans in North America, Africa, Asia, and in the Iberian Peninsula in Europe. Relapsing fever borreliae are phylogenetically closely related, yet they differ in pathogenicity and vectors. Their long-term taxonomy, based on geography and vector grouping, needs to be re-apprised in a genomic context. We therefore embarked into genomic analyses of relapsing fever borreliae, focusing on species found in Africa. Results: Genome-wide phylogenetic analyses group Old World Borrelia crocidurae, Borrelia hispanica, B. duttonii, and B. recurrentis in one clade, and New World Borrelia turicatae and Borrelia hermsii in a second clade. Accordingly, average nucleotide identity is 99% among B. duttonii, B. recurrentis, and B. crocidurae and 96% between latter borreliae and B. hispanica while the similarity is 86% between Old World and New World borreliae. Comparative genomics indicates that the Old World relapsing fever B. duttonii, B. recurrentis, B. crocidurae, and B. hispanica have a 2,514-gene pan genome and a 933-gene core genome that includes 788 chromosomal and 145 plasmidic genes. Analyzing the role that natural selection has played in the evolution of Old World borreliae species revealed that 55 loci were under positive diversifying selection, including loci coding for membrane, flagellar, and chemotaxis proteins, three categories associated with adaption to specific niches. Conclusion: Genomic analyses led to a reappraisal of the taxonomy of relapsing fever borreliae in Africa. These analyses suggest that B. crocidurae, B. duttonii, and B. recurrentis are ecotypes of a unique genomospecies, while B. hispanica is a distinct species. PMID:25229054

  10. PDL Progenitor-Mediated PDL Recovery Contributes to Orthodontic Relapse.

    PubMed

    Feng, L; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; He, D; Gan, Y; Kou, X; Zhou, Y

    2016-08-01

    Periodontal ligament (PDL) is subjected to mechanical force during physiologic activities. PDL stem /: progenitor cells are the main mesenchymal stem cells in PDL. However, how PDL progenitors participate in PDL homeostasis upon and after mechanical force is largely unknown. In this study, force-triggered orthodontic tooth movement and the following relapse were used as models to demonstrate the response of PDL progenitors and their role in PDL remodeling upon and after mechanical force. Upon orthodontic force, PDL collagen on the compression side significantly degraded, showing a broken and disorganized pattern. After force withdrawal, the degraded PDL collagen recovered during the early stage of relapse. Correspondingly, increased CD90(+) PDL progenitors with suppressed expression of type I collagen (Col-I) were observed upon orthodontic force, whereas these cells accumulated at the degradation regions and regained Col-I expression after force withdrawal during early relapse. Our results further showed that compressive force altered cell morphology and repressed collagen expression in cultured PDL progenitors, which both recovered after force withdrawal. Force withdrawal-induced recovery of collagen expression in cultured PDL progenitors could be regulated by transforming growth factor-β (TGF-β), a key molecule for tissue homeostasis and extracellular matrix remodeling. More interesting, inhibiting the regained Col-I expression in CD90(+) PDL progenitors by blocking TGF-β interrupted PDL collagen recovery and partially inhibited the early relapse. These data suggest that PDL progenitors can respond to mechanical force and may process intrinsic stability to recover to original status after force withdrawal. PDL progenitors with intrinsic stability are required for PDL recovery and consequently contribute to early orthodontic relapse, which can be regulated by TGF-β signaling. PMID:27161015

  11. 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.

  12. Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro

    PubMed Central

    Williams, Marlon D.; Nguyen, Thu; Carriere, Patrick P.; Tilghman, Syreeta L.; Williams, Christopher

    2015-01-01

    The heterotetrameric protein kinase CK2 has been associated with oncogenic transformation, and our previous studies have shown that it may affect estrogenic signaling. Here, we investigate the role of the protein kinase CK2 in regulating ERα (estrogen receptor α) signaling in breast cancer. We determined the correlation of CK2α expression with relapse free breast cancer patient survival utilizing Kaplan Meier Plotter (kmplot.com/analysis/) to mine breast cancer microarrays repositories. Patients were stratified according to ERα status, histological grade, and hormonal therapy. Luciferase reporter assays and flow cytometry were implemented to determine the impact of CK2 inhibition on ERE-mediated gene expression and expression of ERα protein. CK2α expression is associated with shorter relapse free survival among ERα (+) patients with grade 1 or 2 tumors, as well as among those patients receiving hormonal therapy. Biochemical inhibition of CK2 activity results in increased ER-transactivation as well as increased expression among ERα (+) and ERα (−) breast cancer cell lines. These findings suggest that CK2 may contribute to estrogen-independent cell proliferation and breast tumor progression, and may potentially serve as a biomarker and pharmacological target in breast cancer. PMID:26703694

  13. Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma.

    PubMed

    Assouline, S E; Chang, J; Cheson, B D; Rifkin, R; Hamburg, S; Reyes, R; Hui, A-M; Yu, J; Gupta, N; Di Bacco, A; Shou, Y; Martin, P

    2014-01-01

    Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory lymphoma patients who had received ⩾ 2 prior therapies. Thirty patients with a range of histologies received ixazomib 0.125-3.11 mg/m(2) on days 1, 8 and 15 of 28-day cycles. Patients received a median of two cycles (range 1-36). MTD was determined to be 2.34 mg/m(2). Most common drug-related adverse events (AEs) included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia (each 27%). Drug-related grade ⩾ 3 AEs included neutropenia (20%), thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy occurred in four (13%) patients; no grade ⩾ 3 events were reported. Plasma exposure increased dose proportionally from 0.5-3.11 mg/m(2); terminal half-life was 4-12 days after multiple dosing. Of 26 evaluable patients, five achieved responses: 4/11 follicular lymphoma patients (one complete and three partial responses) and 1/4 peripheral T-cell lymphoma patients (partial response). Sustained responses were observed with ⩾ 32 cycles of treatment in two heavily pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is generally well tolerated and may be clinically active in relapsed/refractory lymphoma. PMID:25325301

  14. Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma

    PubMed Central

    Assouline, S E; Chang, J; Cheson, B D; Rifkin, R; Hamburg, S; Reyes, R; Hui, A-M; Yu, J; Gupta, N; Di Bacco, A; Shou, Y; Martin, P

    2014-01-01

    Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory lymphoma patients who had received ⩾2 prior therapies. Thirty patients with a range of histologies received ixazomib 0.125−3.11 mg/m2 on days 1, 8 and 15 of 28-day cycles. Patients received a median of two cycles (range 1−36). MTD was determined to be 2.34 mg/m2. Most common drug-related adverse events (AEs) included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia (each 27%). Drug-related grade ⩾3 AEs included neutropenia (20%), thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy occurred in four (13%) patients; no grade ⩾3 events were reported. Plasma exposure increased dose proportionally from 0.5−3.11 mg/m2; terminal half-life was 4−12 days after multiple dosing. Of 26 evaluable patients, five achieved responses: 4/11 follicular lymphoma patients (one complete and three partial responses) and 1/4 peripheral T-cell lymphoma patients (partial response). Sustained responses were observed with ⩾32 cycles of treatment in two heavily pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is generally well tolerated and may be clinically active in relapsed/refractory lymphoma. PMID:25325301

  15. 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

  16. Microbiome interaction with sugar plays an important role in relapse of childhood caries.

    PubMed

    Tian, Jing; Qin, Man; Ma, Wenli; Xia, Bin; Xu, He; Zhang, Qian; Chen, Feng

    Childhood caries have a high relapse rate after full mouth therapy. This study aimed to elucidate the relationship between the microbiome, sugar, and the relapse of childhood caries after therapy. A total of 24 children aged 2-4 years who underwent one caries treatment session participated in this study. Supragingival plaque was collected before therapy and 1 and 7 months after therapy, then sequenced using the 16S rRNA high-throughput approach. We found 11 phyla, 140 genera, and 444 species in 72 samples. The children were divided into relapse-free (n = 13) and relapse (n = 11) groups according to whether they relapsed 7 months after therapy. The bacterial community richness, diversity, structure, and relative abundance of bacterial taxa were significantly different between the two groups 7 months after therapy. The two groups also differed in the relative abundance of bacterial taxa, both before and 1 month after therapy. Bacterial community richness and diversity were lower in the relapse-free group 1 month after therapy. Using different operational taxonomic units between the relapse-free and relapse groups 1 month after therapy, a relapse-risk assessment model was built with 75% accuracy, 0.1905 out-of-bag error, and 66.67% validation accuracy. Patients in the relapse group had higher sugar intake frequencies than those in the relapse-free group during follow-up. Interactions between the microbiome and sugar intake frequency were found through co-occurrence networks. We conclude that the microbiome is significantly different between the relapse-free and relapse groups at the time of relapse. Supragingival plaque collected immediately after therapy can be used to predict the risk of relapse. Furthermore, the correlation between sugar intake frequency and microbiome is associated with the relapse. PMID:26505801

  17. 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. PMID:24142147

  18. 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.

  19. The histological aspects of fillers complications.

    PubMed

    Zimmermann, Ute S; Clerici, Thierry J

    2004-12-01

    The histological aspects of resorbable heterologous fillers (bovine collagen, acid hyaluronique), autologous fillers (lipofilling, dermis-fat graft), biodegradable fillers (New-Fill), and permanent fillers (silicone, Artecoll, Evolution, Aquamid, DermaLive, DermaDeep, Bioplastique, Paraffin) are described. This article relates the morphological aspect of these materials, the normal tissue reaction after injection, and its chronological evolution as the morphological aspects from the different side effects, more frequently observed for the permanent fillers. They mainly consist of granulomatous reactions which may appear long after injection. PMID:15745233

  20. A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma.

    PubMed

    Siegel, David; Jagannath, Sundar; Vesole, David H; Borello, Ivan; Mazumder, Amitabha; Mitsiades, Constantine; Goddard, Jill; Dunbar, Joi; Normant, Emmanuel; Adams, Julian; Grayzel, David; Anderson, Kenneth C; Richardson, Paul

    2011-12-01

    Abstract A phase 1 study of IPI-504 (retaspimycin hydrochloride) administered intravenously twice weekly for 2 weeks at 22.5, 45, 90, 150, 225, 300 or 400 mg/m(2) followed by 10 days off-treatment was conducted to determine the safety and maximum tolerated dose (MTD) of IPI-504 in patients with relapsed or relapsed/refractory multiple myeloma (MM). Anti-tumor activity and pharmacokinetics were also evaluated. Eighteen patients (mean age 60.5 years; median 9 prior therapies) were enrolled. No dose-limiting toxicities (DLTs) were reported for IPI-504 doses up to 400 mg/m(2). The most common treatment-related adverse event was grade 1 infusion site pain (four patients). All other treatment-related events were assessed as grade 1 or 2 in severity. The area under the curve (AUC) increased with increasing dose, and the mean half-life was approximately 2-4 h for IPI-504 and its metabolites. Four patients had stable disease, demonstrating modest single-agent activity in relapsed or relapsed/refractory MM. PMID:21851215

  1. SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections.

    PubMed Central

    Johnson, L L

    1992-01-01

    Lymphodeficient scid/scid (SCID) mice died from acute infection with a strain of Toxoplasma gondii that causes chronic infection with mild symptoms in immunocompetent non-SCID mice. However, most SCID mice reconstituted with spleen cells from immunocompetent mice 1 month prior to T. gondii infection survived in good health after a transient period during which they appeared ill. Unreconstituted SCID mice given sulfadiazine in their drinking water from day 10 of Toxoplasma infection onward survived the acute phase of infection and lived for many weeks without overt symptoms. Histological examination revealed Toxoplasma cysts in their brains. However, if sulfadiazine was withdrawn from the drinking water of these chronically infected SCID mice, the mice died within 1 week with large numbers of trophozoites throughout their brains. These findings establish SCID mice as a potentially useful resource with which to study various aspects of immunological control of T. gondii infection during either its acute or chronic phase. Furthermore, the ability to produce chronic infections with avirulent T. gondii in SCID mice and to cause acute relapsing infections at will suggests that SCID mice may be helpful in evaluating potential therapies for acute and chronic T. gondii infections in immunocompromised patients. Images PMID:1500181

  2. 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…

  3. 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…

  4. 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...

  5. Relapse Prevention in Health Promotion: Strategies and Long-Term Outcome.

    ERIC Educational Resources Information Center

    Gintner, Gary G.

    1988-01-01

    Reviews the efficacy of maintenance enhancement procedures to prevent relapse in smoking cessation, weight control, and exercise programs. Presents models of maintenance enhancement, reviews studies that have used relapse prevention strategies, and discusses ways of incorporating relapse prevention techniques into health promotion programs.…

  6. Retrospective and Prospective Reports of Precipitants to Relapse in Pathological Gambling

    ERIC Educational Resources Information Center

    Hodgins, David C.; el-Guebaly, Nady

    2004-01-01

    A prospective design was used to explore the precipitants of relapse in a naturalistic sample of pathological gamblers (N = 101) who had recently quit gambling. Relapse rates were high; only 8% were entirely free of gambling during the 12-month follow-up. Relapses were highly variable but occurred most frequently in the evening, when the person…

  7. The Relationship between Relapse Prevention Treatment Outcome and Self-Efficacy.

    ERIC Educational Resources Information Center

    Cantrell, Peggy J.; And Others

    The majority of alcoholics and drug addicts relapse after treatment, with many substance abusers developing a chronic relapse pattern. For this study, 43 patients, who went through a 3-week inpatient relapse prevention program, answered the Situational Confidence Questionnaire (a measure of self-efficacy for alcohol-related, high-risk situations)…

  8. 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. PMID:24319324

  9. The "PIP problem": clinical and histologic characteristics.

    PubMed

    Correia-Sá, Inês; Rodrigues-Pereira, Pedro; Marques, Marisa

    2013-10-01

    Implants from Poly Implant Prothése (PIP), the French manufacturer, showed increased risk of implant rupture and silicone leakage through the shell. Concerns also exist about the potential irritant behavior of silicone gel filler in these implants. This report presents the clinical, histologic, and microbiologic characteristics of a capsule and a siliconoma from a patient with a ruptured PIP implant. A 41-year-old woman submitted to breast augmentation in 2005 with PIP silicone gel implants presented with a recent history of progressive asymmetric breast enlargement and an enlarged lymph node on her right axilla. No capsular contracture was observed. A breast ultrasonography showed intra- and extracapsular ruptures of the right implant. The woman underwent explantation. Histologic analysis of the breast capsules showed a thin capsule with a chronic, mild inflammatory response. Microbiologic analysis showed no bacterial agent. The irritant behavior of the PIP silicone gel previously described was not able to produce capsular contracture or an exuberant inflammatory reaction. Studies to evaluate the potential risks of the silicone gel and to define the hazards for women implanted with those prostheses are urgently needed. PMID:23943050

  10. Molecular histology in skin appendage morphogenesis.

    PubMed

    Widelitz, R B; Jiang, T X; Noveen, A; Ting-Berreth, S A; Yin, E; Jung, H S; Chuong, C M

    1997-08-15

    Classical histological studies have demonstrated the cellular organization of skin appendages and helped us appreciate the intricate structures and function of skin appendages. At this juncture, questions can be directed to determine how these cellular organizations are achieved. How do cells rearrange themselves to form the complex cyto-architecture of skin appendages? What are the molecular bases of the morphogenesis and histogenesis of skin appendages? Recently, many new molecules expressed in a spatial and temporal specific manner during the formation of skin appendages were identified by molecular biological approaches. In this review, novel molecular techniques that are useful in skin appendage research are discussed. The distribution of exemplary molecules from different categories including growth factors, intracellular signaling molecules, homeobox genes, adhesion molecules, and extracellular matrix molecules are summarized in a diagram using feather and hair as models. We hope that these results will serve as the ground work for completing the molecular mapping of skin appendages which will refine and re-define our understanding of the developmental process beyond relying on morphological criteria. We also hope that the listed protocols will help those who are interested in this venture. This new molecular histology of skin appendages is the foundation for forming new hypotheses on how molecules are mechanistically involved in skin appendage development and for designing experiments to test them. This may also lead to the modulation of healing and regeneration processes in future treatment modalities. PMID:9297695

  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 favorable view: progress in cancer prevention and screening.

