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Sample records for relapsing polychondritis involving

  1. Vascular involvement in relapsing polychondritis.

    PubMed Central

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

    1977-01-01

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

  2. Relapsing Polychondritis with Central Nervous System Involvement: Experience of Three Different Cases in a Single Center.

    PubMed

    Jeon, Chan Hong

    2016-11-01

    Relapsing polychondritis (RP) is an autoimmune disorder characterized by inflammation in cartilaginous structures including the ears, noses, peripheral joints, and tracheobronchial tree. It rarely involves the central nervous system (CNS) but diagnosis of CNS complication of RP is challenging because it can present with varying clinical features. Herein we report 3 cases of relapsing polychondritis involving CNS with distinct manifestations and clinical courses. The first patient presented with rhombencephalitis resulting in brain edema and death. The second patient had acute cognitive dysfunction due to limbic encephalitis. He was treated with steroid pulse therapy and recovered without sequelae. The third patient suffered aseptic meningitis that presented as dementia, which was refractory to steroid and immune suppressive agents. We also reviewed literature on CNS complications of RP.

  3. Relapsing Polychondritis with Central Nervous System Involvement: Experience of Three Different Cases in a Single Center

    PubMed Central

    2016-01-01

    Relapsing polychondritis (RP) is an autoimmune disorder characterized by inflammation in cartilaginous structures including the ears, noses, peripheral joints, and tracheobronchial tree. It rarely involves the central nervous system (CNS) but diagnosis of CNS complication of RP is challenging because it can present with varying clinical features. Herein we report 3 cases of relapsing polychondritis involving CNS with distinct manifestations and clinical courses. The first patient presented with rhombencephalitis resulting in brain edema and death. The second patient had acute cognitive dysfunction due to limbic encephalitis. He was treated with steroid pulse therapy and recovered without sequelae. The third patient suffered aseptic meningitis that presented as dementia, which was refractory to steroid and immune suppressive agents. We also reviewed literature on CNS complications of RP. PMID:27709866

  4. Respiratory complications of relapsing polychondritis

    PubMed Central

    Gibson, G. J.; Davis, P.

    1974-01-01

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

  5. Active aortitis in relapsing polychondritis

    PubMed Central

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

    2001-01-01

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

  6. Leprosy with Atypical Skin Lesions Masquerading as Relapsing Polychondritis

    PubMed Central

    Munganda, Hariharan; Bangia, Amit; Rani, Uma; Budhiraja, Rajesh; Brajpuriya, Swapnil

    2016-01-01

    Leprosy can present with a variety of clinical manifestations depending on the immune status of the individual. After dermatological and neurological involvement, rheumatic features specially various forms of arthritis are the third most common manifestation of the disease. We describe a unique case of a 22-year-old patient presenting with external ear involvement mimicking relapsing polychondritis along with inflammatory joint symptoms and skin lesions. Ear involvement in relapsing polychondritis characteristically is painful and spares the noncartilaginous ear lobules, in contrast to painless ear involvement in leprosy affecting the lobules as well. Histopathology confirmed the diagnosis, although the ear and skin lesions were not classical of leprosy. Such a presentation of leprosy closely mimicking relapsing polychondritis has not been described previously. Tissue diagnosis should always be attempted whenever possible in patients presenting with autoimmune features, so that inappropriate therapy with immunosuppressants is avoided. PMID:28116186

  7. Immunopathologic Studies in Relapsing Polychondritis

    PubMed Central

    Herman, Jerome H.; Dennis, Marie V.

    1973-01-01

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

  8. Relapsing Polychondritis Presented with Encephalitis Followed by Brain Atrophy

    PubMed Central

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

    2017-01-01

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

  9. Early aortic valve cusp rupture in relapsing polychondritis.

    PubMed Central

    Marshall, D A; Jackson, R; Rae, A P; Capell, H A

    1992-01-01

    Aortic regurgitation associated with relapsing polychondritis usually occurs late in the disease as a result of aortic root dilatation. A case where aortic regurgitation occurred early and was due to cusp rupture with a normal aortic root is reported. The patient required urgent aortic valve replacement within six weeks of developing a murmur despite apparent control of inflammation with immunosuppressive treatment. The possibility of cusp rupture with sudden haemodynamic deterioration should be considered in patients with relapsing polychondritis who develop aortic regurgitation. Images PMID:1575597

  10. Hypertrophic Pachymeningitis as an Early Manifestation of Relapsing Polychondritis: Case Report and Review of the Literature

    PubMed Central

    Ushiyama, Satoru; Kinoshita, Tomomi; Shimojima, Yasuhiro; Ohashi, Nobuhiko; Kishida, Dai; Miyazaki, Daigo; Nakamura, Katsuya; Sekijima, Yoshiki; Ikeda, Shu-ichi

    2016-01-01

    Neurological involvement in relapsing polychondritis (RP) is relatively rare. We describe the case of an 80-year-old man who presented with hypertrophic pachymeningitis (HP) together with arthritis as the first manifestation of RP. Auricular chondritis, which subsequently determined the diagnosis of RP, occurred a few weeks after the detection of HP. The neurological symptoms, as well as arthritis, were promptly improved by treatment with corticosteroids. It is generally difficult to diagnose RP in the absence of typical cartilaginous involvement; however, the present case suggests that HP may occur as an early clinical manifestation of RP. PMID:27920712

  11. A nationwide study of the epidemiology of relapsing polychondritis

    PubMed Central

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

    2016-01-01

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

  12. Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

    PubMed Central

    File, Ibolya; Trinn, Csilla; Mátyus, Zsolt; Ujhelyi, László; Balla, József; Mátyus, János

    2014-01-01

    Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease. PMID:25516870

  13. Relapsing polychondritis associated with psoriasis vulgaris successfully treated with adalimumab: A case report with published work review.

    PubMed

    Matsuo, Haruka; Asahina, Akihiko; Fukuda, Takeshi; Umezawa, Yoshinori; Nakagawa, Hidemi

    2017-03-07

    Relapsing polychondritis (RP) is a rare autoimmune-mediated disease characterized by inflammation involving cartilaginous tissues. We report here a case of RP in a 38-year-old Japanese man with 13-year duration of psoriasis vulgaris treated with topical steroids and vitamin D3 . The patient presented with tender swelling and erythema of both auricles, and the antibody to type II collagen was detected. The biopsy specimen revealed a dense mixed cell infiltration over the auricular cartilage. We reviewed eight cases with the association of RP and psoriasis, and in all cases the clinical course of psoriasis did not correlate with that of RP. The severity of RP was mild in the majority of cases, and our case was unique in that the patient had no joint symptoms. Adalimumab treatment was effective for both RP and psoriasis. Fat-suppressed contrast-enhanced magnetic resonance imaging was beneficial, not only to demonstrate subclinical inflammation in the nasal septum, but also to subjectively assess the improvement of RP.

  14. Local Cartilage Trauma as a Pathogenic Factor in Autoimmunity (One Hypothesis Based on Patients with Relapsing Polychondritis Triggered by Cartilage Trauma)

    PubMed Central

    Cañas, Carlos A.; Bonilla Abadía, Fabio

    2012-01-01

    In the recent years, it has been of great interest to study the binding mechanism between the innate and adaptive immune responses as interrelated processes for the development of multiple autoimmune diseases. Infection has been a well-known trigger of autoimmunity and trauma has been related as well too. Cryptogenic antigens release, recognition of pathogenic structure, and metabolic changes generated by both stimuli begin an inflammatory process which in turn activates the immune system amplifying T and B cell responses. The development of relapsing polychondritis after trauma may have a direct association with these events and in turn probably trigger autoimmune phenomena. PMID:22110903

  15. Relapsing polychondritis: prevalence of cardiovascular diseases and its risk factors, and general disease features according to gender.

    PubMed

    Pallo, Pablo Arturo Olivo; Levy-Neto, Maurício; Pereira, Rosa Maria Rodrigues; Shinjo, Samuel Katsuyuki

    2017-02-20

    The comorbidities in relapsing polychondritis (RP) have been scarcely described in the literature. Moreover, apart from a few RP epidemiological studies, no studies specifically addressing RP distribution according to gender are available. Therefore, the objetives of the present study were: (a) to analyse the prevalence of cardiovascular diseases and its risk factors in a series of patients with RP; (b) to determine the influence of gender on RP. A cross-sectional tertiary single center study evaluating 30 RP cases from 1990 to 2016 was carried out. To compare comorbidities, 60 healthy individuals matched for age-, gender-, ethnicity- and body mass index were recruted. The mean age of RP patientes was 49.0±12.4 years, the median disease duration 6.0 years, and 70% were women. A higher frequency of arterial hypertension (53.3% vs. 23.3%; p=0.008) and diabetes mellitus (16.7% vs. 3.3%; p=0.039) was found in the RP group, compared to the control group. As an additional analysis, patients were compared according to gender distribution (9 men vs. 21 women). The clinical disease onset features were comparable in both genders. However, over the follow-up period, male patients had a greater prevalence of hearing loss, vestibular disorder and uveitis events, and also received more cyclophosphamide therapy (p<0.05). There was a high prevalence of arterial hypertension and diabetes mellitus, and the male patients seemed to have worse prognosis than the female patients in the follow up.

  16. LIMBIC ENCEPHALITIS ASSOCIATED WITH RELAPSING POLYCHONDRITIS RESPONDED TO INFLIXIMAB AND MAINTAINED ITS CONDITION WITHOUT RECURRENCE AFTER DISCONTINUATION: A CASE REPORT AND REVIEW OF THE LITERATURE

    PubMed Central

    KONDO, TAKESHI; FUKUTA, MAMIKO; TAKEMOTO, AYUMU; TAKAMI, YUICHIRO; SATO, MOTOKI; TAKAHASHI, NORIYUKI; SUZUKI, TOMIO; SATO, JUICHI; ATSUTA, NAOKI; SOBUE, GEN; TAKAHASHI, YUKITOSHI; BAN, NOBUTARO

    2014-01-01

    ABSTRACT Central nervous system (CNS) manifestations are rare complications of relapsing polychondritis (RP). The majority of patients respond well to glucocorticoid therapy, but need to maintain it. Some patients are refractory to initial glucocorticoid therapy and to additional immunosuppressants, and end up with an outcome worse than at therapy initiation. The standardized therapeutic protocol for this condition has not been established. The effects of anti-tumor necrosis factor (TNF) -α agents have been reported recently. We experienced a patient with RP and limbic encephalitis who was refractory to initial high-dose glucocorticoid, but subsequently responded to infliximab and did not show deterioration of signs and symptoms after stopping therapy. We report this case together with a systematic literature review. This is the first case report of RP with CNS manifestations successfully treated by an anti-TNF-α agent without recurrence after discontinuation. PMID:25741046

  17. 3-D printouts of the tracheobronchial tree generated from CT images as an aid to management in a case of tracheobronchial chondromalacia caused by relapsing polychondritis.

    PubMed

    Tam, Matthew David; Laycock, Stephen David; Jayne, David; Babar, Judith; Noble, Brendon

    2013-08-01

    This report concerns a 67 year old male patient with known advanced relapsing polychondritis complicated by tracheobronchial chondromalacia who is increasingly symptomatic and therapeutic options such as tracheostomy and stenting procedures are being considered. The DICOM files from the patient's dynamic chest CT in its inspiratory and expiratory phases were used to generate stereolithography (STL) files and hence print out 3-D models of the patient's trachea and central airways. The 4 full-sized models allowed better understanding of the extent and location of any stenosis or malacic change and should aid any planned future stenting procedures. The future possibility of using the models as scaffolding to generate a new cartilaginous upper airway using regenerative medical techniques is also discussed.

  18. Acute Myeloid Leukemia Relapse Presenting as Complete Monocular Vision Loss due to Optic Nerve Involvement

    PubMed Central

    2016-01-01

    Acute myeloid leukemia (AML) involvement of the central nervous system is relatively rare, and detection of leptomeningeal disease typically occurs only after a patient presents with neurological symptoms. The case herein describes a 48-year-old man with relapsed/refractory AML of the mixed lineage leukemia rearrangement subtype, who presents with monocular vision loss due to leukemic eye infiltration. MRI revealed right optic nerve sheath enhancement and restricted diffusion concerning for nerve ischemia and infarct from hypercellularity. Cerebrospinal fluid (CSF) analysis showed a total WBC count of 81/mcl with 96% AML blasts. The onset and progression of visual loss were in concordance with rise in peripheral blood blast count. A low threshold for diagnosis of CSF involvement should be maintained in patients with hyperleukocytosis and high-risk cytogenetics so that prompt treatment with whole brain radiation and intrathecal chemotherapy can be delivered. This case suggests that the eye, as an immunoprivileged site, may serve as a sanctuary from which leukemic cells can resurge and contribute to relapsed disease in patients with high-risk cytogenetics. PMID:27668104

  19. [Chronic atrophic polychondritis and renal and cardiopulmonary amylosis: a case report and literature review (author's transl)].

    PubMed

    Lambrozo, J; Baubion, D; Brodaty, Y; Leclerc, J P

    1981-01-01

    Glomerular lesions with a nephrotic syndrome and impaired renal function developed secondary to a chronic atrophic polychondritis confirmed by auricular biopsy. In the absence of renal histology data, the possibility of an iatrogenic complication or a renal lesion specific to the affection itself were successively eliminated. Pos-mortem histological examination demonstrated renal and cardiopulmonary amylosis, the latter being clinically asymptomatic. The probable autoimmune origin of the chronic atrophic polychondritis has to be discussed in parallel with the dysimmunity mechanism responsible for the amyloid lesions, but no relationship between them was demonstrated.

  20. Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy

    PubMed Central

    Wrobel, Tomasz; Usnarska-Zubkiewicz, Lidia; Brzezniakiewicz, Katarzyna; Jamroziak, Krzysztof; Giannopoulos, Krzysztof; Przybylowicz-Chalecka, Anna; Ratajczak, Blazej; Czerwinska-Rybak, Joanna; Nowicki, Adam; Joks, Monika; Czechowska, Elzbieta; Zawartko, Magdalena; Szczepaniak, Tomasz; Grzasko, Norbert; Morawska, Marta; Bochenek, Maciej; Kubicki, Tadeusz; Morawska, Michalina; Tusznio, Katarzyna; Jakubowiak, Andrzej; Komarnicki, Mieczysław

    2016-01-01

    Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance. PMID:27527861

  1. 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

  2. Upfront Chemotherapy and Involved-Field Radiotherapy Results in More Relapses Than Extended Radiotherapy for Intracranial Germinomas: Modification in Radiotherapy Volume Might Be Needed

    SciTech Connect

    Eom, Keun-Yong; Kim, Il Han Park, Charn Il; Kim, Hak Jae; Kim, Jin Ho.; Kim, Kyubo; Kim, Seung Ki; Wang, Kyu-Chang; Cho, Byung-Gyu; Jung, Hee-Won; Heo, Dae Seog; Kang, Hyoung Jin; Shin, Hee Young; Ahn, Hyo Seop

    2008-07-01

    Purpose: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma. Methods and Materials: Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months. Results: The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT-three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106). Conclusions: The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.

  3. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

    PubMed Central

    Montesinos, Pau; Díaz-Mediavilla, Joaquín; Debén, Guillermo; Prates, Virginia; Tormo, Mar; Rubio, Vicente; Pérez, Inmaculada; Fernández, Isolda; Viguria, Maricruz; Rayón, Chelo; González, José; de la Serna, Javier; Esteve, Jordi; Bergua, Juan M.; Rivas, Concha; González, Marcos; González, Jose D.; Negri, Silvia; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2009-01-01

    Background The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. Results Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. Conclusions This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors. PMID:19608685

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

    PubMed

    Wallace, B C

    1989-01-01

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

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

    PubMed

    Chivot, M; Midoun, H

    1990-01-01

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

  6. Relapses in Patients With Giant Cell Arteritis

    PubMed Central

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

    2014-01-01

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

  7. Animal Models of Fear Relapse

    PubMed Central

    Goode, Travis D.; Maren, Stephen

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. Relapsing pityriasis rosea.

    PubMed

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

    2014-01-01

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

  10. 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

  11. 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…

  12. Relapsing fever in Jordan

    PubMed Central

    Babudieri, B.

    1957-01-01

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

  13. Relapse Prevention and the Five Rules of Recovery.

    PubMed

    Melemis, Steven M

    2015-09-01

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

  14. 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

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

    PubMed

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

    2013-04-01

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

  16. Possibilities for Relapsing Fever Reemergence

    PubMed Central

    2006-01-01

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

  17. Teriflunomide in relapsing multiple sclerosis: therapeutic utility.

    PubMed

    Freedman, Mark S

    2013-09-01

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

  18. 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.

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

    PubMed

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

    2016-04-22

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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. Resistance to change and relapse of observing.

    PubMed

    Thrailkill, Eric A; Shahan, Timothy A

    2012-05-01

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

  5. Modeling relapse in infectious diseases.

    PubMed

    van den Driessche, P; Zou, Xingfu

    2007-05-01

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

  6. Early relapse after rituximab chemoimmunotherapy.

    PubMed

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

    2008-02-01

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

  7. 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

  8. Periplasmic flagellar export apparatus protein, FliH, is involved in post-transcriptional regulation of FlaB, motility and virulence of the relapsing fever spirochete Borrelia hermsii.

    PubMed

    Guyard, Cyril; Raffel, Sandra J; Schrumpf, Merry E; Dahlstrom, Eric; Sturdevant, Daniel; Ricklefs, Stacy M; Martens, Craig; Hayes, Stanley F; Fischer, Elizabeth R; Hansen, Bryan T; Porcella, Stephen F; Schwan, Tom G

    2013-01-01

    Spirochetes are bacteria characterized in part by rotating periplasmic flagella that impart their helical or flat-wave morphology and motility. While most other bacteria rely on a transcriptional cascade to regulate the expression of motility genes, spirochetes employ post-transcriptional mechanism(s) that are only partially known. In the present study, we characterize a spontaneous non-motile mutant of the relapsing fever spirochete Borrelia hermsii that was straight, non-motile and deficient in periplasmic flagella. We used next generation DNA sequencing of the mutant's genome, which when compared to the wild-type genome identified a 142 bp deletion in the chromosomal gene encoding the flagellar export apparatus protein FliH. Immunoblot and transcription analyses showed that the mutant phenotype was linked to the posttranscriptional deficiency in the synthesis of the major periplasmic flagellar filament core protein FlaB. Despite the lack of FlaB, the amount of FlaA produced by the fliH mutant was similar to the wild-type level. The turnover of the residual pool of FlaB produced by the fliH mutant was comparable to the wild-type spirochete. The non-motile mutant was not infectious in mice and its inoculation did not induce an antibody response. Trans-complementation of the mutant with an intact fliH gene restored the synthesis of FlaB, a normal morphology, motility and infectivity in mice. Therefore, we propose that the flagellar export apparatus protein regulates motility of B. hermsii at the post-transcriptional level by influencing the synthesis of FlaB.

  9. 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…

  10. 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…

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

    PubMed Central

    Bhaskar, Atul; Patni, Piyush

    2013-01-01

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

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

    PubMed

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

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

  13. Very late relapse of medulloblastoma.

    PubMed

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

    2004-01-01

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

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

    ERIC Educational Resources Information Center

    Goodrick, G. Ken; And Others

    1984-01-01

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

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

    PubMed

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

    2015-07-02

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

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

    PubMed Central

    Sumrall, Bradley; Diethelm, Lisa; Brown, Archie

    2013-01-01

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

  17. The nature of relapse in schizophrenia

    PubMed Central

    2013-01-01

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

  18. The neurobiology of relapse in schizophrenia.

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2012-09-01

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

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

    PubMed

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

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

  1. 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…

  2. 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…

  3. Primaquine treatment and relapse in Plasmodium vivax malaria.

    PubMed

    Rishikesh, Kumar; Saravu, Kavitha

    2016-01-01

    The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once 'neglected' species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients' G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe.

  4. Primaquine treatment and relapse in Plasmodium vivax malaria

    PubMed Central

    2016-01-01

    The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once ‘neglected’ species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients’ G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe. PMID:27077309

  5. Menstrual phase effects on smoking relapse

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-06-15

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

  7. 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

  8. Management of relapsing Plasmodium vivax malaria

    PubMed Central

    Chu, Cindy S; White, Nicholas J

    2016-01-01

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

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

    SciTech Connect

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

    2009-09-01

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

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

    PubMed

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

    2005-02-01

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

  11. [Management of relapses in smoking dehabituation].

    PubMed

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

    2006-03-01

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

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

    PubMed

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

    2016-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Ismail, Mohd Tahir; Alias, Siti Nor Shadila

    2014-07-01

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

  14. A parametric estimation procedure for relapse time distributions.

    PubMed

    Ahlström, L; Olsson, M; Nerman, O

    1999-06-01

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

  15. 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)

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

    PubMed

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

    2007-03-01

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2011-01-01

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

  19. Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse

    PubMed Central

    Krzeminski, Patryk; Corchete, Luis A.; García, Juan L.; López-Corral, Lucía; Fermiñán, Encarna; García, Eva M.; Martín, Ana A.; Hernández-Rivas, Jesús M.; García-Sanz, Ramón; Miguel, Jesús F. San; Gutiérrez, Norma C.

    2016-01-01

    Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse. PMID:27811368

  20. Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.

    PubMed

    Krzeminski, Patryk; Corchete, Luis A; García, Juan L; López-Corral, Lucía; Fermiñán, Encarna; García, Eva M; Martín, Ana A; Hernández-Rivas, Jesús M; García-Sanz, Ramón; San Miguel, Jesús F; Gutiérrez, Norma C

    2016-12-06

    Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.

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

    PubMed

    Sabatini, Camila

    2012-03-01

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

  2. Medical treatment for biochemical relapse after radiotherapy.

    PubMed

    Quero, L; Hennequin, C

    2014-10-01

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

  3. 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.

  4. Risk of Ovarian Cancer Relapse Score

    PubMed Central

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

    2015-01-01

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

  5. Retention and relapse in clinical practice.

    PubMed

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

    2017-03-01

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

  6. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-03-02

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

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

    PubMed Central

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

    2016-01-01

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

  9. The gene expression signature of relapse in paediatric acute lymphoblastic leukaemia: implications for mechanisms of therapy failure.

    PubMed

    Beesley, Alex H; Cummings, Aaron J; Freitas, Joseph R; Hoffmann, Katrin; Firth, Martin J; Ford, Jette; de Klerk, Nicolas H; Kees, Ursula R

    2005-11-01

    Despite significant improvements in the treatment of childhood acute lymphoblastic leukaemia (ALL), the prognosis for relapsing patients remains poor. The aim of this study was to generate a transcriptional profile of relapsed ALL to increase our understanding of the mechanisms involved in therapy failure. RNA was extracted from 11 pairs of cryopreserved pre-B ALL bone marrow specimens taken from the same patients at diagnosis and relapse, and analysed using HG-U133A microarrays. Relapse specimens overexpressed genes that are involved with cell growth and proliferation, in keeping with their aggressive phenotype. When tested in 72 independent specimens of pre-B ALL and T-ALL, the identified genes could successfully differentiate between diagnosis and relapse in either lineage, indicating the existence of relapse mechanisms common to both. These genes have functions relevant for oncogenesis, drug resistance and metastasis, but are not related to classical multidrug-resistance pathways. Increased expression of the top-ranked gene (BSG) at diagnosis was significantly associated with adverse outcome. Several chromosomal loci, including 19p13, were identified as potential hotspots for aberrant gene expression in relapsed ALL. Our results provide evidence for a link between drug resistance and the microenvironment that has previously only been considered in the context of solid tumour biology.

  10. Attributions and Relapse in Opiate Addicts.

    ERIC Educational Resources Information Center

    Bradley, Brendan P.; And Others

    1992-01-01

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

  11. A Typology of Relapse Promoting Situations.

    ERIC Educational Resources Information Center

    Shiffman, Saul

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

  12. Resistance to Change and Relapse of Observing

    ERIC Educational Resources Information Center

    Thrailkill, Eric A.; Shahan, Timothy A.

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2004-01-01

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

  15. 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…

  16. The Role of Family Atmosphere in the Relapse Behavior of Iranian Opiate Users: a Qualitative Study

    PubMed Central

    Peyrovi, Hamid; Seyedfatemi, Naiemeh; Jalali, Amir

    2015-01-01

    Introduction Many Iranian opiate users live with family members and family atmosphere can be influential on reducing such social behaviors of opiate users as substance use and relapses. This paper reports the impact of family atmosphere on relapse behavior as a part of the findings of a larger study that explored the relapse process among Iranian opiate users. Methods: In this qualitative research, we selected 17 participants (5 women and 12 men). The questions were been asked through semi-structured interviews. The researchers analyzed the verbatim transcripts using content analysis method. Results: "Family atmosphere" with three sub-themes (family and tribes' interaction, family challenges and family structure) was been found as determinants of relapse behavior. The quality of the family atmosphere could be in harmony with or against the willingness or motivation of the opiate user towards the relapse. Conclusion Health care providers should reinforce involvement of the family members in the treatment and rehabilitation of opiate users. The opiate user's family and even relatives may benefit from learning how to manage their own feelings and attitude towards the client and being supportive during interactions. PMID:26464835

  17. Ocular rosacea: an underdiagnosed cause of relapsing conjunctivitis-blepharitis in the elderly.

    PubMed

    De Marchi, Sergio Umberto; Cecchin, Emanuela; De Marchi, Sergio

    2014-09-19

    Red eye and relapsing conjunctivitis-blepharitis are among the most common ocular disease in elderly patients. In these cases the search for causes is difficult and frustrating. We report the case of a 79-year-old woman with a long history of red eye and relapsing conjunctivitis-blepharitis caused by ocular rosacea. In this patient the proper diagnosis was performed after 10 years of ocular disease, and repeated evaluations by general practitioners and clinical specialists, only after the appearance of facial signs of erythematotelangiectatic rosacea. Adequate therapy with oral doxycycline led to the improvement of the clinical picture that previously had shown a poor response to several topical treatments. The possibility of ocular rosacea should be considered in evaluating an elderly patient with persistent red eye and relapsing conjunctivitis-blepharitis. Making the proper diagnosis is crucial because ocular rosacea does not respond as expected to topical therapy and may lead to severe corneal involvement.

  18. Predicting Post-External Beam Radiation Therapy PSA Relapse of Prostate Cancer Using Pretreatment MRI

    SciTech Connect

    Fuchsjaeger, Michael H.; Pucar, Darko; Zelefsky, Michael J.; Zhang Zhigang; Mo Qianxing; Ben-Porat, Leah S.; Shukla-Dave, Amita; Wang Liang; Reuter, Victor E.; Hricak, Hedvig

    2010-11-01

    Purpose: To investigate whether pretreatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer treated with external beam radiation therapy (EBRT). Methods and Materials: Between January 2000 and January 2002, 224 patients (median age, 69 years; age range, 45-82 years) with biopsy-proven prostate cancer underwent endorectal MRI before high-dose ({>=}81Gy) EBRT. The value of multiple clinical and MRI variables in predicting prostate-specific antigen (PSA) relapse at 5 years was determined by use of univariate and multivariate stepwise Cox regression. Clinical variables included pretreatment PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and radiation dose. Magnetic resonance imaging variables, derived from retrospective consensus readings by two radiologists, were used to measure intraprostatic and extraprostatic tumor burden. Results: After a median follow-up of 67 months, PSA relapse developed in 37 patients (16.5%). The significant predictors of PSA relapse on univariate analysis were pretreatment PSA, clinical T stage, and multiple MRI variables, including MRI TN stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors on multivariate analysis (p < 0.05 for both). Extracapsular extension status was associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. Conclusions: Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pretreatment PSA being significant independent predictors of this endpoint.