    PubMed

    Greenwald, Peter

    2007-01-01

    Clifton Leaf, in his article "Why We're Losing the War on Cancer," presents criticisms of past research approaches and the small impact of this research thus far on producing cures or substantially extending the life of many cancer patients. It is true that gains in long-term survival for people with advanced cancers have been modest, hindered in part by the heterogeneity of tumors, which allows the cancers to persist using alternate molecular pathways and so evade many cancer therapeutics. In contrast, clinical trials have demonstrated that it is possible to reduce the incidence or improve cancer survival through prevention and early detection. Strides have been made in preventing or detecting early the four deadliest cancers in the United States (i.e., lung, breast, prostate, and colorectal). For example, 7-year follow-up data from the Breast Cancer Prevention Trial (BCPT) provides evidence that tamoxifen reduces the occurrence of invasive breast tumors by more than 40%; recent studies using aromatase inhibitors and raloxifene are also promising. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride reduced prostate cancer incidence by 25%, and the ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT) is investigating selenium and vitamin E for prostate cancer prevention based on encouraging results from earlier studies. Living a healthy lifestyle, including regular physical activity, avoiding obesity, and eating primarily a plant-based diet has been associated with a lower risk of colorectal cancer. In addition, noninvasive stool DNA tests for early detection are being studied, which may lessen the reluctance of people to be screened for colorectal polyps and cancer. Behavioral and medical approaches for smoking prevention are ways to reduce the incidence of lung cancer, with antinicotine vaccines on the horizon that may help former smokers to avoid relapse. The US National Lung Screening Trial is testing whether early detection via

  13. 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

  14. Structures of Neural Correlation and How They Favor Coding.

    PubMed

    Franke, Felix; Fiscella, Michele; Sevelev, Maksim; Roska, Botond; Hierlemann, Andreas; da Silveira, Rava Azeredo

    2016-01-20

    The neural representation of information suffers from "noise"-the trial-to-trial variability in the response of neurons. The impact of correlated noise upon population coding has been debated, but a direct connection between theory and experiment remains tenuous. Here, we substantiate this connection and propose a refined theoretical picture. Using simultaneous recordings from a population of direction-selective retinal ganglion cells, we demonstrate that coding benefits from noise correlations. The effect is appreciable already in small populations, yet it is a collective phenomenon. Furthermore, the stimulus-dependent structure of correlation is key. We develop simple functional models that capture the stimulus-dependent statistics. We then use them to quantify the performance of population coding, which depends upon interplays of feature sensitivities and noise correlations in the population. Because favorable structures of correlation emerge robustly in circuits with noisy, nonlinear elements, they will arise and benefit coding beyond the confines of retina. PMID:26796692

  15. Lagooning of wastewaters favors dissemination of clinically relevant Pseudomonas aeruginosa.

    PubMed

    Petit, Stéphanie M-C; Lavenir, Raphaël; Colinon-Dupuich, Céline; Boukerb, Amine M; Cholley, Pascal; Bertrand, Xavier; Freney, Jean; Doléans-Jordheim, Anne; Nazaret, Sylvie; Laurent, Frédéric; Cournoyer, Benoit

    2013-10-01

    The significance of wastewater treatment lagoons (WWTLs) as point sources of clinically relevant Pseudomonas aeruginosa that can disseminate through rural and peri-urban catchments was investigated. A panel of P. aeruginosa strains collected over three years from WWTLs and community-acquired infections was compared by pulsed field gel electrophoresis (PFGE) DNA fingerprinting and multilocus sequence typing (MLST). Forty-four distantly related PFGE profiles and four clonal complexes were found among the WWTL strains analyzed. Some genotypes were repeatedly detected from different parts of WWTLs, including the influent, suggesting an ability to migrate and persist over time. MLST showed all investigated lineages to match sequence types described in other countries and strains from major clinical clones such as PA14 of ST253 and "C" of ST17 were observed. Some of these genotypes matched isolates from community-acquired infections recorded in the WWTL geographic area. Most WWTL strains harbored the main P. aeruginosa virulence genes; 13% harbored exoU-encoded cytoxins, but on at least six different genomic islands, with some of these showing signs of genomic instability. P. aeruginosa appeared to be highly successful opportunistic colonizers of WWTLs. Lagooning of wastewaters was found to favor dissemination of clinically relevant P. aeruginosa among peri-urban watersheds. PMID:23792168

  16. 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.

  17. 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. PMID:26561887

  18. Does short sleep duration favor abdominal adiposity in children?

    PubMed

    Chaput, Jean-Philippe; Tremblay, Angelo

    2007-01-01

    The main aim of this cross-sectional study was to determine whether the increased body mass index (BMI) characterizing short-duration sleeping children is related to an increased predisposition to abdominal adiposity. A total of 422 children (211 boys and 211 girls) involved in the "Québec en Forme" Project were tested for body weight, height, waist circumference, and sleep duration. As there was no gender interaction with the other factors, a partial regression of waist circumference on hours of sleep was performed for both genders combined, adjusting for age, sex, BMI, parental obesity, parental education, total annual family income, frequency of taking breakfast, watching television, playing videogames, computer use, and frequency of practicing sports activities outside of school. Sleep duration had an independent effect on waist circumference, with the correlation between these variables remaining significant after adjustment for BMI and the several other covariates (r=- 0.17, p<0.001). In conclusion, these results suggest that short sleep duration favors abdominal adiposity in children. This finding is of particular concern since abdominal obesity is an important feature of the metabolic syndrome. PMID:17999284

  19. Adaptation of Cupriavidus necator to conditions favoring polyhydroxyalkanoate production.

    PubMed

    Cavalheiro, João M B T; de Almeida, M Catarina M D; da Fonseca, M Manuela R; de Carvalho, Carla C C R

    2012-12-15

    The fatty acid (FA) composition of the bacterial membrane of Cupriavidus necator DSM 545 was assessed during the time course of two-stage fed-batch cultivations for the production of short-chain polyhydroxyalkanoates (PHA). Changes in the relative proportion of straight, methyl and cyclopropyl saturated, unsaturated, hydroxy substituted and polyunsaturated FA were observed, depending on the C sources and cultivation conditions used to favor the synthesis of poly(3-hydroxybutyrate) (P(3HB)), poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) or poly(3-hydroxybutyrate-4-hydroxybutyrate-3-hydroxyvalerate) (P(3HB-4HB-3HV)), under N limiting conditions. The relative percentage of each FA class was studied using glucose or waste glycerol (GRP), as main C source for P(3HB) production. The FA profile was also assessed when GRP was used together with i) γ-butyrolactone (GBL) (precursor of 4HB monomers) for P(3HB-4HB) synthesis and ii) GBL and propionic acid (PA) (3HV precursor) to yield P(3HB-4HB-3HV). The effect of GBL and PA utilization as PHA monomer precursors on the FA profile of the cell membrane was studied under two different dissolved oxygen concentrations (DOC). PMID:23376842

  20. On favorable thermal fields for detached Bridgman growth

    NASA Astrophysics Data System (ADS)

    Stelian, Carmen; Volz, Martin P.; Derby, Jeffrey J.

    2009-06-01

    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 analysis [C. Stelian, A. Yeckel, J.J. Derby, Influence of thermal phenomena on crystal reattachment during the dewetted Bridgman growth, J. Cryst. Growth, in press] 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.

  1. 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.

  2. Ecological Conditions Favoring Budding in Colonial Organisms under Environmental Disturbance

    PubMed Central

    Nakamaru, Mayuko; Takada, Takenori; Ohtsuki, Akiko; Suzuki, Sayaki U.; Miura, Kanan; Tsuji, Kazuki

    2014-01-01

    Dispersal is a topic of great interest in ecology. Many organisms adopt one of two distinct dispersal tactics at reproduction: the production of small offspring that can disperse over long distances (such as seeds and spawned eggs), or budding. The latter is observed in some colonial organisms, such as clonal plants, corals and ants, in which (super)organisms split their body into components of relatively large size that disperse to a short distance. Contrary to the common dispersal viewpoint, short-dispersal colonial organisms often flourish even in environments with frequent disturbances. In this paper, we investigate the conditions that favor budding over long-distance dispersal of small offspring, focusing on the life history of the colony growth and the colony division ratio. These conditions are the relatively high mortality of very small colonies, logistic growth, the ability of dispersers to peacefully seek and settle unoccupied spaces, and small spatial scale of environmental disturbance. If these conditions hold, budding is advantageous even when environmental disturbance is frequent. These results suggest that the demography or life history of the colony underlies the behaviors of the colonial organisms. PMID:24621824

  3. 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. PMID:23852354

  4. West Florida shelf response to upwelling favorable wind forcing: Kinematics

    NASA Astrophysics Data System (ADS)

    Li, Zhenjiang; Weisberg, Robert H.

    1999-06-01

    The barotropic responses of the west Florida continental shelf to idealized upwelling favorable alongshore and offshore wind stresses are studied using the three-dimensional, time-dependent, primitive equation Princeton Ocean Model (POM). When forced with uniform winds, the shelf circulation evolves quickly to a quasi steady state. A southeastward alongshore wind lowers sea level along the coast and drives a southeastward coastal jet with a relatively weak northwestward return flow farther offshore. A southwestward offshore wind lowers sea level along the west Florida coast and raises sea level along the Panhandle coast. Two independent circulation gyres are set up in association with these regionally different sea level distributions: an anticyclonic gyre off the west Florida coast consisting of a southeastward coastal jet and a broad return flow over the middle shelf and a cyclonic gyre off the Panhandle coast consisting of a strong northwestward coastal jet and an adjacent narrow southeastward undercurrent. These gyres are separated by the Big Bend region. In both cases (alongshore and offshore wind forcing) the circulations are fully three-dimensional, with opposing surface and bottom boundary layer flows accounting for the across-shelf transports. The shapes of the coastline and the isobaths are important determinants of the shelf-wide responses. Several locally maximum upwelling regions are identified for geometrical reasons. These include the Panhandle coast south of Apalachicola Bay, the west Florida coast south of Tampa Bay, along the Florida Keys, and at the shelf break where topographic Rossby waves are evident.

  5. Genetic control of the innate immune response to Borrelia hermsii influences the course of relapsing fever in inbred strains of mice.

    PubMed

    Benoit, Vivian M; Petrich, Annett; Alugupalli, Kishore R; Marty-Roix, Robin; Moter, Annette; Leong, John M; Boyartchuk, Victor L

    2010-02-01

    Host susceptibility to infection is controlled in large measure by the genetic makeup of the host. Spirochetes of the genus Borrelia include nearly 40 species of vector-borne spirochetes that are capable of infecting a wide range of mammalian hosts, causing Lyme disease and relapsing fever. Relapsing fever is associated with high-level bacteremia, as well as hematologic manifestations, such as thrombocytopenia (i.e., low platelet numbers) and anemia. To facilitate studies of genetic control of susceptibility to Borrelia hermsii infection, we performed a systematic analysis of the course of infection using immunocompetent and immunocompromised inbred strains of mice. Our analysis revealed that sensitivity to B. hermsii infections is genetically controlled. In addition, whereas the role of adaptive immunity to relapsing fever-causing spirochetes is well documented, we found that innate immunity contributes significantly to the reduction of bacterial burden. Similar to human infection, the progression of the disease in mice was associated with thrombocytopenia and anemia. Histological and fluorescence in situ hybridization (FISH) analysis of infected tissues indicated that red blood cells (RBCs) were removed by tissue-resident macrophages, a process that could lead to anemia. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream by tissue phagocytes. PMID:19995898

  6. 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…

  7. Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

    PubMed

    Sica, S; Di Mario, A; Pagano, L; Etuk, B; Salutari, P; Leone, G

    1992-01-01

    Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT. PMID:1519431

  8. Alkaline diets favor lean tissue mass in older adults1234

    PubMed Central

    Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa

    2008-01-01

    Background Maintaining muscle mass while aging is important to prevent falls and fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from diets that are rich in net acid–producing protein and cereal grains relative to their content of net alkali–producing fruit and vegetables may therefore contribute to a reduction in lean tissue mass in older adults. Objective We aimed to determine whether there was an association of 24-h urinary potassium and an index of fruit and vegetable content of the diet with the percentage lean body mass (%LBM) or change in %LBM in older subjects. Design Subjects were 384 men and women ≥65 y old who participated in a 3-y trial comparing calcium and vitamin D with placebo. Potassium was measured in 24-h urine collections at baseline. The %LBM, defined as total body nonfat, nonbone tissue weight ÷ weight × 100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3 y. Physical activity, height, and weight were assessed at baseline and at 3 y. Results At baseline, the mean urinary potassium excretion was 67.0 ± 21.1 mmol/d. Urinary potassium (mmol/d) was significantly positively associated with %LBM at baseline (β = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by 2.6 ± 3.6%. Conclusion Higher intake of foods rich in potassium, such as fruit and vegetables, may favor the preservation of muscle mass in older men and women. PMID:18326605

  9. 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

  10. Favored Bc decay modes to search for a Majorana neutrino

    NASA Astrophysics Data System (ADS)

    Mandal, Sanjoy; Sinha, Nita

    2016-08-01

    Recently, the LHCb collaboration reported the observation of the decay mode Bc-→B¯s 0π- with the largest exclusive branching fraction amongst the known decay modes of all the B mesons. Here we propose a search for a few lepton-number violating (Δ L =2 ) decay modes of Bc which can only be induced by Majorana neutrinos. Distinguishing between Dirac and Majorana nature of neutrinos is an outstanding problem and hence, all possible searches for Majorana neutrinos need to be carried out. Since the lepton number violating modes are expected to be rare, when using meson decay modes for these searches one expects CKM favored modes to be the preferred ones; Bc→Bs is one such transition. With a resonance enhancement of the Majorana neutrino mediating the Bc-→B¯s 0ℓ1-ℓ2-π+ modes one can hope to observe these rare modes, or, even their nonobservation can be used to obtain tight constraints on the mixing angles of the heavy Majorana singlet with the light flavour neutrinos from upper limits of the branching fractions. Using these modes we obtain exclusion curves for the mixing angles which are tighter or compatible with results from earlier studies. However, we find that the relatively suppressed mode Bc-→J /ψ ℓ1- ℓ2-π+ can provide even tighter constraints on |Ve N|2, |Vμ N|2, |Ve NVμ N|, and in a larger range of the heavy neutrino mass. Further, exclusion regions for |Ve NVτ N|, |Vμ NVτ N| can also be obtained for masses larger than those accessible in tau decays. Upper limits on B (Bc-→π+ℓ1- ℓ2-) can also result in stringent exclusion curves for all the mixing elements, including that for |Vτ N|2 in a mass range where it is unconstrained thus far.

  11. Ground states of stealthy hyperuniform potentials: I. Entropically favored configurations

    NASA Astrophysics Data System (ADS)

    Zhang, G.; Stillinger, F. H.; Torquato, S.

    2015-08-01

    Systems of particles interacting with "stealthy" pair potentials have been shown to possess infinitely degenerate disordered hyperuniform classical ground states with novel physical properties. Previous attempts to sample the infinitely degenerate ground states used energy minimization techniques, introducing algorithmic dependence that is artificial in nature. Recently, an ensemble theory of stealthy hyperuniform ground states was formulated to predict the structure and thermodynamics that was shown to be in excellent agreement with corresponding computer simulation results in the canonical ensemble (in the zero-temperature limit). In this paper, we provide details and justifications of the simulation procedure, which involves performing molecular dynamics simulations at sufficiently low temperatures and minimizing the energy of the snapshots for both the high-density disordered regime, where the theory applies, as well as lower densities. We also use numerical simulations to extend our study to the lower-density regime. We report results for the pair correlation functions, structure factors, and Voronoi cell statistics. In the high-density regime, we verify the theoretical ansatz that stealthy disordered ground states behave like "pseudo" disordered equilibrium hard-sphere systems in Fourier space. The pair statistics obey certain exact integral conditions with very high accuracy. These results show that as the density decreases from the high-density limit, the disordered ground states in the canonical ensemble are characterized by an increasing degree of short-range order and eventually the system undergoes a phase transition to crystalline ground states. In the crystalline regime (low densities), there exist aperiodic structures that are part of the ground-state manifold but yet are not entropically favored. We also provide numerical evidence suggesting that different forms of stealthy pair potentials produce the same ground-state ensemble in the zero

  12. 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

  13. Patients with Spinal Cord Injuries Favor Administration of Methylprednisolone.

    PubMed

    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

  14. Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy.

    PubMed

    Farkas, Klaudia; Lakatos, Péter László; Nagy, Ferenc; Szepes, Zoltán; Miheller, Pál; Papp, Mária; Palatka, Károly; Bálint, Anita; Bor, Renáta; Wittmann, Tibor; Molnár, Tamás

    2013-12-01

    BACKGROUND. Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. The RASH study revealed that previous use of biological therapy and dose intensification are associated with restarting of biological therapy in Crohn's disease. The aim of the study was to assess the disease course and frequency of relapse of ulcerative colitis (UC) following discontinuation of infliximab in patients with remission and to determine predictive factors for relapse. PATIENTS AND METHODS. Fifty-one UC patients who had achieved clinical remission following 1 year of infliximab therapy and for whom infliximab was then discontinued participated in this prospective observational study. 15.7% of the patients received infliximab before the 1-year period of biological therapy analyzed in the study. Biological therapy was restarted in case of recurrent clinical activity. Data were collected from four Hungarian IBD centers. RESULTS. Thirty-five percent of the patients needed to be retreated with infliximab within 1 year after treatment cessation. Logistic regression analysis revealed that previous biological therapy (p = 0.021) was associated with the need of restarting infliximab. None of the data relating to patients' demographic and clinical characteristics, concomitant therapy and CRP level showed association with the need for restarting biological therapy. CONCLUSIONS. Biological therapy was restarted at a median of 4 months after discontinuation in more than every third UC patients who had been in clinical remission following 1 year of infliximab therapy. Response to retreatment with infliximab was favorable in the majority of the patients who relapsed. PMID:24131338

  15. Factors Mediating Alcohol Craving and Relapse: Stress, Compulsivity, and Genetics

    PubMed Central

    Rodd, Zachary A.; Anstrom, Kristin K; Knapp, Darin J.; Racz, Ildiko; Zimmer, Andreas; Serra, Salvatore; Bell, Richard L.; Woodward, Donald J.; Breese, George R.; Colombo, Giancarlo

    2010-01-01

    This article represents the proceedings of a symposium at the 2004 annual meeting of the International Society for Biomedical Research on Alcoholism in Heidelberg, Germany. The symposium was organized by Zachary A. Rodd and Giancarlo Colombo. The presentations were (1) Pharmacological reversal of cycled withdrawal-sensitized or stress-sensitized withdrawal anxiety and enhanced ethanol drinking, by Darin J. Knapp and George R. Breese, (2) Alcohol craving and relapse in rats genetically selected for high alcohol preference, by Zachary A. Rodd and Richard L. Bell, (3) Exposure to stress increases dopaminergic burst firing in awake rats, by Kristin Anstrom and Donald J. Woodward, (4) Involvement of cannabinoid CB1 and GABAB receptors in the control of relapse-like drinking in alcohol-preferring Sardinian alcohol-preferring rats by Giancarlo Colombo and Salvatore Serra, and (5) Stress-induced ethanol drinking in CB1−/−, POMC, and PENK knockout mice, by Idiko Racz and Andreas Zimmer. PMID:16088996

  16. 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

  17. An ecological momentary assessment of relapse crises in dieting.

    PubMed

    Carels, Robert A; Douglass, Olivia M; Cacciapaglia, Holly M; O'Brien, William H

    2004-04-01

    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 sedentary, postmenopausal women (N = 37) during the final week of a weight-loss intervention. Mood was associated with reports of dietary lapse. Abstinence-violation effects were more strongly associated with dietary lapses than temptations. Finally, coping responses distinguished dietary temptations from lapses. Education on the factors associated with relapse crises in dieting may be imperative for weight loss success and maintenance. PMID:15065966

  18. Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy

    PubMed Central

    Kobayashi, Takaaki; Moody, Sandra; Komori, Masafumi; Jibatake, Akira; Yaegashi, Makito

    2015-01-01

    Relapsing polychondritis is a rare inflammation of cartilaginous tissues, the diagnosis of which is usually delayed by a mean period of 2.9 years from symptom onset. We present the case of a 36-year-old man with nasal pain and fever. Physical examination of the nose was grossly unremarkable, but there was significant tenderness of the nasal bridge. Acute sinusitis was initially diagnosed due to thickened left frontal sinus mucosa on computed tomography (CT); however, there was no improvement after antibiotic intake. Repeat CT showed edematous inflammation of the nasal septum; biopsy of this site demonstrated erosion and infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils in the hyaline cartilage. Relapsing polychondritis was confirmed by the modified McAdam's criteria and can be diagnosed at an early stage by nasal septum biopsy; it should be considered as a differential diagnosis in patients presenting with nasal symptoms alone or persistent sinus symptoms. PMID:26843866

  19. 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. PMID:26186517

  20. Mutations driving CLL and their evolution in progression and relapse.

    PubMed

    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 L; Rosenberg, Mara; Hess, Julian M; Edelmann, Jennifer; Kless, Sabrina; Kneba, Michael; Ritgen, Matthias; Fink, Anna; Fischer, Kirsten; Gabriel, Stacey; Lander, Eric S; Nowak, Martin A; Döhner, Hartmut; Hallek, Michael; Neuberg, Donna; Getz, Gad; Stilgenbauer, Stephan; Wu, Catherine J

    2015-10-22

    Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set 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 data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome. PMID:26466571

  1. 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

  2. Outcome of and prognostic factors for relapse in children and adolescents with mature B-cell lymphoma and leukemia treated in three consecutive prospective "Lymphomes Malins B" protocols. A Société Française des Cancers de l'Enfant study.

    PubMed

    Jourdain, Anne; Auperin, Anne; Minard-Colin, Véronique; Aladjidi, Nathalie; Zsiros, Josef; Coze, Carole; Gandemer, Virginie; Bertrand, Yves; Leverger, Guy; Bergeron, Christophe; Michon, Jean; Patte, Catherine

    2015-06-01

    To describe relapsed B-cell lymphoma or leukemia in children/adolescents treated with a "Lymphomes Malins B" regimen and their outcome and to identify prognostic factors for survival, we studied relapses in the LMB89, 96 and 2001 studies of the Société Française d'Oncologie Pédiatrique (Société Française des Cancers de l'Enfant). Therapeutic guidelines at relapse were to obtain a second complete remission and to consolidate the remission with high-dose chemotherapy followed by autologous stem-cell transplantation. Between July 1989 and March 2007, 67 patients of 1322 (5%) relapsed: 57 had Burkitt lymphoma and 10 had large-cell histology. Three patients were initially treated in risk group A, 41 in group B and 23 in group C. Thirty-three patients had a relapse in one site (15 in the central nervous system) and 34 at multiple sites. Sixty-five patients received salvage chemotherapy and 33 achieved complete remission. Forty-one patients also received high-dose chemotherapy followed by autologous (n=33) or allogeneic (n=8) transplantation. With a median follow-up of 6.4 years, the 5-year survival rate was 29.9%. Nineteen patients were still alive, all but one (group A) received consolidation treatment. Multivariate analysis showed the following factors to be significantly associated with better survival: relapse at one site (P=0.0006), large-cell histology (P=0.012), initial prognostic group A or B with lactate dehydrogenase level below twice the normal value (P=0.005), and time to relapse more than 6 months (P=0.04). PMID:25724577

  3. Outcome of and prognostic factors for relapse in children and adolescents with mature B-cell lymphoma and leukemia treated in three consecutive prospective “Lymphomes Malins B” protocols. A Société Française des Cancers de l’Enfant study

    PubMed Central

    Jourdain, Anne; Auperin, Anne; Minard-Colin, Véronique; Aladjidi, Nathalie; Zsiros, Josef; Coze, Carole; Gandemer, Virginie; Bertrand, Yves; Leverger, Guy; Bergeron, Christophe; Michon, Jean; Patte, Catherine

    2015-01-01

    To describe relapsed B-cell lymphoma or leukemia in children/adolescents treated with a “Lymphomes Malins B” regimen and their outcome and to identify prognostic factors for survival, we studied relapses in the LMB89, 96 and 2001 studies of the Société Française d’Oncologie Pédiatrique (Société Française des Cancers de l’Enfant). Therapeutic guidelines at relapse were to obtain a second complete remission and to consolidate the remission with high-dose chemotherapy followed by autologous stem-cell transplantation. Between July 1989 and March 2007, 67 patients of 1322 (5%) relapsed: 57 had Burkitt lymphoma and 10 had large-cell histology. Three patients were initially treated in risk group A, 41 in group B and 23 in group C. Thirty-three patients had a relapse in one site (15 in the central nervous system) and 34 at multiple sites. Sixty-five patients received salvage chemotherapy and 33 achieved complete remission. Forty-one patients also received high-dose chemotherapy followed by autologous (n=33) or allogeneic (n=8) transplantation. With a median follow-up of 6.4 years, the 5-year survival rate was 29.9%. Nineteen patients were still alive, all but one (group A) received consolidation treatment. Multivariate analysis showed the following factors to be significantly associated with better survival: relapse at one site (P=0.0006), large-cell histology (P=0.012), initial prognostic group A or B with lactate dehydrogenase level below twice the normal value (P=0.005), and time to relapse more than 6 months (P=0.04). PMID:25724577

  4. Relapse of a maxillary median diastema: closure and permanent retention.

    PubMed

    Mattos, Claudia Trindade; da Silva, Dayanne Lopes; Ruellas, Antonio Carlos de Oliveira

    2012-01-01

    The purpose of this article was to describe the closure of a maxillary median diastema of a 26-year-old woman that had been corrected before during orthodontic treatment but reopened after dental trauma in a car accident. A clear esthetic device made from a tray like those used for home bleaching was used, providing a comfortable, nearly undetectable, and efficient solution. A permanent fixed retainer was bonded again to the maxillary central incisors to prevent relapse. PMID:22196198

  5. Stress Enhancement of Craving During Sobriety: A Risk for Relapse

    PubMed Central

    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

    2010-01-01

    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. Immune response to racotumomab in a child with relapsed neuroblastoma

    PubMed Central

    Sampor, C.; Guthmann, M. D.; Scursoni, A.; Cacciavillano, W.; Torbidoni, A.; Galluzzo, L.; Camarero, S.; Lopez, J.; de Dávila, M. T. G.; Fainboim, L.; Chantada, G. L.

    2012-01-01

    Immunotherapy targeting ganglioside antigens is a powerful tool for the treatment of high risk neuroblastoma. However, only treatment with anti-GD2 antibodies has been used in clinical practice and other options may be pursued. We report the use of racotumomab, an anti-idiotype vaccine against N-glycolyl neuraminic acid (NeuGc)- containing gangliosides, eliciting an immune response in a child with relapsed neuroblastoma expressing the NeuGcGM3 ganglioside. PMID:23267436

  7. Relapsing fever in pregnancy: analysis of high-risk factors.

    PubMed

    Melkert, P W

    1988-10-01

    The diagnosis of tick-borne relapsing fever was established in 27 pregnant patients by demonstration of Borrelia spirochaetes in a thick blood smear and the borrelia index was estimated to calculate the density of the spirochaetaemia. Clinical findings are described and compared with those reported from Rwanda. The results suggest that the density of the spirochaetaemia and the gestational age are the main high-risk factors. PMID:3191046

  8. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

    Hughes, Russell; Qian, Bin-Zhi; Rowan, Charlotte; Muthana, Munitta; Keklikoglou, Ioanna; Olson, Oakley C.; Tazzyman, Simon; Danson, Sarah; Addison, Christina; Clemons, Mark; Gonzalez-Angulo, Ana Maria; Joyce, Johanna A.; De Palma, Michele; Pollard, Jeffrey W.; Lewis, Claire E.

    2016-01-01

    Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1+TIE2HiCXCR4Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1+ TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1+ TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID:26269531

  9. [Fatigue in multiple sclerosis relapsing-remitting form].

    PubMed

    Mendes, M F; Tilbery, H P; Balsimell, S; Felipe, E; Moreira, M A; Barão-Cruz, A M

    2000-06-01

    In 95 patients with the remitting-relapsing form of multiple sclerosis we investigated fatigue. All of them were evaluated with the Fatigue Severity Scale and we found it in 64 patients (67.4%). Gender, age, depression and fuctional incapacity was not predictive of fatigue occurrence, while anxiety and time of disease seems to be correlated with it. When we analysed the fatigue severity, a correlation between the EDSS and the increasing fatigue severity was found. PMID:10920409

  10. Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse

    PubMed Central

    Yasur-Landau, Daniel; Jaffe, Charles L.; David, Lior; Baneth, Gad

    2016-01-01

    Background Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies. Methodology/Principal Findings Following our observation of clinical disease relapse in dogs under allopurinol treatment, we tested susceptibility to allopurinol of L. infantum isolated from groups of dogs pre-treatment, treated in remission, and with disease relapse during treatment. Promastigote isolates obtained from four treated relapsed dogs (TR group) showed an average half maximal inhibitory concentration (IC50) of 996 μg/mL. A significantly lower IC50 (P = 0.01) was found for isolates from ten dogs before treatment (NT group, 200 μg/mL), as well as for five isolates obtained from treated dogs in remission (TA group, 268 μg/mL). Axenic amastigotes produced from isolates of the TR group also showed significantly higher (P = 0.002) IC50 compared to the NT group (1678 and 671 μg/mL, respectively). The lower sensitivity of intracellular amastigotes from the TR group relative to those from the NT group (P = 0.002) was confirmed using an infected macrophage model (6.3% and 20% growth inhibition, respectively at 300 μg/mL allopurinol). Conclusions This is the first study to demonstrate allopurinol resistance in L. infantum and to associate it with disease relapse in the canine host. These findings are of concern as allopurinol is the main drug used for long term control of the disease in dogs, and resistant L. infantum strains may enhance uncontrolled transmission to humans and to other dogs. PMID:26735519

  11. 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.

  12. Hippocampal neurogenesis protects against cocaine-primed relapse

    PubMed Central

    Deschaux, Olivier; Vendruscolo, Leandro; Schlosburg, Joel; Diaz-Aguilar, Luis; Yuan, Clara J.; Sobieraj, Jeffery C.; George, Olivier; Koob, George F.; Mandyam, Chitra D.

    2012-01-01

    Accumulating evidence demonstrates a functional role for the hippocampus in mediating relapse to cocaine-seeking behavior and extinction-induced inhibition of cocaine seeking, and dentate gyrus neurogenesis in the hippocampus may have a role. Here, we tested the hypothesis that disruption of normal hippocampal activity during extinction alters relapse to cocaine-seeking behavior as a function of dentate gyrus neurogenesis. Adult rats were trained to self-administer cocaine on a fixed-ratio schedule, followed by extinction and cocaine-primed reinstatement testing. Some rats received low frequency stimulation (LFS; 2 Hz for 25 min) after each extinction session in the dorsal or ventral hippocampal formation. All rats received an injection of the mitotic marker 5-bromo-2′-deoxyuridine (BrdU) to label developing dentate gyrus neurons during self-administration, as well as before or after extinction and LFS. We found that LFS during extinction did not alter extinction behavior, but enhanced cocaine-primed reinstatement. Cocaine self-administration reduced levels of twenty-four day old BrdU cells and dentate gyrus neurogenesis, which was normalized by extinction. LFS during extinction prevented extinction-induced normalization of dentate gyrus neurogenesis and potentiated cocaine-induced reinstatement of drug seeking. LFS inhibition of extinction-induced neurogenesis was not due to enhanced cell death, revealed by quantification of activated caspase3 labeled cells. These data suggest that LFS during extinction disrupts hippocampal networking via disrupting neurogenesis and also strengthens relapse-like behaviors. Thus, newly born dentate gyrus neurons during withdrawal and extinction learning facilitate hippocampal networking that mediates extinction-induced inhibition of cocaine seeking and may play a key role in preventing relapse. PMID:23278919

  13. Brevibacterium casei isolated as a cause of relapsing peritonitis.

    PubMed

    Althaf, Mohammed Mahdi; Abdelsalam, Mohamed Said; Alsunaid, Mohammed Sunaid; Hussein, Maged Hassan

    2014-01-01

    We report a case of relapsing peritonitis in a 33-year-old woman on automated peritoneal dialysis. End-stage renal disease was secondary to systemic lupus erythematosus complicated with lupus nephritis. The organism isolated was Brevibacterium casei that was not readily identified, delaying appropriate management with an extended antibiotic course. Definite management of B casei peritonitis was peritoneal dialysis catheter removal. PMID:24648477

  14. 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

  15. 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

  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. Norepinephrine at the nexus of arousal, motivation and relapse.

    PubMed

    España, Rodrigo A; Schmeichel, Brooke E; Berridge, Craig W

    2016-06-15

    Arousal plays a critical role in cognitive, affective and motivational processes. Consistent with this, the dysregulation of arousal-related neural systems is implicated in a variety of psychiatric disorders, including addiction. Noradrenergic systems exert potent arousal-enhancing actions that involve signaling at α1- and β-noradrenergic receptors within a distributed network of subcortical regions. The majority of research into noradrenergic modulation of arousal has focused on the nucleus locus coeruleus. Nevertheless, anatomical studies demonstrate that multiple noradrenergic nuclei innervate subcortical arousal-related regions, providing a substrate for differential regulation of arousal across these distinct noradrenergic nuclei. The arousal-promoting actions of psychostimulants and other drugs of abuse contribute to their widespread abuse. Moreover, relapse can be triggered by a variety of arousal-promoting events, including stress and re-exposure to drugs of abuse. Evidence has long-indicated that norepinephrine plays an important role in relapse. Recent observations suggest that noradrenergic signaling elicits affectively-neutral arousal that is sufficient to reinstate drug seeking. Collectively, these observations indicate that norepinephrine plays a key role in the interaction between arousal, motivation, and relapse. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26773688

  18. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    PubMed

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  19. [Treatment of cocaine dependence. Intoxication, withdrawal and prevention of relapse].

    PubMed

    Preuss, U W; Bahlmann, M; Koller, G; Soyka, M

    2000-05-01

    The aim of this review article is to evaluate the treatment of cocaine-withdrawal, cocaine-intoxication and long-term relapse prevention of cocaine-addicts. Some 25% of police recognized first time drug users in Germany consume cocaine. However, there is an increasing number of cocaine-abusers and -addicts in the USA. The withdrawal of cocaine can be divided into three phases dominated mainly by psychiatric symptoms. Life-threatening condition can occur in cocaine-intoxication mainly in combination with other drug-use. A high risk of relapse is seen in follow-up trials of cocaine-addicts. Intensive craving, high cocaine- and substance-abuse is reported regularly in cocaine-addicts after detoxification therapy. Recommendations in the treatment of cocaine-intoxication, withdrawal and long-term relapse prevention are made. The use of antidepressives, anticonvulsants, dopaminergic and serotonergic medications as well as behavioural, psychoanalytical and combined therapies and their efficacy in clinical and trails is evaluated. A short review of new experimental therapies in the treatment of cocaine-dependence is shown. PMID:10858947

  20. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia.