  19. Targeting heparanase overcomes chemoresistance and diminishes relapse in myeloma

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-06-01

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

  1. Melioidosis with a Pericardial Effusion, which Relapsed as a Chest Wall Abscess: A Rare Presentation

    PubMed Central

    Mathai K., Rashmi Teresa; Bhat, K. Sundara; Ashraf, Mohammed; Sarawag, Mayank; K.P., Kumar

    2013-01-01

    Melioidosis, which is caused by a soil saprophyte, Burkholderia pseudomallei, is most prevalent in the south–west coast of India. Although it is frequently seen in immunocompromised patients, melioidosis can occur in apparently normal individuals. Melioidosis can involve almost any organ. A relapse of melioidosis is usually associated with a poor adherence to the eradication therapy, a multifocal involvement and bacteraemia. A relapsing melioidosis is usually known to follow a similar pattern of organ involvement in the first and second episodes of the infection. We are discussing here, a rare case of melioidosis in a 38-year-old construction-worker, with no risk factors, who presented initially with a pericardial effusion. It relapsed 6 months after he completed the prescribed eradication therapy for 3 months, as an anterior chest wall abscess. The author recommends a high index of suspicion for the relapsed melioidosis cases, inspite of the primary episode being non-bacteraemic and compliant with the recommended therapy, in order to avoid further complications. PMID:23730667

  2. 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

  3. Granulomatosis with polyangiitis presenting with diffuse alveolar hemorrhage requiring extracorporeal membrane oxygenation with rapid multiorgan relapse

    PubMed Central

    Vanoli, Jennifer; Riva, Marta; Vergnano, Beatrice; D’Andrea, Gabriele; L’Imperio, Vincenzo; Pozzi, Maria Rosa; Grassi, Guido

    2017-01-01

    Abstract Rationale: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitis affecting small- and medium-sized blood vessels, mostly involving lung and kidney. Patient concerns: We report the case of a 33-year-old man that presented with acute respiratory distress syndrome caused by alveolar hemorrhage. Diagnoses: Aggressive GPA presenting with diffuse alveolar hemorrhage and multiorgan involvement. Inteventions: Immunosuppressive therapy, plasma exchange, extracorporeal membrane oxygenation (ECMO). Outcomes: Relapse occurred very early, despite immunosuppressive treatment, with a rare involvement of genital system (epididymitis) and rapidly progressive glomerulonephritis difficult to treat. Lessons: GPA is a challenging, multifaceted disease that can require aggressive supportive therapy and is associated with a high rate of relapse that may present with uncommon site of involvement. PMID:28353556

  4. Relapses in multiple sclerosis: Relationship to disability.

    PubMed

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

    2016-03-01

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

  5. Pathways Linking Socioeconomic Status and Postpartum Smoking Relapse

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-05-01

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

  7. Factors associated with relapse in adult patients discharged from the emergency department following acute asthma: a systematic review

    PubMed Central

    Hill, Jesse; Arrotta, Nicholas; Villa-Roel, Cristina; Dennett, Liz; Rowe, Brian H

    2017-01-01

    A significant proportion of patients discharged from the emergency department (ED) with asthma exacerbations will relapse within 4 weeks. This systematic review summarises the evidence regarding relapses and factors associated with relapse in adult patients discharged from EDs after being treated for acute asthma. Following a registered protocol, comprehensive literature searches were conducted. Studies tracking outcomes for adults after ED management and discharge were included if they involved adjusted analyses. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS) and the Risk of Bias (RoB) Tool. Results were summarised using medians and IQRs or mean and SD, as appropriate. 178 articles underwent full-text review and 10 studies, of various methodologies, involving 32 923 patients were included. The majority of the studies were of high quality according to NOS and RoB Tool. Relapse proportions were 8±3%, 12±4% and 14±6% at 1, 2 and 4 weeks, respectively. Female sex was the most commonly reported and statistically significant factor associated with an increased risk of relapse within 4 weeks of ED discharge for acute asthma. Other factors significantly associated with relapse were past healthcare usage and previous inhaled corticosteroids (ICS) usage. A median of 17% of patients who are discharged from the ED will relapse within the first 4 weeks. Factors such as female sex, past healthcare usage and ICS use at presentation were commonly and significantly associated with relapse occurrence. Identifying patients with these features could provide clinicians with guidance during their ED discharge decision-making. PMID:28176972

  8. Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations

    PubMed Central

    Ljungström, Viktor; Cortese, Diego; Young, Emma; Pandzic, Tatjana; Mansouri, Larry; Plevova, Karla; Ntoufa, Stavroula; Baliakas, Panagiotis; Clifford, Ruth; Sutton, Lesley-Ann; Blakemore, Stuart J.; Stavroyianni, Niki; Agathangelidis, Andreas; Rossi, Davide; Höglund, Martin; Kotaskova, Jana; Juliusson, Gunnar; Belessi, Chrysoula; Chiorazzi, Nicholas; Panagiotidis, Panagiotis; Langerak, Anton W.; Smedby, Karin E.; Oscier, David; Gaidano, Gianluca; Schuh, Anna; Davi, Frederic; Pott, Christiane; Strefford, Jonathan C.; Trentin, Livio; Pospisilova, Sarka; Ghia, Paolo; Stamatopoulos, Kostas; Sjöblom, Tobias

    2016-01-01

    Fludarabine, cyclophosphamide, and rituximab (FCR) is first-line treatment of medically fit chronic lymphocytic leukemia (CLL) patients; however, despite good response rates, many patients eventually relapse. Although recent high-throughput studies have identified novel recurrent genetic lesions in adverse prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, and BIRC3), a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases, selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal before treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid, evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared with wild-type RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology. PMID:26675346

  9. Trends and tenets in relapsing and progressive opsoclonus-myoclonus syndrome.

    PubMed

    Pranzatelli, Michael R; Tate, Elizabeth D

    2016-05-01

    Despite advances in inducing remission in pediatric opsoclonus-myoclonus syndrome (OMS), relapse remains a challenge. By definition, relapse is not a characteristic of monophasic OMS, but occurs at any time in the course of multiphasic OMS. Due to variability and heterogeneity, patients are best approached and treated on a case-by-case basis, using precepts derived from clinical and scientific studies. Treatment of provocations, such as infection or immunotherapy tapering, is the short-term goal, but discovering unresolved neuroinflammation and re-configuring disease-modifying agents is crucial in the long-term. The working hypothesis is that much of the injury in OMS results from neuroinflammation involving dysregulated B cells, which may cause loss of tolerance and autoantibody production. Biomarkers of disease activity include cerebrospinal fluid (CSF) B cell frequency, oligoclonal bands (OCB), B cell attractants (CXCL13) and activating factors (BAFF). Measuring these markers comprises modern detection and characterization of neuroinflammation or verifies 'no evidence of disease activity'. The decision making process is three-tiered: deciding if the relapse is bone fide, identifying its etiology, and formulating a therapeutic plan. Relapsing-remitting OMS is treatable, and combination multimodal/multi-mechanistic immunotherapy is improving the outcome. However, some patients progress to a refractory state with cognitive impairment and disability from failure to go into remission, multiple relapses, or more aggressive disease. This report provides new insights on underappreciated risks and pitfalls inherent in relapse, pro-active efforts to avoid progression, the need for early and sufficient treatment beyond corticosteroids and immunoglobulins, and utilization of disease activity biomarkers to identify high-risk patients and safely withdraw immunotherapy.

  10. 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.

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

    PubMed

    Sinha, Rajita

    2011-10-01

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

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

    PubMed

    Falussy, Linda; Balla, Petra; Frecska, Ede

    2014-09-01

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

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

    PubMed

    Ku, Bon D; Yoon, Sung Sang

    2011-01-01

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

  14. Risk of relapse after natalizumab withdrawal

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Piñeiro, Bárbara; Becoña, Elisardo

    2013-01-01

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

  16. Prospective noninterventional study on peripheral blood stem cell mobilization in patients with relapsed lymphomas.

    PubMed

    van Gorkom, Gwendolyn; Finel, Herve; Giebel, Sebastian; Pohlreich, David; Shimoni, Avichai; Ringhoffer, Mark; Sucak, Gülsan; Schaap, Nicolaas; Dreger, Peter; Sureda, Anna; Schouten, Harry C

    2016-09-10

    High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) to rescue hematopoiesis is considered standard care for patients with a relapsed chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for poor mobilization in several studies. The aim of this prospective noninterventional clinical audit was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010 and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were prospectively registered. Almost all patients were mobilized with chemotherapy plus G-CSF (96%), but there was a large variation in chemotherapy schedules. Thirty (11%) of them were poor mobilizers (<2 × 10(6) CD 34+ cells/kg body weight) at the first mobilization. Poor mobilization was not associated with gender, age, bone marrow involvement at diagnosis, primary diagnosis, number of previous chemotherapy lines, previous radiotherapy or mobilization with G-CSF alone. The use of high dose cyclophosphamide alone was associated with mobilization failure (P = 0.0006), whereas the use of a platinum-containing regimen was associated with a good mobilization outcome (P = 0.013). Because failure rate is low, we can conclude from this study that PBSC mobilization failure in relapsed lymphomas is not an important problem in the EBMT centers.

  17. Aleukemic Leukemia Cutis Presenting as a Sole Sign of Relapsed Paediatric Acute Lymphoblastic Leukemia.

    PubMed

    Joshi, Kshitij; Panchal, Harsha; Parikh, Sonia; Modi, Gaurang; Talele, Avinash; Anand, Asha; Uparkar, Urmila; Joshi, Nitin; Khatawani, Itesh

    2016-06-01

    The author describes paediatric case of relapsed acute lymphoblastic leukaemia (ALL) presented as aleukemic leukaemia cutis (ALC). A 2 year old child was admitted in tertiary oncology centre. He suffered from pre B cell ALL with absent Philadelphia chromosome. This patient received multiagent induction chemotherapy as per Berlin-Frankfurt-Munster (BFM) protocol for ALL. He achieved remission after 28 days of treatment. Subsequently he presented with multiple skin lesions in the form of multiple small erythematous violaceous macules, papules, plaques and nodules on face, chest and back regions. Histopathological examination of biopsy of skin revealed diffuse infiltration of tumor cells with prominent nucleoli, scant eosinophilic cytoplasm and numerous mitotic figures consistent with LC. Immunohistochemistry was positive for CD 10, CD 19, CD 22, CD 24, CD 79-a and TdT while negative for surface immunoglobulin. At the time of presentation his peripheral blood smear and bone marrow examination was negative for malignant cells. Sanctuary sites including central nervous system and testicles were not involved. So patient was diagnosed as ALC. He was managed as per BFM relapse protocol for ALL. Skin lesions disappeared completely after 2 weeks of treatment. Unfortunately patient developed bone marrow and testicular relapse after 2 months. He was given testicular radiotherapy and systemic chemotherapy for relapsed ALL. But his marrow was showing persistent activity and he expired after 4 months.

  18. 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

  19. Pemphigus erythematosus relapse associated with atorvastatin intake

    PubMed Central

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

    2014-01-01

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

  20. 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

  1. Predictors of Exercise Relapse in a College Population.

    ERIC Educational Resources Information Center

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

    2000-01-01

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

  2. 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

  3. 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…

  4. 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…

  5. A case of late herpes simplex encephalitis relapse.

    PubMed

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

    2013-09-01

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

  6. 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.

  7. 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

  8. Alcoholics Anonymous and Relapse Prevention as Maintenance Strategies After Conjoint Behavioral Alcohol Treatment for Men: 18-Month Outcomes

    ERIC Educational Resources Information Center

    McCrady, Barbara S.; Epstein, Elizabeth E.; Kahler, Christopher W.

    2004-01-01

    Ninety men with alcohol problems and their female partners were randomly assigned to 1 of 3 outpatient conjoint treatments: alcohol behavioral couples therapy (ABCT), ABCT with relapse prevention techniques (RP/ABCT), or ABCT with interventions encouraging Alcoholics Anonymous (AA) involvement (AA/ABCT). Couples were followed for 18 months after…

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

    PubMed

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

    2016-01-01

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

  10. IL-12Rβ2 has a protective role in relapsing-remitting experimental autoimmune encephalomyelitis

    PubMed Central

    Xie, Chong; Ciric, Bogoljub; Yu, Shuo; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2016-01-01

    IL-12Rβ2 participates in the receptors of IL-12 and IL-35, two cytokines that are involved in a variety of immune responses. In this study we evaluate the role of IL-12Rβ2 in relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE). We found that the IL-12Rβ2 deficient SJL/J EAE mice presented more severe symptoms and had more frequent, more severe relapses compared with wild type controls. IL-12Rβ2 deficient EAE mice also had more infiltrating mononuclear cells in the central nervous system, as well as higher splenic proliferative capacity and decreased IFN-γ production at the periphery. These findings suggest a protective role of IL-12Rβ2 in RR-EAE, an animal model of RR-MS, the most prevalent form of MS. PMID:26857496

  11. Relapsed acute lymphoblastic leukemia with unusual multiple bone invasions: A case report

    PubMed Central

    HANGAI, MAYUMI; WATANABE, KENTARO; SHIOZAWA, RYOSUKE; HIWATARI, MITSUTERU; IDA, KOHMEI; TAKITA, JUNKO

    2014-01-01

    The present study describes a unique pediatric case with multiple bone invasions of acute lymphoblastic leukemia (ALL) during remission. An eight-year-old male with a history of ALL was admitted complaining of intermittent and migrating pain in the limb 2 years following complete remission. Magnetic resonance imaging and whole-body positron emission tomography with 18F-fluorodeoxyglucose revealed abnormal multifocal involvement in the bones and corresponding soft tissues. Repeated bone marrow (BM) aspiration indicated normal cellular marrow without leukemic cells, and marked leukemic cell infiltration in different sections of the ilium, respectively. These findings suggested isolated bone relapse, and it is probable that systematic BM relapse occurred as a consequence. PMID:24944655

  12. Glioblastoma following treatment with fingolimod for relapsing-remitting multiple sclerosis.

    PubMed

    Sharim, Justin; Tashjian, Randy; Golzy, Nima; Pouratian, Nader

    2016-08-01

    Glioblastoma is an uncommon and aggressive primary brain tumor with incidence of 3 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within threeyears of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development.

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

    SciTech Connect

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

    1984-10-01

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

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

    PubMed Central

    Seyedfatemi, Naiemeh; Peyrovi, Hamid; Jalali, Amir

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Miller, Colleen E.; Jezewski, Mary Ann

    2012-01-01

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

  17. Pure Testicular Seminoma Relapsing Late with Somatic Type Malignancy

    PubMed Central

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

    2017-01-01

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

  18. 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

  19. SncRNA (microRNA & snoRNA) opposite expression pattern found in multiple sclerosis relapse and remission is sex dependent

    PubMed Central

    Muñoz-Culla, Maider; Irizar, Haritz; Sáenz-Cuesta, Matías; Castillo-Triviño, Tamara; Osorio-Querejeta, Iñaki; Sepúlveda, Lucía; López de Munain, Adolfo; Olascoaga, Javier; Otaegui, David

    2016-01-01

    Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission). Recently, non-coding RNAs have emerged as new players in transcriptome regulation, and in turn, they could have a significant role in MS pathogenesis. In this context, our aim was to investigate the involvement of microRNAs and snoRNAs in the relapse-remission dynamics of MS in peripheral blood leucocytes, to shed light on the molecular and regulatory mechanisms that underlie this complex process. With this approach, we found that a subset of small non-coding RNAs (sncRNA) is altered in relapse and remission, revealing unexpected opposite changes that are sex dependent. Furthermore, we found that a relapse-related miRNA signature regulated general metabolism processes in leucocytes, and miRNA altered in remission are involved in the regulation of innate immunity. We observed that sncRNA dysregulation is different in relapse and remission leading to differences in transcriptome regulation, and that this process is sex dependent. In conclusion, relapse and remission have a different molecular background in men and women. PMID:26831009

  20. SncRNA (microRNA &snoRNA) opposite expression pattern found in multiple sclerosis relapse and remission is sex dependent.

    PubMed

    Muñoz-Culla, Maider; Irizar, Haritz; Sáenz-Cuesta, Matías; Castillo-Triviño, Tamara; Osorio-Querejeta, Iñaki; Sepúlveda, Lucía; López de Munain, Adolfo; Olascoaga, Javier; Otaegui, David

    2016-02-01

    Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission). Recently, non-coding RNAs have emerged as new players in transcriptome regulation, and in turn, they could have a significant role in MS pathogenesis. In this context, our aim was to investigate the involvement of microRNAs and snoRNAs in the relapse-remission dynamics of MS in peripheral blood leucocytes, to shed light on the molecular and regulatory mechanisms that underlie this complex process. With this approach, we found that a subset of small non-coding RNAs (sncRNA) is altered in relapse and remission, revealing unexpected opposite changes that are sex dependent. Furthermore, we found that a relapse-related miRNA signature regulated general metabolism processes in leucocytes, and miRNA altered in remission are involved in the regulation of innate immunity. We observed that sncRNA dysregulation is different in relapse and remission leading to differences in transcriptome regulation, and that this process is sex dependent. In conclusion, relapse and remission have a different molecular background in men and women.

  1. Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse.

    PubMed

    Ackerman, I; Malone, S; Thomas, G; Franssen, E; Balogh, J; Dembo, A

    1996-02-01

    Fifty-four patients with recurrent endometrial carcinoma were identified from a retrospective review of charts of 304 endometrial cancer patients seen between 1983 and 1989 at our center. A review was undertaken to identify the patterns of relapse, to determine the outcome of salvage treatment, to examine the factors predictive of effective salvage, and, if salvage is effective, to assess an alternative strategy to routine adjuvant postoperative pelvic radiotherapy. Forty percent of the entire recurrent population are long-term survivors. Of the 54 relapsing patients, primary therapy had been surgery alone in 32 and surgery and adjuvant radiotherapy (rt) in 22. Isolated pelvic recurrence was the predominate relapse site in those who had not received adjuvant pelvic RT as primary therapy (23 of 32 or 72%). Distant relapse predominated in those who received adjuvant RT (17 or 22 or 77%). Twenty-eight (54%) failed in the pelvis alone, and 26 (46%) had a component of distant failure. Of the 28 with isolated pelvic relapse, 16 had vaginal mucosal disease involvement only and 12 had disease in the parametrium and/or the pelvic sidewall. With a minimum follow-up for the survivors of 5 years, 21 of the 28 with isolated pelvic relapse received radical radiotherapy and 14 or 67% had maintained pelvic control until death or last follow-up. Eleven of 14 (79%) with disease confined to the mucosa had pelvic control, whereas only 3 of 7 (43%) with extramucosal disease were controlled. No patient experienced major treatment-related toxicity. Tumor size, anatomic extent of pelvic recurrence, RT dose, and disease-free interval were examined for prognostic significance for pelvic control and survival by univariate analysis. Only anatomic extent of pelvic recurrence showed a nonstatistically significant trend as a predictor for control with P = 0.08. In conclusion, a significant proportion of patients with disease recurrence confined to the pelvis can be rendered disease-free long

  2. 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.

  3. 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.

  4. Cognitive Therapy to Prevent Depressive Relapse in Adults

    PubMed Central

    2015-01-01

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

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

    PubMed

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

    2017-03-15

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

  6. Assessing changes in relapse rates in multiple sclerosis.

    PubMed

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

    2010-12-01

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

  7. A Motion Videogame for Opioid Relapse Prevention

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    1996-12-01

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

  10. Female Ex-Offender Perspectives on Drug Initiation, Relapse, and Desire to Remain Drug Free

    PubMed Central

    Nyamathi, Adeline M.; Srivastava, Neha; Salem, Benissa E.; Wall, Sarah; Kwon, Jordan; Ekstrand, Maria; Hall, Elizabeth; Turner, Susan F.; Faucette, Mark

    2016-01-01

    Recently-released homeless women residing in temporary residential drug treatment programs are at a critical juncture in the process of recovery, transition and reentry. The purpose of this study was to explore factors influencing initial use of drugs and relapse triggers among a sample of incarcerated women exiting jails and prisons, and who are residing in a residential drug treatment (RDT) program and preparing for reentry into their communities. Among this population, relapse to drug use and recidivism are common. A qualitative study was conducted utilizing focus groups to understand the perspectives of formerly incarcerated, currently homeless women residing in a RDT program. Content analysis generated the development of three broad categories: a) factors associated with first drug use; b) factors involved in relapse; c) factors influencing desire to remain drug free. A discussion follows highlighting the importance of targeted interventions at RDT sites that integrate physical, psychological and social needs to optimize reentry into communities. This would include a focus on building self-esteem, life skills, and providing access to resources such as housing, employment, and healthcare. PMID:27195929

  11. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse

    PubMed Central

    Al-Temaimi, Rabeah A.; Tan, Tuan Zea; Marafie, Makia J.; Thiery, Jean Paul; Quirke, Philip; Al-Mulla, Fahd

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Metastasis remains the primary cause of CRC death. Predicting the possibility of metastatic relapse in early-stage CRC is of paramount importance to target therapy for patients who really need it and spare those with low-potential of metastasis. Ninety-six stage II CRC cases were stratified using high-resolution array comparative genomic hybridization (aCGH) data based on a predictive survival algorithm and supervised clustering. All genes included within the resultant copy number aberrations were each interrogated independently at mRNA level using CRC expression datasets available from public repositories, which included 1820 colon cancers, and 167 normal colon tissues. Reduced mRNA expression driven by copy number losses and increased expression driven by copy number gains revealed 42 altered transcripts (29 reduced and 13 increased transcripts) associated with metastatic relapse, short disease-free or overall survival, and/or epithelial to mesenchymal transition (EMT). Resultant genes were classified based on gene ontology (GO), which identified four functional enrichment groups involved in growth regulation, genomic integrity, metabolism, and signal transduction pathways. The identified 42 genes may be useful for predicting metastatic relapse in stage II CRC. Further studies are necessary to validate these findings. PMID:27136531

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

    PubMed Central

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

    2005-01-01

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

  13. Highly Expressed Integrin-α8 Induces Epithelial to Mesenchymal Transition-Like Features in Multiple Myeloma with Early Relapse

    PubMed Central

    Ryu, Jiyeon; Koh, Youngil; Park, Hyejoo; Kim, Dae Yoon; Kim, Dong Chan; Byun, Ja Min; Lee, Hyun Jung; Yoon, Sung-Soo

    2016-01-01

    Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-α8 (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-α8 is largely unknown. We functionally overexpressed integrin-α8 in MM cell lines, and surprisingly, stemness features including HIF1α, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-α8 expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-α8, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target. PMID:28008160

  14. Prevalence and Serological Diagnosis of Relapse in Paracoccidioidomycosis Patients

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

    Nochajski, Thomas H; Stasiewicz, Paul R

    2006-03-01

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

  17. Voluntary exercise during extinction of auditory fear conditioning reduces the relapse of fear associated with potentiated activity of striatal direct pathway neurons.

    PubMed

    Mika, Agnieszka; Bouchet, Courtney A; Bunker, Preston; Hellwinkel, Justin E; Spence, Katie G; Day, Heidi E W; Campeau, Serge; Fleshner, Monika; Greenwood, Benjamin N

    2015-11-01

    Relapse of previously extinguished fear presents a significant, pervasive obstacle to the successful long-term treatment of anxiety and trauma-related disorders. Thus, identification of a novel means to enhance fear extinction to stand the passage of time and generalize across contexts is of the utmost importance. Acute bouts of exercise can be used as inexpensive, noninvasive treatment strategies to reduce anxiety, and have been shown to enhance memory for extinction when performed in close temporal proximity to the extinction session. However, it is unclear whether acute exercise can be used to prevent relapse of fear, and the neural mechanisms underlying this potential effect are unknown. The current study therefore examined whether acute exercise during extinction of auditory fear can protect against the later relapse of fear. Male F344 rats lacking an extended history of wheel running were conditioned to fear a tone CS and subsequently extinguished within either a freely mobile running wheel, a locked wheel, or a control context lacking a wheel. Rats exposed to fear extinction within a freely mobile wheel ran during fear extinction, and demonstrated reduced fear as well as attenuated corticosterone levels during re-exposure to the extinguished CS during the relapse test in a novel context 1week later. Examination of cfos mRNA patterns elicited by re-exposure to the extinguished CS during the relapse test revealed that acute exercise during extinction decreased activation of brain circuits classically involved in driving fear expression and interestingly, increased activity within neurons of the direct striatal pathway involved in reward signaling. These data suggest that exercise during extinction reduces relapse through a mechanism involving the direct pathway of the striatum. It is suggested that a positive affective state could become associated with the CS during exercise during extinction, thus resulting in a relapse-resistant extinction memory.

  18. Voluntary exercise during extinction of auditory fear conditioning reduces the relapse of fear associated with potentiated activity of striatal direct pathway neurons

    PubMed Central

    Mika, Agnieszka; Bouchet, Courtney A.; Bunker, Preston; Hellwinkel, Justin E.; Spence, Katie G.; Day, Heidi E.W.; Campeau, Serge; Fleshner, Monika

    2015-01-01

    Relapse of previously extinguished fear presents a significant, pervasive obstacle to the successful long-term treatment of anxiety and trauma-related disorders. Thus, identification of a novel means to enhance fear extinction to stand the passage of time and generalize across contexts is of the utmost importance. Acute bouts of exercise can be used as inexpensive, noninvasive treatment strategies to reduce anxiety, and have been shown to enhance memory for extinction when performed in close temporal proximity to the extinction session. However, it is unclear whether acute exercise can be used to prevent relapse of fear, and the neural mechanisms underlying this potential effect are unknown. The current study therefore examined whether acute exercise during extinction of auditory fear can protect against the later relapse of fear. Male, F344 rats lacking an extended history of wheel running were conditioned to fear a tone CS and subsequently extinguished within either a freely mobile running wheel, a locked wheel, or a control context lacking a wheel. Rats exposed to fear extinction within a freely mobile wheel ran during fear extinction, and demonstrated reduced fear as well as attenuated corticosterone levels during re-exposure to the extinguished CS during the relapse test in a novel context 1 week later. Examination of cfos mRNA patterns elicited by re-exposure to the extinguished CS during the relapse test revealed that acute exercise during extinction decreased activation of brain circuits classically involved in driving fear expression and interestingly, increased activity within neurons of the direct striatal pathway involved in reward signaling. These data suggest that exercise during extinction reduces relapse through a mechanism involving the direct pathway of the striatum. It is suggested that a positive affective state could become associated with the CS during exercise during extinction, thus resulting in a relapse-resistant extinction memory. PMID

  19. New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia.

    PubMed

    van der Velden, Vincent H J; de Launaij, Daphne; de Vries, Jeltje F; de Haas, Valerie; Sonneveld, Edwin; Voerman, Jane S A; de Bie, Maaike; Revesz, Tamas; Avigad, Smadar; Yeoh, Allen E J; Swagemakers, Sigrid M A; Eckert, Cornelia; Pieters, Rob; van Dongen, Jacques J M

    2016-03-01

    In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray-analysis, we discovered multiple differentially expressed genes between B-cell precursor (BCP) ALL cells in bone marrow (BM) and BCP-ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real-time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP-ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP-ALL cells (>1%) with a 'CNS protein profile' (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP-ALL cells with a 'CNS protein profile' at diagnosis (particularly SCD-positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.

  20. Quality of life is predictive of relapse in schizophrenia

    PubMed Central

    2013-01-01

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

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

    PubMed

    Mangiarotti, P; Pizzini, C; Fanos, V

    2000-04-01

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

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2003-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-10

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

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

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. Chemokines and relapses in childhood acute lymphoblastic leukemia: A role in migration and in resistance to antileukemic drugs.

    PubMed

    Gómez, Ana M; Martínez, Carolina; González, Miguel; Luque, Alfonso; Melen, Gustavo J; Martínez, Jesús; Hortelano, Sonsoles; Lassaletta, Álvaro; Madero, Luís; Ramírez, Manuel

    2015-10-01

    We studied whether chemokines may have a role in relapses in childhood acute lymphoblastic leukemia (ALL). We compared the levels of chemokine receptors in marrow samples from 82 children with ALL at diagnosis versus 15 at relapses, and quantified the levels of chemokines in central system fluid (CSF) samples. The functional role of specific chemokines was studied in vitro and in vivo. The expression of some chemokine receptors was upregulated upon leukemic relapse, both in B- and in T-ALL, and in cases of medullary and extramedullary involvement. CXCL10 induced chemotaxis in leukemic cell lines and in primary leukemic cells, depending upon the levels of CXCR3 expression. CXCL10 specifically diminished chemotherapy-induced apoptosis on ALL cells expressing CXCR3, partially inhibiting caspase activation and maintaining the levels of the antiapoptotic protein Bcl-2. Finally, immunodeficient mice engrafted with CXCR3-expressing human leukemic cells showed decreased infiltration of marrow, spleen, and CNS after receiving a CXCR3-antagonist molecule. CXCR3 signaling in ALL may have a dual function: chemotactic for the localisation of leukemic blasts in specific niches, and it may also confer resistance to chemotherapy, enhancing the chances for relapses.

  11. Outcome of relapsing Clostridium difficile infections do not correlate with virulence-, spore- and vegetative cell-associated phenotypes.

    PubMed

    Plaza-Garrido, Ángela; Miranda-Cárdenas, Camila; Castro-Córdova, Pablo; Olguín-Araneda, Valeria; Cofré-Araneda, Glenda; Hernández-Rocha, Cristian; Carman, Robert; Ibáñez, Patricio; Fawley, Warren N; Wilcox, Mark H; Gil, Fernando; Calderón, Iván L; Fuentes, Juan A; Guzmán-Durán, Ana María; Alvarez-Lobos, Manuel; Paredes-Sabja, Daniel

    2015-12-01

    One of the main clinical challenges of Clostridium difficile infections (CDI) is the high rate of relapse episodes. The main determinants involved in relapse of CDI include the presence of antibiotic-resistant C. difficile spores in the colonic environment and a permanent state of dysbiosis of the microbiota caused by antibiotic therapy. A possible scenario is that phenotypes related to the persistence of C. difficile spores might contribute to relapsing infections. In this study, 8 C. difficile isolates recovered from 4 cases with relapsing infection, and 9 isolates recovered from single infection cases were analyzed for PCR ribotyping and the presence of tcdA, tcdB and cdtAB genes. Factors associated to spore persistence, sporulation, spore adherence and biofilm formation and sporulation during biofilm formation were characterized. We also evaluated motility and cytotoxicity. However, we observed no significant difference in the analyzed phenotypes among the different clinical outcomes, most likely due to the high variability observed among strains within clinical backgrounds in each phenotype and the small sample size. It is noteworthy that C. difficile spores adhered to similar extents to undifferentiated and differentiated Caco-2 cells. By contrast, spores of all clinical isolates tested had increased germination efficiency in presence of taurocholate, while decreased sporulation rate during biofilm development in the presence of glucose. In conclusion, these results show that, at least in this cohort of patients, the described phenotypes are not detrimental in the clinical outcome of the disease.

  12. Changes in brain-derived neurotrophic factor (BDNF) during abstinence could be associated with relapse in cocaine-dependent patients.

    PubMed

    Corominas-Roso, Margarida; Roncero, Carlos; Daigre, Constanza; Grau-Lopez, Lara; Ros-Cucurull, Elena; Rodríguez-Cintas, Laia; Sanchez-Mora, Cristina; Lopez, Maria Victoria; Ribases, Marta; Casas, Miguel

    2015-02-28

    Brain-derived neurotrophic factor (BDNF) is involved in cocaine craving in humans and drug seeking in rodents. Based on this, the aim of this study was to explore the possible role of serum BDNF in cocaine relapse in abstinent addicts. Forty cocaine dependent subjects (DSM-IV criteria) were included in an inpatient 2 weeks abstinence program. Organic and psychiatric co-morbidities were excluded. Two serum samples were collected for each subject at baseline and at after 14 abstinence days. After discharge, all cocaine addicts underwent a 22 weeks follow-up, after which they were classified into early relapsers (ER) (resumed during the first 14 days after discharge,) or late relapsers (LR) (resumed beyond 14 days after discharge). The only clinical differences between groups were the number of consumption days during the last month before detoxification. Serum BDNF levels increased significantly across the 12 days of abstinence in the LR group (p=0.02), whereas in the ER group BDNF remained unchanged. In the ER group, the change of serum BDNF during abstinence negatively correlated with the improvement in depressive symptoms (p=0.02). These results suggest that BDNF has a role in relapse to cocaine consumption in abstinent addicts, although the underlying neurobiological mechanisms remain to be clarified.