    PubMed

    Yang, Jun J; Cheng, Cheng; Devidas, Meenakshi; Cao, Xueyuan; Fan, Yiping; Campana, Dario; Yang, Wenjian; Neale, Geoff; Cox, Nancy J; Scheet, Paul; Borowitz, Michael J; Winick, Naomi J; Martin, Paul L; Willman, Cheryl L; Bowman, W Paul; Camitta, Bruce M; Carroll, Andrew; Reaman, Gregory H; Carroll, William L; Loh, Mignon; Hunger, Stephen P; Pui, Ching-Hon; Evans, William E; Relling, Mary V

    2011-03-01

    Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries, not all children have benefited equally from this progress. Ethnic differences in survival after childhood ALL have been reported in many clinical studies, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse. PMID:21297632

  1. Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

    PubMed Central

    Jung, Young-Chul

    2006-01-01

    Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence. These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence. PMID:16642544

  2. Bevacizumab is safe in acute relapses of neuromyelitis optica

    PubMed Central

    Mealy, Maureen A.; Shin, Kyong; John, Gareth; Levy, Michael

    2015-01-01

    Objectives Neuromyelitis optica (NMO) is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. Current treatment for acute NMO attacks is immunosuppression with high-dose corticosteroids and/or plasmapheresis. Preclinical animal studies suggest that bevacizumab might be beneficial in limiting the extent of inflammation during a NMO relapse by reducing the disruption of the blood–brain barrier. Methods We carried out an open-label phase 1b safety and proof-of-concept trial in 10 participants with NMO immunoglobulin G seropositive NMO, NMO spectrum disease and those at high risk for developing NMO/NMO spectrum disease who presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused 10 mg/kg of bevacizumab intravenously on day 1 of treatment. The primary outcome measure was safety and the secondary outcome measure was efficacy. Results Of the 10 participants enrolled, five presented with acute transverse myelitis, four with acute optic neuritis and one with a brainstem lesion. Bevacizumab was safe in all 10 participants, with only one serious adverse event within the 90-day follow up that was not attributed to the medication. Three patients recovered to pre-attack neurological function or better, and no patients required escalation to plasmapheresis. Conclusions Bevacizumab is a safe add-on therapy to high-dose corticosteroids for NMO/NMO spectrum disease patients presenting with an acute relapse. PMID:26834844

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

    PubMed

    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

  4. 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

  5. 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.

  6. 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

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

    ClinicalTrials.gov

    2016-08-03

    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

  8. A Novel Surface Antigen of Relapsing Fever Spirochetes Can Discriminate between Relapsing Fever and Lyme Borreliosis▿ † ‡

    PubMed Central

    Lopez, Job E.; Schrumpf, Merry E.; Nagarajan, Vijayaraj; Raffel, Sandra J.; McCoy, Brandi N.; Schwan, Tom G.

    2010-01-01

    In a previous immunoproteome analysis of Borrelia hermsii, candidate antigens that bound IgM antibodies from mice and patients infected with relapsing fever spirochetes were identified. One candidate that was identified is a hypothetical protein with a molecular mass of 57 kDa that we have designated Borrelia immunogenic protein A (BipA). This protein was further investigated as a potential diagnostic antigen for B. hermsii given that it is absent from the Borrelia burgdorferi genome. The bipA locus was amplified and sequenced from 39 isolates of B. hermsii that had been acquired from western North America. bipA was also expressed as a recombinant fusion protein. Serum samples from mice and patients infected with B. hermsii or B. burgdorferi were used to confirm the immunogenicity of the recombinant protein in patients infected with relapsing fever spirochetes. Lastly, in silico and experimental analysis indicated that BipA is a surface-exposed lipoprotein in B. hermsii. These findings enhance the capabilities of diagnosing infection with relapsing fever spirochetes. PMID:20147497

  9. 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

  10. 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

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

    PubMed

    Olivares, José M; Sermon, Jan; Hemels, Michiel; Schreiner, Andreas

    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, were

  12. Histology of salmonid testes during maturation.

    PubMed

    Dziewulska, Katarzyna; Domagała, Józef

    2003-03-01

    The commonly applied classification systems of fish gonad maturity divide the maturation process into certain stages. However, the scales do not entirely reflect the continuity of the maturation process. Based on light microscope observations, the paper describes a comprehensive pattern of testicular transformations during maturation. The study was carried out on precocious underyearling and 1-year-old males of sea trout (Salmo trutta m. trutta L.), 1-year-old males of salmon (Salmo salar L.), and males of brown trout (Salmo trutta m. fario L.) aged from 7 months to 4 years. A total of 821 gonads collected during all seasons of the year were examined. The fish were fixed in Bouin's fluid. Histological slides of the mid-part of the gonad were made using the standard paraffin technique. The 3-6 microm sections were stained with Heidenhain haematoxylin. Histological changes of testes during maturation were similar in the three species studied. Immature and resting gonads contained type A spermatogonia in lobules only. The appearance of cystic structures containing type B spermatogonia in the lobules signalled the beginning of the sexual cycle in male gonads. Type B spermatogonia underwent synchronous mitotic divisions resulting in an increase in the total number of spermatogonia. As the spermatogenesis continued, the gonads showed a gradual increase in the number of cysts containing cells at all the spermatogenetic stages: type B spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa. The well-formed spermatozoa were released to the lobule lumen once the Sertoli cells and spermatozoa connections broke up and the cyst disappeared. This was a continuous process observed throughout the spawning season. The spermatozoa were moved to the efferent duct. While some of the germ cells were completing spermatogenesis, the lobules contained less and less cysts with type B spermatogonia, primary and secondary spermatocytes, and spermatids; eventually all

  13. Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy

    SciTech Connect

    Vrabec, T.R.; Augsburger, J.J.; Gamel, J.W.; Brady, L.W.; Hernandez, C.; Woodleigh, R. )

    1991-06-01

    The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

  14. Extremity Soft Tissue Sarcoma: Tailoring Resection to Histologic Subtype.

    PubMed

    Cable, Matthew G; Randall, R Lor

    2016-10-01

    Soft tissue sarcomas comprise tumors originating from mesenchymal or connective tissue. Histologic grade is integral to prognosis. Because sarcoma management is multimodal, histologic subtype should inform optimum treatment. Appropriate biopsy and communication between surgeon and pathologist can help ensure a correct diagnosis. Treatment often involves surgical excision with wide margins and adjuvant radiotherapy. There is no consensus on what constitutes an adequate margin for histologic subtypes. An appreciation of how histology corresponds with tumor biology and surgical anatomic constraints is needed for management of this disease. Even with the surgical goal of wide resection being obtained, many patients do not outlive their disease. PMID:27591492

  15. Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10-year single-institution experience of 142 consecutive patients.

    PubMed

    Leahy, Michael F; Turner, J Harvey

    2011-01-01

    Radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) has achieved objective response rates in clinical trials comparable with standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, but is relatively underused in routine practice. In this article, we report our clinical experience in 142 consecutive patients who received iodine-131 rituximab radioimmunotherapy for low-grade, predominantly follicular, relapsed NHL. Objective response rates of 67%, with complete response (CR) in 50% and median overall survival of 32 months, matched the response rates in a phase 2 clinical trial of (131)I-rituximab radioimmunotherapy and compares favorably with those reported for (131)I-tositumomab or (90)Y-ibritumomab tiuxetan. Progression-free survival was 18 months overall and 32 months in CR or CR-unconfirmed patients. Our patients comprised 107 (75%) follicular lymphoma, 21 (15%) small lymphocytic lymphoma, 6 (4%) mucosa-associated lymphoid tissue/marginal zone lymphoma, and 8 (6%) mantle-cell lymphoma, with median follow-up of 32 months and 8-year overall survival of 48%. Toxicity was limited to hematologic grade 4 neutropenia, occurring in 10% and thrombocytopenia in 6%. There were no episodes of bleeding or infection requiring hospital admission. Radioimmunotherapy with (131)I-rituximab in routine clinical outpatient practice provides cost-effective, safe treatment of relapsed/refractory indolent NHL, with half of patients achieving durable, complete remission with potential for repeat radioimmunotherapy on relapse. PMID:20864582

  16. Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters

    PubMed Central

    Wachtel, Mitchell S; Shome, Goutam; Sutherland, Mhairi; McGlone, John J

    2009-01-01

    Background The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure. Results The first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86). Conclusion A definition of murine histologic alterations resembling

  17. 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. PMID:25992042

  18. 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

  19. Spermatogenesis in Leptodactylus chaquensis. Histological study.

    PubMed

    Iruzubieta Villagra, Ana Lucrecia; Cisint, Susana Beatriz; Crespo, Claudia Alejandra; Medina, Marcela Fátima; Ramos, Inés; Fernández, Silvia Nélida

    2014-08-01

    The organization and the histological characteristics of Leptodactylus chaquensis testis throughout the reproductive cycle were analyzed in the presented study. Gonads of adult males, processed with routine techniques for optical microscopy, revealed that during the reproductive period the seminiferous tubules were characterized by presentation of a large number of cysts, germ cells at the same maturation stage supported by Sertoli cells. All the germ line cells were also present in the postreproductive period and maintained their morphological characteristics. Primary spermatogonia were large-sized cells found isolated or in small groups. The rest of the cells of the germ line formed cysts. Secondary spermatogonia showed morphological characteristics similar to their predecessors, although they were smaller. Primary and secondary spermatocytes showed images of the different stages of the first and second meiotic division respectively. One finding was the presence of intercytoplasmic bridges between the secondary spermatocytes. Primary spermatids were rounded cells with an acrosomal vesicle associated with the nucleus and had cysts that were characterized by large intercellular spaces. Secondary spermatids were elongated cells with a well defined acrosome, which in the spermatozoa had the shape of an arrowhead. Another peculiar characteristic of this species was the fusion of the walls of the seminiferous tubule with the efferent duct that formed a path for spermatozoa during spermiation. The presence in the seminiferous tubules of all stages of the spermatogenic line during the two periods of the cycle studied indicated that Leptodactylus chaquensis had a potentially continuous reproductive cycle. PMID:23171585

  20. Histological investigations on the Tyrolean Ice Man.

    PubMed

    Hess, M W; Klima, G; Pfaller, K; Künzel, K H; Gaber, O

    1998-08-01

    The 5,200-year-old Tyrolean Ice Man discovered in 1991 in the Otztal Alps is the world's most ancient known human glacier mummy. Histological investigation was aimed at 1) optimizing specimen preparation and 2) documenting the preservation state of (sub)cellular components. Minute pieces of frozen tissue were removed endoscopically from rib bone and cartilage, major blood vessels, oral cavity and alimentary tract, liver, spleen, diaphragm, respiratory system, femoral muscle and nerve, sympathetic trunk, brain, and skin. Double fixation with glutaraldehyde followed by osmium tetroxide and embedding in Epon/Araldite epoxy resins proved to be the method of choice for both light and transmission electron microscopy combined with classical histochemistry. In particular, mild evacuation of the desiccated tissue was determined to be essential to ensure homogeneous infiltration with fixatives and resins; as a result, sections of excellent quality could be obtained with any kind of sample. With regard to the preservation degree of (sub)cellular components, distinct tissue-specific patterns were observed. There were highly intact skeletal and connective tissues proper, however, most interestingly, there were remarkably intact nervous tissue components as well. By contrast, epithelial, muscle, and reticular connective tissues as well as blood had generally disintegrated due to autolysis, freeze/thaw damage, and adipocere formation. For a tentative interpretation of these patterns, we considered general aspects of cryopreservation, such as physicochemical properties of subcellular constituents and tissue physiology. PMID:9712480

  1. 45 CFR 73.735-501 - Prohibited acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Prohibited acceptance of gifts, entertainment, and favors. 73.735-501 Section 73.735-501 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-501 Prohibited acceptance of gifts, entertainment, and favors....

  2. Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption.

    PubMed

    Vengeliene, Valentina; Noori, Hamid R; Spanagel, Rainer

    2015-12-01

    Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effects on alcohol consumption. We conclude that targeting the melatonergic system in alcohol-dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behavior. PMID:25994077

  3. 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

  4. 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

  5. [Emerging new therapies for relapsing remitting multiple sclerosis].

    PubMed

    Anis, Saar; Achiron, Anat

    2014-11-01

    For the last 20 years the classic treatment for relapsing remitting multiple sclerosis was based on injectable disease-modifying drugs, interferon-β and glatiramer acetate (copaxone). Currently, new disease-modifying drugs have been added to the clinician's arsenal with similar and even improved efficacy and safety profiles. Some of these drugs are given orally and are recommended as first line treatment. In this review we will discuss the various innovative and emerging disease-modifying drugs including the method of administration, mechanism of action, efficacy, safety and major side effects. PMID:25563027

  6. Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis.

    PubMed

    Delval, Arnaud; Stojkovic, Tanya; Vermersch, Patrick

    2006-02-01

    A 72-year-old man presented with oculomotor dysfunction, subacute relapsing sensorimotor neuropathy, elevated erythrocyte sedimentation rate, IgM monoclonal paraprotein, cold agglutinins, and antidisialosyl IgM antibodies, features previously described by the acronym CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M protein, agglutination, and disialosyl antibodies). The patient also had extramembranous glomerulopathy associated with this syndrome. Treatment with corticosteroids improved both the neuropathy and glomerulopathy. This case suggests that the spectrum of neuropathy associated with monoclonal gammopathy may be broader than originally believed. PMID:16258949

  7. Rituximab add-on therapy for breakthrough relapsing multiple sclerosis

    PubMed Central

    Naismith, R.T.; Piccio, L.; Lyons, J.A.; Lauber, J.; Tutlam, N.T.; Parks, B.J.; Trinkaus, K.; Song, S.K.; Cross, A.H.

    2010-01-01

    Objective: B cells and the humoral immune system have been implicated in the pathogenesis of multiple sclerosis (MS). This study sought to evaluate the efficacy, safety, and tolerability of add-on therapy with rituximab, a monoclonal antibody that depletes circulating B cells, in subjects with relapsing MS with breakthrough disease defined by clinical and MRI activity (Class III evidence). Methods: Thirty subjects with a relapse within the past 18 months despite use of an injectable disease-modifying agent, and with at least 1 gadolinium-enhancing (GdE) lesion on any of 3 pretreatment MRIs, received rituximab administered at 375 mg/m2 weekly × 4 doses. Three monthly posttreatment brain MRI scans were obtained beginning 12 weeks after the first infusion. Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were obtained at baseline and throughout the posttreatment follow-up. Results: GdE lesions were reduced after treatment with rituximab, with 74% of posttreatment MRI scans being free of GdE activity compared with 26% free of GdE activity at baseline (p < 0.0001). Median GdE lesions were reduced from 1.0 to 0, and mean number was reduced from 2.81 per month to 0.33 after treatment (88% reduction). MSFC improved as well (p = 0.02). EDSS remained stable. Conclusion: Rituximab add-on therapy was effective based upon blinded radiologic endpoints in this phase II study. In combination with standard injectable therapies, rituximab was well-tolerated with no serious adverse events. B-cell–modulating therapy remains a potential option for treatment of patients with relapsing MS with an inadequate response to standard injectable therapies. Classification of evidence: This study provides Class III evidence that add-on rituximab reduces gadolinium-enhancing brain lesions in multiple sclerosis. GLOSSARY DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; FOV = field of view; GdE = gadolinium-enhancing; HACA = human

  8. Progressive relapse of ligamentum flavum ossification following decompressive surgery.

    PubMed

    Ando, Kei; Imagama, Shiro; Ito, Zenya; Kobayashi, Kazuyoshi; Ukai, Junichi; Muramoto, Akio; Shinjo, Ryuichi; Matsumoto, Tomohiro; Nakashima, Hiroaki; Ishiguro, Naoki

    2014-12-01

    Thoracic ossification of the ligamentum flavum (T-OLF) is a relatively rare spinal disorder that generally requires surgical intervention, due to its progressive nature and the poor response to conservative therapy. The prevalence of OLF has been reported at 3.8%-26%, which is similar to that of cervical ossification of the posterior longitudinal ligament (OPLL). The progression of OPLL after cervical laminoplasty for the treatment of OPLL is often shown in long-term follow-up. However, there have been no reports on the progression of OLF following surgery. We report a case of thoracic myelopathy secondary to the progressive relapse of OLF following laminectomy. PMID:25558329

  9. Could magnetic resonance provide in vivo histology?

    PubMed Central

    Dominietto, Marco; Rudin, Markus

    2014-01-01

    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. PMID:24454320

  10. Adequate histologic sectioning of prostate needle biopsies.

    PubMed

    Bostwick, David G; Kahane, Hillel

    2013-08-01

    No standard method exists for sampling prostate needle biopsies, although most reports claim to embed 3 cores per block and obtain 3 slices from each block. This study was undertaken to determine the extent of histologic sectioning necessary for optimal examination of prostate biopsies. We prospectively compared the impact on cancer yield of submitting 1 biopsy core per cassette (biopsies from January 2010) with 3 cores per cassette (biopsies from August 2010) from a large national reference laboratory. Between 6 and 12 slices were obtained with the former 1-core method, resulting in 3 to 6 slices being placed on each of 2 slides; for the latter 3-core method, a limit of 6 slices was obtained, resulting in 3 slices being place on each of 2 slides. A total of 6708 sets of 12 to 18 core biopsies were studied, including 3509 biopsy sets from the 1-biopsy-core-per-cassette group (January 2010) and 3199 biopsy sets from the 3-biopsy-cores-percassette group (August 2010). The yield of diagnoses was classified as benign, atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, and cancer and was similar with the 2 methods: 46.2%, 8.2%, 4.5%, and 41.1% and 46.7%, 6.3%, 4.4%, and 42.6%, respectively (P = .02). Submission of 1 core or 3 cores per cassette had no effect on the yield of atypical small acinar proliferation, prostatic intraepithelial neoplasia, or cancer in prostate needle biopsies. Consequently, we recommend submission of 3 cores per cassette to minimize labor and cost of processing. PMID:23764163

  11. Lip enhancement: surgical alternatives and histologic aspects.

    PubMed

    Niechajev, I

    2000-03-01

    This study included 66 consecutive patients, 58 women and 8 men, who underwent 86 surgical procedures on the lips during 1989-1998. Lip enlargement was performed in 59 patients, and lip reduction was performed in 7 patients. Indications were purely aesthetic in 61 cases and reconstructive in 5 cases. The following surgical techniques were used for lip augmentation: implantation of crystal silicone, polyacrylamide hydrogel, Gore-Tex tubes, autologous fat, and dermis-fat graft. A new instrument originally designed by the author, the dermis-fat graft passer, significantly speeded up and facilitated execution of the latter procedure. Other operations included V-Y plasty, lip lifting by buffalo horn excision, lip lengthening by frenulum plasty, and lip reduction by wavy tangential excision. Eighty-six percent of patients could be followed up; the mean length of follow-up was 4.2 years. Use of silicone microparticles (Bioplastique) was abandoned because of the tendency for lumping. Polyacrylamide gel is promising because of its ease of use, and Gore-Tex tubes are promising because of their ability to create and accentuate the Cupid's bow form for the upper lip. However, these products are new, and follow-up studies with longer observation times are needed to reach definite conclusions. Of these studied methods, autologous fat transplant was found to be particularly useful for enlargement and restoration in cases of age-related atrophy of the lips and perioral tissues. Dermis-fat grafting was the most efficient, versatile, and reliable method of lip enlargement. Long-term survival of transplanted autologous tissues was confirmed by histologic studies of biopsy specimens. PMID:10724279

  12. 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.