  13. Relapse of Multiple Myeloma Presenting as Lower Lip Numbness

    PubMed Central

    Al-Riyami, Yusra M.; Bakathir, Abdulaziz; Al-Farsi, Khalil; Al-Azri, Faisal

    2016-01-01

    Multiple myeloma (MM) is an uncommon malignancy characterised by the proliferation of clonal plasma cells. There are few published reports describing the extramedullary presentation of MM manifesting primarily in the head and neck region. In addition, the occurrence of an isolated relapse of MM in these sites is exceedingly rare. We report a 56-year-old female who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2010 with sudden-onset numbness of the lower lip. She had a history of MM in remission following chemotherapy and a bone marrow transplant. Clinical and radiographic examinations were indicative of a possible relapse of MM, which was subsequently confirmed by bone marrow aspiration and histopathological evaluation. This unique case highlights the unusual site of relapse of a haematolymphoid malignancy. PMID:28003900

  14. Carfilzomib boosted combination therapy for relapsed multiple myeloma

    PubMed Central

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

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

  15. Carfilzomib boosted combination therapy for relapsed multiple myeloma.

    PubMed

    Steiner, Raphael E; Manasanch, Elisabet E

    2017-01-01

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

  16. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

    PubMed Central

    White, Michael T.; Shirreff, George; Karl, Stephan; Ghani, Azra C.; Mueller, Ivo

    2016-01-01

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes. PMID:27030414

  17. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria.

    PubMed

    White, Michael T; Shirreff, George; Karl, Stephan; Ghani, Azra C; Mueller, Ivo

    2016-03-30

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.

  18. Relapse of visceral leishmaniasis in an HIV-infected patient successfully treated with a combination of miltefosine and amphotericin B.

    PubMed

    McQuarrie, Shauna; Kasper, Ken; Moffatt, Dana C; Marko, Daniel; Keynan, Yoav

    2015-01-01

    The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm(3), despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

  19. Relapse of visceral leishmaniasis in an HIV-infected patient successfully treated with a combination of miltefosine and amphotericin B

    PubMed Central

    McQuarrie, Shauna; Kasper, Ken; Moffatt, Dana C; Marko, Daniel; Keynan, Yoav

    2015-01-01

    The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated. PMID:26744591

  20. Relapsed small cell lung cancer: treatment options and latest developments

    PubMed Central

    Ohkuni, Yoshihiro; Kaneko, Norihiro; Yamaguchi, Etsuro; Kubo, Akihito

    2014-01-01

    According to recent analyses, there was a modest yet significant improvement in median survival time and 5-year survival rate of limited stage small cell lung cancer (SCLC) in North America, Europe, Japan and other countries over the last 30 years. The median survival time of limited stage SCLC is 15–20 months and 5-year survival rate is 15% or less. In terms of extensive stage SCLC, a median survival time of 9.4–12.8 months and 2-year survival of 5.2–19.5% are still disappointing. Despite being highly sensitive to first-line chemotherapy and radiotherapy treatments, most patients with SCLC experience relapse within 2 years and die from systemic metastasis. While several clinical trials of cytotoxic chemotherapies and molecular targeting agents have been investigated in the treatment of relapsed SCLC, none showed a significant clinical activity to be able to exceed topotecan as second-line chemotherapy. There are problematic issues to address for relapsed SCLC, such as standardizing the treatment for third-line chemotherapy. Topotecan alone was the first approved therapy for second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a variety of trials evaluating its efficacy have been carried out. Amrubicin has shown superiority to topotecan in a Japanese population, but was not superior in a study of western patients. There are some controversial issues for relapsed SCLC, such as treatment for older patients, third-line chemotherapy and efficacy of molecular targeting therapy. This article reviews current standard treatment, recent clinical trials and other topics on relapsed SCLC. PMID:24587832

  1. Relapse of Multiple Myeloma Presenting as Extramedullary Plasmacytomas in Multiple Organs

    PubMed Central

    Köse, Murat; Buraniqi, Ersida; Akpinar, Timur Selçuk; Kayacan, Seyit Mehmet; Tükek, Tufan

    2015-01-01

    Multiple myeloma is a neoplastic plasma cell disorder. It is characterized by collections of abnormal plasma cells accumulating in the bone marrow, where they interfere with the production of normal blood cells. It usually presents as a multisystemic involvement, whose symptoms and signs vary greatly. Some patients have slowly progressive disease while others have aggressive clinical behavior by extramedullary involvement. In addition to renal failure, anemia, hypercalcemia, lytic bone lesions, and immunodeficiency, it also affects multiple organ system, such as pancreas, adrenal glands, kidney, skin, lung, liver, spleen, lymph nodes, and bone. To raise awareness of the variable presentations of this disease, we report a 53-year-old male patient, with multiple myeloma in his first remission who relapsed with extramedullary plasmacytomas (EMPs) involving multiple organs, such as pancreas, adrenal glands, kidney, skin, lung, liver, spleen, and lymph nodes. PMID:25694834

  2. Relapsing cardial stenosis after laparoscopic nissen treated by esophageal stenting.

    PubMed

    Pouderoux, Philippe; Verdier, Eric; Courtial, Philippe; Bapin, Catherine; Deixonne, Bernard; Balmès, Jean-Louis

    2003-01-01

    Dysphagia after antireflux surgery is often a challenging situation. We report the case of a patient with relapsing cardial stricture and a weight loss of 24 kg following a laparoscopic Nissen procedure. Initial presentation was consistent with the diagnosis of pseudoachalasia and was resistant to endoscopic dilatation. Dysphagia was relieved by surgery, which showed cardial strangulation by tightly sutured diaphragmatic pillars. Symptoms and cardial stricture relapsed after a few months with no significant relief after repeated dilatations. Conservative treatment by endoscopic transcardial prosthesis for six weeks allowed a return to normal diet and a weight gain of 10 kg within a 30-month followup period.

  3. A simple technique for correction of relapsed overjet.

    PubMed

    Kakkirala, Neelima; Saxena, Ruchi

    2014-01-01

    Class III malocclusions are usually growth related discrepancies, which often become more severe when growth is completed Orthognathic surgery can be a part of the treatment plan, although a good number of cases can be treated non-surgically by camouflage treatment. The purpose of this report is to review the relapse tendency in patients treated non-surgically. A simple technique is described to combat one such post-treatment relapse condition in an adult patient who had undergone orthodontic treatment by extraction of a single lower incisor.

  4. Relapse among substance-abusing women: components and processes.

    PubMed

    Sun, An-Pyng

    2007-01-01

    This article is based on part of a project in which 32 women who experienced substance use-related problems were interviewed. The purpose of the article is to explore factors related to the women's relapse so that practitioners can better understand the nature of women's relapse and more effectively help them. Qualitative in-depth interviews were conducted, audiotaped (with the exception of three women), and transcribed. The interview was guided by open-ended questions - exploring factors that led to the women's initial substance use, abstinence, and relapse; factors that prompted them to come for treatment; and their experience with the treatment. These open-ended questions were supplemented with follow-up questions probing further critical elements shared by participants initially. The mean age of the sample was 34 years old, with over half being white, followed by Latina/Hispanic, African American, and Native American. Most women reported being poly-drug users, followed by methamphetamine/amphetamines, heroine, cocaine, and alcohol. The average number of years of education was 11 years. Four major themes representing factors contributing to the women's relapse were identified: (1) low self-worth and its connection to intimate relationships with men; (2) interpersonal conflicts and/or negative emotion; (3) less ability to sever the tie with the using network and to establish a tie with the non-using network; and (4) a lack of AOD-related knowledge and relapse prevention coping skills. The qualitative approach enables the study to report not only the four general themes but also the multiple dimensions and building blocks underlying each theme so that the pertinent contexts and specific meanings of women's relapses can be understood. Many of the factors appeared to be related to women's socialization and the gender-role formation process as well as their disadvantageous social reality. The study suggests several topics for inclusion in women's relapse prevention

  5. Antigenic variation among Borrelia spp. in relapsing fever.

    PubMed Central

    Kehl, K S; Farmer, S G; Komorowski, R A; Knox, K K

    1986-01-01

    Seven antigens of Borrelia hermsii, B. parkeri, and B. turicatae with isoelectric points in the range of 4.4 to 5.0 and molecular masses of 40 to 43 kilodaltons played a role in the relapse phenomenon of relapsing fever. Based upon location of the antigens in the outer envelope, the molecular weight, and Western blot analysis, the antigens from each phase of spirochetemia appeared to be a mixture of the serotype-specific antigens of cloned B. hermsii. Images PMID:3536750

  6. Relapsed Pulmonary Cryptococcosis during Tumor Necrosis Factor α Inhibitor Treatment

    PubMed Central

    Takazono, Takahiro; Sawai, Toyomitsu; Tashiro, Masato; Saijo, Tomomi; Yamamoto, Kazuko; Imamura, Yoshifumi; Miyazaki, Taiga; Suyama, Naofumi; Izumikawa, Koichi; Kakeya, Hiroshi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    2016-01-01

    A 35-year-old non-HIV patient developed pulmonary cryptococcosis after the initiation of infliximab. He recovered by fluconazole treatment and completed the therapy for a total of 6 months. However, he experienced a relapse 16 months later during retreatment with infliximab, revealing an interesting clinical course contradicting retreatment. This case also represents the first case of relapsed pulmonary cryptococcosis suspected during treatment with a biologic agent. Both of these aspects generated important clinical questions about the length of pulmonary cryptococcosis treatment and the necessity of introducing a second prophylaxis for such patients. PMID:27725552

  7. p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy

    PubMed Central

    Frackelton, A Raymond; Lu, Li; Davol, Pamela A; Bagdasaryan, Robert; Hafer, Laurie J; Sgroi, Dennis C

    2006-01-01

    Introduction Shc adapter proteins are secondary messenger proteins involved in various cellular pathways, including those mediating receptor tyrosine kinase signaling and apoptosis in response to stress. We have previously reported that high levels of tyrosine-phosphorylated Shc (PY-Shc) and low levels of its inhibitory p66 Shc isoform are strongly prognostic for identifying both early node-negative and more advanced, node-positive, primary breast cancers with high risk for recurrence. Because aberrant activation of tyrosine kinases upstream of Shc signaling proteins has been implicated in resistance to tamoxifen – the most widely prescribed drug for treatment of estrogen receptor-positive breast cancer – we hypothesized that Shc isoforms may identify patients at increased risk of relapsing despite tamoxifen treatment. Methods Immunohistochemical analyses of PY-Shc and p66 Shc were performed on archival primary breast cancer tumors from a population-based cohort (60 patients, 9 relapses) and, for validation, an independent external cohort (31 patients, 13 relapses) in which all patients received tamoxifen as a sole systemic adjuvant prior to relapse. Results By univariate and multivariate analyses, the Shc proteins were very strong and independent predictors of treatment failure in both the population-based cohort (interquartile hazard ratio = 8.3, 95% confidence interval [CI] 1.8 to 38, P = 0.007) and the validating cohort (interquartile relative risk = 12.1, 95% CI 1.7 to 86, P = 0.013). Conclusion These results suggest that the levels of PY-Shc and p66 Shc proteins in primary tumors identify patients at high risk for relapsing despite treatment with tamoxifen and therefore with further validation may be useful in guiding clinicians to select alternative adjuvant treatment strategies. PMID:17196107

  8. NIDA-Drug Addiction Treatment Outcome Study (DATOS) Relapse as a Function of Spirituality/Religiosity

    PubMed Central

    Schoenthaler, Stephen J.; Blum, Kenneth; Braverman, Eric R.; Giordano, John; Thompson, Ben; Oscar-Berman, Marlene; Badgaiyan, Rajendra D.; Madigan, Margaret A.; Dushaj, Kristina; Li, Mona; Demotrovics, Zsolt; Waite, Roger L.; Gold, Mark S.

    2015-01-01

    Background The connection between religion/spirituality and deviance, like substance abuse, was first made by Durkheim who defined socially expected behaviors as norms. He explained that deviance is due in large part to their absence (called anomie), and concluded that spirituality lowers deviance by preserving norms and social bonds. Impairments in brain reward circuitry, as observed in Reward Deficiency Syndrome (RDS), may also result in deviance and as such we wondered if stronger belief in spirituality practice and religious belief could lower relapse from drugs of abuse. Methods The NIDA Drug Addiction Treatment Outcome Study data set was used to examine post hoc relapse rates among 2,947 clients who were interviewed at 12 months after intake broken down by five spirituality measures. Results Our main findings strongly indicate, that those with low spirituality have higher relapse rates and those with high spirituality have higher remission rates with crack use being the sole exception. We found significant differences in terms of cocaine, heroin, alcohol, and marijuana relapse as a function of strength of religious beliefs (x2 = 15.18, p = 0.028; logistic regression = 10.65, p = 0.006); frequency of attending religious services (x2 = 40.78, p < 0.0005; logistic regression = 30.45, p < 0.0005); frequency of reading religious books (x2 = 27.190, p < 0.0005; logistic regression = 17.31, p < 0.0005); frequency of watching religious programs (x2 = 19.02, p = 0.002; logistic regression = ns); and frequency of meditation/prayer (x2 = 11.33, p = 0.045; logistic regression = 9.650, p = 0.002). Across the five measures of spirituality, the spiritual participants reported between 7% and 21% less alcohol, cocaine, heroin, and marijuana use than the non-spiritual subjects. However, the crack users who reported that religion was not important reported significantly less crack use than the spiritual participants. The strongest association between remission and spirituality

  9. 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…

  10. 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

  11. 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…

  12. Non-Hodgkin lymphoma with relapses in the lacrimal glands

    PubMed Central

    Couceiro, Rita; Proença, Helena; Pinto, Filomena; Fonseca, Ana; Monteiro-Grillo, Manuel

    2015-01-01

    Objective: To report an unusual case of systemic non-Hodgkin lymphoma (NHL) with repeated relapse in the lacrimal glands, in spite of complete remission for several years after treatment. Methods: A 78-year-old male with small lymphocytic B cell NHL, stage IV disease (lung invasion), was submitted to surgery and chemotherapy in 2001, with complete remission of the disease. In 2003 he developed a nodular lesion in the right lacrimal fossa. Pathology results revealed a local relapse of NHL. Radiation and chemotherapy were initiated and complete remission was again achieved. In 2012 the patient developed a new nodular lesion located in the left lacrimal fossa, resulting in diplopia, ptosis and proptosis of the left eye. Orbital computerized tomography (CT), ocular ultrasound and incisional biopsy were performed. Results: Orbital CT revealed a lesion infiltrating the left lacrimal gland and encircling the globe. Biopsy results confirmed a local relapse of B cell NHL. The patient was submitted to local radiation therapy with progressive resolution of ptosis, proptosis and diplopia. Response to treatment was monitored with ocular ultrasound. Conclusions: Patients with NHL diagnosis should be immediately investigated if ophthalmic or orbital symptoms develop. NHL extension to the orbit and adnexa is infrequent (5% of NHL cases) but may occur at any stage of the disease, including as a relapse site. In such cases, radiation and chemotherapy achieve good results, inducing long periods of remission. PMID:27625948

  13. 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…

  14. 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…

  15. 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…

  16. Relapsing fever group Borrelia in Southern California rodents.

    PubMed

    Nieto, Nathan C; Teglas, Mike B

    2014-09-01

    Wild rodent reservoir host species were surveyed prospectively for infection with Borrelia hermsii, the causative agent of tick-borne relapsing fever in the western United States. Trapping occurred during the summer of 2009-2012 at field sites surrounding Big Bear Lake, CA, a region where human infection has been reported for many years. Using quantitative polymerase chain reaction (qPCR), we tested 207 rodents from 11 species and found chipmunks (Tamias spp.) and a woodrat (Neotoma macrotis) infected. Chipmunks represented the majority of captures at these sites. Sixteen of the 207 (7.7%; CI = 4.6-12.4) animals were qPCR-positive for Borrelia spp. associated with relapsing fever, and of those, we obtained bacterial DNA sequences from eight. The phylogram made from these sequences depict a clear association with B. hermsii genomic group I. In addition, we identified an infection with Borrelia coriaceae in a Tamias merriami, a potentially nonpathogenic member of the tick-borne relapsing fever group. Our findings support the hypothesis that chipmunk species play an important role in the maintenance of Borrelia species that cause tick-borne relapsing fever in the western United States, and therefore the risk of infection to people.

  17. Hereditary neuralgic amyotrophy associated with a relapsing multifocal sensory neuropathy.

    PubMed Central

    Thomas, P K; Ormerod, I E

    1993-01-01

    A family with neuralgic amyotrophy (idiopathic brachial plexus neuropathy) associated with a multifocal sensory neuropathy is described. Four members over two generations were affected by neuralgic amyotrophy, inherited as an apparent autosomal dominant trait; two also had a multifocal relapsing sensory neuropathy with the clinical features of Wartenberg's migrant neuropathy. PMID:8429311

  18. Doctors’ views of disulfiram and their response to relapse in alcohol-dependent patients, Free State, 2009

    PubMed Central

    2016-01-01

    Background Disulfiram is the oldest and best known drug to prevent relapse after detoxification from alcohol. Effective use of the drug is dependent on stringent monitoring and high levels of external motivation. Doctors’ perceptions about the drug have not been investigated extensively. Aim We investigated the perceptions and practices of doctors involved in relapse prevention in alcoholics with regard to disulfiram and their response to relapse. Setting The study population consisted of 60 doctors from the Free State Province, involved in the follow-up of alcoholics across various work settings. Methods A cross-sectional descriptive study design was used, and data collection involved the use of a questionnaire and semi-structured interviews. Quantitative results are presented in figures and percentages to provide a background for the qualitative findings that are clustered in themes. Results A quarter of participants did not prescribe disulfiram, another quarter prescribed disulfiram routinely after detoxification, and half of them prescribed it for selected cases only. Subject to affordability, selection of disulfiram was mainly determined by the perceived level of the patient’s motivation. External motivation sometimes took the form of threats of bodily harm or death caused by drinking. Some participants regarded relapse as confirmation of poor motivation and even a valid reason for terminating the doctor-patient relationship. Conclusion Doctors perceive disulfiram as a psychological tool to induce motivation through creating fear of drinking. Failure and success are perceived as related to the level of motivation. These perceptions could be unfair as biological factors in inter-patient variability in response are ignored. PMID:27380787

  19. Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome

    PubMed Central

    Ostrovnaya, Irina; Rubnitz, Kaitlyn R.; Ali, Siraj M.; Miller, Vincent A.; Mossé, Yael P.; Maris, John M.

    2016-01-01

    Neuroblastoma is characterized by a relative paucity of recurrent somatic mutations at diagnosis. However, recent studies have shown that the mutational burden increases at relapse, likely as a result of clonal evolution of mutation-carrying cells during primary treatment. To inform the development of personalized therapies, we sought to further define the frequency of potentially actionable mutations in neuroblastoma, both at diagnosis and after chemotherapy. We performed a retrospective study to determine mutation frequency, the only inclusion criterion being availability of cancer gene panel sequencing data from Foundation Medicine. We analyzed 151 neuroblastoma tumor samples: 44 obtained at diagnosis, 42 at second look surgery or biopsy for stable disease after chemotherapy, and 59 at relapse (6 were obtained at unknown time points). Nine patients had multiple tumor biopsies. ALK was the most commonly mutated gene in this cohort, and we observed a higher frequency of suspected oncogenic ALK mutations in relapsed disease than at diagnosis. Patients with relapsed disease had, on average, a greater number of mutations reported to be recurrent in cancer, and a greater number of mutations in genes that are potentially targetable with available therapeutics. We also observed an enrichment of reported recurrent RAS/MAPK pathway mutations in tumors obtained after chemotherapy. Our data support recent evidence suggesting that neuroblastomas undergo substantial mutational evolution during therapy, and that relapsed disease is more likely to be driven by a targetable oncogenic pathway, highlighting that it is critical to base treatment decisions on the molecular profile of the tumor at the time of treatment. However, it will be necessary to conduct prospective clinical trials that match sequencing results to targeted therapeutic intervention to determine if cancer genomic profiling improves patient outcomes. PMID:27997549

  20. 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.

  1. Allogeneic Transplantation for Relapsed Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma.

    PubMed

    Cornell, Robert F; Bachanova, Veronika; D'Souza, Anita; Woo-Ahn, Kwang; Martens, Michael; Huang, Jiaxing; Al-Homsi, A Samer; Chhabra, Saurabh; Copelan, Edward; Diaz, Miguel-Angel; Freytes, Cesar O; Gale, Robert Peter; Ganguly, Siddhartha; Hamadani, Mehdi; Hildebrandt, Gerhard; Kamble, Rammurti T; Kharfan-Dabaja, Mohamed; Kindwall-Keller, Tamila; Lazarus, Hillard M; Marks, David I; Nishihori, Taiga; Olsson, Richard F; Saad, Ayman; Usmani, Saad; Vesole, David H; Yared, Jean; Mark, Tomer; Nieto, Yago; Hari, Parameswaran

    2017-01-01

    Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is characterized by lymphoplasmacytic proliferation, lymph node and spleen enlargement, bone marrow involvement, and IgM production. Treatment varies based on the extent and biology of disease. In some patients, the use of allogeneic hematopoietic cell transplantation (alloHCT) may have curative potential. We evaluated long-term outcomes of 144 patients who received adult alloHCT for WM/LPL. Data were obtained from the Center for International Blood and Marrow Transplant Research database (2001 to 2013). Patients received myeloablative(n = 67) or reduced-intensity conditioning (RIC; n = 67). Median age at alloHCT was 53 years, and median time from diagnosis to transplantation was 41 months. Thirteen percent (n = 18) failed prior autologous HCT. About half (n = 82, 57%) had chemosensitive disease at the time of transplantation, whereas 22% had progressive disease. Rates of progression-free survival, overall survival, relapse, and nonrelapse mortality at 5 years were 46%, 52%, 24%, and 30%, respectively. Patients with chemosensitive disease and better pretransplant disease status experienced significantly superior overall survival. There were no significant differences in progression-free survival based on conditioning (myeloablative, 50%, versus RIC, 41%) or graft source. Conditioning intensity did not impact treatment-related mortality or relapse. The most common causes of death were primary disease and graft-versus-host disease (GVHD). AlloHCT yielded durable survival in select patients with WM/LPL. Strategies to reduce mortality from GVHD and post-transplant relapse are necessary to improve this approach.

  2. 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.

  3. 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.

  4. External auditory canal and middle ear relapse of acute promyelocytic leukemia treated with arsenic trioxide: case report and review of the literature.

    PubMed

    Lafayette, Thereza Christina Sampaio; Coser, Virginia Maria; Brûlé, Alice Odette; Coser, Pedro Luis; Pereira, Waldir Veiga

    2010-04-01

    Extramedullary involvement occurs infrequently in acute promyelocytic leukemia and is said to be more common after treatment with all-trans retinoic acid. We describe a 9-year-old girl who had an isolated external auditory canal and middle ear relapse after treatment with all-trans retinoic acid and chemotherapy. A patient with cytogenetically and molecularly confirmed acute promyelocytic leukemia developed isolated extramedullary relapse in the auditory canal and middle ear 4 years and 9 months after initial diagnosis, while in hematologic and molecular remission, successfully treated with arsenic trioxide alone.

  5. 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…

  6. 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...

  7. 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…

  8. Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

    2008-01-01

    The outcome of a sequential treatment strategy that included cognitive behavioral therapy (CBT) in the prevention of major depressive disorder relapse among 46 youths is examined. Results show that youths under the antidepressant medication management plus relapse prevention CBT treatment was at lower risk for relapse than those under the…

  9. Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes

    PubMed Central

    Lindqvist, C. Mårten; Lundmark, Anders; Nordlund, Jessica; Freyhult, Eva; Ekman, Diana; Almlöf, Jonas Carlsson; Raine, Amanda; Övernäs, Elin; Abrahamsson, Jonas; Frost, Britt-Marie; Grandér, Dan; Heyman, Mats; Palle, Josefine; Forestier, Erik; Lönnerholm, Gudmar

    2016-01-01

    To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency. PMID:27590521

  10. A content analysis of self-reported barriers and facilitators to preventing postpartum smoking relapse among a sample of current and former smokers in an underserved population

    PubMed Central

    Wen, Kuang-Yi; Miller, Suzanne M.; Roussi, Pagona; Belton, Tanisha D.; Baman, Jayson; Kilby, Linda; Hernandez, Enrique

    2015-01-01

    To characterize the barriers and facilitators thatprevent postpartum relapse and maintain smoking abstinence among a socioeconomically underserved population, recruited through Philadelphia-area women, infants, and children clinics, in-person interviews were conducted with 30 women who had quit smoking for one or more pregnancies in the past 3 years to retrospectively describe their attempts to remain abstinent during the postpartum period. Responses were analysed using the constructs from the Cognitive-Social Health Information Processing model, which identifies the cognitive, affective and behavioral factors involved in goal-oriented self-regulatory actions, in the context of a vulnerable population of women. Motherhood demands were a significant source of relapse stress. Stresses associated with partner and family relationships also contributed to relapse. The presence of other smokers in the environment was mentioned by many women in our sample as affecting their ability to remain smoke-free postpartum. Participants reported four main strategies that helped them to successfully cope with postpartum cravings and relapses, including being informed of smoking risks, maintaining goal-oriented thoughts, focusing on their concerns about the baby’s health and receiving positive social support from families and friends. Results provide guidance for the design of smoking relapse interventions that may address the unique stressors reported by underserved postpartum women. PMID:25099776

  11. [Blastic plasmacytoid dendritic cell neoplasm with complete clinical remission with chemotherapy and central nervous system relapse: Report of one case].

    PubMed

    Contreras, Loreto; Mercado, Loreto; Delgado, Carolina; Cabezas, Claudia; Starke, Laksmi; Romero, Mónica; Ibieta, Fernando; Henríquez, Mauricio; Chandia, Mauricio

    2017-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy that most commonly manifests as cutaneous lesions with or without bone marrow involvement and leukemic dissemination. The demonstration of tumor cells with the characteristic immunophenotype with expression of CD56, generally CD4 and dendritic cell antigens (CD123, cyTCL-1, HLA-DR), in the absence of myeloid or lymphoid lineage markers is required for the diagnosis. Responses to chemotherapy are initially satisfactory, with frequent systemic and central nervous system relapses. We report a 24 year-old male with BPDCN, initially diagnosed and treated as non-Hodgkin CD4+ T-cell lymphoma, with initial complete remission who evolved with early central nervous system relapse. A second attempt of chemotherapy failed and the patient died two months later.

  12. 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

  13. Mitoxantrone, teniposide, chlorambucil and prednisone (MVLP) for relapsed non-Hodgkin's lymphoma. The impact of advanced age and performance status.

    PubMed

    Haak, H L; Gerrits, W B; Wijermans, P W; Kerkhofs, H

    1993-04-01

    Fifty-seven patients with relapsed non-Hodgkin's lymphoma (NHL) of low, intermediate and high-grade malignancy were treated with mitoxantrone, teniposide (Vm26), chlorambucil (Leukeran) and prednisone (MVLP). The median age was 71 years; none of the patients was excluded due to poor performance status (PS). Out of 44 patients with PS (according to WHO) < or = 2, 38 responded with a median progression free survival (PFS) of 21.5 months. Of 13 patients with PS > 2, 6 responded with a median PFS of 8.2 months. Haematopoietic toxicity was related to PS rather than to dose intensity or bone marrow involvement. Three patients died within a short time due to toxicity; another two died later as a result of cardiac failure probably due to accumulated toxicity of adriamycin and mitoxantrone. MVLP chemotherapy is effective and feasible and has only moderate toxicity in patients with relapsed NHL and PS < or = 2, despite advanced age.

  14. Disseminated Penicillium marneffei mimicking paradoxical response and relapse in a non-HIV patient with pulmonary tuberculosis.

    PubMed

    Wang, Ping-Huai; Wang, Hao-Chien; Liao, Chun-Hsing

    2015-04-01

    Clinical deterioration during the treatment of tuberculosis remains a diagnostic challenge. We describe the case of a 46-year-old man with a history of oral cancer status after a radical operation who had pulmonary tuberculosis with pleura and neck lymph node involvement. The clinical condition improved after antituberculosis therapy. However, the patient suffered from low-grade fever, progressive dyspnea, and cough after 7 weeks of the therapy. The findings of chest plain films were relapse and progression of left lung haziness. The deterioration was caused by disseminated Penicillium marneffei infection. Disseminated P. marneffei in a non-HIV patient with tuberculosis is rarely seen, and the manifestations are similar to a paradoxical response and relapse of pulmonary tuberculosis, thereby making it difficult to establish a diagnosis.

  15. [Local involvement of the optic nerve by acute lymphoblastic leukemia].

    PubMed

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

    The leucemias quite commonly involve the eyes and adnexa. In some cases it causes visual complants. Both, the anterior chamber of the eye and the posterior portion of the globe may sites of acute or chronic leukemia and leucemic relapse. We report an unique case of a 14 years old leucemic patient who suffered visual loss and papilloedema, due to a unilateral local involvement within optic nerve, during second relapse of acute lymphocytic leuemia. In spite of typical treatment of main disease, the boy had died. The authors present typical ophthalmic features of the leucemia, too.

  16. 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

  17. Protective factors against relapse for practicing nurse anesthetists in recovery from anesthetic opiate dependency.

    PubMed

    Wright, E Laura; McGuinness, Teena; Schumacher, Joseph E; Zwerling, Arthur; Moneyham, Linda D

    2014-01-01

    This qualitative inquiry explored factors that protect recovering anesthetic opioid-dependent nurse anesthetists from relapse after their return to anesthesia practice. Practicing nurse anesthetists in recovery from potent opioids were recruited through online advertising and individually interviewed over the telephone. The interview consisted of open-ended questions that aided description of personal experience of individual factors. Content analysis of the interviews revealed an overarching theme of a commitment to the recovery process, which provided the foundational protective element against relapse. Within this context, two major thematic factors emerged: personal factors and external factors. Personal factors came from within the individual and included such features as removing the obsession to use, self-realization, inner strength, and seeing the future. External factors were external to the individual and described as time away from practice, state regulatory agency involvement, and talking with significant others. Although the Twelve-Step process was not a factor per se, it was credited by all participants as the structure on which their recovery was built. This process provided mechanisms for developing the motivation and learning the tools necessary to maintain their sobriety.

  18. Pregnane X-receptor promotes stem cell-mediated colon cancer relapse.

    PubMed

    Planque, Chris; Rajabi, Fatemeh; Grillet, Fanny; Finetti, Pascal; Bertucci, François; Gironella, Meritxell; Lozano, Juan José; Beucher, Bertrand; Giraud, Julie; Garambois, Véronique; Vincent, Charles; Brown, Daniel; Caillo, Ludovic; Kantar, Jovana; Pelegrin, André; Prudhomme, Michel; Ripoche, Jérémie; Bourgaux, Jean François; Ginestier, Christophe; Castells, Antoni; Hollande, Frédéric; Pannequin, Julie; Pascussi, Jean Marc

    2016-08-30

    Colorectal cancer lethality usually results from post-treatment relapse in the majority of stage II-IV patients, due to the enhanced resistance of Cancer Stem Cells (CSCs). Here, we show that the nuclear receptor Pregnane X Receptor (PXR, NR1I2), behaves as a key driver of CSC-mediated tumor recurrence. First, PXR is specifically expressed in CSCs, where it drives the expression of genes involved in self-renewal and chemoresistance. Clinically, high levels of PXR correlate with poor recurrence-free survival in a cohort of >200 stage II/III colorectal cancer patients treated with chemotherapy, for whom finding biomarkers of treatment outcome is an urgent clinical need. shRNA silencing of PXR increased the chemo-sensitivity of human colon CSCs, reduced their self-renewal and tumor-initiating potential, and drastically delayed tumor recurrence in mice following chemotherapy. This study uncovers PXR as a key factor for CSC self-renewal and chemoresistance and targeting PXR thus represents a promising strategy to minimize colorectal cancer relapse by selectively sensitizing CSCs to chemotherapy.

  19. Pregnane X-receptor promotes stem cell-mediated colon cancer relapse

    PubMed Central

    Grillet, Fanny; Finetti, Pascal; Bertucci, François; Gironella, Meritxell; Lozano, Juan José; Beucher, Bertrand; Giraud, Julie; Garambois, Véronique; Vincent, Charles; Brown, Daniel; Caillo, Ludovic; Kantar, Jovana; Pelegrin, André; Prudhomme, Michel; Ripoche, Jérémie; Bourgaux, Jean François; Ginestier, Christophe; Castells, Antoni; Hollande, Frédéric; Pannequin, Julie; Pascussi, Jean Marc

    2016-01-01

    Colorectal cancer lethality usually results from post-treatment relapse in the majority of stage II-IV patients, due to the enhanced resistance of Cancer Stem Cells (CSCs). Here, we show that the nuclear receptor Pregnane X Receptor (PXR, NR1I2), behaves as a key driver of CSC-mediated tumor recurrence. First, PXR is specifically expressed in CSCs, where it drives the expression of genes involved in self-renewal and chemoresistance. Clinically, high levels of PXR correlate with poor recurrence-free survival in a cohort of >200 stage II/III colorectal cancer patients treated with chemotherapy, for whom finding biomarkers of treatment outcome is an urgent clinical need. shRNA silencing of PXR increased the chemo-sensitivity of human colon CSCs, reduced their self-renewal and tumor-initiating potential, and drastically delayed tumor recurrence in mice following chemotherapy. This study uncovers PXR as a key factor for CSC self-renewal and chemoresistance and targeting PXR thus represents a promising strategy to minimize colorectal cancer relapse by selectively sensitizing CSCs to chemotherapy. PMID:27448961

  20. Using conditioned place preference to identify relapse prevention medications.

    PubMed

    Napier, T Celeste; Herrold, Amy A; de Wit, Harriet

    2013-11-01

    Stimuli, including contexts, which predict the availability or onset of a drug effect, can acquire conditioned incentive motivational properties. These conditioned properties endure after withdrawal, and can promote drug-seeking which may result in relapse. Conditioned place preference (CPP) assesses the associations between drugs and the context in which they are experienced. Here, we review the potential utility of CPP procedures in rodents and humans to evaluate medications that target conditioned drug-seeking responses. We discuss the translational potential of the CPP procedure from rodents to humans, and review findings with FDA-approved treatments that support the use of CPP to develop relapse-reduction medications. We also discuss challenges and methodological questions in applying the CPP procedure to this purpose. We argue that an efficient and valid CPP procedure in humans may reduce the burden of full clinical trials with drug-abusing patients that are currently required for testing promising treatments.

  1. 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.

  2. 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

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

    SciTech Connect

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

    1987-01-01

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

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

    PubMed

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

    2017-02-13

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

  5. Relapse of Yellow Nail Syndrome with Pulmonary Lymphedema.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2000-03-01

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

  7. Menarche Increases Relapse Risk in Pediatric Multiple Sclerosis

    PubMed Central

    Lulu, Sabeen; Graves, Jennifer; Waubant, Emmanuelle

    2015-01-01

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

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

    PubMed

    Warner, Richard; Thomas, Del; Martin, Roswell

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

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

    PubMed

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

    2010-09-01

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

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

    PubMed

    Friedberg, Jonathan W

    2011-01-01

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

  11. Changes in urinary metabolomic profile during relapsing renal vasculitis

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-06-09

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

  13. 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

  14. On Involvement.

    ERIC Educational Resources Information Center

    Greene, Michael B.

    Involvement Ratings In Settings (IRIS), a multi-dimensional non-verbal scale of involvement adaptable to a time-sampling method of data collection, was constructed with the aid of the videotapes of second-grade Follow Through classrooms made by CCEP. Scales were defined through observations of involved and alienated behavior, and the IRIS was…

  15. NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematological Malignancies

    PubMed Central

    Alyea, Edwin P.; DeAngelo, Daniel J.; Moldrem, Jeffrey; Pagel, John M.; Przepiorka, Donna; Riddell, Stan; Sadelin, Michel; Young, James W.; Giralt, Sergio; Bishop, Michael

    2011-01-01

    Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance post-transplant, better characterize the T-cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify population at very high risk for relapse in order to accelerate clinical development and avoid toxicity in patients not at risk for relapse. PMID:20580849

  16. 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.

  17. Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study.

    PubMed

    Kim, Seok Jin; Hong, Jun Sik; Chang, Myung Hee; Kim, Jeong-A; Kwak, Jae-Yong; Kim, Jin Seok; Yoon, Dok Hyun; Lee, Won Sik; Do, Young Rok; Kang, Hye Jin; Eom, Hyeon-Seok; Park, Yong; Won, Jong-Ho; Mun, Yeung-Chul; Kim, Hyo Jung; Kwon, Jung Hye; Kong, Jee Hyun; Oh, Sung Yong; Lee, Sunah; Bae, Sung Hwa; Yang, Deok-Hwan; Jun, Hyun Jung; Kim, Yang Soo; Yun, Hwan Jung; Lee, Soon Il; Kim, Min Kyoung; Park, Eun Kyung; Kim, Won Seog; Suh, Cheolwon

    2016-11-01

    Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

  18. Relapsing macrophage activating syndrome in a 15-year-old girl with Still's disease: a case report

    PubMed Central

    2009-01-01

    Introduction Macrophage activating syndrome is a severe, potentially life-threatening condition that may accompany Still's disease. It is characterized by fever, hepatosplenomegaly, lymphadenopathy, severe cytopenia, serious liver dysfunction, coagulopathy and neurologic involvement. The principal treatment for patients with this syndrome includes etoposide 150 mg/2 M twice a week for two weeks, dexamethasone 10 mg/2 M for two weeks and cyclosporine 3 mg/kg to 5 mg/kg for a longer period. Cases of relapse of macrophage activating syndrome are relatively rare. Case presentation We describe the case of a 15-year-old Iraqi girl with Still's disease who developed macrophage activating syndrome with acute respiratory distress syndrome that required resuscitation and mechanical ventilation. Following intensive treatment, including high dose steroids and cyclosporine, the patient improved significantly. Two weeks after cyclosporine was discontinued, however, she was readmitted with an acute relapse of macrophage activating syndrome manifested by spiking fever, arthralgias, maculopapular rash and leukocytosis. This time the patient recovered following the reintroduction of treatment with cyclosporine and the addition of mycophenolate mofetil (Cellcept). Conclusion We believe that cyclosporine is a cornerstone for the treatment of Still's disease. We recommend continuing this medication for several weeks following the patient's clinical recovery in order to prevent macrophage activating syndrome relapses. PMID:20062775

  19. CTLA-4 genotype and relapse incidence in patients with acute myeloid leukemia in first complete remission after induction chemotherapy.

    PubMed

    Pérez-García, A; Brunet, S; Berlanga, J J; Tormo, M; Nomdedeu, J; Guardia, R; Ribera, J M; Heras, I; Llorente, A; Hoyos, M; Esteve, J; Besalduch, J; Bueno, J; Sierra, J; Gallardo, D

    2009-03-01

    The recently described single-nucleotide polymorphism CT60, located in the 3'-untranslated region of the CTLA4 (cytotoxic T-lymphocyte antigen 4 ) gene, has been associated with susceptibility to several autoimmune diseases and has also been shown to be involved in immune responses following allogeneic stem cell transplantation (SCT). However, the contribution of the CTLA4 genotype to the control of minimal residual disease in patients with acute myeloid leukemia (AML) has yet to be explored. We investigated the association between the CTLA4 CT60 A/G genotype and the incidence of leukemic relapse in 143 adult patients with AML in first complete remission after the same chemotherapy protocol (CETLAM LAM'03). The CT60 AA genotype was associated with a higher rate of leukemic relapse (56.4 vs 35.6%, P=0.004; hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.36-5.14) and lower overall survival at 3 years (39.4 vs 68.4%, P=0.004; HR=2.80, 95% CI=1.39-5.64). This is the first study to report an association between polymorphisms at CTLA-4 and AML relapse.

  20. 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.

  1. Ocular involvement in pemphigus vulgaris.

    PubMed

    Akhyani, Maryam; Keshtkar-Jafari, Alireza; Chams-Davatchi, Cheyda; Lajevardi, Vahide; Beigi, Sara; Aghazadeh, Nessa; Rayati Damavandi, Maede; Arami, Shabnam

    2014-07-01

    Pemphigus vulgaris (PV) is an autoimmune disorder affecting the skin and mucous membranes. Ocular involvement in PV has been reported but its prevalence and clinical characteristics are not well defined. This prospective cross-sectional study of 103 PV patients was designed to determine the prevalence, clinical types and epidemiological trends of ocular involvement in a population of Iranian patients with PV. Ocular involvement was present in 17 (16.5%) patients. Conjunctivitis was the most prevalent type of ocular involvement (9/17, 52.9%), followed by erosion of the palpebral conjunctiva (7/17, 41.2%). Erosion of the bulbar conjunctiva was noted in only one patient (5.9%). The most commonly reported symptoms were eye irritation (76.5%) and redness (76.5%). No significant relation was found between ocular involvement and disease activity (partial remission or relapse). Mucoid discharge was significantly more common in patients with conjunctival erosions as compared to patients with conjunctivitis (P = 0.038). We conclude that ocular involvement is not rare in PV; 16.5% of PV patients develop ocular disease independent of the disease activity and extension. Conjunctivitis is the most common type of involvement, however, palpebral conjunctival erosion is more frequent than previously realized.

  2. Single high-dose etoposide and melphalan with non-cryopreserved autologous marrow rescue as primary therapy for relapsed, refractory and poor-prognosis Hodgkin's disease.

    PubMed Central

    Seymour, L. K.; Dansey, R. D.; Bezwoda, W. R.

    1994-01-01

    A simplified schedule of high-dose chemotherapy (HDC) consisting of melphalan (140 mg m-2) plus VP16 (2.5 g m-2) given over 12-18 h together with autologous non-cryopreserved autologous bone marrow transplant (ABMT) was used for treatment of relapsed (37 patients) and refractory (seven patients) patients and as first-line treatment (four patients) for poor-prognosis Hodgkin's disease. Two patients had a second HDC-ABMT after relapse following prior HDC-ABMT, giving a total of 50 procedures among 48 patients. The haematological recovery rate was 98% with a complete response rate of the Hodgkin's disease of > 90%. Factors significantly influencing response rate were performance status and the presence of liver involvement. Thirty-nine patients are alive, with 37 in continuous complete remission. The median duration of survival and median duration of remission have not been reached at a median follow-up time of 45 months. Adverse prognostic factors for survival were disease status at the time of HDC-ABMT (refractory versus relapse, with primarily refractory patients showing significantly poor survival) and the presence of liver involvement. High-dose chemotherapy with short-duration chemotherapy and non-cryopreserved bone marrow is an effective and safe treatment modality for patients with relapsed and poor-prognosis Hodgkin's disease. PMID:8080741

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

    ClinicalTrials.gov

    2017-03-17

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

  4. NEURAL SUBSTRATES OF CUE-REACTIVITY: ASSOCIATION WITH TREATMENT OUTCOMES AND RELAPSE

    PubMed Central

    Courtney, Kelly E.; Schacht, Joseph P.; Hutchison, Kent; Roche, Daniel J.O.; Ray, Lara A.

    2016-01-01

    Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue-reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue-reactivity paradigms for the prediction of relapse, and as a means to investigate psychosocial and pharmacological treatment effects on cue-elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine, and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided. PMID:26435524

  5. T lymphocyte-derived demyelinating activity in multiple sclerosis patients in relapse.

    PubMed Central

    Selmaj, K; Alam, R; Perkin, G D; Rose, F C

    1987-01-01

    Supernatants of cultured T lymphocytes of multiple sclerosis patients were tested for a demyelinating activity in rat cerebellum explant cultures. Supernatants of unstimulated T lymphocytes in seven out of 10 multiple sclerosis patients in relapse produced demyelination when checked by phase contrast microscopy. Supernatants of unstimulated T lymphocytes from healthy subjects did not produce demyelination, but when T cells were stimulated by phytohaemagglutinin (PHA), 50% of tested supernatants produced demyelination, which was, however, never as advanced as in multiple sclerosis supernatant treated cerebellum cultures. The demyelinating activity proved to be heat labile. Gel filtration study revealed two fractions of the demyelinating activity 12.5-29.0 kD and 43.0-66.0 kD. The results suggest that lymphokines can be directly involved in the pathogenesis of demyelination in multiple sclerosis. Images PMID:3495638

  6. Syndrome In Question*

    PubMed Central

    do Nascimento, Ana Cláudia Mendes; Gaspardo, Daniela Barros Cortez; Cortez, Tatiana Mimura; Miot, Hélio Amante

    2014-01-01

    The authors present a male 40-year-old patient with established diagnosis of Behçet's disease which had evolved to recurrent bilateral auricular polychondritis crises. MAGIC syndrome (mouth and genital ulcers with inflamed cartilage) is rare and groups together patients with this clinical picture without necessarily fulfilling the clinical criteria for Behçet's disease or relapsing polychondritis, demonstrating an independent disorder. PMID:24626673

  7. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.

    PubMed

    Myint, Thein; Anderson, Albert M; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W; Jhaveri, Malhar; Greenberg, Richard N; Bamberger, David M; Rodgers, Mark; Crawford, Timothy N; Wheat, L Joseph

    2014-01-01

    Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91-55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL. Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

  8. 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

  9. Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

    SciTech Connect

    Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Eagan, Patricia; Gruber, Deborah; Gruber, Michael L.

    2012-01-01

    Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R{sup 2} = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

  10. Etiologies and prognostic factors of leukocytoclastic vasculitis with skin involvement

    PubMed Central

    Bouiller, Kévin; Audia, Sylvain; Devilliers, Hervé; Collet, Evelyne; Aubriot, Marie Hélène; Leguy-Seguin, Vanessa; Berthier, Sabine; Bonniaud, Philippe; Chavanet, Pascal; Besancenot, Jean-François; Vabres, Pierre; Martin, Laurent; Samson, Maxime; Bonnotte, Bernard

    2016-01-01

    Abstract In this study, outcomes of patients with leukocytoclastic vasculitis (LCV) were analyzed focusing on clinical, histopathology and laboratory findings, relapses, and survival. Data from patients with cutaneous vasculitis diagnosed between January 1, 2000, and December 31, 2010, at Dijon University Hospital (France) were retrospectively reviewed. LCV was defined as perivascular neutrophilic infiltrate, endothelial cell nuclear swelling, extravasation of red blood cells, and/or fibrin deposition in vessels. Patients were classified according to the 2012 Chapel Hill Consensus Conference. Relapses were defined as the recurrence of vasculitis symptoms after a period of remission >1 month. Time to relapse and/or death was calculated from the date of diagnosis. Univariate and multivariate (Cox model) analyses were performed. A total of 112 patients (57 males and 55 females), with a mean age of 60 ± 19 (18–98) years, were analyzed. Overall follow-up was 61 ± 38 months. At diagnosis, all patients had skin lesions, purpura being the most common (n = 83). Lesions were associated with systemic involvement in 55 (51%) patients. Only 41 (36.6%) patients received specific treatment: glucocorticoids in 29 of 41 (70.7%) and immunosuppressants in 9 of 41 (22%). Sixty-two patients (55%) had LCV due to underlying causes, 29 (25.9%) had single-organ cutaneous small vessel vasculitis (SoCSVV), and 21 (18.8%) had unclassifiable LCV. Twenty patients of the cohort (18%) experienced relapse, 14 ± 13 (1–40) months after the diagnosis of LCV. None of the 29 patients with SoCSVV relapsed. Independent risk factors for relapse were vascular thrombosis in the biopsy [hazard ratio (HR) = 4.9; P = 0.017], peripheral neuropathy (HR = 9.8; P = 0.001), hepatitis (HR = 3.1; P = 0.004), and positive antineutrophil cytoplasm antibodies (ANCA, HR = 5.9 P = 0.005). In contrast, SoCSVV was a protective factor for relapse (HR = 0.12; P = 0.043). The 1-, 3-, and 6-year overall

  11. Family Involvement.

    ERIC Educational Resources Information Center

    Liontos, Lynn Balster

    1992-01-01

    Family involvement in schools will work only when perceived as an enlarged concept focusing on all children, including those from at-risk families. Each publication reviewed here is specifically concerned with family involvement strategies concerned with all children or targeted at primarily high risk students. Susan McAllister Swap looks at three…

  12. 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

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

    PubMed

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

    2015-11-12

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

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

    PubMed

    Sutton, D R

    1982-07-01

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

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

    PubMed Central

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

    2012-01-01

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

  16. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed

    Ellis, E; Gallo, W J

    1986-07-01

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

  19. 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

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

    PubMed

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

    2016-05-01

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

  1. 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.

  2. Behavioral momentum and relapse of extinguished operant responding.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2009-11-01

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

  3. Predicting relapse risk in childhood acute lymphoblastic leukaemia.

    PubMed

    Teachey, David T; Hunger, Stephen P

    2013-09-01

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

  4. 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.

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Gabellier, Ludovic; Cartron, Guillaume

    2016-04-01

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

  8. 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.

  9. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-11-08

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

    2016-01-01

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

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

    PubMed

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

    2017-04-03

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

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

    PubMed

    Irving, Julie A E

    2016-03-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    1989-05-01

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

  16. Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats.

    PubMed

    Dhaher, Ronnie; Toalston, Jamie E; Hauser, Sheketha R; Bell, Richard L; McKinzie, David L; McBride, William J; Rodd, Zachary A

    2012-02-01

    Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1-10mg/kg, subcutaneously [s.c.]; n=8/dose), LY255582 (LY; 0.03-1mg/kg, s.c.; n=8/dose), or vehicle were injected 30min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors.

  17. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  18. Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis.

    PubMed

    Moreira, M A; Souza, A L S; Lana-Peixoto, M A; Teixeira, M M; Teixeira, A L

    2006-04-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5 +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

  19. Glutathione-S-Transferase (GST) polymorphisms are associated with relapse after radical prostatectomy

    PubMed Central

    Cotignola, Javier; Leonardi, Daiana B.; Shahabi, Ahva; Acuña, Alejandro D.; Stern, Mariana C.; Navone, Nora; Scorticati, Carlos; De Siervi, Adriana; Mazza, Osvaldo; Vazquez, Elba

    2013-01-01

    Background Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-Transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GSTs activities may modify the risk of PCa recurrence. Methods We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GSTs polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313 A>G (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex-PCR. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate these associations. Results Patients with GSTP1 c.313 GG genotype showed shorter biochemical relapse-free survival (BRFS) (p=0.003) and higher risk for recurrence in unadjusted (Hazard Ratio (HR)=3.16, 95% Confidence Interval (95% CI)=1.41–7.06, p=0.005) and multivariate models (HR=3.01, 95% CI=1.13–8.02, p=0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (p=0.010) and increased risk for recurrence for patients having 2 or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR=3.06, 95% CI=1.20–7.80, p=0.019). Conclusions Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. This is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted. PMID:23146971

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

    PubMed Central

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

    2014-01-01

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

  1. [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

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

    PubMed

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

    2015-06-01

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

  3. Cerebrospinal fluid involvement in acute promyelocytic leukaemia at presentation

    PubMed Central

    Mishra, Jyoti; Gupta, Mayank

    2015-01-01

    In acute promyelocytic leukaemia (APL), extramedullary disease (EMD) is rare but can occur in those who relapse following therapy. Although the most common site of EMD in APL is central nervous system (CNS) and skin, CNS involvement in recently diagnosed patients with APL is very rare and rarely described. We report cerebrospinal fluid involvement in a case of APL, on day 3 of induction therapy. PMID:25754165

  4. Autoimmune-related nasal septum perforation: A case report and systematic review

    PubMed Central

    Guntupalli, Lohitha; Patel, Kunjan; Faraji, Farhoud

    2017-01-01

    Background: Inflammatory injury of nasal respiratory mucosa is a common feature of multisystem autoimmune disease. Certain autoimmune disorders are associated with nasal septum perforation (NSP). We performed a systematic review of the literature to better understand the association of NSP with specific autoimmune disorders. This is a case report of a 29-year-old woman with a history of arthralgia, autoreactive antibody titers, platelet dysfunction, and NSP. The constellation of symptoms and potential familial involvement indicated that the NSP in this patient was an early sign of an autoimmune disorder, an unknown autoimmune disorder, or a known disease with incomplete penetrance. Methods: A systematic review of the literature was performed by two independent reviewers. Relevant articles were reviewed, and data that pertained to autoimmune-related NSP were extracted and analyzed. Results: Overall, 140 cases of autoimmune-associated NSPs were reported. Granulomatosis with polyangiitis (48%), relapsing polychondritis (26%), and cocaine-induced midline lesions (15%) constituted 89.3% of the reported cases. Conclusion: NSP is a potential sign of systemic disease. The identification of an NSP, especially in the context of other unexplained symptoms or workup suggestive of an autoimmune disorder, should prompt clinical evaluation for multisystem autoimmune disease with consideration of granulomatosis with polyangiitis, relapsing polychondritis, or cocaine-induced midline lesions. PMID:28381327

  5. 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.

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

    PubMed

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

    2013-01-01

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

  7. Relapse of Biphenotypic Acute Leukemia as a Breast Mass

    PubMed Central

    2016-01-01

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

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

    PubMed

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

    2014-01-01

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

  9. A Case of Relapsing Polyarthritis Associated With Hidradenitis Suppurativa

    PubMed Central

    Adiga, Avinash; Pixley, John

    2016-01-01

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

  10. 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

  11. 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…

  12. 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…

  13. 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…

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

    PubMed Central

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

    2008-01-01

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

  15. 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…

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

    PubMed

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

    2015-03-19

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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…

  19. 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…

  20. 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.…

  1. 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.

  2. 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.

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

    PubMed Central

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

    2016-01-01

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

  4. Mindfulness-based relapse prevention for substance craving.

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2012-09-01

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

  6. RESISTANCE TO EXTINCTION AND RELAPSE IN COMBINED STIMULUS CONTEXTS

    PubMed Central

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

    2012-01-01

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

  7. 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

  8. Investigation of Elimination Rate, Persistent Subpopulation Removal, and Relapse Rates of Mycobacterium tuberculosis by Using Combinations of First-Line Drugs in a Modified Cornell Mouse Model

    PubMed Central

    Pertinez, Henry; Ortega-Muro, Fatima; Alameda-Martin, Laura; Liu, Yingjun; Schipani, Alessandro; Davies, Geraint; Coates, Anthony

    2016-01-01

    Currently, the most effective tuberculosis control method involves case finding and 6 months of chemotherapy. There is a need to improve our understanding about drug interactions, combination activities, and the ability to remove persistent bacteria using the current regimens, particularly in relation to relapse. We aimed to investigate the therapeutic effects of three main components, rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA), in current drug regimens using a modified version of the Cornell mouse model. We evaluated the posttreatment levels of persistent Mycobacterium tuberculosis in the organs of mice using culture filtrate derived from M. tuberculosis strain H37Rv. When RMP was combined with INH, PZA, or INH-PZA, significant additive activities were observed compared to each of the single-drug treatments. However, the combination of INH and PZA showed a less significant additive effect than either of the drugs used on their own. Apparent culture negativity of mouse organs was achieved at 14 weeks of treatment with RMP-INH, RMP-PZA, and RMP-INH-PZA, but not with INH-PZA, when conventional tests, namely, culture on solid agar and in liquid broth, indicated that the organs were negative for bacteria. The relapse rates for RMP-containing regimens were not significantly different from a 100% relapse rate at the numbers of mice examined in this study. In parallel, we examined the organs for the presence of culture filtrate-dependent persistent bacilli after 14 weeks of treatment. Culture filtrate treatment of the organs revealed persistent M. tuberculosis. Modeling of mycobacterial elimination rates and evaluation of culture filtrate-dependent organisms showed promise as surrogate methods for efficient factorial evaluation of drug combinations in tuberculosis in mouse models and should be further evaluated against relapse. The presence of culture filtrate-dependent persistent M. tuberculosis is the likely cause of disease relapse in this modified Cornell

  9. Development and Pilot Evaluation of an Online Relapse-Prevention Program Based on Acceptance and Commitment Therapy for Chronic Pain Patients

    PubMed Central

    2015-01-01

    Background A significant number of chronic pain patients experience a decline in therapeutic effects after rehabilitation. As face-to-face contacts with health care professionals are not always feasible after treatment, new, innovative, fully automated relapse-prevention programs are highly needed. Objective In this study an online, automated relapse-prevention program based on acceptance and commitment therapy (ACT)—both as a website and as a mobile app—was developed and evaluated. At each step of the development, end users (ie, chronic pain patients) were consulted in order to fully address their needs. Methods In a step-by-step process, a contextual inquiry, requirement specification, and design were executed with chronic pain patients by conducting, respectively, a focus group (n=10), interviews with rapid prototyping (n=28), and a user- and expert-based usability evaluation (n=14). Furthermore, a pilot evaluation was conducted with 14 chronic pain or fatigue patients who had received the online relapse-prevention program following a multidisciplinary ACT treatment. They were interviewed about their usage and the usefulness of the program in supporting them to maintain changed behaviors and prevent relapses in avoidance and pain control behaviors. Results The three stages provided information about the expected needs of end users, comments about the usefulness of the proposed features, and feedback about the design and usability of the program. This resulted in a fully operational, online relapse-prevention program. Results from the pilot evaluation showed that 9 patients used the online program after treatment, 5 of whom indicated that the program supported them after treatment. Of all the patients, 4 of them indicated that the program did not support them because they wanted more social interaction with other users. Conclusions This study showed that an innovative, automated, online program that is user friendly can be developed by involving the end users

  10. Melarsoprol Sensitivity Profile of Trypanosoma brucei gambiense Isolates from Cured and Relapsed Sleeping Sickness Patients from the Democratic Republic of the Congo

    PubMed Central

    Pyana Pati, Patient; Van Reet, Nick; Mumba Ngoyi, Dieudonné; Ngay Lukusa, Ipos; Karhemere Bin Shamamba, Stomy; Büscher, Philippe

    2014-01-01

    Background Sleeping sickness caused by Trypanosoma brucei (T.b.) gambiense constitutes a serious health problem in sub-Sahara Africa. In some foci, alarmingly high relapse rates were observed in patients treated with melarsoprol, which used to be the first line treatment for patients in the neurological disease stage. Particularly problematic was the situation in Mbuji-Mayi, East Kasai Province in the Democratic Republic of the Congo with a 57% relapse rate compared to a 5% relapse rate in Masi-Manimba, Bandundu Province. The present study aimed at investigating the mechanisms underlying the high relapse rate in Mbuji-Mayi using an extended collection of recently isolated T.b. gambiense strains from Mbuji-Mayi and from Masi-Manimba. Methodology/Principal Findings Forty five T.b. gambiense strains were used. Forty one were isolated from patients that were cured or relapsed after melarsoprol treatment in Mbuji-Mayi. In vivo drug sensitivity tests provide evidence of reduced melarsoprol sensitivity in these strains. This reduced melarsoprol sensitivity was not attributable to mutations in TbAT1. However, in all these strains, irrespective of the patient treatment outcome, the two aquaglyceroporin (AQP) 2 and 3 genes are replaced by chimeric AQP2/3 genes that may be associated with resistance to pentamidine and melarsoprol. The 4 T.b. gambiense strains isolated in Masi-Manimba contain both wild-type AQP2 and a different chimeric AQP2/3. These findings suggest that the reduced in vivo melarsoprol sensitivity of the Mbuji-Mayi strains and the high relapse rates in that sleeping sickness focus are caused by mutations in the AQP2/AQP3 locus and not by mutations in TbAT1. Conclusions/Significance We conclude that mutations in the TbAQP2/3 locus of the local T.b. gambiense strains may explain the high melarsoprol relapse rates in the Mbuji-Mayi focus but other factors must also be involved in the treatment outcome of individual patients. PMID:25275572

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

    PubMed

    Snow, D; Anderson, C

    2000-07-01

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

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

    PubMed Central

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

    2010-01-01

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

  13. Tacrolimus Triggers Transient Receptor Potential Vanilloid-1-Dependent Relapse of Pancreatitis-Related Pain in Mice.

    PubMed

    Terada, Yuka; Tsubota, Maho; Sugo, Hiiragi; Wakitani, Kohei; Sekiguchi, Fumiko; Wada, Kyoichi; Takada, Mitsutaka; Oita, Akira; Kawabata, Atsufumi

    2017-01-01

    Transient receptor potential vanilloid-1 (TRPV1) expressed in nociceptors is directly phosphorylated and activated by protein kinase C, and involved in the signaling of pancreatic pain. On the other hand, Cav3.2 T-type Ca2+ channels expressed in nociceptors are functionally upregulated by phosphorylation with protein kinase A and also play a role in pancreatitis-related pain. Calcineurin, a phosphatase, negatively regulates various channel functions including TRPV1, and calcineurin inhibitor-induced pain syndrome by tacrolimus, a calcineurin inhibitor, used as an immunosuppressant, has been a clinical problem. We thus examined the effect of tacrolimus on pancreatitis-related pain in mice. Repeated treatment with cerulein caused referred hyperalgesia accompanying acute pancreatitis, which was unaffected by tacrolimus. Pancreatitis-related symptoms disappeared in 24 h, whereas the referred hyperalgesia recurred following the administration of tacrolimus, which was abolished by the blockers of TRPV1 but not T-type Ca2+ channels. Thus, tacrolimus appears to cause the TRPV1-dependent relapse of pancreatitis-related pain, suggesting the involvement of calcineurin in the termination of pancreatic pain.