  13. 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…

  14. Bowenoid papulosis: clinical and histological study of eight cases.

    PubMed Central

    Gimeno, E; Vilata, J J; Sanchez, J L; Lloret, A; Fortea, J M

    1987-01-01

    Eight cases of bowenoid papulosis are reported. The clinical diagnoses were confirmed by histology. In one case an immunoperoxidase method showed the presence of papillomavirus antigen in the nucleus of the most superficial epidermal cells. We consider bowenoid papulosis to be a condition with specific features that distinguish it clinically and histologically from carcinoma in situ and condylomata acuminata. Images PMID:3034760

  15. Amplification of D22S283 as a favorable prognostic indicator in liver fluke related cholangiocarcinoma

    PubMed Central

    Thanasai, Jongkonnee; Limpaiboon, Temduang; Jearanaikoon, Patcharee; Bhudhisawasdi, Vajarabhongsa; Khuntikeo, Narong; Sripa, Banchob; Miwa, Masanao

    2006-01-01

    AIM: To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma (CCA) and define its correlation with clinical parameters. METHODS: Quantitative real time PCR (qPCR) was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the χ2 test. Cox regression analysis was used for determining patient’s survival. RESULTS: Amplifications of the TP (22q13.33), TOB2 (22q13.2-13.31), D22S283 (22q12.3), TIMP3 (22q12.3) and NF2 (22q12.2) were found in 35 (53.8%), 28 (43.1%), 27 (41.5%), 24 (36.9%), and 24 (36.9%), respectively. Losses at the D22S423 (22q13.1-13.2) and BIK (22q13.31) were detected in 26 (40%) and 23 (35.4%), respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK (P = 0.025) and D22S283 (P = 0.041). Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis (P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779) and blood vessel invasion as an independent poor prognostic factor (P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571) in CCA patients. CONCLUSION: This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA. This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA. PMID:16865775

  16. Atypical pediatric ganglioglioma is common and associated with a less favorable clinical course.

    PubMed

    Patibandla, Mohana Rao; Ridder, Thomas; Dorris, Kathleen; Torok, Michelle R; Liu, Arthur K; Handler, Michael H; Stence, Nicholas V; Fenton, Laura Z; Hankinson, Todd C

    2016-01-01

    OBJECT Ganglioglioma (GG) is commonly recognized as a low-grade tumor located in the temporal lobe, often presenting with seizures. Most are amenable to complete resection and are associated with excellent oncological outcome. The authors encountered several GGs in various locations, which seem to have a less favorable clinical course than GGs in the temporal lobe. METHODS The authors performed a single-center retrospective review of all children with a histological diagnosis of GG who were treated at Children's Hospital Colorado between 1997 and 2013. Each tumor was categorized by 2 pediatric neuroradiologists as typical or atypical based on preoperative MRI appearance. Typical lesions were cortically based, within a single cerebral lobe, well-circumscribed, and solid or mixed solid/cystic. The treatment and clinical course of each patient was analyzed. RESULTS Thirty-seven children were identified, with a median age at presentation of 8.2 years and median follow-up of 38.0 months. Eighteen tumors (48.6%) were typical and 19 (51.4%) were atypical. All typical lesions presented with seizures, whereas no atypical lesions did so. Sixteen (88.9%) typical lesions were located in the temporal lobe. In the atypical group, tumor location was variable, including 11 (57.9%) in the brainstem. Death during follow-up was statistically more common in the atypical group (31.6% vs 0%, p = 0.02). Gross-total resection (GTR) was achieved for 15 of 16 typical tumors (93.8%), compared with 3 atypical tumors (15.8%, p < 0.0001). Presentation with seizure or non-brainstem location were each associated with survival (p = 0.02 and 0.004, respectively). The presence of mutation in BRAF exon 15 did not differ between the 2 groups. CONCLUSIONS Pediatric GG with typical imaging features is associated with excellent rates of GTR and overall survival. Atypical GG is commonly encountered, less amenable to GTR, and associated with a worse outcome. This may relate to anatomical or biological

  17. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing.

    PubMed

    Ding, Li; Ley, Timothy J; Larson, David E; Miller, Christopher A; Koboldt, Daniel C; Welch, John S; Ritchey, Julie K; Young, Margaret A; Lamprecht, Tamara; McLellan, Michael D; McMichael, Joshua F; Wallis, John W; Lu, Charles; Shen, Dong; Harris, Christopher C; Dooling, David J; Fulton, Robert S; Fulton, Lucinda L; Chen, Ken; Schmidt, Heather; Kalicki-Veizer, Joelle; Magrini, Vincent J; Cook, Lisa; McGrath, Sean D; Vickery, Tammi L; Wendl, Michael C; Heath, Sharon; Watson, Mark A; Link, Daniel C; Tomasson, Michael H; Shannon, William D; Payton, Jacqueline E; Kulkarni, Shashikant; Westervelt, Peter; Walter, Matthew J; Graubert, Timothy A; Mardis, Elaine R; Wilson, Richard K; DiPersio, John F

    2012-01-26

    Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions. PMID:22237025

  18. Impact of childhood trauma on risk of relapse requiring psychiatric hospital admission for psychosis.

    PubMed

    Petros, N; Foglia, E; Klamerus, E; Beards, S; Murray, R M; Bhattacharyya, S

    2016-08-01

    Relapse in psychosis typically necessitates admission to hospital placing a significant financial burden on the health service. Exposure to childhood trauma is associated with an increased risk of psychosis, however, the extent to which this influences relapse is unclear. This report summarises current research investigating the influence of childhood trauma on relapse requiring psychiatric hospital admission for psychosis. Seven studies were included; two revealed a positive association between childhood trauma and relapse admission, two studies found a negative relationship and three found no significant difference. Inconsistent current evidence suggests a need for further research in this area. PMID:27151070

  19. Predictors of relapse in Filipino male methamphetamine users: a mixed methods approach.

    PubMed

    Tuliao, Antover P; Liwag, Maria Emma Concepcion D

    2011-01-01

    Using a simultaneous mixed methods design, this article studies the relapse predictors of Filipino methamphetamine abusers. Results of the quantitative study, with 32 relapsed and 19 abstaining individuals, indicate that self-efficacy, negative affect, motivation, coping, and craving were found to predict relapse and functional social support did not. In-depth interviews with 11 relapse and 10 abstaining individuals supported the quantitative study. Although the results mirror existing literature, the issue of social support was given emphasis in the discussion. Implications for treatment, limitations, and recommendations for future study are also discussed. PMID:21678148

  20. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-11

    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

  1. Dermoscopy of Grover's disease: Variability according to histological subtype.

    PubMed

    Errichetti, Enzo; De Francesco, Vincenzo; Pegolo, Enrico; Stinco, Giuseppe

    2016-08-01

    Distinguishing Grover's disease from other papular dermatoses is often a troublesome task. According to two relatively recent case reports, dermoscopy may be useful in assisting the diagnosis of such a disorder by showing a peculiar pattern. The aim of this study was to evaluate the dermoscopic features of Grover's disease in a larger series of patients and correlate dermoscopy with histopathological findings. Seven patients with histopathologically confirmed Grover's disease were included in the study, with three of them displaying a Darier-like histology and the remaining four cases having a spongiotic histological pattern. The results of our study suggest that Grover's disease may display different features according to the histological subtype, with a central star-shaped/branched polygonal/roundish-oval brownish area surrounded by a whitish halo being characteristic of the Darier-like histological subtype and whitish scales over a reddish-yellowish background being characteristic of the spongiotic histological subtype. PMID:26892381

  2. Histological Study of Fresh Versus Frozen Semitendinous Muscle Tendon Allografts

    PubMed Central

    Bitar, Alexandre Carneiro; Santos, Luiz Augusto Ubirajara; Croci, Alberto Tesconi; Pereira, João Alberto Ramos Maradei; França Bisneto, Edgard N.; Giovani, Arlete Mazzini Miranda; Oliveira, Claudia Regina G. C. M.

    2010-01-01

    OBJECTIVE: The purpose of this study was to histologically analyze allografts from cadaveric semitendinous muscle after cryopreservation at −80°C in comparison to a control group kept at only −4°C to test the hypothesis that the histological characteristics of the tissue are maintained when the tendons are kept at lower temperatures. METHODS: In a tissue bank, 10 semitendinous tendons from 10 cadavers were frozen at −80ºC as a storage method for tissue preservation. They were kept frozen for 40 days, and then a histological study was carried out. Another 10 tendon samples were analyzed while still “fresh”. RESULTS: There was no histological difference between the fresh and frozen samples in relation to seven variables. CONCLUSIONS: Semitendinous muscle tendon allografts can be submitted to cryopreservation at −80ºC without suffering histological modifications. PMID:20360921

  3. Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma: NPI-0052-101 Part 1.

    PubMed

    Richardson, Paul G; Zimmerman, Todd M; Hofmeister, Craig C; Talpaz, Moshe; Chanan-Khan, Asher A; Kaufman, Jonathan L; Laubach, Jacob P; Chauhan, Dharminder; Jakubowiak, Andrzej J; Reich, Steven; Trikha, Mohit; Anderson, Kenneth C

    2016-06-01

    Marizomib (MRZ) is a novel, irreversible proteasome inhibitor in clinical development for the treatment of relapsed or relapsed and refractory multiple myeloma (RRMM). MRZ inhibits the 3 proteolytic activities of the 20S proteasome with specificity distinct from bortezomib and carfilzomib. Study NPI-0052-101 Part 1 enrolled relapsed or RRMM patients into an open-label, dose-escalation design to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of MRZ administered intravenously on 2 different schedules: schedule A (0.025-0.7 mg/m(2) once weekly on days 1, 8, and 15 of 4-week cycles) and schedule B (0.15-0.6 mg/m(2) twice weekly on days 1, 4, 8, and 11 of 3-week cycles; concomitant dexamethasone was allowed with schedule B). Patients had received an average of 4.9 and 7.3 prior treatment regimens (schedules A and B, respectively). MRZ schedule A was administered to 32 patients, and the RP2D was established as 0.7 mg/m(2) infused over 10 minutes. Schedule B was administered to 36 patients, and the RP2D was determined to be 0.5 mg/m(2) infused over 2 hours. The most common (>20% of patients) related adverse events were fatigue, headache, nausea, diarrhea, dizziness, and vomiting. Six patients achieved clinical benefit responses (defined as minimal response or better), including 5 partial responses (1 patient on schedule A and 4 on schedule B; 3 of these 4 patients received concomitant dexamethasone). MRZ was generally well tolerated, and results suggest activity in previously treated RRMM patients. Combination studies using pomalidomide and dexamethasone are now underway. The trial was registered at www.clinicaltrials.gov as #NCT00461045. PMID:27009059

  4. Granuloma Annulare Mimicking Sarcoidosis: Report of Patient With Localized Granuloma Annulare Whose Skin Lesions Show 3 Clinical Morphologies and 2 Histology Patterns.

    PubMed

    Cohen, Philip R; Carlos, Casey A

    2015-07-01

    Granuloma annulare, a benign dermatosis of undetermined etiology, typically presents in a localized or generalized form. It has 3 distinctive histologic patterns: an infiltrative (interstitial) pattern, a palisading granuloma pattern, and an epithelioid nodule (sarcoidal granuloma) pattern. A man whose granuloma annulare skin lesions mimicked sarcoidosis is described. His localized granuloma annulare presented with a total of 3 lesions that each had a distinctive clinical morphology: an annular lesion of individual papules, a dermal nodule, and a linear arrangement of 3 papules. Two of his lesions showed a palisading granuloma histology pattern of granuloma annulare; however, the linear papules on his posterior neck lesion demonstrated noncaseating granulomas consistent with either the epithelioid nodule histology pattern of granuloma annulare or sarcoidal granuloma compatible with sarcoidosis. A comprehensive evaluation excluded the diagnosis of systemic sarcoidosis. Using the PubMed database, an extensive literature search was performed on granuloma annulare, epithelioid nodule, sarcoidal granuloma, and sarcoidosis. The histology patterns of granuloma annulare-emphasizing the history and differentiating features of the epithelioid nodule pattern from cutaneous sarcoidosis-were reviewed. The epithelioid nodule (sarcoidal granuloma) histology pattern of granuloma annulare is uncommon and may mimic the histology changes observed in sarcoidosis skin lesions; the absence of asteroid or other giant cell inclusions and an increase in mucin deposition between the collagen bundles favor the diagnosis of granuloma annulare. In addition, the epithelioid nodule pattern of granuloma annulare can rarely also show other histologic patterns of granuloma annulare in the same biopsy specimen or concurrently present with other clinical lesions of granuloma annulare that demonstrate a palisading granuloma, or possibly an infiltrative, histology pattern. However, the presence of an

  5. ITAREPS: information technology aided relapse prevention programme in schizophrenia.

    PubMed

    Spaniel, Filip; Vohlídka, Pavel; Hrdlicka, Jan; Kozený, Jirí; Novák, Tomás; Motlová, Lucie; Cermák, Jan; Bednarík, Josef; Novák, Daniel; Höschl, Cyril

    2008-01-01

    ITAREPS presents a mobile phone-based telemedicine solution for weekly remote patient monitoring and disease management in schizophrenia and psychotic disorders in general. The programme provides health professionals with home telemonitoring via a PC-to-phone SMS platform that identifies prodromal symptoms of relapse, to enable early intervention and prevent unnecessary hospitalizations. Its web-based interface offers the authorized physician a longitudinal analysis of the dynamics and development of possible prodromes. This work presents preliminary findings from a one-year mirror-design follow-up evaluation of the programme's clinical effectiveness in 45 patients with psychotic illness. There was a statistically significant 60% decrease in the number of hospitalizations during the mean 283.3+/-111.9 days of participation in the ITAREPS, compared to the same time period before the ITAREPS entry (sign test, p<0.004). Variables significantly influencing the number of hospitalizations after the ITAREPS entry (medication compliance along with factors intrinsic to the ITAREPS, i.e. adherence to the programme and involvement of a family member) suggest a critical role of the programme in controlling the number of relapses and subsequent hospitalizations in psychosis. PMID:17920245

  6. 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. PMID:26466819

  7. Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma.

    PubMed

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

    2016-01-12

    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

  8. 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. PMID:26644094

  9. 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. PMID:24700533

  10. Lenalidomide for the treatment of relapsed and refractory multiple myeloma

    PubMed Central

    van de Donk, Niels WCJ; Görgün, Güllü; Groen, Richard WJ; Jakubikova, Jana; Mitsiades, Constantine S; Hideshima, Teru; Laubach, Jacob; Nijhof, Inger S; Raymakers, Reinier A; Lokhorst, Henk M; Richardson, Paul G; Anderson, Kenneth C

    2012-01-01

    Lenalidomide is an amino-substituted derivative of thalidomide with direct antiproliferative and cytotoxic effects on the myeloma tumor cell, as well as antiangiogenic activity and immunomodulatory effects. Together with the introduction of bortezomib and thalidomide, lenalidomide has significantly improved the survival of patients with relapsed and refractory myeloma. The most common adverse events associated with lenalidomide include fatigue, skin rash, thrombocytopenia, and neutropenia. In addition, when lenalidomide is combined with dexamethasone or other conventional cytotoxic agents, there is an increase in the incidence of venous thromboembolic events. There is now evidence that continued treatment with lenalidomide has a significant impact on survival by improving the depth and duration of response. This highlights the value of adverse event management and appropriate dose adjustments to prevent toxicity, and of allowing continued treatment until disease progression. In this review, we will discuss the different lenalidomide-based treatment regimens for patients with relapsed/refractory myeloma. This is accompanied by recommendations of how to manage and prevent adverse events associated with lenalidomide-based therapy. PMID:22956884

  11. 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.