  14. 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

  15. 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.

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

    PubMed

    Vengeliene, Valentina; Bilbao, Ainhoa; Spanagel, Rainer

    2014-05-01

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

  17. Optical coherence tomography segmentation analysis in relapsing remitting versus progressive multiple sclerosis

    PubMed Central

    Behbehani, Raed; Abu Al-Hassan, Abdullah; Al-Salahat, Ali; Sriraman, Devarajan; Oakley, J. D.; Alroughani, Raed

    2017-01-01

    Introduction Optical coherence tomography (OCT) with retinal segmentation analysis is a valuable tool in assessing axonal loss and neuro-degeneration in multiple sclerosis (MS) by in-vivo imaging, delineation and quantification of retinal layers. There is evidence of deep retinal involvement in MS beyond the inner retinal layers. The ultra-structural retinal changes in MS in different MS phenotypes can reflect differences in the pathophysiologic mechanisms. There is limited data on the pattern of deeper retinal layer involvement in progressive MS (PMS) versus relapsing remitting MS (RRMS). We have compared the OCT segmentation analysis in patients with relapsing-remitting MS and progressive MS. Methods Cross-sectional study of 113 MS patients (226 eyes) (29 PMS, 84 RRMS) and 38 healthy controls (72 eyes). Spectral domain OCT (SDOCT) using the macular cube acquisition protocol (Cirrus HDOCT 5000; Carl Zeiss Meditec) and segmentation of the retinal layers for quantifying the thicknesses of the retinal layers. Segmentation of the retinal layers was carried out utilizing Orion software (Voxeleron, USA) for quantifying the thicknesses of individual retinal layers. Results The retinal nerve finer layer (RNFL) (p = 0.023), the ganglion-cell/inner plexiform layer (GCIPL) (p = 0.006) and the outer plexiform layer (OPL) (p = 0.033) were significantly thinner in PMS compared to RRMS. There was significant negative correlation between the outer nuclear layer (ONL) and EDSS (r = -0.554, p = 0.02) in PMS patients. In RRMS patients with prior optic neuritis, the GCIPL correlated negatively (r = -0.317; p = 0.046), while the photoreceptor layer (PR) correlated positively with EDSS (r = 0.478; p = 0.003). Conclusions Patients with PMS exhibit more atrophy of both the inner and outer retinal layers than RRMS. The ONL in PMS and the GCIPL and PR in RRMS can serve as potential surrogate of disease burden and progression (EDSS). The specific retinal layer predilection and its

  18. 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

  19. Intrathecal donor lymphocyte infusion for isolated leukemia relapse in the central nervous system following allogeneic stem cell transplantation: a case report and literature review.

    PubMed

    Yanagisawa, Ryu; Nakazawa, Yozo; Sakashita, Kazuo; Saito, Shoji; Tanaka, Miyuki; Shiohara, Masaaki; Shimodaira, Shigetaka; Koike, Kenichi

    2016-01-01

    An 8-year-old boy with a bone marrow relapse of T cell acute lymphoblastic leukemia underwent stem-cell transplantation from a human leukocyte antigen (HLA)-haploidentical mother. Five months later, he relapsed with central nervous system (CNS) involvement. Systemic chemotherapy and repeated intrathecal chemotherapy induced consciousness disturbances and frequent arrhythmia, prompting us to discontinue the chemotherapy. He had already received an 18-Gy prophylactic cranial irradiation, an 8-Gy total body irradiation, and a 15-Gy local irradiation for pituitary gland involvement. We therefore performed five intrathecal donor lymphocyte infusions (IDLIs) in escalating doses from 1 × 10(4) up to 1 × 10(6) cells/kg. All IDLIs were safe without infusion reactions or graft-versus-host disease. After the second and later IDLIs, donor mononuclear cells were continuously detected in cerebrospinal fluid; however, he did not achieve donor-dominant chimerism. Based on our case and four cases reported in the literature, the efficacy of IDLI therapy is limited for CNS relapse of hematological malignancies. However, we suggest that IDLI remains a feasible and safe option, as no GVHD or other adverse effects occurred, even in the HLA-haploidentical setting. We will make further efforts to increase the efficacy.

  20. 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

  1. 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.

  2. 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.

  3. Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study

    PubMed Central

    Kim, Seok Jin; Hong, Jun Sik; Chang, Myung Hee; Kim, Jeong-A; Kwak, Jae-Yong; Kim, Jin Seok; Yoon, Dok Hyun; Lee, Won Sik; Do, Young Rok; Kang, Hye Jin; Eom, Hyeon-Seok; Park, Yong; Won, Jong-Ho; Mun, Yeung-Chul; Kim, Hyo Jung; Kwon, Jung Hye; Kong, Jee Hyun; Oh, Sung Yong; Lee, Sunah; Bae, Sung Hwa; Yang, Deok-Hwan; Jun, Hyun Jung; Kim, Yang Soo; Yun, Hwan Jung; Il Lee, Soon; Kim, Min Kyoung; Park, Eun Kyung; Kim, Won Seog; Suh, Cheolwon

    2016-01-01

    Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4–29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448. PMID:27713132

  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. Ipilimumab for Patients with Relapse after Allogeneic Transplantation

    PubMed Central

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

    2016-01-01

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

  6. 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

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

    PubMed

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

    2017-03-01

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

  8. 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.

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

    PubMed

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

    2014-08-30

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

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. The GABAB Positive Allosteric Modulator, ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats.

    PubMed

    Augier, Eric; Dulman, Russell S; Damadzic, Ruslan; Pilling, Andrew; Hamilton, J Paul; Heilig, Markus

    2017-03-15

    GABAergic signaling is involved in modulating the reinforcing properties of alcohol, and GABAB receptors have been proposed as a potential target for clinical treatment of alcoholism. The orthosteric GABAB receptor agonist baclofen has been shown to suppress operant self-administration of alcohol in animals and alcohol use in alcohol dependent patients, but its utility is limited by a narrow therapeutic index. We tested the effects of ADX71441, a novel GABAB receptor positive allosteric modulator on alcohol-related behaviors in rats. We first assessed the effects of ADX71441 (1, 3, 10 and 30 mg/kg, I.P.) on both non-dependent and dependent male Wistar rats trained to self-administer 20% alcohol. We then determined the effects of ADX71441 on stress-induced as well as cue-induced relapse-like behavior. Finally, we sought to identify the brain regions through which ADX71441 may act to prevent relapse-like behavior by mapping the neuronal activation induced by stress-induced reinstatement of alcohol-seeking using c-Fos immunohistochemistry. ADX71441 dose-dependently decreased alcohol self-administration of both dependent and non-dependent animals, but its potency was higher in alcohol-dependent rats. Furthermore, both cue- and stress-induced alcohol seeking were blocked by the GABAB receptor positive allosteric modulator. Finally, pretreatment with 3 mg/kg of ADX71441 before stress-induced reinstatement significantly decreased c-Fos expression in a network of brain regions implicated in stress induced relapse, comprising the nucleus accumbens shell, the dorsal raphe nucleus and the medial prefrontal cortex. Our findings support a causal role of GABAB receptors in alcohol reinforcement and relapse to alcohol seeking. These effects are observed in the absence of significant sedative side effects. Jointly, these observations indicate that GABAB receptor positive allosteric modulators merit being tested clinically for the treatment of alcoholism. Our data also point to

  13. 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

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

    PubMed

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

    2013-06-01

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

  15. 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

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

    PubMed

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

    2015-01-01

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

  17. Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography

    PubMed Central

    Song, Yoo Sung; Lee, Won Woo; Lee, Jong Seok; Kim, Sang Eun

    2015-01-01

    Abstract Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [18F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients. The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [18F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated. Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (≥10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan–Meir survival analysis between high TLG50 (>2000) and low TLG50 (≤2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 ± 134.3 days and 1968.6 ± 18.3 days, respectively (P < 0.001). High TLG50 on [18F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients. PMID:26554808

  18. 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.

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

    PubMed

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

    2017-02-15

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

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

    PubMed

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

    2015-08-01

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

  1. Risk Knowledge in Relapsing Multiple Sclerosis (RIKNO 1.0) - Development of an Outcome Instrument for Educational Interventions

    PubMed Central

    Heesen, C.; Kasper, J.; Fischer, K.; Köpke, S.; Rahn, A.; Backhus, I.; Poettgen, J.; Vahter, L.; Drulovic, J.; Van Nunen, A.; Beckmann, Y.; Liethmann, K.; Giordano, A.; Solari, A.

    2015-01-01

    Background Adequate risk knowledge of patients is a prerequisite for shared decision making but few attempts have been made to develop assessment tools. Multiple Sclerosis (MS) is a chronic inflammatory disease of young adults with an increasing number of partially effective immunotherapies and therefore a paradigmatic disease to study patient involvement. Objective/methods Based on an item bank of MS risk knowledge items and patient feedback including perceived relevance we developed a risk knowledge questionnaire for relapsing remitting (RR) MS (RIKNO 1.0) which was a primary outcome measure in a patient education trial (192 early RRMS patients). Results Fourteen of the RIKNO 1.0 multiple-choice items were selected based on patient perceived relevance and item difficulty indices, and five on expert opinion. Mean item difficulty was 0.58, ranging from 0.14 to 0.79. Mean RIKNO 1.0 score increased after the educational intervention from 10.6 to 12.4 (p = 0.0003). Selected items were particularly difficult (e.g. those on absolute risk reductions of having a second relapse) and were answered correctly in only 30% of the patients, even after the intervention. Conclusion Despite its high difficulty, RIKNO 1.0 is a responsive instrument to assess risk knowledge in RRMS patients participating in educational interventions. PMID:26430887

  2. The Role of the Social Environment in Alcohol or Drug Relapse of Probationers Recently Released from Jail

    PubMed Central

    Owens, Mandy D.; McCrady, Barbara S.

    2014-01-01

    Objectives: Many individuals involved with the criminal justice system also meet criteria for a substance use disorder. Social support has been identified as an important factor in alcohol and drug relapse, and also for individuals who are incarcerated. The purposes of this study were to describe personal characteristics and the social networks of adult male probationers with substance use disorders and test how changes in social networks related to alcohol or drug use after release from jail. Methods: Fifty adult male probationers who were recently incarcerated (60 to 210 days prior to screening) were recruited from a large Southwest Probation and Parole Division office, and were administered a single assessment that assessed demographic information, social networks, and quantity and frequency of alcohol and drug use before and after incarceration. Results: In this sample there was an over-representation of ethnic minorities, higher rates of unemployment, lower educational levels, and lower median income than national averages. Results showed that there were significant changes in social networks from pre- to post-incarceration. Additionally, changes in social networks significantly predicted substance use after release from jail, even after controlling for substance use prior to incarceration, and the percentage of social network members who were heavy drug users mediated percent days abstinent from alcohol and drugs from pre- to post-incarceration. Conclusions: Social networks and social support may operate as dynamic factors in relapse, and may be a target for intervention for adult males with substance use disorders being released from jail. PMID:25598744

  3. Patterns of Relapse From a Phase 3 Study of Response-Based Therapy for Intermediate-Risk Hodgkin Lymphoma (AHOD0031): A Report From the Children's Oncology Group

    SciTech Connect

    Dharmarajan, Kavita V.; Friedman, Debra L.; Schwartz, Cindy L.; Chen, Lu; FitzGerald, T.J.; McCarten, Kathleen M.; Constine, Louis S.; Wolden, Suzanne L.

    2015-05-01

    Purpose: The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma. We examined patterns of first relapse in the study. Patients and Methods: From September 2002 to July 2010, 1712 patients <22 years old with stage I-IIA with bulk, I-IIAE, I-IIB, and IIIA-IVA with or without doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide were enrolled. Patients were categorized as rapid (RER) or slow early responders (SER) after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21 Gy involved field radiation therapy (IFRT). RER patients were stipulated to undergo 2 additional ABVE-PC cycles and were then randomized to 21 Gy IFRT or no further treatment if complete response (CR) was achieved. RER without CR patients were non-randomly assigned to 21 Gy IFRT. Relapses were characterized without respect to site (initial, new, or both; and initial bulk or initial nonbulk), and involved field radiation therapy field (in-field, out-of-field, or both). Patients were grouped by treatment assignment (SER; RER/no CR; RER/CR/IFRT; and RER/CR/no IFRT). Summary statistics were reported. Results: At 4-year median follow-up, 244 patients had experienced relapse, 198 of whom were fully evaluable for review. Those who progressed during treatment (n=30) or lacked relapse imaging (n=16) were excluded. The median time to relapse was 12.8 months. Of the 198 evaluable patients, 30% were RER/no CR, 26% were SER, 26% were RER/CR/no IFRT, 16% were RER/CR/IFRT, and 2% remained uncategorized. The 74% and 75% relapses involved initially bulky and nonbulky sites, respectively. First relapses rarely occurred at exclusively new or out-of-field sites. By contrast, relapses usually occurred at nodal sites of initial bulky and nonbulky disease. Conclusion: Although

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Hoy, Sheridan M

    2016-04-01

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

  6. Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis

    PubMed Central

    2013-01-01

    Background Multiple sclerosis (MS) is a disease of central nervous system that causes the removal of fatty myelin sheath from axons of the brain and spinal cord. Autoimmunity plays an important role in this pathology outcome and body's own immune system attacks on the myelin sheath causing the damage. The etiology of the disease is partially understood and the response to treatment cannot easily be predicted. Results We presented the results obtained using 8 genetically predisposed randomly chosen individuals reproducing both the absence and presence of malfunctions of the Teff-Treg cross-balancing mechanisms at a local level. For simulating the absence of a local malfunction we supposed that both Teff and Treg populations had similar maximum duplication rates. Results presented here suggest that presence of a genetic predisposition is not always a sufficient condition for developing the disease. Other conditions such as a breakdown of the mechanisms that regulate and allow peripheral tolerance should be involved. Conclusions The presented model allows to capture the essential dynamics of relapsing-remitting MS despite its simplicity. It gave useful insights that support the hypothesis of a breakdown of Teff-Treg cross balancing mechanisms. PMID:24564794

  7. Relapsing-remitting CNS autoimmunity mediated by GFAP-specific CD8 T cells

    PubMed Central

    Sasaki, Katsuhiro; Bean, Angela; Shah, Shivanee; Schutten, Elizabeth; Huseby, Priya G.; Peters, Bjorn; Shen, Zu T.; Vanguri, Vijay; Liggitt, Denny; Huseby, Eric S.

    2014-01-01

    Multiple Sclerosis (MS) is an inflammatory disease of the CNS that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons and axons. Historically, MS has been thought to be a CD4 T cell-mediated autoimmune disease of CNS white matter. However, recent studies have identified CD8 T cell infiltrates and gray matter lesions in MS patients. These findings suggest that CD8 T cells, and CNS antigens other than myelin proteins may be involved during the MS disease process. Here we show that CD8 T cells reactive to glial fibrillary acidic protein (GFAP), a protein expressed in astrocytes, can avoid tolerance mechanisms, and depending upon the T cell triggering event, drive unique aspects of inflammatory CNS autoimmunity. In GFAP-specific CD8 T cell receptor transgenic (BG1) mice, tissue resident memory-like CD8 T cells spontaneously infiltrate the gray matter and white matter of the CNS, resulting in a relapsing-remitting CNS autoimmunity. The frequency, severity and remissions from spontaneous disease are controlled by the presence of polyclonal B cells. In contrast, a viral trigger induces GFAP-specific CD8 T effector cells to exclusively target the meninges and vascular/perivascular space of the gray and white matter of the brain, causing a rapid, acute CNS disease. These findings demonstrate that the type of CD8 T cell-triggering event can determine the presentation of distinct CNS autoimmune disease pathologies. PMID:24591371

  8. Tumor-Infiltrating Macrophages in Post-Transplant, Relapsed Classical Hodgkin Lymphoma Are Donor-Derived.

    PubMed

    Crane, Genevieve M; Samols, Mark A; Morsberger, Laura A; Yonescu, Raluca; Thiess, Michele L; Batista, Denise A S; Ning, Yi; Burns, Kathleen H; Vuica-Ross, Milena; Borowitz, Michael J; Gocke, Christopher D; Ambinder, Richard F; Duffield, Amy S

    Tumor-associated inflammatory cells in classical Hodgkin lymphoma (CHL) typically outnumber the neoplastic Hodgkin/Reed-Sternberg (H/RS) cells. The composition of the inflammatory infiltrate, particularly the fraction of macrophages, has been associated with clinical behavior. Emerging work from animal models demonstrates that most tissue macrophages are maintained by a process of self-renewal under physiologic circumstances and certain inflammatory states, but the contribution from circulating monocytes may be increased in some disease states. This raises the question of the source of macrophages involved in human disease, particularly that of CHL. Patients with relapsed CHL following allogeneic bone marrow transplant (BMT) provide a unique opportunity to begin to address this issue. We identified 4 such patients in our archives. Through molecular chimerism and/or XY FISH studies, we demonstrated the DNA content in the post-BMT recurrent CHL was predominantly donor-derived, while the H/RS cells were derived from the patient. Where possible to evaluate, the cellular composition of the inflammatory infiltrate, including the percentage of macrophages, was similar to that of the original tumor. Our findings suggest that the H/RS cells themselves define the inflammatory environment. In addition, our results demonstrate that tumor-associated macrophages in CHL are predominantly derived from circulating monocytes rather than resident tissue macrophages. Given the association between tumor microenvironment and disease progression, a better understanding of macrophage recruitment to CHL may open new strategies for therapeutic intervention.

  9. Tumor-Infiltrating Macrophages in Post-Transplant, Relapsed Classical Hodgkin Lymphoma Are Donor-Derived

    PubMed Central

    Morsberger, Laura A.; Yonescu, Raluca; Thiess, Michele L.; Batista, Denise A. S.; Ning, Yi; Burns, Kathleen H.; Vuica-Ross, Milena; Borowitz, Michael J.; Gocke, Christopher D.; Ambinder, Richard F.; Duffield, Amy S.

    2016-01-01

    Tumor-associated inflammatory cells in classical Hodgkin lymphoma (CHL) typically outnumber the neoplastic Hodgkin/Reed-Sternberg (H/RS) cells. The composition of the inflammatory infiltrate, particularly the fraction of macrophages, has been associated with clinical behavior. Emerging work from animal models demonstrates that most tissue macrophages are maintained by a process of self-renewal under physiologic circumstances and certain inflammatory states, but the contribution from circulating monocytes may be increased in some disease states. This raises the question of the source of macrophages involved in human disease, particularly that of CHL. Patients with relapsed CHL following allogeneic bone marrow transplant (BMT) provide a unique opportunity to begin to address this issue. We identified 4 such patients in our archives. Through molecular chimerism and/or XY FISH studies, we demonstrated the DNA content in the post-BMT recurrent CHL was predominantly donor-derived, while the H/RS cells were derived from the patient. Where possible to evaluate, the cellular composition of the inflammatory infiltrate, including the percentage of macrophages, was similar to that of the original tumor. Our findings suggest that the H/RS cells themselves define the inflammatory environment. In addition, our results demonstrate that tumor-associated macrophages in CHL are predominantly derived from circulating monocytes rather than resident tissue macrophages. Given the association between tumor microenvironment and disease progression, a better understanding of macrophage recruitment to CHL may open new strategies for therapeutic intervention. PMID:27685855

  10. 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

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

    PubMed

    Prikuls, V F

    2000-01-01

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

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

    PubMed

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

    2008-08-01

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

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

    PubMed

    Brincat, S; Mantell, B S

    1986-07-01

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

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

    PubMed Central

    Dutta, Ranjan; Trapp, Bruce D.

    2014-01-01

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

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

    PubMed Central

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

    1982-01-01

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

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

    DTIC Science & Technology

    1997-12-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed

    Gavrilenko, A V; Vakhrat'ian, P E

    2012-01-01

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

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2007-04-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2015-08-26

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed

    Moreau, Philippe

    2012-07-01

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

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

    PubMed

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

    2012-02-16

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2015-06-01

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

  14. The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

    PubMed

    Paterson, Louise M; Flechais, Remy S A; Murphy, Anna; Reed, Laurence J; Abbott, Sanja; Boyapati, Venkataramana; Elliott, Rebecca; Erritzoe, David; Ersche, Karen D; Faluyi, Yetunde; Faravelli, Luca; Fernandez-Egea, Emilio; Kalk, Nicola J; Kuchibatla, Shankar S; McGonigle, John; Metastasio, Antonio; Mick, Inge; Nestor, Liam; Orban, Csaba; Passetti, Filippo; Rabiner, Eugenii A; Smith, Dana G; Suckling, John; Tait, Roger; Taylor, Eleanor M; Waldman, Adam D; Robbins, Trevor W; Deakin, J F William; Nutt, David J; Lingford-Hughes, Anne R

    2015-09-01

    Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.

  15. Squamous cell carcinoma of pancreas: an unusual site of relapse from early-stage lung cancer: 12-month postsurgery

    PubMed Central

    Sharma, Anand; Alfa-Wali, Maryam; Rodriguez-Justo, Manuel; Polychronis, Andreas

    2013-01-01

    A 57-year-old man presented with abdominal pain and backache, weight loss of 10 kg and irregular bowel movements. He was previously diagnosed with Stage IB squamous cell carcinoma of lung and had undergone lobectomy 12 months previously. Investigations including imaging revealed a cystic mass in the body and tail of the pancreas which was biopsied and it was confirmed to be a recurrence of the squamous lung cancer involving the pancreas. He was treated with systemic chemotherapy and has shown a partial response on repeat imaging. This case illustrates a rare and unusual site of relapse in lung cancer after adjuvant therapy and a key message for follow-up surveillance for these patients. PMID:23608858

  16. Vaccines against morphine/heroin and its use as effective medication for preventing relapse to opiate addictive behaviors.

    PubMed

    Anton, Benito; Salazar, Alberto; Flores, Anabel; Matus, Maura; Marin, Rodrigo; Hernandez, Jorge-Alberto; Leff, Philippe

    2009-04-01

    Current pharmacotherapies for treating morphine/heroin dependence are designed to substitute or block addiction by targeting the drug itself rather than the brain. The heroin addict is still being exposed to addictive opiates, and consequently may develop tolerance to and experience withdrawal and drug's toxic effects from the treatment with high incidence of relapse to addictive drug consumption. As for other drugs of abuse, an alternative approach for morphine/heroin addiction is an antibody-based antagonism of heroin's brain entry. This review summarizes the literature examining important aspects of neurobiological and pharmacological processes involved in opiate dependence. Thereafter, classical pharmacological interventions for opiate dependence treatment and its major clinical limitations are reviewed. Finally, relevant preclinical studies are examined for comparisons in the design, use, immunogenic profile and efficacy of several models of morphine/heroin vaccine as immunologic interventions on the pharmacokinetics and behavioral of morphine/heroin in the rat as animal model.

  17. Predictors of injection drug use cessation and relapse in a prospective cohort of young injection drug users in San Francisco, CA (UFO Study)

    PubMed Central

    Evans, Jennifer L.; Hahn, Judith A.; Lum, Paula J.; Stein, Ellen S.; Page, Kimberly

    2009-01-01

    Background Studies of injection drug use cessation have largely sampled adults in drug treatment settings. Little is known about injection cessation and relapse among young injection drug users (IDU) in the community. Methods A total of 365 HCV-negative IDU under age 30 years were recruited by street outreach and interviewed quarterly for a prospective cohort between January 2000 and February 2008. Participants were followed for a total of 638 person-years and 1996 visits. We used survival analysis techniques to identify correlates of injection cessation (≥3 months) and relapse to injection. Results 67% of subjects were male, median age was 22 years (interquartile range (IQR) 20 - 26) and median years injecting was 3.6 (IQR 1.3 – 6.5). 28.8% ceased injecting during the follow-up period. Among those that ceased injecting, nearly one-half resumed drug injection on subsequent visits, one-quarter maintained injecting cessation, and one-quarter were lost to follow-up. Participating in a drug treatment program in the last 3 months and injecting less than 30 times per month were associated with injection cessation. Injecting heroin or heroin mixed with other drugs, injecting the residue from previously used drug preparation equipment, drinking alcohol, and using benzodiazepines were negatively associated with cessation. Younger age was associated with relapse to injection. Conclusion These results suggest that factors associated with stopping injecting involve multiple areas of intervention, including access to drug treatment and behavioral approaches to reduce injection and sustain cessation. The higher incidence of relapse in the younger subjects in this cohort underscores the need for earlier detection and treatment programs targeted to adolescents and transition-age youth. PMID:19181458

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2001-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2013-03-01

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

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

    SciTech Connect

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

    2010-11-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2017-01-01

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

  12. Plasmodium vivax infections in U.S. Army troops: failure of primaquine to prevent relapse in studies from Somalia.

    PubMed

    Smoak, B L; DeFraites, R F; Magill, A J; Kain, K C; Wellde, B T

    1997-02-01

    Different strains of Plasmodium vivax vary in their sensitivity to primaquine, the only drug that prevents relapses. Described are the clinical data and relapse pattern for 75 soldiers treated for vivax malaria since returning from Somalia. Following their initial attack of malaria, 60 of the 75 cases received a standard course of primaquine (15 mg base daily for 14 days). Twenty-six of the 60 soldiers subsequently relapsed for a failure rate of 43%. Eight soldiers had a second relapse following primaquine therapy after both the primary attack and first relapse. Three of these soldiers had received a higher dosage of primaquine (30 mg base daily for 14 days) after their second attack. The apparent ineffectiveness of primaquine therapy in preventing relapses suggests the presence of primaquine-resistant P. vivax strains in Somalia.

  13. Changes in angiogenesis and hypoxia-inducible factor-1α protein expression in relapsed/refractory indolent non-Hodgkin lymphomas.

    PubMed

    Minoia, Carla; Quero, Carmela; Asselti, Mariaconsilia; Galise, Ida; Marzano, Alessia L; Iacobazzi, Angela; Rana, Antonio; Merchionne, Francesca; Serratì, Simona; De Tullio, Giacoma; Quintana, Giovanni; Casiello, Michela; Maiorano, Eugenio; Simone, Giovanni; Zito, Francesco A; Iacopino, Pasquale; Guarini, Attilio

    2013-12-01

    Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin lymphomas (NHL), and hypoxia-inducible factor-1α (HIF-1α, also termed HIF1A) might contribute to this process. Currently, there is no direct evidence that the clinical progression of indolent NHL is associated with angiogenesis, and the expression of HIF-1α at recurrence is unknown. Matched lymph node biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients were analysed by immunohistochemical and morphometric analysis. We observed an increased vascular network and HIF-1α protein expression in the second biopsy, providing direct evidence that angiogenesis is an essential process for disease progression.

  14. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia

    PubMed Central

    Oshima, Koichi; Khiabanian, Hossein; da Silva-Almeida, Ana C.; Tzoneva, Gannie; Abate, Francesco; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Carpenter, Zachary; Penson, Alex; Perez-Garcia, Arianne; Eckert, Cornelia; Nicolas, Concepción; Balbin, Milagros; Sulis, Maria Luisa; Kato, Motohiro; Koh, Katsuyoshi; Paganin, Maddalena; Basso, Giuseppe; Gastier-Foster, Julie M.; Devidas, Meenakshi; Loh, Mignon L.; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A.

    2016-01-01

    Although multiagent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die because of chemorefractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape at relapse in pediatric ALL cases. These analyses identified numerous relapse-associated mutated genes intertwined in chemotherapy resistance-related protein complexes. In this context, RAS-MAPK pathway-activating mutations in the neuroblastoma RAS viral oncogene homolog (NRAS), kirsten rat sarcoma viral oncogene homolog (KRAS), and protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) genes were present in 24 of 55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, whereas in others RAS mutant clones present at diagnosis were replaced by RAS wild-type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Consistently, functional dissection of mouse and human wild-type and mutant RAS isogenic leukemia cells demonstrated induction of methotrexate resistance but also improved the response to vincristine in mutant RAS-expressing lymphoblasts. These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution in relapsed ALL, and demonstrate a previously unrecognized dual role of RAS mutations as drivers of both sensitivity and resistance to chemotherapy. PMID:27655895

  15. Two-year outcome of internet-based relapse prevention for partially remitted depression.

    PubMed

    Holländare, Fredrik; Anthony, Susanne A; Randestad, Mia; Tillfors, Maria; Carlbring, Per; Andersson, Gerhard; Engström, Ingemar

    2013-11-01

    The objective of the study was to investigate the long-term effects of internet-based relapse prevention for sufferers of partially remitted depression. Eighty-four individuals with partially remitted unipolar depression were randomized to either internet-based CBT (iCBT) or to a control group. After the ten week intervention period the participants were followed for 24 months and diagnostic interviews conducted to detect relapse. The intervention and monthly self-ratings of depressive symptoms were administered via an internet-based platform that ensured secure communication with all participants. Significantly fewer participants in the iCBT group had experienced a relapse compared with those in the control group two years after the internet-based intervention. The relapse rate in the iCBT group was 13.7% (CI 95%=2.5-24.9) and in the control group it was 60.9% (CI 95%=44.8-77). Furthermore, a significantly larger proportion of the iCBT group experienced remission two years after the intervention compared with the control group. Internet-based CBT seems promising for preventing relapse in sufferers of partially remitted depression.

  16. Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation

    PubMed Central

    Kelemen, Katalin; Galani, Komal; Conley, Christopher R.; Greipp, Patricia T.

    2015-01-01

    The acquisition of Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia after HCT that developed a BCR/ABL-1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to acute myeloid leukemia and relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: a deletion 20q abnormality subsequently acquired deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias. PMID:25074248

  17. Neurocognitive rehabilitation for addiction medicine: From neurophysiological markers to cognitive rehabilitation and relapse prevention.

    PubMed

    Campanella, Salvatore

    2016-01-01

    Currently, relapse prevention remains the main challenge in addiction medicine, indicating that the established treatment methods combining psychotherapy with neuropharmacological interventions are not entirely effective. Therefore, there is a push to develop alternatives to psychotherapy- and medication-based approaches to addiction treatment. Two major cognitive factors have been identified that trigger relapse in addicted patients: attentional biases directed toward drug-related cues, which increase the urge to consume, and impaired response inhibition toward these cues, which makes it more difficult for addicted people to resist temptation. Recent studies on newly detoxified alcoholic patients have shown that by using the appropriate tasks to index these cognitive functions with event-related potentials (ERPs), it is possible to discriminate between future relapsers and nonrelapsers. These preliminary data suggest that the ERP technique has great clinical potential for preventing relapse in alcohol-dependent patients, as well as for addictive states in general. Indeed, ERPs may help to identify patients highly vulnerable to relapse and allow the development of individually adapted cognitive rehabilitation programs. The implementation of this combined approach requires an intense collaboration between psychiatry departments, clinical neurophysiology laboratories, and neuropsychological rehabilitation centers. The potential pitfalls and limitations of this approach are also discussed.