  12. Longitudinal pancreaticojejunostomy in chronic relapsing pancreatitis with onset in childhood.

    PubMed Central

    Scott, H W; Neblett, W W; O'Neill, J A; Sawyers, J L; Avant, G S; Starnes, V A

    1984-01-01

    Despite the rarity of chronic relapsing pancreatitis in children, in the last 15 years at Vanderbilt University Medical Center and its Children's Hospital we have used longitudinal pancreaticojejunostomy in treatment of eight patients whose symptoms began in childhood. Duration of symptoms ranged from 2 to 36 years. Seven of the eight patients had hereditary pancreatitis. Recurrent epigastric pain was characteristic and serum amylase was elevated in all patients on admission or shortly thereafter. Demonstration of an obstructed dilated pancreatic duct in all and stones in seven of eight patients by operative pancreatography in three early patients and by endoscopic retrograde cholangiopancreatography (ERCP) in five others established the therapeutic problem and facilitated treatment by removal of stones and longitudinal pancreaticojejunostomy. Results were uniformly excellent, both in the early postoperative period and in long-range follow-ups. Early diagnosis and early surgical drainage of the obstructed pancreatic duct by longitudinal pancreaticojejunostomy are desirable objectives in chronic relapsing pancreatitis with onset in childhood. Images Fig. 6. Fig. 7. Fig. 8. PMID:6721610

  13. ["Fossa" carcinoma - a relapse or "rest" carcinoma of the kidney?].

    PubMed

    Panchev, P; Ianev, K; Georgiev, M; Kirilov, S; Kumanov, Kh

    2000-01-01

    The local relapse represents a unique variant of the advanced stage of a disease (A Esrig et 1992). Presumably, "fossa" carcinoma may result from incomplete resection or persisting tumor in the regional contiguous lymph nodes (JB D Kernion 1978). The average time interval for a relapse to occur is 31 months after nephrectomy, and in most patients it becomes manifest with symptoms, such as losing weight, fatigability and lumbar discomfort (D Esrig et al 1992). In cases with local recurrence a long-term survivorship may be attained by resorting to aggressive surgical intervention (S Tanguag et al 1996). This is a report on twenty-three patients with "fossa" carcinoma covering the period 1994 through 1999, with a total of 425 patients with renal carcinoma operated during the same period of time. All patients undergo operation--lumbar access is used in 22 cases, and transperitoneal--in one. In one patients resection of colon is necessitated, whereas in five the neoplastic mass hardly lends itself to complete excision, with enucleation alone being done. At follow-up study the survival terms are as follows: up to 1 year--18 patients, up to 3 year--16 patients, up to 5 year--12 patients. PMID:11692915

  14. Relapsing CD8+ encephalitis-looking for a solution.

    PubMed

    Salam, Sharfaraz; Mihalova, Tatiana; Ustianowski, Andrew; McKee, David; Siripurapu, Rehka

    2016-01-01

    CD8+ encephalitis (CD8+E) is an emerging and incompletely understood HIV-associated neurological syndrome, typically presenting as a steroid-responsive subacute encephalopathy with prominent white matter changes in patients with apparently well-controlled HIV infection. Some cases can be associated with the phenomenon of 'viral escape' (disproportionate replication within the cerebrospinal fluid), but the most important pathophysiology of CD8+E is thought to involve an attack on HIV-infected CD4+ lymphocytes by autoreactive CD8+ cells. We report a case of CD8+E where the initial positive response to steroid treatment was followed by several relapses on withdrawal. This led to the use of mycophenolate mofetil (MMF) as a long-term steroid-sparing agent, which is the first time this approach has been reported in the literature. The patient has now been on treatment with MMF for 10 months and it has been possible to taper the steroids down to a minimal maintenance dose without further relapse. PMID:27335359

  15. IL-1β inhibits ILC3 while favoring NK-cell maturation of umbilical cord blood CD34(+) precursors.

    PubMed

    Ambrosini, Paolo; Loiacono, Fabrizio; Conte, Romana; Moretta, Lorenzo; Vitale, Chiara; Mingari, Maria Cristina

    2015-07-01

    NK cells are innate lymphocytes characterized by the expression of nuclear factor interleukin 3 regulated (NFIL3 or E4BP4), eomesodermin (EOMES) transcription factors (TFs), and by the ability to exert cytolytic activity and release IFN-γ. In the haploidentical-hematopoietic stem cell transplantation (haplo-HSCT) setting, CD34(+) donor derived NK cells play a major role in the control of leukemic relapses. Therefore, it is important to better define cytokines that influence NK-cell differentiation from CD34(+) precursors. We analyzed the effects of IL-1β on NK-cell differentiation from umbilical cord blood (UCB) CD34(+) cells. While IL-1β inhibited CD161(+) CD56(+) cell proliferation, an increased expression of LFA-1, CD94/NKG2A, KIRs, and perforin on CD56(+) cells was detected. In addition, within the CD161(+) CD56(+) IL-1RI(+) LFA-1(-) cell fraction (representing group 3 innate lymphoid cells, ILC3-like cells), a significant increase of EOMES, NKp46, and CD94/NKG2A receptors, cytolytic granules, and IFN-γ was detected. This increase was paralleled by a decrease of related orphan receptors (RORγt) TF, NKp44 expression, and IL-22 production. These data suggest that IL-1β inhibits ILC3- while favoring NK-cell maturation. Since in haplo-HSCT conditioning regimen, infections or residual leukemia cells may induce IL-1β production, this may influence the NK/ILC3 development from donor-derived CD34(+) precursors. PMID:25847448

  16. Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study

    PubMed Central

    Kermani, Tanaz A.; Warrington, Kenneth J.; Cuthbertson, David; Carette, Simon; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; Maksimowicz-McKinnon, Kathleen; McAlear, Carol A.; Monach, Paul A.; Seo, Philip; Merkel, Peter A.; Ytterberg, Steven R.

    2015-01-01

    Objective To evaluate the frequency, timing, and clinical features of relapses in giant cell arteritis (GCA). Methods Patients with GCA enrolled in a prospective, multicenter, longitudinal study were included in the analysis. Relapse was defined as either new disease activity after a period of remission or worsening disease activity. Results The study included 128 subjects: 102 women (80%) and 26 men (20%). Mean ± SD age at diagnosis of GCA was 69.9 ± 8.6 years. Mean followup for the cohort was 21.4 ± 13.9 months. Median (interquartile range) duration of disease at study enrollment was 4.6 months (1.2, 16.8). During followup, 59 relapses were observed in 44 patients (34%). Ten patients (8%) experienced 2 or more relapses. The most common symptoms at relapse were headache (42%) and polymyalgia rheumatica (51%), but ischemic (some transient) manifestations (visual symptoms, tongue or jaw claudication, and/or limb claudication) occurred in 29% of relapses (12% cohort). Forty-three relapses (73%) occurred while patients were taking glucocorticoid therapy at a median (range) prednisone dose of 7.5 (0–35) mg. In 21% of relapses, both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal. Among 69 patients enrolled in the cohort with newly diagnosed disease, 24% experienced a first relapse within 12 months after diagnosis. Conclusion Among patients with GCA, relapses are common, often occurring during treatment. ESR and CRP are frequently normal at times of clinical relapse, highlighting the need for better biomarkers to assess disease activity in GCA. There remains a need for effective therapeutic alternatives to glucocorticoids in GCA. PMID:25877501

  17. Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

    PubMed Central

    HU, WANGQIANG; WANG, XIAOXIA; YANG, RONGRONG

    2016-01-01

    Despite the outstanding advances made over the past decade regarding our knowledge of acute leukemia (AL), relapsed AL remains to be associated with a dismal prognosis. A better understanding of AL relapse and monitoring of the D-dimer and lactate dehydrogenase (LDH) plasma levels following chemotherapy may aid clinicians in determining whether relapse may occur in the subsequent phases of the disease. The present study evaluated D-dimer and LDH levels in 204 patients with relapsed AL. Data were collected at the initial onset of AL, at complete remission (CR) and in patients with relapsed AL. D-dimer plasma levels were significantly increased in patients with initial AL and in patients with relapsed AL (P=0.005 and P=0.007, respectively) but not in those with CR. LDH levels were significantly increased in AL patients at the initial onset of disease and at relapse compared with patients achieving CR, irrespective of cell type. Plasma prothrombin time, activated partial thromboplastin time and fibrinogen levels were not significantly different across patients (with the exception of acute promyelocytic leukemia patients) at the initial onset, relapsed AL or CR. Routine hematological parameters (white blood cell count, hemoglobin, platelet count) were significantly different at the initial onset of AL (P=0.002, P<0.001 and P=0.001, respectively) and during relapsed AL (P=0.009, P=0.003 and P<0.001, respectively) compared with patients achieving CR, suggesting an association between D-dimer, LDH and relapsed AL. These results also indicate that determination of D-dimer and LDH levels may be useful for predicting the probability of relapse during chemotherapy, but should also be combined with routine hematological parameters. PMID:27347185

  18. Efficacy of Salvage Radiotherapy Plus 2-Year Androgen Suppression for Postradical Prostatectomy Patients With PSA Relapse

    SciTech Connect

    Choo, Richard; Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick; Pearse, Maria

    2009-11-15

    Purpose: To determine the efficacy of a combined approach of radiotherapy (RT) plus 2-year androgen suppression (AS) as salvage treatment for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP). Methods and Materials: Seventy-five patients with PSA relapse after RP were treated with salvage RT plus 2-year AS, as per a pilot, prospective study. AS started within 1 month after completion of salvage RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate including freedom from PSA relapse was estimated using the Kaplan-Meier method. PSA relapse was defined as a PSA rise above 0.2 ng/mL with two consecutive increases over a minimum of 3 months. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Results: Median age of the cohort was 63 years at the time of salvage RT. Median follow-up from salvage RT was 6.4 years. All achieved initially complete PSA response (< 0.2) with the protocol treatment. Relapse-free rate including the freedom from PSA relapse was 91.5% at 5 years and 78.6% at 7 years. Overall survival rate was 93.2% at both 5 and 7 years. On Cox regression analysis, pT3 stage and PSA relapse less than 2 years after RP were significant prognostic factors for relapse. Conclusion: The combined treatment of salvage RT plus 2-year AS yielded an encouraging result for patients with PSA relapse after RP and needs a confirmatory study.

  19. Histology, imaging and new diagnostic work-flows in pathology

    PubMed Central

    Gilbertson, John; Yagi, Yukako

    2008-01-01

    Introduction Since their introduction in 1999, fully automated, high speed, high-resolution whole slide imaging devices have become increasing more reliable, fast and capable. While by no means perfect, these devices have evolved to a point where one can consider placing them in a pre-diagnostic role in a clinical histology lab. Methods At the Massachusetts General Hospital, we are running a pilot study placing high end WSI devices in our main clinical histology lab (after the cover slipper and before slides are sent to the pathologist) to examine the requirement for both the machine and the laboratory. Results Placing WSI systems in the clinical lab stresses the system in terms of reliability and throughput. Significantly however, success requires significant modification to the lab workflow. It is likely laboratories need to move from manual, large batch processes to increasingly automated, continuous flow (or mini-batch) processes orchestrated by the LIS using bar coding to track and direct slides, and incorporating the decision to image into the specimen type and the histology orders. Furthermore, image quality, capture speed and reliability are functions of the quality of the histology presented to the WSI devices. Conclusion Imaging in pathology does not begin in a WSI robot but in the grossing room and in the histology lab. As more and more imaging devices are placed in histology lab, the inter-relationships histology and pathology imaging will become increasing understood. PMID:18673502

  20. 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. PMID:23144485

  1. 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

  2. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers.

    PubMed

    Korshunov, Andrey; Ryzhova, Marina; Hovestadt, Volker; Bender, Sebastian; Sturm, Dominik; Capper, David; Meyer, Jochen; Schrimpf, Daniel; Kool, Marcel; Northcott, Paul A; Zheludkova, Olga; Milde, Till; Witt, Olaf; Kulozik, Andreas E; Reifenberger, Guido; Jabado, Nada; Perry, Arie; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Jones, David T W

    2015-05-01

    Pediatric glioblastoma (pedGBM) is amongst the most common malignant brain tumors of childhood and carries a dismal prognosis. In contrast to adult GBM, few molecular prognostic markers for the pediatric counterpart have been established. We, therefore, investigated the prognostic significance of genomic and epigenetic alterations through molecular analysis of 202 pedGBM (1-18 years) with comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin-embedded tumor samples were assessed for genome-wide DNA methylation profiles, with known candidate genes screened for alterations via direct sequencing or FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %) displayed methylation profiles similar to those of either low-grade gliomas or pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %), H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36 %). These subgroups were associated with specific cytogenetic aberrations, MGMT methylation patterns and clinical outcomes. Analysis of follow-up data identified a set of biomarkers feasible for use in risk stratification: pedGBM with any oncogene amplification and/or K27M mutation (n = 124) represents a particularly unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors without these markers (n = 38) define a more favorable group (3-year OS ~70 %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had distinct molecular features associated with a more favorable outcome. This refined prognostication method for pedGBM using a molecular risk algorithm may allow for improved therapeutic choices and better planning of clinical trial stratification for this otherwise devastating

  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. Relationship between Histological and Clinical Course of Psoriasis: A Pilot Investigation by Reflectance Confocal Microscopy during Goeckerman Treatment.

    PubMed

    Archid, Rami; Duerr, Hans Peter; Patzelt, Alexa; Philipp, Sandra; Röwert-Huber, Hans-Joachim; Ulrich, Martina; Meinke, Martina Claudia; Knorr, Fanny; Lademann, Jürgen

    2016-01-01

    Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis. PMID:26841099

  5. Relapsing experimental allergic encephalomyelitis. An autoimmune model of multiple sclerosis.

    PubMed

    Lublin, F D

    1985-01-01

    R-EAE is a valuable model for human MS. Table 2 outlines the similarities between R-EAE and MS. The clinical course and pathologic changes seen in this model accurately reflect the pattern of MS. The immunologic changes seen in animals with R-EAE also are similar to those seen in MS. Therefore, the clinicopathologic features of MS can be duplicated with a purely autoimmune model. Although this is of considerable pathogenic significance in understanding MS, we do not know what the inciting event is in MS that would be the equivalent of immunizing an animal with neural antigen. Despite this, R-EAE has and should continue to provide experimental data of considerable importance to an understanding of the mechanisms involved in the evolution of inflammatory demyelination. Other important models of MS utilize viral-induced demyelination. Although the clinical picture of most of the chronic demyelinating viral infections does not show as clear a relapsing or remitting pattern as seen in R-EAE, viral etiologies better fit the epidemiology of MS [16]. Several studies have demonstrated development of an acute EAE-like disease with sensitization to neural antigens following viral infection [12, 30, 56]. Thus, one can hypothesize an initial viral illness causing sensitization of the host to a neural antigen (?MBP) with a subsequent immunopathogenic course similar to that seen in R-EAE. Whether this will in fact be the case remains unproven as yet. Our understanding of the immunopathogenic mechanisms underlying inflammatory demyelination has been enlarged through studies of R-EAE. It is now clear that the minimal myelin antigen necessary for production of the disease is MBP, although this may differ in some species. The relapsing nature of this disorder is mediated in part through lymphocytes, as demonstrated in transfer studies, and thus does not require persistent antigenic depots. There is a genetic susceptibility to development of the CNS autoimmune state, and we speculate

  6. Total cost comparison in relapsed/refractory multiple myeloma

    PubMed Central

    Durie, Brian; Binder, Gary; Pashos, Chris; Khan, Zeba; Hussein, Mohamad; Borrello, Ivan

    2013-01-01

    Objectives Advances in survival in multiple myeloma have focused payer attention on the cost of care. An assessment was conducted to compare the costs of two recent treatments for relapsed/refractory multiple myeloma (rrMM), from the perspective of a US payer. Methods An economic model estimated the total costs of care for two guideline-recommended therapies in rrMM patients: bortezomib (BORT) and lenalidomide plus dexamethasone (LEN/DEX). To evaluate total treatment costs, the costs associated with drug treatment, medical resource utilization, and adverse event (AE) management were determined for each regimen over a common 1-year period. Medical costs and grade 3/4 AE costs were based on rates from published literature, package inserts, and fee schedules (US dollars). To evaluate cost per outcome, assessments determined the monthly costs without disease progression based on pivotal clinical trials (APEX [BORT] and MM-009/MM-010 [LEN/DEX]). Univariate sensitivity analyses and alternative scenarios were also conducted. Results Drug costs for the treatments were very similar, differing by under $10 per day. Medical and AE management costs for BORT were higher by more than $40 per day. Treatment with BORT had annual excess total costs of >$17,000 compared with LEN/DEX. A cost advantage for LEN/DEX was maintained across a variety of sensitivity analyses. Total cost per month without progression was 11% lower with LEN/DEX. Limitations This analysis relied on separate studies having similar comparators, populations, and end-points. Actual treatment patterns and costs pre- and post-relapse may vary from the base scenario and sensitivities modeled. The 12-month time frame captures the preponderance of costs for a relapse line of therapy, yet may not reflect the entirety of costs. There is insufficient evidence to determine whether, or how, a difference in the lifetime costs of the two regimens would vary from the 1-year cost difference. Conclusion While rrMM treatment with

  7. 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. PMID:26015534

  8. [Incus homograft--histological study of implanted ossicles (author's transl)].

    PubMed

    Sprem, N; Zirdum, A

    1976-11-01

    The methodes of obtaining, preparing and storing of ossicles for homoiotransplantation is described. Using this method, 21 patients have been operated. Four reoperations have been performed, and in two cases implants were found and subsequently subjected to histological analysis. The method of preparing the histological slides is described. The study of examined homografts revealed the normal bone structure and signs of revitalisation, which is clearly shown in the micrographs. On the basis of functional results and histological examination, the authors conclude that the use of devitalised homografts is recommanded in total and/or partial defects of ossicles. PMID:136576

  9. 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…

  10. 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…

  11. RALLE pilot: response-guided therapy for marrow relapse in acute lymphoblastic leukemia in children.

    PubMed

    Saarinen-Pihkala, Ulla M; Parto, Katriina; Riikonen, Pekka; Lähteenmäki, Päivi M; Békàssy, Albert N; Glomstein, Anders; Möttönen, Merja

    2012-05-01

    Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses. PMID:22246158

  12. Craving for Alcohol, Loss of Control, and Relapse: A Cognitive-Behavioral Analysis

    ERIC Educational Resources Information Center

    Marlatt, G. Alan

    This paper provides a critical review of the relapse process as traditionally defined within the medical or "disease" model of alcoholism. A detailed case study of a relapse is presented, as seen through the eyes of one alcoholic client. The sequence of events in this case study is used to illustrate the theoretical and experimental literature…

  13. 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…

  14. Sleep Disturbance as a Universal Risk Factor for Relapse in Addictions to Psychoactive Substances

    PubMed Central

    Brower, Kirk J.; Perron, Brian E.

    2009-01-01

    Relapse to uncontrolled use of a psychoactive substance is arguably the single most defining characteristic of an addiction. Relapse following addiction treatment is very common with serious consequences to individuals, families, and the public system of care, making predictors of relapse a highly significant area of study. Before the turn of the century, most of the addiction treatment outcome literature focused on psychosocial predictors of relapse. More recently, investigating biological predictors of relapse specifically and treatment outcome broadly has gained momentum. This line of research has linked sleep disturbances to the risk of relapse among persons who are recovering from an alcohol addiction. Given common neurobiological and psychosocial processes in sleep and addictive behaviors, we hypothesize that the link between sleep disturbance and relapse risk observed among alcohol addiction generalizes to all other types of psychoactive substances. This hypothesis has the potential for helping develop more effective and targeted treatment approaches for persons with addiction. As initial support for the hypothesis, this paper reviews evidence on common neurobiological processes among various types of psychoactive substances that suggests sleep is a universal risk factor for relapse. A conceptual framework is also presented to articulate causal mechanisms. The paper concludes with implications for research and practice. PMID:19910125

  15. 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.…

  16. 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…

  17. 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. PMID:26974214

  18. 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…

  19. 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…

  20. The Role of Sexual Trauma in the Treatment of Chemically Dependent Women: Addressing the Relapse Issue.

    ERIC Educational Resources Information Center

    Wadsworth, Rick; And Others

    1995-01-01

    Explores issues surrounding sexual trauma and chemical dependency. Aims to provide direction for relapse prevention with a relapse-prone population and explores application of traditional milieu substance-abuse treatment for sexual-trauma survivors. Makes recommendations for working with sexual-trauma survivors who are also substance abusers. (RJM)

  1. EMT, CTCs and CSCs in tumor relapse and drug-resistance

    PubMed Central

    Mitra, Abhisek; Mishra, Lopa; Li, Shulin

    2015-01-01

    Tumor relapse and metastasis are the primary causes of poor survival rates in patients with advanced cancer despite successful resection or chemotherapeutic treatment. A primary cause of relapse and metastasis is the persistence of cancer stem cells (CSCs), which are highly resistant to chemotherapy. Although highly efficacious drugs suppressing several subpopulations of CSCs in various tissue-specific cancers are available, recurrence is still common in patients. To find more suitable therapy for relapse, the mechanisms underlying metastasis and drug-resistance associated with relapse-initiating CSCs need to be identified. Recent studies in circulating tumor cells (CTCs) of some cancer patients manifest phenotypes of both CSCs and epithelial-mesenchymal transition (EMT). These patients are unresponsive to standard chemotherapies and have low progression free survival, suggesting that EMT-positive CTCs are related to co-occur with or transform into relapse-initiating CSCs. Furthermore, EMT programming in cancer cells enables in the remodeling of extracellular matrix to break the dormancy of relapse-initiating CSCs. In this review, we extensively discuss the association of the EMT program with CTCs and CSCs to characterize a subpopulation of patients prone to relapses. Identifying the mechanisms by which EMT-transformed CTCs and CSCs initiate relapse could facilitate the development of new or enhanced personalized therapeutic regimens. PMID:25986923

  2. Cutaneous relapse of an ampullary carcinoma: an unusual presentation

    PubMed Central

    Lamarca, Angela; Martinez-Marin, Virginia; Feliu, Jaime

    2012-01-01

    This is the first ever reported case about a cutaneous relapse of small bowel adenocarcinoma. The ampulla of Vater is the area of the small bowel that presents more frequently malignant transformation, nevertheless ampullary adenocarcinomas are rare but aggressive diseases. However, distant metastases are infrequent. Cutaneous metastases constitute the 5.3% of skin tumours, and are usually found in the 12% of malignancies. Their management usually includes local treatment if they are unique and systemic treatment when they are multiple. Chemotherapy schemes used in ampullary adenocarcinoma are those used in cholangiocarcinomas, pancreas and tumours of the gallbladder; nevertheless, given the intestinal origin of these tumours combinations of capecitabine and oxaliplatin are commonly used. PMID:22761197

  3. Relapsing Polychondritis in a Patient with Ankylosing Spondylitis Using Etanercept

    PubMed Central

    Azevedo, Valderilio Feijó; Galli, Natalia Bassalobre; Kleinfelder, Alais Daiane Fadini; D'Ippolito, Julia Farabolini; Gulin Tolentino, Andressa; Paiva, Eduardo

    2014-01-01

    Relapsing polychondritis (RP) is an autoimmune disease characterized by recurrent episodes of inflammation and progressive destruction of cartilaginous tissues, especially of the ears, nose, joints, and tracheobronchial tree. Its etiology is not well understood, but some studies have linked its pathophysiology with autoimmune disease and autoantibody production. We described a case of a 46-year-old male patient with ankylosing spondylitis who developed RP after the use of etanercept. Few similar cases have been described in the literature. However, they show a possible association between the use of biological inhibitors of tumor necrosis factor (anti-TNFα), which potentially produces autoantibodies, and the development of RP. The treatment was based on data in the literature and included the cessation of biological therapy and the addition of corticosteroids with substantial improvement. PMID:25276463

  4. Tickborne Relapsing Fever Diagnosis Obscured by Malaria, Togo

    PubMed Central

    Nordstrand, Annika; Bunikis, Ignas; Larsson, Christer; Tsogbe, Kodjo; Schwan, Tom G.; Nilsson, Mikael

    2007-01-01

    Given the prevalence of relapsing fever (RF) in Senegal, this disease may cause illness and death in other areas of West Africa. We performed a cross-sectional, clinic-based study to investigate the presence of RF in Togo during 2002–2004. Blood samples from patients with fever were examined for RF spirochetes by microscopy, PCR, and DNA sequencing of amplicons and for antibodies to the glycerophosphodiester phosphodiesterase antigen. Although no spirochetes were seen in blood smears, ≈10% of the patients were positive by PCR and ≈13% were seropositive for spirochetes. DNA sequencing demonstrated that Borrelia crocidurae and B. duttonii were present. Most patients were treated for malaria whether or not plasmodia were observed. Thus, many RF patients originally had a misdiagnosis of malaria, which resulted in ineffective treatment. The inability of microscopic analysis to detect spirochetes compared with PCR demonstrates the need for tests with greater sensitivity. PMID:17370524

  5. Novel Agents for Relapsing Forms of Multiple Sclerosis.

    PubMed

    Straus Farber, Rebecca; Harel, Asaff; Lublin, Fred

    2016-01-01

    Since 2004, five drugs with new mechanisms of action have been approved by the US Food and Drug Administration for the treatment of relapsing forms of multiple sclerosis (MS). The expanded armamentarium of treatment options offers new opportunities for improved disease control and increased tolerability of medications, and also presents new safety concerns and monitoring requirements with which physicians must familiarize themselves. We review each of the newly approved agents-natalizumab, fingolimod, teriflunomide, dimethyl fumarate, and alemtuzumab-with regard to their mechanism of action, clinical trial data, safety and tolerability concerns, and monitoring requirements. We also review available data for promising agents that are currently in late-phase clinical trials, including daclizumab, ocrelizumab, and ofatumumab. PMID:26394285

  6. 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.

  7. [Vestibular rehabilitation in patients with relapsing-remitting multiple sclerosis].

    PubMed

    Pavan, Karina; Marangoni, Bruna E M; Schmidt, Kizi B; Cobe, Fernanda A; Matuti, Gabriela S; Nishino, Lúcia K; Thomaz, Rodrigo B; Mendes, Maria Fernanda; Lianza, Sérgio; Tilbery, Charles Peter

    2007-06-01

    Multiple sclerosis (MS) is a demyelinating, inflammatory illness, that attack the white matter of the central nervous system, and abnormal vestibular sensations (vertigo, disequilibrium) are frequent. The vestibular rehabilitation (VR) is determined by mechanisms of adaptations, neural substitutions and compensations. This study evaluated the improvement of the central or peripheral vertigo in patients with relapsing-remitting MS submitted to the VR (exercises of Cawthorne-Cooksey), through the scale of Berg and Dizziness Handicap Inventory (DHI). In this sample of 4 cases the VR, carried through in a period of 2 months, demonstrated the improvement in 3 patients according to the Berg scale and in 2 patients considering that of the DHI. PMID:17607438

  8. 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

  9. Relapsing Fever Spirochetes Retain Infectivity After Prolonged in vitro Cultivation

    PubMed Central

    Schrumpf, Merry E.; Raffel, Sandra J.; Policastro, Paul F.; Porcella, Stephen F.; Schwan, Tom G.

    2008-01-01

    Abstract Borrelia hermsii and Borrelia burgdorferi, two closely related spirochetes, are the etiological agents of tick-borne relapsing fever and Lyme disease, respectively. Previous studies have shown the loss of infectivity of B. burgdorferi is associated with in vitro cultivation. This diminished infectivity of B. burgdorferi has occurred as early as three in vitro passages, and the loss of plasmids have been observed with these less virulent to noninfective cultures. The effects of long-term in vitro cultivation on B. hermsii have not been investigated. However, understanding the degree of genomic degradation during in vitro cultivation is important for investigating pathogenic mechanisms of spirochetes. In this study, we analyzed the effects of continuous in vitro cultivation on the genomic composition and infectivity of B. hermsii and B. turicatae. We report that all seven isolates of B. hermsii and the one isolate of B. turicatae examined retained infectivity in mice after 1 year of continuous in vitro cultivation. Furthermore, there were few apparent differences in the plasmid profiles after long-term cultivation. Two isolates of B. hermsii remained infective after high passage despite losing a portion of the 200-kb linear plasmid containing the fhbA gene encoding the factor H binding protein. Also, sequence analysis of multiple B. hermsii isolates demonstrated two types of fhbA with complete congruence with the two genomic groups of B. hermsii spirochetes. Therefore, these results suggest that relapsing fever spirochetes are genetically stable during in vitro cultivation, and the fhbA-containing segment of DNA that is lost during cultivation is not required for infection. PMID:18637723

  10. ESHAP as salvage therapy for relapsed or refractory Hodgkin's lymphoma.

    PubMed

    Labrador, Jorge; Cabrero-Calvo, Mónica; Pérez-López, Estefanía; Mateos, María Victoria; Vázquez, Lourdes; Caballero, María Dolores; García-Sanz, Ramón

    2014-10-01

    The management of relapsed or refractory Hodgkin's lymphoma (RR-HL) remains a challenge for hematologists and oncologists. Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for RR-HL. However, one of the most controversial aspects is which the best salvage protocol could be. We retrospectively analyzed 82 consecutive RR-HL who received etoposide, steroids, ara-C, and cisplatin (ESHAP) as salvage therapy followed by ASCT. Fifty percent of patients were refractory and 23 % early relapses. Overall response rate (ORR) was 67 % (50 % complete remission (CR)). Ninety one percent of patients (75/82) were transplanted. With a mean follow-up of 87 ± 53 months, the median progression-free survival (PFS) and time to tumor progression (TTP) for the whole population were 52 and 56 months, respectively, and the 5-year overall survival was 72.6 %. Achieving CR after ESHAP was associated with a longer PFS (78 vs 16 % 5-year PFS, respectively, P < 0.01) and TTP (80 vs 19 % 5-year TTP, respectively, P < 0.01). However, there were no differences for overall survival (OS) when comparing CR and partial response (PR) after ESHAP. Toxicity was low and <10 % of patients developed neutropenic fever, with no toxic deaths. Mobilization was possible in 94 % of patients. ESHAP is a safe and efficient therapeutic option for patients with RR-HL who are candidates for ASCT, since it combines a high response rate and mobilizing potential with a low toxicity profile. PMID:24863692

  11. 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

  12. 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.

  13. Do changes in mood and concerns about weight relate to smoking relapse in the postpartum period?

    PubMed Central

    Levine, M. D.; Marcus, M. D.

    2008-01-01

    Summary The majority of women who quit smoking during pregnancy will resume smoking during the postpartum period. Little is known, however, about the predictors of postpartum relapses to smoking. Changes in mood and increases in concerns about weight are common during the postpartum period, and these factors may affect women's postpartum smoking behavior. In this paper, we present a model of the relationship among mood, weight concerns and postpartum smoking. Data from previous postpartum relapse prevention trials are reviewed and evidence of a connection between changes in mood and weight concerns to postpartum relapse is presented. Directions for future research on the prevention of smoking relapses during the postpartum period, and the roles of mood and weight concerns in smoking relapse are presented. PMID:15241661

  14. Deletion analysis of p16(INKa) and p15(INKb) in relapsed childhood acute lymphoblastic leukemia.

    PubMed

    Graf Einsiedel, Hagen; Taube, Tillmann; Hartmann, Reinhard; Wellmann, Sven; Seifert, Georg; Henze, Günter; Seeger, Karl

    2002-06-15

    This study aimed at determining the prevalence of INK4 deletions and their impact on outcome in 125 children with acute lymphoblastic leukemia (ALL) at first relapse using real-time quantitative polymerase chain reaction. Patients were enrolled into relapse trials ALL-REZ BFM (ALL-Relapse Berlin-Frankfurt-Münster) 90 and 96. The prevalence of p16(INK4a) and p15(INK4b) homozygous deletions was 35% (44 of 125) and 30% (38 of 125), respectively. A highly significant association of both gene deletions was found with the 2 major adverse prognostic factors known for relapsed childhood ALL: T-cell immunophenotype and first remission duration. There was no correlation between INK4 deletions and probability of event-free survival. These findings argue against an independent prognostic role of INK4 deletions in relapsed childhood ALL. PMID:12036898

  15. Orexin Receptor Targets for Anti-Relapse Medication Development in Drug Addiction

    PubMed Central

    Zhou, Luyi; Sun, Wei-Lun; See, Ronald E.

    2011-01-01

    Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches. PMID:23997653

  16. 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...

  17. 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...

  18. The enlightenments from ITMIG Consensus on WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting

    PubMed Central

    Wu, Jie; Fang, Wentao

    2016-01-01

    The World Health Organization (WHO) histological classification of the thymoma and thymic carcinoma (TC) has been criticized for poor interobserver reproducibility or inconsistencies in the routine pathological diagnosis. The International Thymic Malignancy Interest Group (ITMIG) panel achieved an agreement to maintain the widely accepted WHO framework but to refine historic definitions and histological criteria, and further introduce some new terms with the aim to improve interobserver reproducibility. This review addresses the enlightenments we can get from the ITMIG consensus on the WHO histological classification of the thymoma and TC, which may be helpful for most pathologists. PMID:27114842

  19. 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

  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. Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials

    PubMed Central

    Kotoula, Vassiliki; Chatzopoulos, Kyriakos; Lakis, Sotiris; Alexopoulou, Zoi; Timotheadou, Eleni; Zagouri, Flora; Pentheroudakis, George; Gogas, Helen; Galani, Eleni; Efstratiou, Ioannis; Zaramboukas, Thomas; Koutras, Angelos; Aravantinos, Gerasimos; Samantas, Epaminontas; Psyrri, Amanda; Kourea, Helen; Bobos, Mattheos; Papakostas, Pavlos; Kosmidis, Paris; Pectasides, Dimitrios; Fountzilas, George

    2016-01-01

    Background Tumor infiltrating lymphocytes (TILs) are considered in the prognosis of breast cancer (BC) patients. Here, we investigated the prognostic/predictive effect of TILs in patients treated in the frame of four prospective trials with adjuvant anthracycline-based chemotherapy in the pre- and post-trastuzumab era. Methods TILs density was histologically assessed as percentage of stromal area on whole routine sections of 2613 BC (1563 Luminal A/B; 477 Luminal HER2; 246 HER2-enriched; 327 triple negative [TNBC]) and were evaluated as high/low at three cut-offs (c/o; 50% [lymphocytic predominance, LP], 35% and 25%), in separate training and validation sets. Results High TILs were present in 3.5%, 6.5% and 11.5% of all tumors, using the 50%, 35% and 25% c/o, respectively. TILs status did not interact with BC subtypes or trastuzumab treatment. LPBC patient outcome was not affected by nodal status, while high TILs were favorable in TNBC with unfavorable nodal status. When adjusted for standard clinicopathological parameters and treatment, high TILs independently predicted for favorable outcome, e.g., disease-free survival with the 35% c/o in the entire cohort (HR = 0.44, 95% CI 0.28-0.69, p < 0.001) and in specific subtypes. Conclusions High TILs tumors, especially LPBC seem worthy validating as a separate entity of favorable prognosis in breast cancer. PMID:26506242

  2. 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. PMID:26298189

  3. 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. PMID:23683830

  4. Drinking resumption: problematic alcohol use relapse after rehabilitation. A phenomenological hermeneutical perspective.