  18. Relapse and Risk-taking among Iranian Methamphetamine Abusers Undergoing Matrix Treatment Model

    PubMed Central

    Taymoori, Parvaneh; Pashaei, Tahereh

    2016-01-01

    Background This study investigated the correlation between risk-taking and relapse among methamphetamine (MA) abusers undergoing the Matrix Model of treatment. Methods This cross-sectional study was conducted on male patients who were stimulant drug abusers undergoing the matrix treatment in the National Center for Addiction Research. A sampling was done using the availability method including 92 male patients. Demographic questionnaires and drug abuse related questionnaire were completed for each patient. Then, Bart’s balloon risk-taking test was administered to the patients. Findings Participants had a mean age ± standard deviation (SD) of 27.59 ± 6.60 years with an age range of 17-29 years. Unemployment, unmarried status, criminal offense, and also addiction family history increased the probability of relapse. In addition, a greater adjusted score of the risk-taking test increased the odds of relapse by more than 97%. The simultaneous abuse of opium and stimulants compared to the abuse of stimulants only, revealed no statistically significant differences for relapse. Patients with higher risk-taking behavior had a more probability of relapse. Conclusion This finding indirectly implies the usefulness of Bart’s risk-taking test in assessing risk-taking behavior in stimulant drug abusers. PMID:27274793

  19. Multiple myeloma treatment at relapse after autologous stem cell transplantation: A practical analysis.

    PubMed

    Malard, F; Harousseau, J L; Mohty, M

    2017-01-01

    Over the past decade, significant advances have been made in the field of multiple myeloma. Introduction of the so-called novel agents, proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care have resulted in significantly better outcome. Standard first line treatment in fit patients include PI and IMiD based induction, high dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) and consolidation/maintenance. However, despite these progresses MM remains incurable for the majority of patients and most patients will relapse. Next generation PI (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes: monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some of these new agents are now approved for multiple myeloma treatment at relapse. However choosing the most appropriate treatment at relapse may be difficult. This review sum up the most important studies and provide evidence to choose the most relevant therapeutic strategy for relapse after ASCT, based on disease, patient and previous treatment related parameters.

  20. Toward a model of drug relapse: An assessment of the validity of the reinstatement procedure

    PubMed Central

    Epstein, David H.; Preston, Kenzie L.; Stewart, Jane; Shaham, Yavin

    2006-01-01

    Background and Rationale The reinstatement model is widely used animal model of relapse to drug addiction. However, the model’s validity is open to question. Objective We assess the reinstatement model in terms of criterion and construct validity. Research highlights and Conclusions We find that the reinstatement model has adequate criterion validity in the broad sense of the term, as evidenced by the fact that reinstatement in laboratory animals is induced by conditions reported to provoke relapse in humans. The model’s criterion validity in the narrower sense, as a medication screen, seems promising for relapse to heroin, nicotine, and alcohol. For relapse to cocaine, criterion validity has not yet established, primarily because clinical studies have examined medication’s effects on reductions in cocaine intake rather than relapse during abstinence. The model’s construct validity faces more substantial challenges and is yet to be established, but we argue that some of the criticisms of the model in this regard may have been overstated. PMID:17019567

  1. Relapse specific mutations in NT5C2 in childhood acute lymphoblastic leukemia

    PubMed Central

    Meyer, Julia A.; Wang, Jinhua; Hogan, Laura E.; Yang, Jun J.; Dandekar, Smita; Patel, Jay P.; Tang, Zuojian; Zumbo, Paul; Li, Sheng; Zavadil, Jiri; Levine, Ross L.; Cardozo, Timothy; Hunger, Stephen P.; Raetz, Elizabeth A.; Evans, William E.; Morrison, Debra J.; Mason, Christopher E.; Carroll, William L.

    2013-01-01

    Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis despite intensive retreatment, due to intrinsic drug resistance1-2. The biological pathways that mediate resistance are unknown. Here we report the transcriptome profiles of matched diagnosis and relapse bone marrow specimens from ten pediatric B lymphoblastic leukemia patients using RNA-sequencing. Transcriptome sequencing identified 20 newly acquired novel non-synonymous mutations not present at initial diagnosis, of which two patients harbored relapse specific mutations in the same gene, NT5C2, a 5′-nucleotidase. Full exon sequencing of NT5C2 was completed in 61 additional relapse specimens, identifying five additional cases. Enzymatic analysis of mutant proteins revealed that base substitutions conferred increased enzymatic activity and resistance to treatment with nucleoside analogue therapies. Clinically, all patients who harbored NT5C2 mutations relapsed early, or within 36 months of initial diagnosis (p=0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug resistant clones in ALL. PMID:23377183

  2. Tick-borne Relapsing Fever in Children in the North-west of Iran, Qazvin.

    PubMed

    Ayazi, Parviz; Mahyar, Abolfazl; Oveisi, Sonia; Esmailzadehha, Neda; Nooroozi, Sadralnesa

    2015-01-01

    Relapsing fever is caused by the Borrelia species of spirochetes. Louse-borne epidemics of the disease may happen but the endemic disease is generally transmitted to humans by the bite of an infected tick (Ornithodorus). Clinical and laboratory findings of tick-borne relapsing fever in children in the north-west of Iran, Qazvin, were evaluated. This study was conducted from September 1992 to September 2012. Records from 53 cases of tick-borne relapsing fever (TBRF) were reviewed. In positive cases, febrile illness, and spirochetes were recognized in peripheral blood preparations. Of the 53 children younger than 12 years, fifty two percent were male and about one third (34%) of the patients were in the age range of 7-12 years. The disease is recorded through the whole year but its peak occurs during summer (52.8%) and autumn (32.1%). Sixty eight percent of patients were living in urban areas but had frequent travel to rural area. Thirty two percent of the cases were living in rural areas where their dwellings were close to animal shelters. All (100%) of the 53 subjects were febrile. Travellers to the rural areas with high prevalence of the disease should be attentive of the risk of tick-borne relapsing fever and use suitable control measures. Consequently relapsing fever should be considered when patients who live in or have vacationed in north-west of Iran show a recurring febrile illness.

  3. Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia.

    PubMed

    Rossi, M R; Masera, G; Zurlo, M G; Amadori, S; Mandelli, F; Bagnulo, S; Carli, M; Zanesco, L; Dini, G; Guazzelli, C

    1986-01-01

    This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.

  4. Effects of a therapeutic camping program on addiction recovery. The Algonquin Haymarket Relapse Prevention Program.

    PubMed

    Bennett, L W; Cardone, S; Jarczyk, J

    1998-01-01

    A group of 13 men and women in substance abuse treatment participated in a 3-day residential program experience based on integrated principles from adventure therapy, therapeutic camping, and relapse prevention. The experimental group is compared to a group of 18 men and women who received the usual and customary relapse prevention program. Both groups completed pre- and postintervention questionnaires. There were no differences in drinking-related locus of control, stress, or problem-solving between groups at postinterview, but there were significant improvements in autonomic arousal, frequency of negative thoughts, and alcohol craving. Participants in both groups were interviewed 10 months after the 3-day intervention. Considering individuals who were unreachable as relapsed, the 10-month follow-up relapse rate was 31% for the experimental group and 58% for the comparison group. These results add to the limited body of research supporting outdoor adventure and therapeutic camping experiences integrated with traditional relapse prevention activities as an adjunct to substance abuse treatment.

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

    PubMed

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

    2015-07-01

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

  6. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.

    PubMed

    Meyer, Julia A; Wang, Jinhua; Hogan, Laura E; Yang, Jun J; Dandekar, Smita; Patel, Jay P; Tang, Zuojian; Zumbo, Paul; Li, Sheng; Zavadil, Jiri; Levine, Ross L; Cardozo, Timothy; Hunger, Stephen P; Raetz, Elizabeth A; Evans, William E; Morrison, Debra J; Mason, Christopher E; Carroll, William L

    2013-03-01

    Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis, despite intensive retreatment, owing to intrinsic drug resistance. The biological pathways that mediate resistance are unknown. Here, we report the transcriptome profiles of matched diagnosis and relapse bone marrow specimens from ten individuals with pediatric B-lymphoblastic leukemia using RNA sequencing. Transcriptome sequencing identified 20 newly acquired, novel nonsynonymous mutations not present at initial diagnosis, with 2 individuals harboring relapse-specific mutations in the same gene, NT5C2, encoding a 5'-nucleotidase. Full-exon sequencing of NT5C2 was completed in 61 further relapse specimens, identifying additional mutations in 5 cases. Enzymatic analysis of mutant proteins showed that base substitutions conferred increased enzymatic activity and resistance to treatment with nucleoside analog therapies. Clinically, all individuals who harbored NT5C2 mutations relapsed early, within 36 months of initial diagnosis (P = 0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug-resistant clones in ALL.

  7. Insights on chronic-relapsing opsoclonus-myoclonus from a pilot study of mycophenolate mofetil.

    PubMed

    Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Baumgardner, Christine A; Gowda, Narayana V; Halthore, Sri N; Kerstan, Peter; Kossak, Brian D; Mitchell, Wendy G; Taub, Jeffrey W

    2009-03-01

    Opsoclonus-myoclonus syndrome is characterized by abnormal lymphocyte trafficking into brain. The authors hypothesized that mycophenolate mofetil, a lymphocyte proliferation inhibitor, might be therapeutic. The cerebrospinal fluid and blood immunophenotypes of 15 children with predominantly chronic-relapsing opsoclonus-myoclonus syndrome were compared before and after treatment by flow cytometry. Mycophenolate mofetil reduced the cerebrospinal fluid expansion of HLA-DR+ activated T cells (-40%); the frequency of other T-cell or natural killer cell subsets remained unchanged, but cerebrospinal fluid B cells increased significantly. Adrenocorticotropic hormone dose was lowered by 64% over an average of 1.5 years, yet 73% eventually relapsed despite therapeutic drug levels. Prior treatment with rituximab prevented relapse-associated increase in cerebrospinal fluid B cells, without hindering mycophenolate mofetil-induced reduction in T-cell activation. These data demonstrate resistant immunologic problems in chronic-relapsing opsoclonus-myoclonus syndrome. Mycophenolate mofetil did not prevent relapse. The novel effect of mycophenolate mofetil on chronically activated T cells may contribute to its efficacy in T-cell mediated neurological disorders.

  8. Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation.

    PubMed

    Kelemen, Katalin; Galani, Komal; Conley, Christopher R; Greipp, Patricia T

    2014-06-01

    The acquisition of the Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias.

  9. Neurogentics of Dopaminergic Receptor Super-sensitivity in Activation of Brain Reward Circuitry and Relapse: Proposing “Deprivation-Amplification Relapse Therapy” (DART)

    PubMed Central

    Downs, B. William; Bowirrat, Abdalla; Waite, Roger L.; Braverman, Eric R.; Madigan, Margaret; Oscar-Berman, Marlene; DiNubile, Nicholas; Gold, Mark

    2013-01-01

    Background and Hypothesis It is well known that after prolonged abstinence, individuals who imbibe or use their drug of choice experience a powerful euphoria that precipitates serious relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed “super sensitivity” might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundrum relates to the paradoxical finding that the dopaminergic agonist bromocriptine induces stronger activation of brain reward circuitry in individuals who carry the DRD2 A1 allele compared to DRD2 A2 allele carriers. Based upon the fact that carriers of the A1 allele relative to the A2 allele of the DRD2 gene have significantly lower D2 receptor density, a reduced sensitivity to dopamine agonist activity would be expected in the former. Thus, it is perplexing that with low D2 density there is an increase in reward sensitivity with the dopamine agonist bromocriptine. Moreover, under chronic or long-term therapy, the potential proliferation of D2 receptors with bromocriptine has been shown in vitro. This seems to lead to a positive outcome and significantly better treatment compliance only in A1 carriers. Proposal and Conclusion We propose that low D2 receptor density and polymorphisms of the D2 gene are associated with risk for relapse of substance abuse including alcohol dependence, heroin craving, cocaine dependence, methamphetamine abuse, nicotine sensitization, and glucose craving. With this in mind, we suggest a putative physiological mechanism that may help to explain the enhanced sensitivity following intense acute dopaminergic D2 receptor activation: “denervation supersensitivity.” Thus, the administration of dopamine D2 agonists would target D2 sensitization and attenuate relapse, especially in D2 receptor A1 allele carriers. This hypothesized mechanism is supported by clinical trials utilizing the amino-acid neurotransmitter precursors

  10. Lifetime Alcoholics Anonymous attendance as a predictor of spiritual gains in the Relapse Replication and Extension Project (RREP).

    PubMed

    Tonigan, J Scott; McCallion, Elizabeth A; Frohe, Tessa; Pearson, Matthew R

    2017-02-01

    This study investigated the association between extent of lifetime attendance in Alcoholics Anonymous (AA) and spiritual gains among treatment seeking adults for alcohol use disorder. Participants included 246 individuals from 2 of the 3 sites in the Relapse Replication and Extension Project (Lowman, Allen, Stout, & The Relapse Research Group, 1996). Baseline characteristics included 63% male, 39.9% single, and the average age was 34 years (SD = 8.2). The Alcoholics Anonymous Involvement questionnaire (Tonigan, Connors, & Miller, 1996) was used to assess lifetime AA attendance. The Religious Beliefs & Behaviors Questionnaire (Connors, Tonigan, & Miller, 1996) was used to assess spirituality. Percent days abstinent (PDA) and drinks per drinking day (DPDD) were measured using the Form 90. At baseline, adults with more extensive AA histories were more severely alcohol impaired although they were no older relative to adults with less past AA exposure. Clear patterns of AA engagement were found between the high-low AA history groups over follow-up, with adults with less AA experience reporting less AA participation across a swath of AA-specific measures. Gains in spiritual practices significantly mediated AA-related benefit as measured by PDA and DPDD. Tests for moderated-mediation indicated that the magnitude of the mediational effect of spiritual gains did not differ between high-low AA history groups. Having an extensive AA history did not advantage (or disadvantage) adults in mobilizing future spiritual practices that are prescribed in AA. Clinical assessment of client AA history is important, however, because it predicts both the nature and extent that clients may participate in AA. (PsycINFO Database Record

  11. Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia.

    PubMed

    Stein, Anthony; Palmer, Joycelynne; Tsai, Ni-Chun; Al Malki, Monzr M; Aldoss, Ibrahim; Ali, Haris; Aribi, Ahmed; Farol, Len; Karanes, Chatchada; Khaled, Samer; Liu, An; O'Donnell, Margaret; Parker, Pablo; Pawlowska, Anna; Pullarkat, Vinod; Radany, Eric; Rosenthal, Joseph; Sahebi, Firoozeh; Salhotra, Amandeep; Sanchez, James F; Schultheiss, Tim; Spielberger, Ricardo; Thomas, Sandra H; Snyder, David; Nakamura, Ryotaro; Marcucci, Guido; Forman, Stephen J; Wong, Jeffrey

    2017-04-01

    Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue. We conducted a phase I trial in 51 patients (age range, 16 to 57 years) with relapsed/refractory acute leukemia undergoing HSCT (matched related, matched unrelated, or 1-allele mismatched unrelated) with active disease, combining escalating doses of TMLI (range, 1200 to 2000 cGy) with cyclophosphamide (CY) and etoposide (VP16). The maximum tolerated dose was declared at 2000 cGy, as TMLI simulation studies indicated that >2000 cGy might deliver doses toxic for normal organs at or exceeding those delivered by standard TBI. The post-transplantation nonrelapse mortality (NRM) rate was only 3.9% (95% confidence interval [CI], .7 to 12.0) at day +100 and 8.1% (95% CI, 2.5 to 18.0) at 1 year. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 43.1% (95% CI, 29.2 to 56.3) and for grade III and IV, it was 13.7% (95% CI, 6.9 to 27.3). The day +30 complete remission rate for all patients was 88% and was 100% for those treated at 2000 cGy. The overall 1-year survival was 55.5% (95% CI, 40.7 to 68.1). The TMLI/CY/VP16 conditioning regimen is well tolerated at TMLI doses up to 2000 cGy with a low 100-day and 1-year NRM rate and no increased risk of GVHD with higher doses of radiation.

  12. Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma

    PubMed Central

    Terpos, Evangelos; Kanellias, Nikolaos; Christoulas, Dimitrios; Kastritis, Efstathios; Dimopoulos, Meletios A

    2013-01-01

    Multiple myeloma remains an incurable disease despite the introduction of the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib that have improved the outcome of patients with both newly diagnosed and relapsed/refractory disease. However, patients who relapse after treatment with these agents or are refractory to them represent an unmet need and highlight the necessity for the development of novel anti-myeloma agents. Pomalidomide is an IMiD, structurally related to thalidomide, with enhanced antiangiogenic, antineoplastic, and anti-inflammatory properties and exhibiting potent anti-myeloma activity in vitro and in vivo. Pomalidomide has shown remarkable activity in patients who were refractory to both bortezomib and lenalidomide in Phase II and III studies. This paper reviews the chemistry and mechanisms of action of pomalidomide as well as all the available data from clinical trials on pomalidomide use in patients with refractory/relapsed multiple myeloma. PMID:23690693

  13. A relapse of near-fatal thunderstorm-asthma in pregnancy.

    PubMed

    D'Amato, G; Corrado, A; Cecchi, L; Liccardi, G; Stanziola, A; Annesi-Maesano, I; D'Amato, M

    2013-05-01

    Thunderstorm-related asthma is a dramatic example of the allergenic potential of pollen antigens. Pollen allergic patients who encounter the allergenic cloud of pollen during a thunderstorm are at higher risk of having an asthma attack. Relapse is also possible and we describe here the first case of relapse of near fatal thunderstorm-asthma occurred in a 36 years old, 20 weeks pregnant woman affected by seasonal asthma and sensitized to allergens released by Parietariapollen. Patients suffering from pollen allergy should be alerted of the danger of being outdoors during a thunderstorm in the pollen season and if they experienced an episode of severe thunderstorm-related asthma could be at risk of a relapse during a heavy precipitation event.

  14. The next generation of novel therapies for the management of relapsed multiple myeloma.

    PubMed

    Gonsalves, Wilson I; Milani, Paolo; Derudas, Daniel; Buadi, Francis K

    2017-01-01

    The advent of various novel therapies such as immunomodulators and proteasome inhibitors has transformed the treatment paradigm for patients with multiple myeloma (MM). As a result, the overall survival has improved dramatically over the last decade. Despite these advances, MM remains mostly incurable and most patients experience disease relapse after enjoying a period of disease control or remission. Fortunately, the scientific community continues to make strides in developing 'next-generation' therapies for the management of patients with relapsed MM. This review will summarize the efficacy of some of the newest therapeutic agents available for the treatment of patients with relapsed MM after their upfront treatment with the original novel agents such as thalidomide, lenalidomide and bortezomib.

  15. The Ponseti technique and improved ankle dorsiflexion in children with relapsed clubfoot: a retrospective data analysis.

    PubMed

    Marquez, Erika; Pacey, Verity; Chivers, Alison; Gibbons, Paul; Gray, Kelly

    2017-03-01

    This study quantifies the change in passive ankle range of motion following modified Ponseti casting in children with relapsed idiopathic clubfoot. Fifty-three cases (feet) were retrospectively reviewed, with 6-month follow-up data available for 72% of participants. The median improvement in dorsiflexion was 15° (95% confidence interval: 12.5°-17.5°, P≤0.05), with 85% achieving dorsiflexion≥10°. At the 6-month follow-up, dorsiflexion remained significantly improved and 12 feet (32%) presented with subsequent relapse. Nine were referred for further casting and three were recommended for extra-articular surgery. Repeat modified Ponseti management clinically and statistically improves passive ankle dorsiflexion in relapsed idiopathic clubfoot.

  16. Intrastriatal gene delivery of GDNF persistently attenuates methamphetamine self-administration and relapse in mice.

    PubMed

    Yan, Yijin; Miyamoto, Yoshiaki; Nitta, Atsumi; Muramatsu, Shin-Ichi; Ozawa, Keiya; Yamada, Kiyofumi; Nabeshima, Toshitaka

    2013-08-01

    Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. In our well-established mouse models of methamphetamine (Meth) self-administration and reinstatement, bilateral microinjection of adeno-associated virus vectors expressing GDNF (AAV-Gdnf) into the striatum significantly reduced Meth self-administration, without affecting locomotor activity. Moreover, the intrastriatal AAV-Gdnf attenuated cue-induced reinstatement of Meth-seeking behaviour in a sustainable manner. In addition, this manipulation showed that Meth-primed reinstatement of Meth-seeking behaviour was reduced. These findings suggest that the AAV vector-mediated Gdnf gene transfer into the striatum is an effective and sustainable approach to attenuate Meth self-administration and Meth-associated cue-induced relapsing behaviour and that the AAV-mediated Gdnf gene transfer in the brain may be a valuable gene therapy against drug dependence and protracted relapse in clinical settings.

  17. [Current status of the foci and morbidity of tick-borne relapsing fever in Uzbekistan].

    PubMed

    Vasil'eva, I S; Sharipov, M K; Ershova, A S; Mansurov, A A; Mukhitdinov, A G

    1984-01-01

    The contemporary state of settlement nidi of tick-borne relapsing fever is discussed on the material collected in the Namanganskaya and Andizhanskaya regions of Uzbek SSR. Despite the control measures and rise of the sanitary culture of population the conditions are still preserved for the maintenance of nidi. As in ancient estates, classical nidi of tick-borne relapsing fever, so in modern ones there are preserved conditions for existence of flourishing populations of vectors, i.e. favourable habitats and the availability of hosts. The analysis of factors is given affecting the contemporary level of sick-rate with tick-borne relapsing fever. Within the limits of the distribution area of the vector a higher sick-rate should be expected than it is registered.

  18. Relationship of posttreatment decentering and cognitive reactivity to relapse in major depression.

    PubMed

    Fresco, David M; Segal, Zindel V; Buis, Tom; Kennedy, Sydney

    2007-06-01

    Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response was associated with gains in decentering-the ability to observe one's thoughts and feelings as temporary, objective events in the mind-and whether these gains moderated the relationship between mood-linked cognitive reactivity and relapse of major depression. Findings revealed that CBT responders exhibited significantly greater gains in decentering compared with ADM responders. In addition, high post acute treatment levels of decentering and low cognitive reactivity were associated with the lowest rates of relapse in the 18-month follow-up period.

  19. Ofatumumab for a rituximab-allergic child with chronic-relapsing paraneoplastic opsoclonus-myoclonus.

    PubMed

    Pranzatelli, Michael R; Tate, Elizabeth D; Shenoy, Shalini; Travelstead, Anna L

    2012-06-01

    Ofatumumab is a fully human anti-CD20 monoclonal antibody in phase II-III trials for various autoimmune and lymphoreticular diseases. We used it to treat a rituximab-allergic child with severe, chronic-relapsing, opsoclonus-myoclonus syndrome (OMS), characterized by persistent cerebrospinal fluid (CSF) B-cell expansion and T-cell dysregulation. He had relapsed despite chemotherapy, plasma exchange with immunoadsorption, and resection of ganglioneuroblastoma, detected 3 years after OMS onset. The four ofatumumab infusions (1,195 mg/m(2) total dose) were well tolerated, and CSF B-cell expansion was eliminated. No further relapses have occurred in 3 years, but he remains on low-dose ACTH with neuropsychiatric residuals of OMS.

  20. Relapsing peritonitis with Bacillus cereus in a patient on continuous ambulatory peritoneal dialysis.

    PubMed

    Magnussen, Eyð Tausen; Vang, Amanda Gratton; á Steig, Torkil; Gaini, Shahin

    2016-04-26

    We present a case where Bacillus cereus was determined to be the causative agent of relapsing peritonitis in a patient on continuous ambulatory peritoneal dialysis (CAPD). The patient, a 70-year-old man from the Faroe Islands, was admitted with relapsing peritonitis four times over a 3-month period. Peritoneal cultures were positive for growth of B. cereus, a rare bacterial cause of peritonitis. The cultures demonstrated susceptibility to vancomycin, and therefore the patient was treated with intraperitoneal vancomycin, intraperitoneal gentamycin and oral ciprofloxacin. As a result of the relapsing B. cereus peritonitis diagnosis and a CT scan showing contraction of the peritoneum after longstanding inflammation, the peritoneal catheter was removed and the patient converted to haemodialysis. To date, the patient has not been readmitted due to peritonitis. A lack of proper hygiene when changing the dialysis bag was the suspected source of infection with B. cereus.

  1. Emerging therapies for the treatment of relapsed or refractory follicular lymphoma

    PubMed Central

    MacDonald, D.; Prica, A.; Assouline, S.; Christofides, A.; Lawrence, T.; Sehn, L.H.

    2016-01-01

    With no treatment standard having been established for relapsed and refractory follicular lymphoma, a number of therapeutic approaches are used in Canada. In patients who relapse early or who eventually become resistant to subsequent treatment, prognosis is poor, and new approaches are needed. A number of novel therapies are being examined in this setting, including monoclonal antibodies, immunoconjugates, immunomodulatory agents, and signal transduction inhibitors. With the body of evidence for those emerging therapies accumulating and the standard upfront treatment changing from rituximab and chop (cyclophosphamide–doxorubicin–vincristine–prednisone) or rituximab and cvp (cyclophosphamide–vincristine–prednisone) to bendamustine and rituximab, treatment decisions in the relapsed and refractory setting have become more complex. The choice of subsequent treatment must consider type of upfront treatment; duration of remission; and patient-related factors such as age, comorbidities, and treatment preferences. This paper summarizes the evidence for novel therapies and proposes recommendations for subsequent treatment options by remission duration after induction and maintenance. PMID:28050137

  2. Evaluation of relapse prevention and reinforcement interventions to promote exercise adherence in sedentary females.

    PubMed

    Marcus, B H; Stanton, A L

    1993-12-01

    An experimental design was employed to assess the effectiveness of a relapse prevention program, a reinforcement program, and an exercise-only control group in increasing exercise program adherence and short-term maintenance in 120 previously sedentary female university employees. The subjects participated in an 18-week exercise program composed of stretching, calisthenics, and aerobic dance. Attendance during the first half of the program was significantly higher for subjects in the relapse prevention group than for those in the control group. A nonsignificant trend in this direction emerged during the second half of the program and at 2-month follow-up. For all treatment groups, attrition (attendance at less than two thirds of the exercise sessions) was substantial, averaging 72% at the end of the 18-week program. These findings indicate that relapse prevention and reinforcement programs may not assist previously sedentary females in long-term adherence to an exercise program.

  3. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    PubMed Central

    Ramos, Nestor R.; Mo, Clifton C.; Karp, Judith E.; Hourigan, Christopher S.

    2015-01-01

    The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. PMID:25932335

  4. Overlooking evolution: a systematic analysis of cancer relapse and therapeutic resistance research.

    PubMed

    Aktipis, C Athena; Kwan, Virginia S Y; Johnson, Kathryn A; Neuberg, Steven L; Maley, Carlo C

    2011-01-01

    Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms in abstracts has remained at about 1% since the 1980s. However, detailed coding of 22 recent papers revealed a higher proportion of papers using evolutionary methods or evolutionary theory, although this number is still less than 10%. Despite the fact that relapse and therapeutic resistance is essentially an evolutionary process, it appears that this framework has not permeated research. This represents an unrealized opportunity for advances in research on therapeutic resistance.

  5. Chlorambucil dosage in frequently relapsing nephrotic syndrome: a controlled clinical trial.

    PubMed

    Baluarte, H J; Hiner, L; Gruskin, A B

    1978-02-01

    A controlled clinical trial was performed using two dosage regimens of chlorambucil to treat children with frequently relapsing nephrotic syndrome. All children concurrently received prednisone (60 mg/m2 on alternate days). Ten children (Group I) were given chlorambucil as a stable dose (0.2 mg/kg/day) for 56 to 60 days, and 11 children (Group II) received increasing doses (0.2 to 0.63 mg/kg/day) for 42 to 77 days. Two children in each group subsequently relapsed. Follow-up averaged 28.6 and 27.2 months in Groups I and II, respectively. Three children in Group II developed infectious complications. The data indicate that a stable dosage regimen for chlorambucil is as effective as an increasing dose regimen in achieving long-term remission of frequently relapsing nephrotic syndrome.

  6. Akathisia in association with herpes simplex encephalitis relapse and opercular syndrome in children.

    PubMed

    Kocak, Ozan; Yarar, Coskun; Yakut, Ayten; Ekici, Arzu; Yimenicioglu, Sevgi; Saylisoy, Suzan

    2014-02-01

    We report a 2-year-old boy with herpes simplex virus type 1 encephalitis (HSE) and opercular syndrome who presented with clinical relapse characterized by chorea-like involuntary movements that suggest akathisia. The patient initially presented with multiple focal seizures that cause epilepsia partialis continua, polymerase chain reaction (PCR) for herpes simplex virus type 1 was positive. He developed hypersalivation, speech and swallowing difficulties within 30days. Based on these findings the patient was diagnosed as having opercular syndrome due to HSE. He developed akathisia on 44th day of admission as a relapse and he was successfully treated with propranolol. Opercular syndrome might be seen HSE in children and it may cause neurological suquela. Akathisia might be seen after encephalitic process as a symptom of relapse, however diagnosis of akathisia is difficult in young children. It should be noted that because propranolol effective for these involuntary movements. It can be add additional choice of treatment in these patients.

  7. Low-Dose Involved-Field Radiotherapy as Alternative Treatment of Nodular Lymphocyte Predominance Hodgkin's Lymphoma

    SciTech Connect

    Haas, Rick L.M. Girinsky, Theo; Aleman, Berthe; Henry-Amar, Michel; Boer, Jan-Paul de; Jong, Daphne de

    2009-07-15

    Purpose: Nodular lymphocyte predominance Hodgkin's lymphoma is a very rare disease, characterized by an indolent clinical course, with sometimes very late relapses occurring in a minority of all patients. Considerable discussion is ongoing on the treatment of primary and relapsed disease. Patients and Methods: A group of 9 patients were irradiated to a dose of 4 Gy on involved areas only. Results: After a median follow-up of 37 months (range, 6-66), the overall response rate was 89%. Six patients had complete remission (67%), two had partial remission (22%), and one had stable disease (11%). Of 8 patients, 5 developed local relapse 9-57 months after radiotherapy. No toxicity was noted. Conclusion: In nodular lymphocyte predominance Hodgkin's lymphoma, low-dose radiotherapy provided excellent response rates and lasting remissions without significant toxicity.

  8. Toxoplasmic encephalitis relapse rates with pyrimethamine-based therapy: systematic review and meta-analysis.

    PubMed

    Connolly, Mark P; Goodwin, Elizabeth; Schey, Carina; Zummo, Jacqueline

    2017-02-01

    Toxoplasmic encephalitis (TE) is caused by Toxoplasma gondii infection and can be a life-threatening disease in immunocompromised patients. This study evaluated the rate of relapse associated with pyrimethamine-based maintenance therapy (i.e. secondary prophylaxis) in patients with human immunodeficiency virus (HIV) or AIDs treated prior to and after the common use (i.e. 1996) of highly active antiretroviral therapy (HAART) (pre-HAART and post-HAART, respectively). PubMed, Google Scholar, and Cochrane databases were searched to 6 June 2016 using search terms: pyrimethamine, Daraprim, Fansidar, Metakelfin, Fansimef, 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine, encephalitis, cerebral, toxoplasmosis, toxoplasmic, and gondii. Single-arm cohort, retrospective, and randomized studies were included. Twenty-six studies with 1,596 patients were included in the analysis; twenty pre-HAART (n = 1,228) studies and six post-HAART (n = 368) were performed. Pooled proportions test for pyrimethamine-based therapy from pre-HAART studies indicated a relapse rate of 19.2% and 18.9% from the fixed-effects and random-effects models, respectively. The relapse rate in the post-HAART studies was 11.1% (fixed and random effects). Continuous therapy was suggestive of lower incidence of relapse compared with intermittent therapy in the pre-HAART era (range, 18.7 to 17.3% vs. 20.9 to 25.6%, respectively). These findings indicate that the likelihood of relapse associated with pyrimethamine-based therepy in patients with HIV and TE decreased after the introduction of HAART to approximately 11%. The findings have important implications as relapse may affect a patient's disease severity and prognosis, increase utilization of health care resources, and result in additional health care expenditure.

  9. Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era

    PubMed Central

    Gisselbrecht, Christian; Glass, Bertram; Mounier, Nicolas; Singh Gill, Devinder; Linch, David C.; Trneny, Marek; Bosly, Andre; Ketterer, Nicolas; Shpilberg, Ofer; Hagberg, Hans; Ma, David; Brière, Josette; Moskowitz, Craig H.; Schmitz, Norbert

    2010-01-01

    Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001). Conclusion In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP. PMID:20660832

  10. Predicting the future relapse of alcohol-dependent patients from structural and functional brain images.

    PubMed

    Seo, Sambu; Mohr, Johannes; Beck, Anne; Wüstenberg, Torsten; Heinz, Andreas; Obermayer, Klaus

    2015-11-01

    In alcohol dependence, individual prediction of treatment outcome based on neuroimaging endophenotypes can help to tailor individual therapeutic offers to patients depending on their relapse risk. We built a prediction model for prospective relapse of alcohol-dependent patients that combines structural and functional brain images derived from an experiment in which 46 subjects were exposed to alcohol-related cues. The patient group had been subdivided post hoc regarding relapse behavior defined as a consumption of more than 60 g alcohol for male or more than 40 g alcohol for female patients on one occasion during the 3-month assessment period (16 abstainers and 30 relapsers). Naïve Bayes, support vector machines and learning vector quantization were used to infer prediction models for relapse based on the mean and maximum values of gray matter volume and brain responses on alcohol-related cues within a priori defined regions of interest. Model performance was estimated by leave-one-out cross-validation. Learning vector quantization yielded the model with the highest balanced accuracy (79.4 percent, p < 0.0001; 90 percent sensitivity, 68.8 percent specificity). The most informative individual predictors were functional brain activation features in the right and left ventral tegmental areas and the right ventral striatum, as well as gray matter volume features in left orbitofrontal cortex and right medial prefrontal cortex. In contrast, the best pure clinical model reached only chance-level accuracy (61.3 percent). Our results indicate that an individual prediction of future relapse from imaging measurement outperforms prediction from clinical measurements. The approach may help to target specific interventions at different risk groups.

  11. Uric acid in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

    PubMed

    Moccia, Marcello; Lanzillo, Roberta; Costabile, Teresa; Russo, Cinzia; Carotenuto, Antonio; Sasso, Gabriella; Postiglione, Emanuela; De Luca Picione, Carla; Vastola, Michele; Maniscalco, Giorgia Teresa; Palladino, Raffaele; Brescia Morra, Vincenzo

    2015-01-01

    Uric acid (UA) is reduced in multiple sclerosis (MS), and possibly relates to MS outcomes, with lower UA levels in subjects experiencing a relapse or presenting higher disability scores. The present retrospective longitudinal study evaluated UA variations in MS, in relation to clinical relapses, disability progression, and cognitive functions. We included 141 subjects with relapsing-remitting MS (RRMS) and performed expanded disability status scale (EDSS), symbol digit modalities test (SDMT) and UA evaluation at baseline visit and after 2-year follow-up. Paired t test showed significantly lower UA levels after 2-year follow-up than at baseline (3.987 ± 1.135 and 4.167 ± 1.207 mg/dL, respectively) (p = 0.001). The difference in UA levels between 2-year follow-up and baseline related to EDSS sustained progression (p < 0.001; OR = 0.099), and presented a trend for clinical relapses at logistic regression (p = 0.211; OR = 0.711) and for the time to relapse at Cox regression (p = 0.236; HR = 0.792). Analysis of variance showed reduced baseline UA levels in subjects with impaired SDMT at baseline (p = 0.045; adjusted R(2) = 0.473) and after 2-year follow-up (p = 0.034; adjusted R(2) = 0.470). This is the first study showing a progressive reduction of UA levels during the course of RRMS, suggesting a progressive decrease of antioxidant reserves, in relation to relapse risk, disability progression and cognitive function.

  12. High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.

    PubMed

    Aurer, Igor; Nemet, Damir; Mitrović, Zdravko; Dujmović, Dino; Bašić-Kinda, Sandra; Radman, Ivo; Sertić, Dubravka; Šantek, Fedor; Kralik, Marko; Dotlić, Snježana; Mazić, Sanja; Labar, Boris

    2016-06-01

    Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options.

  13. Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse.

    PubMed

    Morin, Charles M; Bélanger, Lynda; Bastien, Célyne; Vallières, Annie

    2005-01-01

    Discontinuation of benzodiazepine (BZD) treatment for insomnia can be a difficult task. Cognitive-behavior therapy (CBT) for insomnia, combined with a supervised medication taper, can facilitate withdrawal but there is limited evidence on long-term outcome after discontinuation. The objective of this study was to examine medication-free survival time and predictors of relapse (i.e., resumed BZD hypnotics) over a 2-year period in 47 older adults (mean age 62.1 years) with persistent insomnia and prolonged BZD use (average duration of 18.9 years), who had successfully discontinued BZD following CBT for insomnia, a supervised medication taper program, or a combined approach. The Kaplan-Meier product-limit method was used to estimate survival time, defined as time between end-of-treatment and relapse or end of follow-up. By the end of the 24-month follow-up, 42.6% of the samples had resumed BZD use. Participants in the Combined (33.3%) and Taper (30.8%) groups relapsed significantly less than their counterparts from the CBT group (69.2%). Survival rates at 3 months were 61.5% (CBT), 100% (Taper), and 80.9% (Combined). At 12 months, they were 38.5%, 83.3%, and 70.8%, respectively; and, at 24 months, they were 28.9%, 64.8% and 64.9%, respectively. Mean survival time was significantly longer for both the Taper (18.6 months, SE = 2.1) and Combined groups (12.6 months, SE = 1.4), relative to the CBT group (8.5 months, SE = 1.8). Significant predictors of relapse included treatment condition, end of treatment insomnia severity, and psychological distress. In conclusion, there is a substantial relapse rate following BZD discontinuation among prolonged users. CBT booster sessions might enhance compliance with CBT and prove useful in preventing relapse.

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

    PubMed Central

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

    2016-01-01

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

  15. Cryptococcal meningoencephalitis relapse after an eight-year delay: an interplay of infection and immune reconstitution.

    PubMed

    Katchanov, Juri; Blechschmidt, Cristiane; Nielsen, Kirsten; Branding, Gordian; Arastéh, Keikawus; Tintelnot, Kathrin; Meintjes, Graeme; Boulware, David R; Stocker, Hartmut

    2015-10-01

    We report a case of a symptomatic relapse of HIV-related cryptococcal meningoencephalitis eight years after the first diagnosis on the background of immune reconstitution. The findings as well as the clinical course suggests a combination of smouldering localised infection and enhanced inflammatory reaction related to immune restoration due to antiretroviral therapy. A combination of antifungal and anti-inflammatory therapy resulted in clinical and radiological improvement. Our case challenges the concept that immune reconstitution inflammatory syndrome and microbiological relapse are dichotomous entities.

  16. Epidural analgesia and cesarean delivery in multiple sclerosis post-partum relapses: the Italian cohort study

    PubMed Central

    2012-01-01

    Background Few studies have systematically addressed the role of epidural analgesia and caesarean delivery in predicting the post-partum disease activity in women with Multiple Sclerosis (MS). The objective of this study was to assess the impact of epidural analgesia (EA) and caesarean delivery (CD) on the risk of post-partum relapses and disability in women with MS. Methods In the context of an Italian prospective study on the safety of immunomodulators in pregnancy, we included pregnancies occurred between 2002 and 2008 in women with MS regularly followed-up in 21 Italian MS centers. Data were gathered through a standardized, semi-structured interview, dealing with pregnancy outcomes, breastfeeding, type of delivery (vaginal or caesarean) and EA. The risk of post-partum relapses and disability progression (1 point on the Expanded Disability Status Sclae, EDSS, point, confirmed after six months) was assessed through a logistic multivariate regression analysis. Results We collected data on 423 pregnancies in 415 women. Among these, 349 pregnancies resulted in full term deliveries, with a post-partum follow-up of at least one year (mean follow-up period 5.5±3.1 years). One hundred and fifty-five patients (44.4%) underwent CD and 65 (18.5%) EA. In the multivariate analysis neither CD, nor EA were associated with a higher risk of post-partum relapses. Post-partum relapses were related to a higher EDSS score at conception (OR=1.42; 95% CI 1.11-1.82; p=0.005), a higher number of relapses in the year before pregnancy (OR=1.62; 95% CI 1.15-2.29; p=0.006) and during pregnancy (OR=3.07; 95% CI 1.40-6.72; p=0.005). Likewise, CD and EA were not associated with disability progression on the EDSS after delivery. The only significant predictor of disability progression was the occurrence of relapses in the year after delivery (disability progression in the year after delivery: OR= 4.00; 95% CI 2.0-8.2; p<0.001; disability progression over the whole follow-up period: OR= 2.0; 95

  17. Relapsing inappropriate antidiuretic hormone secretion in an anti-aquaporin-4 antibody positive paediatric patient.

    PubMed

    Kravljanac, Ruzica; Martinović, Vanja; Dujmović, Irena; Djurić, Milena; Kuzmanović, Miloš; Weinshenker, Brian G; Drulović, Jelena

    2014-09-01

    Paediatric patients with the syndrome of an inappropriate antidiuretic hormone secretion (SIADH), as a manifestation of inflammatory demyelinating disorders of the central nervous system, have been rarely described until now, in only a few cases of neuromyelitis optica spectrum disorders (NMOSDs). We present a case of relapsing SIADH associated with NMOSD, in an anti-aquaporin-4 antibody positive 14-year-old girl, who is, to our best knowledge, the first reported paediatric patient with relapsing SIADH and NMOSD. Additionally, our case further supports the notion that paediatric encephalomyelitis associated with SIADH should suggest the diagnosis of NMOSD.

  18. Intracerebral Stem Cell Administration Inhibits Relapse-like Alcohol Drinking in Rats.

    PubMed

    Israel, Yedy; Ezquer, Fernando; Quintanilla, María Elena; Morales, Paola; Ezquer, Marcelo; Herrera-Marschitz, Mario

    2017-01-01

    Study describes the blockade of relapse-like alcohol drinking by mesenchymal stem cells (MSCs). High alcohol-intake bred rats consumed alcohol for 3 months and were subjected to repeated alcohol deprivations for 7-14 days, followed by alcohol reaccess. Upon reaccess, animals consumed 2.2 g alcohol/kg in 60 minutes. A single intra-cerebroventricular MSC administration inhibited relapse-like drinking up to 80-85% for 40 days (P < 0.001). An alcohol-use-disorder was prevented.

  19. Killing the hypnozoite – drug discovery approaches to prevent relapse in Plasmodium vivax

    PubMed Central

    Campo, Brice; Vandal, Omar; Wesche, David L.; Burrows, Jeremy N.

    2015-01-01

    The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse. PMID:25891812

  20. Response to pazopanib in two pediatric patients with pretreated relapsing synovial sarcoma.

    PubMed

    Casanova, Michela; Basso, Eleonora; Magni, Chiara; Bergamaschi, Luca; Chiaravalli, Stefano; Carta, Roberto; Tirtei, Elisa; Massimino, Maura; Fagioli, Franca; Ferrari, Andrea

    2017-01-21

    Pazopanib is an oral multikinase inhibitor that has proved effective in adults treated for relapsing soft tissue sarcoma and synovial sarcoma in particular. Two cases are reported here of pediatric patients with pretreated relapsing synovial sarcoma whose tumors showed a prolonged response to pazopanib given on compassionate grounds. These results suggest that new agents found effective in adult patients might achieve similar results in adolescents with the same disease. Facilitating the availability of new drugs for children and adolescents is a major challenge for pediatric oncologists.

  1. Levamisole therapy in children with frequently relapsing and steroid-dependent nephrotic syndrome: a single-center experience

    PubMed Central

    Kuźma-Mroczkowska, Elżbieta; Pańczyk-Tomaszewska, Małgorzata

    2016-01-01

    Introduction Numerous studies suggest that levamisole, an antihelmintic agent with an immunomodulatory effect, reduces the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome (FRNS/SDNS). The aim of the study was to present a single center’s experience in treatment of FRNS and SDNS with levamisole. Material and methods Among 72 children with FRNS/SDNS treated in our department with levamisole in the years 1984-2011 we studied in detail 53 patients (mean age: 6.5 ±3.0 years), in whom the medication was administered for at least 6 months. In these 53 patients we evaluated: the course of the disease before levamisole, the renal biopsy result, medications used, prednisone dose on levamisole initiation, duration of levamisole treatment, time to first relapse and number of relapses on levamisole, and levamisole side effects. Results The duration of nephrotic syndrome was 3.4 ±2.9 years, and the number of relapses before levamisole treatment was 6.0 ±3.4. The dose of prednisone on initiation of levamisole treatment was 1.2 ±0.6 mg/kg/24 h, and the duration of levamisole treatment was 15.0 ±7.3 months. During levamisole treatment proteinuria relapsed in 34/53 (64.2%) children, and the time to first relapse was 8.8 ±8.1 months. During levamisole therapy relapses of the disease decreased significantly (2.7 ±2.0 vs. 1.8 ±2.1 relapses/year, p = 0.02). Time to first relapse correlated with total number of relapses (R = –0.59, p < 0.001) and number of relapses in one year during levamisole treatment (R = –0.60, p < 0.001). Conclusions Levamisole is effective in reducing the number of relapses in children with frequently relapsing and steroid-dependent nephrotic syndrome. Early relapse of proteinuria on levamisole treatment in children with FRNS/SDNS suggests low efficacy of further treatment. PMID:27833440

  2. NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Porter, David L.; Alyea, Edwin P.; Antin, Joseph H.; DeLima, Marcos; Estey, Eli; Falkenburg, J.H. Frederik; Hardy, Nancy; Kroeger, Nicolaus; Leis, Jose; Levine, John; Maloney, David G.; Peggs, Karl; Rowe, Jacob M.; Wayne, Alan S.; Giralt, Sergio; Bishop, Michael R.; van Besien, Koen

    2010-01-01

    Relapse is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT). Treatment options for relapse have been inadequate and the majority of patients ultimately die of their disease. There is no standard approach to treating relapse after alloHSCT. Withdrawal of immune suppression and donor lymphocyte infusions (DLI) are commonly used for all diseases; although these interventions are remarkably effective for relapsed CML, they have limited efficacy in other hematologic malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective. As such there is an immediate need for well designed, disease-specific trials for treatment of relapse after alloHSCT. This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner. In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT. PMID:20699125

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

    DTIC Science & Technology

    2015-07-01

    confer proliferative advantage to a distinct cell population and contribute to that population’s capability to successfully breach innate anticancer...immune response, multiple types of the cells are involved within innate and adaptive immune ‘arm’ with some cells (e.g. DCs and the NK cells...Drive, Bethesda, MD 20892–3375, USA, 8Department of Life Sciences, Tzu-Chi University, Hualien 970, Taiwan, 9Department of Microbiology and Immunology

  4. Current imaging follow-up of non-Hodgkin lymphoma exposes patients to significant radiation but does not detect asymptomatic relapses.

    PubMed

    Riva, Eloisa; Oliver, Carolina; Pérez, Maria del Carmen; Telis, Osmar; Díaz, Lilian; Mikhael, Joseph R

    2016-01-01

    The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6-12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL.

  5. Taxonomy of high-risk situations for alcohol relapse: evolution and development of a cognitive-behavioral model.

    PubMed

    Marlatt, G A

    1996-12-01

    The purpose of this paper is to provide an historical overview of the development of the taxonomy of high-risk situations for relapse in patients receiving abstinence-based treatment for alcoholism. Research conducted during the 1970s on determinants of relapse is briefly reviewed, beginning with a preliminary analysis of relapse patterns in alcoholics treated with aversion therapy. Theoretical foundations underlying the development of the taxonomy are then discussed with an emphasis on social-learning theory and its implications for cognitive-behavioral interventions for relapse prevention. Findings supporting the efficacy of coping-skills training for high-risk relapse situations, based on a prospective treatment outcome study for inpatient alcoholics, are also presented in support of the clinical validity of the relapse model. The paper concludes with a description of the refined and extended taxonomy of high-risk situations and the associated cognitive-behavioral model of relapse described in the Marlatt & Gordon (1985) text on relapse prevention.

  6. Relapse of Extinguished Fear after Exposure to a Dangerous Context Is Mitigated by Testing in a Safe Context

    ERIC Educational Resources Information Center

    Goode, Travis D.; Kim, Janice J.; Maren, Stephen

    2015-01-01

    Aversive events can trigger relapse of extinguished fear memories, presenting a major challenge to the long-term efficacy of therapeutic interventions. Here, we examined factors regulating the relapse of extinguished fear after exposure of rats to a dangerous context. Rats received unsignaled shock in a distinct context ("dangerous"…

  7. Implicit and Explicit Drug-Related Cognitions during Detoxification Treatment Are Associated with Drug Relapse: An Ecological Momentary Assessment Study

    ERIC Educational Resources Information Center

    Marhe, Reshmi; Waters, Andrew J.; van de Wetering, Ben J. M.; Franken, Ingmar H. A.

    2013-01-01

    Objective: Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments, we examined whether craving and cognitions assessed during drug detoxification treatment were associated with…

  8. Fluoxetine Treatment for Prevention of Relapse of Depression in Children and Adolescents: A Double-Blind, Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Heiligenstein, John H.; Hoog, Sharon L.; Wagner, Karen Dineen; Findling, Robert L.; McCracken, James T.; Nilsson, Mary E.; Jacobson, Jennie G.

    2004-01-01

    Objective: To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of [less than or equal to]28 during treatment with fluoxetine 20 to 60 mg. Method: In this 32-week relapse-prevention phase of a…

  9. Reducing Relapse and Recurrence in Unipolar Depression: A Comparative Meta-Analysis of Cognitive-Behavioral Therapy's Effects

    ERIC Educational Resources Information Center

    Vittengl, Jeffrey R.; Clark, Lee Anna; Dunn, Todd W.; Jarrett, Robin B.

    2007-01-01

    Relapse and recurrence following response to acute-phase treatment for major depressive disorder (MDD) are prevalent and costly. In a meta-analysis of 28 studies including 1,880 adults, the authors reviewed the world's published literature on cognitive-behavioral therapies (CT) aimed at preventing relapse-recurrence in MDD. Results indicate that…

  10. MRD detection of leukemia relapse using HLA typing by FACS in combination with FISH after mismatched allogeneic stem cell transplantation.

    PubMed

    Miyachi, Mitsuru; Watanabe, Eri; Watanabe, Nobukazu; Tsuma, Yusuke; Kawashima-Goto, Sachiko; Tamura, Shinichi; Imamura, Toshihiko; Ishida, Hiroyuki; Hosoi, Hajime

    2014-08-01

    Loss of mismatched HLA is a cause of relapse following HLA-mismatched allo-SCT. We directly detected the loss of mismatched HLA alleles in relapsed leukemic cells at a MRD level using HLA typing by multicolor FACS (HLA-Flow) in combination with FISH in the BM of two patients with MLL-AF9-positive AML, at 6 and 10 months after mismatched allo-SCT. HLA-Flow with FISH analysis detected relapsed leukemic cells not expressing a mismatched HLA allele and harboring the MLL rearrangement. Simultaneously, real-time quantitative RT-PCR detected a low copy number of MLL-AF9 transcripts, consistent with MRD detection. HLA-Flow with FISH is a powerful method for detecting molecular relapse after mismatched allo-SCT and provides important information on the HLA expression status of the relapsed leukemic cells to help determine the next intervention.

  11. A clofarabine-based bridging regimen in patients with relapsed ALL and persistent minimal residual disease (MRD).

    PubMed

    Gossai, N; Verneris, M R; Karras, N A; Gorman, M F; Patel, N J; Burke, M J

    2014-03-01

    In patients with relapsed ALL, minimal residual disease (MRD) identified prior to allogeneic hematopoietic cell transplantation (HCT) is a strong predictor of relapse. We report our experience using a combination of reduced-dosing clofarabine, CY and etoposide as a 'bridge' to HCT in eight patients with high risk or relapsed ALL and pre-HCT MRD. All patients had detectable MRD (>0.01%, flow cytometry) at the start of therapy with all eight achieving MRD reduction following one cycle. The regimen was well tolerated with seven grade 3/4 toxicities occurring among four of the eight patients. Five patients (62.5%) are alive, one died from relapse (12.5%) and two from transplant-related mortality (25%). The combination of reduced-dose clofarabine, CY and etoposide as bridging therapy appears to be well tolerated in patients with relapsed ALL and is effective in reducing pre-HCT MRD.

  12. A novel relapsing fever Borrelia sp. infects the salivary glands of the molted hard tick, Amblyomma geoemydae.

    PubMed

    Takano, Ai; Sugimori, Chieko; Fujita, Hiromi; Kadosaka, Teruki; Taylor, Kyle R; Tsubota, Toshio; Konnai, Satoru; Tajima, Tomoko; Sato, Kozue; Watanabe, Haruo; Ohnishi, Makoto; Kawabata, Hiroki

    2012-09-01

    A novel relapsing fever Borrelia sp. was found in Amblyomma geoemydae in Japan. The novel Borrelia sp. was phylogenetically related to the hard (ixodid) tick-borne relapsing fever Borrelia spp. Borrelia miyamotoi and B. lonestari. The novel relapsing fever Borrelia sp. was detected in 39 A. geoemydae (39/274: 14.2%), of which 14 (14/274: 5.1%) were co-infected with the novel relapsing fever Borrelia sp. and Borrelia sp. tAG, one of the reptile-associated borreliae. Transstadial transmission of the novel relapsing fever Borrelia sp. occurred in the tick midgut and the salivary glands, although Borrelia sp. tAG was only detected in the tick midgut. The difference of the borrelial niche in molted ticks might be associated with borrelial characterization.

  13. Prognostic relevance of DHAP dose-density in relapsed Hodgkin lymphoma: an analysis of the German Hodgkin-Study Group.

    PubMed

    Sasse, Stephanie; Alram, Magdalena; Müller, Horst; Smardová, Lenka; Metzner, Bernd; Doehner, Hartmut; Fischer, Thomas; Niederwieser, Dietger W; Schmitz, Norbert; Schäfer-Eckart, Kerstin; Raemaekers, John M M; Schmalz, Oliver; Tresckow, Bastian V; Engert, Andreas; Borchmann, Peter

    2016-05-01

    Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in relapsed HL. In order to assess the prognostic relevance of DHAP dose density, we performed a retrospective multivariate analysis of the HDR2 trial (N=266). In addition to four risk factors (early or multiple relapse, stage IV disease or anemia at relapse, and grade IV hematotoxicity during the first cycle of DHAP) a delayed start of the second cycle of DHAP>day 22 predicted a significantly poorer progression-free survival (PFS, p=0.0356) and overall survival (OS, p=0.0025). In conclusion, our analysis strongly suggests that dose density of DHAP has a relevant impact on the outcome of relapsed HL patients.

  14. Effects of Interventions on Relapse to Narcotics Addiction: An Event-History Analysis.

    ERIC Educational Resources Information Center

    Hser, Yih-Ing; And Others

    1995-01-01

    Event-history analysis was applied to the life history data of 581 male narcotics addicts to specify the concurrent, postintervention, and durational effects of social interventions on relapse to narcotics use. Results indicate the advisability of supporting methadone maintenance with other prevention strategies. (SLD)

  15. Attributions for Long-Term Maintenance of Smoking Cessation or Relapse.

    ERIC Educational Resources Information Center

    Epstein, Jennifer A.; And Others

    A previous study examined determinants of attributions for success or failure in stopping smoking in a self-help treatment program with and without a drug component. This follow-up study examined the attributions that successful quitters made after remaining abstinent through 12 months, or after they relapsed. Subjects (N=137) had been assigned to…

  16. Relapsing fetal bilateral hydrothorax, an isolated expression of a vein of Galen aneurysmal malformation

    PubMed Central

    Mannaerts, Dominique; Muys, Joke; Ramaekers, Paul; Jacquemyn, Yves

    2015-01-01

    We report a case of bilateral fetal hydrothorax presenting at 20 weeks of pregnancy, spontaneously resolving at 22 weeks and severely relapsing at 28 weeks in a fetus with normal karyotype. The cause was a high-output heart failure caused by vein of Galen malformation. PMID:25628327

  17. Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

    2009-01-01

    This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

  18. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted.

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

    PubMed

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

    2017-06-01

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

  20. Relapse after orthodontic correction of maxillary median diastema: a follow-up evaluation of consecutive cases.

    PubMed

    Shashua, D; Artun, J

    1999-06-01

    An evaluation of 96 treated orthodontic patients with maxillary median diastema ranging from 0.50 mm to 5.62 mm (mean 1.22, SD 0.85) was performed 4.0 to 9.0 years after completion of active treatment. Pre- and posttreatment data were gathered from available records. Follow-up data were gathered from records and interviews of 37 patients, and from phone interviews of 59 patients. The incidence of diastema relapse was 49% when scored as either presence of a measurable space at follow-up, a history of orthodontic or prosthetic retreatment to close a reopened space, or continued use of a retainer to control relapse tendency. Logistic regression analysis revealed that pretreatment diastema size and presence of a family member with a similar condition were the only significant risk factors for relapse (p<0.05), while pretreatment spacing in the maxillary anterior dentition approached significance (p = 0.10). No association was found between relapse and presence of an abnormal frenum or an osseous intermaxillary cleft, although patients with an abnormal frenum had a wider pretreatment diastema than those with a normal frenum (p<0.05). Fremitus of the maxillary incisors was the only parameter at follow-up associated with space reopening (p<0.01).

  1. Neuronal Substrates of Relapse to Cocaine-Seeking Behavior: Role of Prefrontal Cortex

    ERIC Educational Resources Information Center

    Rebec, George V.; Sun, WenLin

    2005-01-01

    The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc),…

  2. Neuropsychological Impairment and Relapse Following Inpatient Detoxification in Severe Alcohol Dependence

    ERIC Educational Resources Information Center

    Morrison, Fraser

    2011-01-01

    The aim of the study was to examine the relationship between neuropsychological impairment in severe alcohol dependence and relapse. This was assessed following inpatient detoxification over a period of three months. Participants were tested on measures of neuropsychological functioning at the end of a seven to ten day stay in an inpatient alcohol…

  3. Behavioral momentum and relapse of ethanol seeking: nondrug reinforcement in a context increases relative reinstatement.

    PubMed

    Pyszczynski, Adam D; Shahan, Timothy A

    2011-02-01

    Drug-related stimuli seem to contribute to the persistence of drug seeking and relapse. Behavioral momentum theory is a framework for understanding how the discriminative-stimulus context in which operant behavior occurs governs the persistence of that behavior. The theory suggests that both resistance to change and relapse are governed by the Pavlovian stimulus-reinforcer relation between a stimulus context and all sources of reinforcement obtained in that context. This experiment examined the role of the Pavlovian stimulus-reinforcer relation in reinstatement of ethanol seeking of rats by including added response-independent nondrug reinforcement in the self-administration context. Although rates of ethanol-maintained responding were lower in a context with added nondrug reinforcement than a context with ethanol alone, relative resistance to extinction and relative reinstatement were greater in the context previously associated with the nondrug reinforcer. Thus, both relative resistance to extinction and relative relapse of ethanol seeking depended on the Pavlovian stimulus-reinforcer relation between a context and all sources of reinforcement in that context. These findings suggest that to understand how drug-related contexts contribute to relapse, it may be necessary to consider not only the history of drug reinforcement in a context, but also the wide variety of other reinforcers obtained in such contexts.