    PubMed

    Kvamme, Brita Odland; Asplund, Kenneth; Bjerke, Trond Nergaard

    2015-12-01

    The majority of patients being treated for alcohol abuse disorders experience one or more relapses after treatment. The fact that people use this inebriant in a way leading to so much harm and suffering might seem a conundrum. Therapists, family and others might find the person's relapse to be dramatic and upsetting, and one might question whether the person has the sufficient will or motivation to change. However, few previous studies have explored relapse from the patient's perspective. The aim of this study was to illuminate the patient's lived experience of relapse and to develop a deeper understanding of this phenomenon. The study consisted of qualitative interviews using a phenomenological hermeneutical approach. Three main themes emerged from the analyses: 'craving', 'self-image' and 'time'. The findings were discussed in the context of phenomenological literature. Cravings could occur unpredictably; nevertheless, craving was a common experience for the patients and signified a risk of relapse. Bodily experiences of craving were frequently mentioned, and alcohol addiction could be understood as to be a disease or a learned habit. Self-image was, at times, adversely affected by relapse episodes. Therefore, feelings of shame, self-respect and recognition were significant concepts. This study found that the perception of time as past, present and future greatly influenced the participants' experiences of relapse and rehabilitation. Thus, relapse was an upsetting and dramatic experience that could cause great discomfort and sometimes life-threatening situations. However, relapse could also be viewed as a planned event. This study highlights important truth and reality about alcoholism and relapse grounded in people's lived experience. PMID:25851272

  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. 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. PMID:27365886

  8. Radiologic and histologic presentation of male mammary myofibroblastoma

    PubMed Central

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

    2016-01-01

    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. PMID:27365886

  9. Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108

    PubMed Central

    Barr, Paul M.; Li, Hongli; Spier, Catherine; Mahadevan, Daruka; LeBlanc, Michael; Ul Haq, Mansoor; Huber, Bryan D.; Flowers, Christopher R.; Wagner-Johnston, Nina D.; Horwitz, Steven M.; Fisher, Richard I.; Cheson, Bruce D.; Smith, Sonali M.; Kahl, Brad S.; Bartlett, Nancy L.; Friedberg, Jonathan W.

    2015-01-01

    Purpose Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Patients and Methods Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. Results Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. Conclusion Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL. PMID:26077240

  10. 45 CFR 73.735-502 - Permissible acceptance of gifts, entertainment, and favors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Permissible acceptance of gifts, entertainment... GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-502 Permissible acceptance of gifts, entertainment, and favors. (a) An employee may accept a gift, gratuity,...

  11. 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

  12. [A Patient with Three-Year Relapse-Free Survival after Surgical Resection for Lung and Liver Metastases of Cholangiocarcinoma].

    PubMed

    Aoki, Shuichi; Mizuma, Masamichi; Oyauchi, Motoki; Yoshida, Hiroshi; Okada, Ryo; Abe, Tomoya; Sakata, Naoaki; Nakagawa, Kei; Hayashi, Hiroki; Morikawa, Takanori; Motoi, Fuyuhiko; Naitoh, Takeshi; Okada, Yoshinori; Unno, Michiaki

    2015-11-01

    We report of a patient with 3-year relapse-free survival after surgical resection for lung and liver metastases of distal cholangiocarcinoma (DCC). A quinquagenarianman was taken to a local hospital in October 2009 for yellow urine. He was diagnosed with DCC and was referred to our hospital for surgery. Pancreaticoduodenectomy was performed, and there was no residual tumor on histological examination. He did not receive any adjuvant therapy. One year 7 months after surgery, an isolated lung metastasis was identified on CT and was surgically removed. Six months after resection of the lung metastasis, a solitary liver metastasis was detected. Although systematic chemotherapy (gemcitabine plus S-1; 2 weeks treatment, 1 week drug free) was administered, the treatment was abandoned because of grade 3 (CTCAE v4.0) of skin disorders during the third course. Partial resection of the liver was performed in April 2012. Alternate-day treatment with S-1 was performed after resection of liver metastasis and is ongoing without adverse events. He has survived for more than 3 years without recurrence after liver resection. In this case of DCC metastasis, prognosis improved with surgical resection. PMID:26805100

  13. 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

  14. 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.

  15. 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. PMID:26294725

  16. 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.

  17. 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.

  18. 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.

  19. Clinical and biological predictors of outcome following relapse of CML post-allo-SCT.

    PubMed

    Jain, N A; Ito, S; Tian, X; Kurlander, R; Battiwalla, M; Lu, K; Savani, B N; Malkovska, V; Rezvani, K; Le, R Q; Shenoy, A; Hourigan, C S; Keyvanfar, K; Koklanaris, E; Superata, J; Muranski, P; Barrett, A J; Yong, A S M

    2015-02-01

    Although there are now fewer allo-SCTs performed for CML, leukemic relapse post transplant remains a persistent problem. To better define clinical and biological parameters determining postrelapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor (TKI) use as significant factors associated with PRS. Analysis of BCR-ABL transcript expression in the hematopoietic progenitor compartment was performed in 36 patients (22 relapsed, 8 non-relapsed and 6 TKI alone controls). Patients with BCR-ABL expression in their early hematopoietic stem cell compartment (Lineage(-)CD34(+)CD38(-)CD90(+)) had worse survival irrespective of the disease status. We conclude that disease status remains the strongest clinical prognostic factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression in the progenitor cell compartment in some patients after SCT emphasizes the need to target CML-leukemia stem cells. PMID:25387087

  20. Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction

    SciTech Connect

    Sawyers, C.L.; Timson, L.; Clark, S.S.; Witte, O.N.; Champlin, R. ); Kawasaki, E.S. )

    1990-01-01

    Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. The authors prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. They used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. They recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Unusual relapse of primary central nervous system lymphoma at site of lumbar puncture.

    PubMed

    Ahmed, Zartaj; Ramanathan, Ramesh K; Ram, Sunil; Newell, James; Halepota, Maqbool

    2014-01-01

    Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma confined to the CNS. Local relapse of this disease is common, but extracranial or subcutaneous metastasis is rare with only a few cases being reported in literature. We report a 63-year-old male patient, who responded well to treatment for PCNSL but relapsed two and half years later with a lumbosacral nodule at the site of a previous lumbar puncture due to microscopic tumor seeding. Clinicians treating patients with PCNSL must remain alert to the possibility of extracranial solitary relapse even after the resolution of initial disease because prompt treatment can result in a good outcome. PMID:25093130

  7. Unusual Relapse of Primary Central Nervous System Lymphoma at Site of Lumbar Puncture

    PubMed Central

    Ramanathan, Ramesh K.; Ram, Sunil; Halepota, Maqbool

    2014-01-01

    Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma confined to the CNS. Local relapse of this disease is common, but extracranial or subcutaneous metastasis is rare with only a few cases being reported in literature. We report a 63-year-old male patient, who responded well to treatment for PCNSL but relapsed two and half years later with a lumbosacral nodule at the site of a previous lumbar puncture due to microscopic tumor seeding. Clinicians treating patients with PCNSL must remain alert to the possibility of extracranial solitary relapse even after the resolution of initial disease because prompt treatment can result in a good outcome. PMID:25093130

  8. Prefrontal cortical regulation of drug seeking in animal models of drug relapse.

    PubMed

    Lasseter, Heather C; Xie, Xiaohu; Ramirez, Donna R; Fuchs, Rita A

    2010-01-01

    Prefrontal cortical dysfunction is thought to underlie maladaptive behaviors displayed by chronic drug users, most notably the high propensity for relapse that severely impedes successful treatment of drug addiction. In animal models of drug relapse, exposure to drug-associated stimuli, small amounts of drug, and acute stressors powerfully reinstate drug seeking by critically engaging the prefrontal cortex, with the anterior cingulate, prelimbic, infralimbic, and orbitofrontal subregions making distinct contributions to drug seeking. Hence, from an addiction treatment perspective, it is necessary to fully explicate the involvement of the prefrontal cortex in drug relapse. PMID:21161751

  9. Two cases of relapses in primary progressive multiple sclerosis after fingolimod withdrawal.

    PubMed

    Davion, Jean-Baptiste; Cambron, M; Duhin, E; Chouraki, A; Lacour, A; Labauge, P; Carra, C; Ayrignac, X; Vermersch, P

    2016-07-01

    We report two cases of primary progressive multiple sclerosis (PPMS) included in the INFORMS cohort, experiencing a relapse related to a single MRI gadolinium-enhancing lesion 3 months after fingolimod withdrawal. These two patients share similarities with relapsing-remitting multiple sclerosis cases described in the same situation, suggesting that the initiating process of the active demyelinating plaques is also present in PPMS, even without relapses, but may be triggered as fingolimod is withdrawn. Although the results of the INFORMS study suggest that fingolimod may not slow down the progression, some PPMS patients might still benefit from a disease-modifying treatment. PMID:27159986

  10. 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. PMID:21679261

  11. The total hospital and community UK costs of managing patients with relapsed breast cancer.

    PubMed

    Thomas, R J; Williams, M; Marshall, C; Glen, J; Callam, M

    2009-02-24

    The complete hospital and community records of 77 women were randomly selected from 232 women who had relapsed breast cancer between 2000 and 2005. Scrutiny of all management activities revealed a total cost of 1,939,329 pound sterling (mean per patient of 25,186 pound sterling , 95% CI 13,705 pound sterling-33,821 pound sterling ). The median survival from time of relapse was 40.07 months and the median total cost per patient was 31 402.62 pound sterling . Including the community cost of a relapse provides a more realistic figure for future cost-effectiveness analysis of adjuvant breast cancer therapies. PMID:19223909

  12. A case of relapsing-remitting tumour-like inflammation of the central nervous system.

    PubMed

    Miante, Silvia; Perini, Paola; Rinaldi, Francesca; Gallo, Paolo

    2015-11-01

    The case of a 37-year-old woman suffering from a relapsing-remitting tumefactive inflammatory disease of the central nervous system (CNS) is described. The patient had four severe relapses over eight years, and was treated with steroids, immunosuppression and plasma-exchange with modest benefit. No magnetic resonance imaging or cerebrospinal spinal fluid findings suggestive of multiple sclerosis emerged during the eight-year follow-up. 'Relapsing-remitting tumefactive inflammation' seems to have the features of a distinct inflammatory CNS disease. PMID:26362889

  13. Multi-class texture analysis in colorectal cancer histology

    PubMed Central

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M.; Schad, Lothar R.; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-01-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies. PMID:27306927

  14. Multi-class texture analysis in colorectal cancer histology.

    PubMed

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M; Schad, Lothar R; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-01-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies. PMID:27306927

  15. 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. PMID:20526171

  16. Multi-class texture analysis in colorectal cancer histology

    NASA Astrophysics Data System (ADS)

    Kather, Jakob Nikolas; Weis, Cleo-Aron; Bianconi, Francesco; Melchers, Susanne M.; Schad, Lothar R.; Gaiser, Timo; Marx, Alexander; Zöllner, Frank Gerrit

    2016-06-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no published results on multiclass texture separation. In this paper we present a new dataset of 5,000 histological images of human colorectal cancer including eight different types of tissue. We used this set to assess the classification performance of a wide range of texture descriptors and classifiers. As a result, we found an optimal classification strategy that markedly outperformed traditional methods, improving the state of the art for tumour-stroma separation from 96.9% to 98.6% accuracy and setting a new standard for multiclass tissue separation (87.4% accuracy for eight classes). We make our dataset of histological images publicly available under a Creative Commons license and encourage other researchers to use it as a benchmark for their studies.

  17. Histological Stains: A Literature Review and Case Study

    PubMed Central

    Alturkistani, Hani A; Tashkandi, Faris M; Mohammedsaleh, Zuhair M

    2016-01-01

    The history of histology indicates that there have been significant changes in the techniques used for histological staining through chemical, molecular biology assays and immunological techniques, collectively referred to as histochemistry. Early histologists used the readily available chemicals to prepare tissues for microscopic studies; these laboratory chemicals were potassium dichromate, alcohol and the mercuric chloride to harden cellular tissues. Staining techniques used were carmine, silver nitrate, Giemsa, Trichrome Stains, Gram Stain and Hematoxylin among others. The purpose of this research was to assess past and current literature reviews, as well as case studies, with the aim of informing ways in which histological stains have been improved in the modern age. Results from the literature review has indicated that there has been an improvement in histopathology and histotechnology in stains used. There has been a rising need for efficient, accurate and less complex staining procedures. Many stain procedures are still in use today, and many others have been replaced with new immunostaining, molecular, non-culture and other advanced staining techniques. Some staining methods have been abandoned because the chemicals required have been medically proven to be toxic. The case studies indicated that in modern histology a combination of different stain techniques are used to enhance the effectiveness of the staining process. Currently, improved histological stains, have been modified and combined with other stains to improve their effectiveness. PMID:26493433

  18. Cerebellopontine angle facial schwannoma relapsing towards middle cranial fossa

    PubMed Central

    Nishizaki, Takafumi; Ikeda, Norio; Nakano, Shigeki; Sakakura, Takanori; Abiko, Masaru; Okamura, Tomomi

    2011-01-01

    Facial nerve schwannomas involving posterior and middle fossas are quite rare. Here, we report an unusual case of cerebellopontine angle facial schwannoma that involved the middle cranial fossa, two years after the first operation. A 53-year-old woman presented with a 3-year history of a progressive left side hearing loss and 6-month history of a left facial spasm and palsy. Magnetic resonance imaging (MRI) revealed 4.5 cm diameter of left cerebellopontine angle and small middle fossa tumor. The tumor was subtotally removed via a suboccipital retrosigmoid approach. The tumor relapsed towards middle cranial fossa within a two-year period. By subtemporal approach with zygomatic arch osteotomy, the tumor was subtotally removed except that in the petrous bone involving the facial nerve. In both surgical procedures, intraoperative monitoring identified the facial nerve, resulting in preserved facial function. The tumor in the present case arose from broad segment of facial nerve encompassing cerebellopontine angle, meatus, geniculate/labyrinthine and possibly great petrosal nerve, in view of variable symptoms. Preservation of anatomic continuity of the facial nerve should be attempted, and the staged operation via retrosigmoid and middle fossa approaches using intraoperative facial monitoring, may result in preservation of the facial nerve. PMID:24765294

  19. Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma.

    PubMed

    Moreau, Philippe; Facon, Thierry; Touzeau, Cyrille; Benboubker, Lotfi; Delain, Martine; Badamo-Dotzis, Julie; Phelps, Charles; Doty, Christopher; Smit, Hans; Fourneau, Nele; Forslund, Ann; Hellemans, Peter; Leleu, Xavier

    2016-07-01

    The maximum tolerated dose (MTD) of quisinostat + bortezomib + dexamethasone in patients with relapsed multiple myeloma was evaluated in a phase-1b, open-label, multicenter, '3 + 3' dose-escalation study. Patients received escalating doses of oral quisinostat (6 mg [n = 3], 8 mg [n = 3], 10 mg [n = 6], and 12 mg [n = 6] on days 1, 3, and 5/week) plus subcutaneous bortezomib (1.3 mg/m(2)) and oral dexamethasone (20 mg) in cycles of 21 (cycles 1-8) or 35 d (cycles 9-11) until MTD was determined. No dose-limiting toxicities were reported in 6/8 mg groups except ventricular fibrillation (Grade 4 cardiac arrest, n = 1 [10 mg] cycle 6) and clinically significant cardiac toxicities (Grade 3 QTc prolongation, Grade 3 atrial fibrillation, n = 2 [12 mg]). Thrombocytopenia (n = 11), asthenia (n = 10), and diarrhea (n = 12) were most common adverse events. Overall, 88.2% patients achieved treatment response, median duration of response, and median progression-free survival were 9.4 and 8.2 months, respectively. The MTD of quisinostat was established as 10 mg thrice weekly oral dose with bortezomib + dexamethasone. PMID:26758913

  20. Relapsing polychondritis with different types of ocular inflammations

    PubMed Central

    Furuya, Nana; Oshitari, Toshiyuki; Yotsukura, Jiro; Baba, Takayuki; Yamamoto, Shuichi

    2015-01-01

    We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation. PMID:26425107