  4. Treatment options for relapse after autograft in multiple myeloma - report from an EBMT educational meeting.

    PubMed

    Garderet, Laurent; Cook, Gordon; Auner, Holger W; Bruno, Benedetto; Lokhorst, Henk; Perez-Simon, Jose Antonio; Sahebi, Firoozeh; Scheid, Christof; Morris, Curly; van Biezen, Anja; Sobh, Mohamad; Michallet, Mauricette; Gahrton, Gösta; Schönland, Stefan; Kröger, Nicolaus

    2017-04-01

    Major improvements have been made in the treatment of myeloma. However, all patients, perhaps with some exceptions, eventually relapse, even after autologous stem cell transplantation (ASCT). In that setting, the combinations of new drugs, namely the IMiDs and the proteasome inhibitors along with steroids, give encouraging results in relapsed patients. The median progression-free survival (PFS) is 20 months with lenalidomide plus dexamethasone plus ixazomib and 26 months with lenalidomide plus dexamethasone plus carfilzomib. Monoclonal antibodies have emerged as an additional new treatment option. The antibody anti-SLAMF7, elotuzumab, in combination with lenalidomide plus dexamethasone gives a median PFS of 20 months. The antibody daratumumab, targeting CD38, alone has an outstanding activity in previously heavily treated patients. Its use in combination is ongoing. Transplantation remains a major treatment option. For patients who relapse at least 18 months from the initial ASCT, a second ASCT can be performed with an expected time to progression of 19 months from the time of transplantation. For patients relapsing earlier and/or with high-risk characteristics and who are still chemosensitive, with a suitable donor, an allogeneic transplantation can be considered. The optimal treatment combination and sequence remain to be determined.

  5. Cognitive Reactivity, Dysfunctional Attitudes, and Depressive Relapse and Recurrence in Cognitive Therapy Responders

    PubMed Central

    Jarrett, Robin B.; Minhajuddin, Abu; Borman, Patricia D.; Dunlap, Lauren; Segal, Zindel V.; Kidner, Cindy L.; Friedman, Edward S.; Thase, Michael E.

    2012-01-01

    Dysfunctional attitudes can foreshadow depressive relapse/recurrence. Priming mood, through induction paradigms, is hypothesized to activate dysfunctional attitudes. Cognitive reactivity (CR) refers to mood-linked increases in dysfunctional attitudes after priming. Here we explored the extent to which CR as well as residual, unprimed, dysfunctional attitudes predicted depressive relapse/recurrence among depressed patients who responded to acute phase cognitive therapy (CT). Consenting adults, aged 18–70, with recurrent major depressive disorder (n = 523) participated in a two-site randomized controlled trial examining the durability of continuation phase treatments. Patients received 16–20 sessions of CT. Among the 245 incompletely remitted responders, 213 agreed to undergo a mood induction paradigm. After 8 months of continuation phase treatments, participants were followed an additional 24 months. Although the mood induction significantly lowered mood in 80% of responders, the expected CR was not evident. By contrast, higher unprimed dysfunctional attitudes following CT did predict relapse/recurrence over 20 and 32 months post randomization. The findings of this large longitudinal study of incompletely remitted CT responders challenge the notion that it is necessary to prime mood in order to maximize dysfunctional attitudes’ prediction of relapse and/or recurrence. While findings cannot be generalized beyond CT responders, they emphasize the clinical importance of reducing dysfunctional attitudes in preventing depression. PMID:22445946

  6. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin's lymphoma.

    PubMed

    Herbaux, Charles; Gauthier, Jordan; Brice, Pauline; Drumez, Elodie; Ysebaert, Loic; Doyen, Hélène; Fornecker, Luc; Bouabdallah, Krimo; Manson, Guillaume; Ghesquières, Hervé; Tabrizi, Reza; Hermet, Eric; Lazarovici, Julien; Thiebaut-Bertrand, Anne; Chauchet, Adrien; Demarquette, Hélène; Boyle, Eileen; Houot, Roch; Yakoub-Agha, Ibrahim; Morschhauser, Franck

    2017-03-07

    Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed and refractory Hodgkin lymphoma (HL). While long-term disease control can be achieved, relapse remains frequent. The programmed death 1 (PD-1) blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in relapsed and refractory HL who did not receive allo-HCT. However, PD-1-blocking strategy can increase the risk of Graft Versus Host Disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in six patients (30%) after nivolumab initiation. All six patients had prior history of acute GVHD. These nivolumab-induced GVHD were managed by standard treatment of acute GVHD. Two patients died of GVHD, one of progressive disease and one of the complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, one-year progression-free and overall survival rates were 58.2% [95%CI, 33.1 - 76.7] and 78.7% [95%CI, 52.4 - 91.5], respectively. Among 13 patients still in response, six received a single dose of nivolumab and seven remain on nivolumab. Compared to standard options in this indication, our results show that nivolumab is effective with an acceptable safety profile.

  7. Disseminated histoplasmosis and aids: relapse and late mortality in endemic area in North-Eastern Brazil.

    PubMed

    Dasmasceno, Lisandra Serra; Novaes, Alberto Ramos; Alencar, Carlos Henrique Morais; Lima, Daniel Teixeira; Sidrim, José Júlio Costa; Gonçalves, Maria Vânia Freitas; de Mesquita, Jacó Ricarte Lima; Leitão, Terezinha do Menino Jesus Silva

    2013-09-01

    The State of Ceará in north-eastern Brazil has one of the highest rates in the world of relapse and death due to disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients. The objective of this study is to characterise the relapse and mortality of DH in AIDS cases residents in Ceará. We performed a retrospective analysis of the medical records of AIDS patients who had a first episode of DH from 2002 to 2008. We analysed the outcomes until December 31, 2010. A total of 145 patients participated in the study. The mean clinical follow-up duration was 3.38 years (SD = 2.2; 95% CI = 3.01-3.75). The majority of the subjects were male with a mean age of 35 years (SD = 2.2; 95% CI = 3.01-3.75) and were born in the capital of Ceará. DH was the first manifestation of AIDS in 59% of the patients. The relapse rate was 23.3%, with a disseminated presentation in 90% of these patients. The overall mortality during the study period was 30.2%. The majority of patients who relapsed or died had irregular treatment with antifungals or highly active antiretroviral therapy and did not have active clinical follow-up. High rates of recurrence and mortality were found in AIDS-associated DH in this area of the country.

  8. Effects of signaled and unsignaled alternative reinforcement on persistence and relapse in children and pigeons.

    PubMed

    Nevin, John A; Mace, F Charles; DeLeon, Iser G; Shahan, Timothy A; Shamlian, Kenneth D; Lit, Keith; Sheehan, Tara; Frank-Crawford, Michelle A; Trauschke, Stephanie L; Sweeney, Mary M; Tarver, Danielle R; Craig, Andrew R

    2016-07-01

    Three experiments explored the impact of different reinforcer rates for alternative behavior (DRA) on the suppression and post-DRA relapse of target behavior, and the persistence of alternative behavior. All experiments arranged baseline, intervention with extinction of target behavior concurrently with DRA, and post-treatment tests of resurgence or reinstatement, in two- or three-component multiple schedules. Experiment 1, with pigeons, arranged high or low baseline reinforcer rates; both rich and lean DRA schedules reduced target behavior to low levels. When DRA was discontinued, the magnitude of relapse depended on both baseline reinforcer rate and the rate of DRA. Experiment 2, with children exhibiting problem behaviors, arranged an intermediate baseline reinforcer rate and rich or lean signaled DRA. During treatment, both rich and lean DRA rapidly reduced problem behavior to low levels, but post-treatment relapse was generally greater in the DRA-rich than the DRA-lean component. Experiment 3, with pigeons, repeated the low-baseline condition of Experiment 1 with signaled DRA as in Experiment 2. Target behavior decreased to intermediate levels in both DRA-rich and DRA-lean components. Relapse, when it occurred, was directly related to DRA reinforcer rate as in Experiment 2. The post-treatment persistence of alternative behavior was greater in the DRA-rich component in Experiment 1, whereas it was the same or greater in the signaled-DRA-lean component in Experiments 2 and 3. Thus, infrequent signaled DRA may be optimal for effective clinical treatment.

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

    PubMed Central

    Cohan, Stanley

    2016-01-01

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

  10. Treating relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: liposome-encapsulated vincristine

    PubMed Central

    Davis, Tyler; Farag, Sherif S

    2013-01-01

    Acute lymphoblastic leukemia (ALL) remains a disease with poor outcomes in adults. While induction chemotherapy achieves a complete remission in almost 90% of patients, the majority will relapse and die of their disease. Relapsed ALL is associated with a high reinduction mortality and chemotherapy resistance, with allogeneic hematopoietic stem cell transplantation offering the only therapy with curative potential. However, there is no efficacious and well tolerated standard regimen accepted as a “bridge” to allogeneic stem cell transplantation or as definitive treatment for patients who are not transplant candidates. Vincristine is an active drug in patients with ALL, but its dose intensity is limited by neurotoxicity, and its full potential as an anticancer drug is thus not realized. Encapsulation of vincristine into sphingomyelin and cholesterol nanoparticle liposomes facilitates dose-intensification and densification to enhanced target tissues with reduced potential for toxicity. Vincristine sulfate liposome injection (VSLI) is associated with significant responses in clinically advanced ALL, and has recently been approved by the US Food and Drug Administration for treatment of relapsed and clinically advanced Philadelphia chromosome-negative ALL. This review provides an overview of the preclinical and clinical studies leading to the approval of VSLI for the treatment of relapsed and refractory ALL, and suggests potential areas of future clinical development. PMID:24072970

  11. Effects of Disasters on Smoking and Relapse: An Exploratory Study of Hurricane Katrina Victims

    ERIC Educational Resources Information Center

    Lanctot, Jennifer Q.; Stockton, Michelle B.; Mzayek, Fawaz; Read, Mary; McDevitt-Murphy, Meghan; Ward, Kenneth

    2008-01-01

    Background: Psychosocial stress maintains cigarette use and precipitates relapse, but little is known about how natural disasters in particular affect smoking. Purpose: To determine the feasibility of recruiting victims soon after a natural disaster for a survey study, and to assess the types and determinants of changes in smoking behavior…

  12. Relationship of Posttreatment Decentering and Cognitive Reactivity to Relapse in Major Depression

    ERIC Educational Resources Information Center

    Fresco, David M.; Segal, Zindel V.; Buis, Tom; Kennedy, Sydney

    2007-01-01

    Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response…

  13. Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations

    PubMed Central

    Wu, Chenglin; Mansouri, Larry; Jurczak, Wojciech; Galazka, Krystyna; Dlugosz-Danecka, Monika; Machaczka, Maciej; Zhang, Huilai; Peng, Roujun; Morin, Ryan D.; Rosenquist, Richard; Sander, Birgitta; Pan-Hammarström, Qiang

    2016-01-01

    The genetic mechanisms underlying disease progression, relapse and therapy resistance in mantle cell lymphoma (MCL) remain largely unknown. Whole-exome sequencing was performed in 27 MCL samples from 13 patients, representing the largest analyzed series of consecutive biopsies obtained at diagnosis and/or relapse for this type of lymphoma. Eighteen genes were found to be recurrently mutated in these samples, including known (ATM, MEF2B and MLL2) and novel mutation targets (S1PR1 and CARD11). CARD11, a scaffold protein required for B-cell receptor (BCR)-induced NF-κB activation, was subsequently screened in an additional 173 MCL samples and mutations were observed in 5.5% of cases. Based on in vitro cell line-based experiments, overexpression of CARD11 mutants were demonstrated to confer resistance to the BCR-inhibitor ibrutinib and NF-κB-inhibitor lenalidomide. Genetic alterations acquired in the relapse samples were found to be largely non-recurrent, in line with the branched evolutionary pattern of clonal evolution observed in most cases. In summary, this study highlights the genetic heterogeneity in MCL, in particular at relapse, and provides for the first time genetic evidence of BCR/NF-κB activation in a subset of MCL. PMID:27224912

  14. Sudden Gains in Cognitive Therapy of Depression and Depression Relapse/Recurrence

    ERIC Educational Resources Information Center

    Tang, Tony Z.; DeRubeis, Robert J.; Hollon, Steven D.; Amsterdam, Jay; Shelton, Richard

    2007-01-01

    Cognitive therapy (CT) may have significant advantages over antidepressants in preventing depression relapses. Many CT patients experience sudden gains: large symptom improvement in 1 between-session interval. Past studies have associated CT sudden gains with in-session cognitive changes but not with life events. This study examined sudden gains…

  15. Microgeographical Differences of Plasmodium vivax Relapse and Re-Infection in the Peruvian Amazon

    PubMed Central

    Chuquiyauri, Raul; Peñataro, Pablo; Brouwer, Kimberly C.; Fasabi, Manuel; Calderon, Maritza; Torres, Sonia; Gilman, Robert H.; Kosek, Margaret; Vinetz, Joseph M.

    2013-01-01

    To determine the magnitude of Plasmodium vivax relapsing malaria in rural Amazonia, we carried out a study in four sites in northeastern Peru. Polymerase chain reaction-restriction fragment length polymorphism of PvMSP-3α and tandem repeat (TR) markers were compared for their ability to distinguish relapse versus reinfection. Of 1,507 subjects with P. vivax malaria, 354 developed > 1 episode during the study; 97 of 354 (27.5%) were defined as relapse using Pvmsp-3α alone. The addition of TR polymorphism analysis significantly reduced the number of definitively defined relapses to 26 of 354 (7.4%) (P < 0.05). Multivariate logistic regression modeling showed that the probability of having > 1 infection was associated with the following: subjects in Mazan (odds ratio [OR] = 2.56; 95% confidence interval [CI] 1.87, 3.51), 15–44 years of age (OR = 1.49; 95% CI 1.03, 2.15), traveling for job purposes (OR = 1.45; 95%CI 1.03, 2.06), and travel within past month (OR = 1.46; 95% CI 1.0, 2.14). The high discriminatory capacity of the molecular tools shown here is useful for understanding the micro-geography of malaria transmission. PMID:23836566

  16. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL.

    PubMed

    Tzoneva, Gannie; Perez-Garcia, Arianne; Carpenter, Zachary; Khiabanian, Hossein; Tosello, Valeria; Allegretta, Maddalena; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Paganin, Maddalena; Basso, Giuseppe; Hof, Jana; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo

    2013-03-01

    Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Despite intensive chemotherapy, 20% of pediatric patients and over 50% of adult patients with ALL do not achieve a complete remission or relapse after intensified chemotherapy, making disease relapse and resistance to therapy the most substantial challenge in the treatment of this disease. Using whole-exome sequencing, we identify mutations in the cytosolic 5'-nucleotidase II gene (NT5C2), which encodes a 5'-nucleotidase enzyme that is responsible for the inactivation of nucleoside-analog chemotherapy drugs, in 20/103 (19%) relapse T cell ALLs and 1/35 (3%) relapse B-precursor ALLs. NT5C2 mutant proteins show increased nucleotidase activity in vitro and conferred resistance to chemotherapy with 6-mercaptopurine and 6-thioguanine when expressed in ALL lymphoblasts. These results support a prominent role for activating mutations in NT5C2 and increased nucleoside-analog metabolism in disease progression and chemotherapy resistance in ALL.

  17. Drug and Multidrug Resistance among Mycobacterium leprae Isolates from Brazilian Relapsed Leprosy Patients

    PubMed Central

    Rocha, Adalgiza da Silva; Cunha, Maria das Graças; Diniz, Lucia Martins; Salgado, Claudio; Aires, Maria Araci P.; Nery, José Augusto; Gallo, Eugênia Novisck; Miranda, Alice; Magnanini, Monica M. F.; Matsuoka, Masanori; Sarno, Euzenir Nunes; Suffys, Philip Noel

    2012-01-01

    Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary. PMID:22495562

  18. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    ERIC Educational Resources Information Center

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  19. Relapse Among Adolescent Drug Abusers Following Treatment: The Role of Probable ADHD Status

    ERIC Educational Resources Information Center

    Latimer, William W.; Ernst, Jenna; Hennessey, Jodi; Stinchfield, Randy D.; Winters, Ken C.

    2004-01-01

    This is a report on a sample of adolescent drug abusers in treatment (N = 220) to estimate the degree to which probable ADHD status increases the odds of posttreatment alcohol, marijuana, and other drug relapse during the initial 6 months following discharge. Drug abusing youth with probable ADHD status exhibited 2.5 times the risk of…

  20. The Efficacy of Colchicine and Dapsone Combination Therapy in Relapsed Immune Thrombocytopenia

    PubMed Central

    Rattanathammethee, Thanawat; Theerajangkhaphichai, Wasan; Rattarittamrong, Ekarat; Hantrakool, Sasinee; Chai-Adisaksopha, Chatree; Norasetthada, Lalita; Tantiworawit, Adisak

    2017-01-01

    The aim of the present paper is to evaluate the efficacy and safety of colchicine and dapsone combination therapy in cases of steroid-dependent, relapsed and refractory immune thrombocytopenia (ITP). This is a retrospective study of ITP patients who attended the Hematology Clinic at Chiang Mai University Hospital (Thailand) from 1 January 2008 to 30 September 2014. Medical records and clinical data were reviewed for efficacy and adverse effects. Sixty-four ITP patients received the combination therapy. The median age was 46 years and 70.3% were female. The majority (65.6%) were relapsed ITP patients. Median platelet count before starting treatment was 22.6×109/L. The response rate was 82.8%, with 75.0% of patients having a complete response. Median time to response was 8 weeks. The response rate was higher in relapsed patients (90.4%) compared to refractory (61.5%) and steroid-dependent patients (77.8%). Steroid treatment was discontinued in 30 patients (50%) following combination therapy. The most common side effect was hemolysis due to dapsone which was found in eight patients (12.5%). We can therefore conclude that combination therapy with colchicine and dapsone is an alternative second-line therapy option in relapsed ITP cases with acceptable side effects. PMID:28286634

  1. Treating relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: liposome-encapsulated vincristine.

    PubMed

    Davis, Tyler; Farag, Sherif S

    2013-01-01

    Acute lymphoblastic leukemia (ALL) remains a disease with poor outcomes in adults. While induction chemotherapy achieves a complete remission in almost 90% of patients, the majority will relapse and die of their disease. Relapsed ALL is associated with a high reinduction mortality and chemotherapy resistance, with allogeneic hematopoietic stem cell transplantation offering the only therapy with curative potential. However, there is no efficacious and well tolerated standard regimen accepted as a "bridge" to allogeneic stem cell transplantation or as definitive treatment for patients who are not transplant candidates. Vincristine is an active drug in patients with ALL, but its dose intensity is limited by neurotoxicity, and its full potential as an anticancer drug is thus not realized. Encapsulation of vincristine into sphingomyelin and cholesterol nanoparticle liposomes facilitates dose-intensification and densification to enhanced target tissues with reduced potential for toxicity. Vincristine sulfate liposome injection (VSLI) is associated with significant responses in clinically advanced ALL, and has recently been approved by the US Food and Drug Administration for treatment of relapsed and clinically advanced Philadelphia chromosome-negative ALL. This review provides an overview of the preclinical and clinical studies leading to the approval of VSLI for the treatment of relapsed and refractory ALL, and suggests potential areas of future clinical development.

  2. Resilience Associated with Self-Disclosure and Relapse Risks in Patients with Alcohol Use Disorders

    PubMed Central

    Yamashita, Ayako; Yoshioka, Shin-ichi

    2016-01-01

    Background The aim of this study was to clarify the self-disclosure and risks of relapse associated with promoting resilience of patients with alcohol use disorders (AUD) and participating in self-help groups. Methods An anonymous, self-administered questionnaire survey was administered to 48 patients with AUD and participating in self-help groups; this questionnaire consisted of basic attributes, a bidimensional resilience scale to assess both innate and acquired resilience factors, a scale to assess depth of self-disclosure, and a scale assessing relapse risks. We conducted an evaluation by dividing the respondents into a high group and low group based on their median values for both innate and acquired resilience. Results Innate/acquired resilience had a mutually reinforcing relationship, and, compared with the low resilience group, the high resilience group had significantly reduced risks for relapses and resulted in deeper self-disclosure. Conclusion Patients with high resilience had lower risk of alcohol relapse and deeper self-disclosure. The results suggest that one way of supporting patients with AUD in recovery is assisting them in building personal relationships with others and in deepening self-disclosure in a setting where they can relax, thus promoting their natural ability to recover. PMID:28070165

  3. 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

  4. Mindfulness-Based Cognitive Therapy to Prevent Relapse in Recurrent Depression

    ERIC Educational Resources Information Center

    Kuyken, Willem; Byford, Sarah; Taylor, Rod S.; Watkins, Ed; Holden, Emily; White, Kat; Barrett, Barbara; Byng, Richard; Evans, Alison; Mullan, Eugene; Teasdale, John D.

    2008-01-01

    For people at risk of depressive relapse, mindfulness-based cognitive therapy (MBCT) has an additive benefit to usual care (H. F. Coelho, P. H. Canter, & E. Ernst, 2007). This study asked if, among patients with recurrent depression who are treated with antidepressant medication (ADM), MBCT is comparable to treatment with maintenance ADM (m-ADM)…

  5. Preventing Relapse/Recurrence in Recurrent Depression With Cognitive Therapy: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Bockting, Claudi L. H.; Schene, Aart H.; Spinhoven, Philip; Koeter, Maarten W. J.; Wouters, Luuk F.; Huyser, Jochanan; Kamphuis, Jan H.

    2005-01-01

    This article reports on the outcome of a randomized controlled trial of cognitive group therapy (CT) to prevent relapse/recurrence in a group of high-risk patients diagnosed with recurrent depression. Recurrently depressed patients (N = 187) currently in remission following various types of treatment were randomized to treatment as usual,…

  6. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    PubMed

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  7. Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

    ERIC Educational Resources Information Center

    Correa-Fernandez, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

    2012-01-01

    Objective: Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method: Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple…

  8. Technology in Treatment: Are Adolescents and Counselors Interested in Online Relapse Prevention?

    ERIC Educational Resources Information Center

    Trudeau, Kimberlee J.; Ainscough, Jessica; Charity, Sadaf

    2012-01-01

    Background: Approximately 75% of adolescents who receive substance abuse treatment relapse within 1 year; therefore, it is important to have effective, easily accessible aftercare resources to support them while they are in recovery. Objective: The goal of this study was twofold: (1) to find out from adolescents and counselors if an online relapse…

  9. Louse-borne relapsing fever in a refugee from Somalia arriving in Belgium.

    PubMed

    Darcis, Gilles; Hayette, Marie-Pierre; Bontems, Sebastien; Sauvage, Anne-Sophie; Meuris, Christelle; Van Esbroeck, Marjan; Leonard, Philippe

    2016-03-01

    We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions.

  10. The impact of residual symptoms on relapse and quality of life among Thai depressive patients

    PubMed Central

    Hiranyatheb, Thanita; Nakawiro, Daochompu; Wongpakaran, Tinakon; Wongpakaran, Nahathai; Bookkamana, Putipong; Pinyopornpanish, Manee; Saisavoey, Nattha; Wannarit, Kamonporn; Satthapisit, Sirina; Tanchakvaranont, Sitthinant

    2016-01-01

    Purpose Residual symptoms of depressive disorder are major predictors of relapse of depression and lower quality of life. This study aims to investigate the prevalence of residual symptoms, relapse rates, and quality of life among patients with depressive disorder. Patients and methods Data were collected during the Thai Study of Affective Disorder (THAISAD) project. The Hamilton Rating Scale for Depression (HAMD) was used to measure the severity and residual symptoms of depression, and EQ-5D instrument was used to measure the quality of life. Demographic and clinical data at the baseline were described by mean ± standard deviation (SD). Prevalence of residual symptoms of depression was determined and presented as percentage. Regression analysis was utilized to predict relapse and patients’ quality of life at 6 months postbaseline. Results A total of 224 depressive disorder patients were recruited. Most of the patients (93.3%) had at least one residual symptom, and the most common was anxiety symptoms (76.3%; 95% confidence interval [CI], 0.71–0.82). After 3 months postbaseline, 114 patients (50.9%) were in remission and within 6 months, 44 of them (38.6%) relapsed. Regression analysis showed that residual insomnia symptoms were significantly associated with these relapse cases (odds ratio [OR] =5.290, 95% CI, 1.42–19.76). Regarding quality of life, residual core mood and insomnia significantly predicted the EQ-5D scores at 6 months postbaseline (B =−2.670, 95% CI, −0.181 to −0.027 and B =−3.109, 95% CI, −0.172 to −0.038, respectively). Conclusion Residual symptoms are common in patients receiving treatment for depressive disorder and were found to be associated with relapses and quality of life. Clinicians need to be aware of these residual symptoms when carrying out follow-up treatment in patients with depressive disorder, so that prompt action can be taken to mitigate the risk of relapse. PMID:28003753

  11. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  12. Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study

    PubMed Central

    Desjonquères, A; Chevallier, P; Thomas, X; Huguet, F; Leguay, T; Bernard, M; Bay, J-O; Tavernier, E; Charbonnier, A; Isnard, F; Hunault, M; Turlure, P; Renaud, M; Bastié, J-N; Himberlin, C; Lepretre, S; Lioure, B; Lhéritier, V; Asnafi, V; Beldjord, K; Lafage-Pochitaloff, M; Béné, M C; Ifrah, N; Dombret, H

    2016-01-01

    The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph− ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph− ALL younger adults (18–63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14–24%) and 13.3% (8–18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21–38%) and 25% (17–33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients. PMID:27935576

  13. Effects of Vocational Consultation on Relapse Rate and Hope among Drug Dependents in Bojnurd, Iran

    PubMed Central

    Hojjat, Seyed Kaveh; Raufpoor, Roghieh; Khalili, Mina Norozi; Hamidi, Mahin; Danesh, Mahsa; Ziarat, Hadiseh Monadi

    2016-01-01

    Introduction Drug addiction is one of the most flagrant social damages that can easily enervate the socio-cultural foundation of a country as well as endanger human dynamism. One of the prevalent problems among most addicted people is their low hope and relapse of drug dependence. The aim of this study was to assess the effect of vocational consultation (for training on problem-solving skills) on hope and relapse rate of patients treated in methadone maintenance clinics. Methods This experiment was conducted on 60 drug abusers treated in a methadone maintenance program in drug addiction centers in Bojnurd, Iran, in 2014. The patients were randomly and equally allocated into two study and control groups. All patients completed the Miller Hope Questionnaire before and after the intervention. Ten sessions of vocational consultation were held for the study group while the control group received no special treatment. Patients were followed up on for relapses for six months. Data were analyzed using SPSS (version 16) and the paired-samples t-test technique. Results The results indicated that the mean and standard deviation of hope on the pre-test in the study group increased on the post-test (from M=175.5, SD=31.8, to M=198.5, SD=20.4), while in the control group the mean of hope decreased from the pre-test to past-test stage (M=184.7, SD=27.7, to M=183.3, SD=26.1), showing a significant relationship, t(56)= 5.657, p<0.05. The relapse rate was not significantly different in the two groups. Conclusion The vocational consultation positively affects hope among drug dependents but did not affect their relapse rate during the six-month follow-up. Increasing the hope in these groups of patients may be effective in other aspects of treatment success in long-term follow-up. PMID:26955440

  14. Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

    PubMed Central

    Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

    2015-01-01

    Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

  15. Initial Response to Salvage Therapy Determines Prognosis in Relapsed Pediatric Hodgkin Lymphoma Patients

    PubMed Central

    Metzger, Monika L.; Hudson, Melissa M.; Krasin, Matthew J.; Wu, Jianrong; Kaste, Sue C.; Kun, Larry E.; Sandlund, John T.; Howard, Scott C.

    2010-01-01

    Background Pediatric Hodgkin lymphoma is a highly curable disease, however once a patient relapses prognostic factors for survival are not clearly defined. Methods Retrospective analysis of 50 pediatric patients with HL that relapsed or progressed between 1990 and 2006 and were retrieved with intense cytoreductive treatment regimens followed by autologous stem-cell transplantation and radiation therapy. A Cox proportional hazard model was used to determine risk factors for second treatment failure and death. Results The median age was 16.1 years (range, 4.9 to 22.1 years) at diagnosis of HL. Fifteen patients developed progressive disease while on therapy, 14 relapsed early and 21 relapsed late. Patients who remained alive at the time of this study had been followed for a median of 4.4 years (range, 1.2 to 16.6 years). The 5-year overall survival of patients who had an inadequate response (n=14) to initial salvage therapy was only 17.9% (95% confidence interval [CI], 3.1% to 42.5%) compared with 97.2% (95% CI, 81.9% to 99.6%) for those who responded (n=36; P < 0.0001). In multiple variable Cox-regression analysis for overall survival, only inadequate response to initial salvage therapy was significant (hazard ratio, 43.6; 95% CI, 5.4 to 354; P = 0.0004). Conclusion Pediatric patients with relapsed HL who have an inadequate response after initial primary salvage chemotherapy have a very poor prognosis and should be considered for novel therapies directed at biological or immunological targets. PMID:20564743

  16. Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival

    PubMed Central

    Koreth, John; Kim, Haesook T.; Nikiforow, Sarah; Milford, Edgar L.; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Alyea, Edwin P.

    2015-01-01

    The impact of early donor cell chimerism on outcomes of T-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill-defined. We evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T-cell chimerism was also assessed. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), relapse and non-relapse mortality (NRM). 688 patients with hematologic malignancies (48% myeloid; 52% lymphoid) and a median age of 57 years (range, 18-74) undergoing RIC HSCT with T-replete donor grafts (97% peripheral blood; 92% HLA-matched) and median follow-up of 58.2 months (range, 12.6-120.7) were evaluated. In multivariable analysis total donor cell and T-cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most predictive. D100 total donor cell chimerism <90% was associated with increased relapse (HR 2.54, 95% CI 1.83-3.51, p<0.0001), impaired PFS (HR 2.01, 95% CI 1.53-2.65, p<0.0001) and worse OS (1.50, 95% CI 1.11-2.04, p=0.009), but not NRM (HR 0.76; 95% CI 0.44-2.27, p=0.33). There was no additional utility of incorporating sustained D30-D100 total donor cell chimerism, or T-cell chimerism. Low donor chimerism early after RIC HSCT is an independent risk factor for relapse and impaired survival. Donor chimerism assessment early after RIC HSCT can prognosticate for long-term outcomes and help identify high-risk patient cohorts that may benefit from additional therapeutic interventions. PMID:24907627

  17. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

    ClinicalTrials.gov

    2017-03-13

    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; Blastic Plasmacytoid Dendritic Cell Neoplasm

  18. Signals from the Fourth Dimension Regulate Drug Relapse.

    PubMed

    Mulholland, Patrick J; Chandler, L Judson; Kalivas, Peter W

    2016-07-01

    Despite the enormous societal burden of alcohol and drug addiction and abundant research describing drug-induced maladaptive synaptic plasticity, there are few effective strategies for treating substance use disorders. Recent awareness that synaptic plasticity involves astroglia and the extracellular matrix is revealing new possibilities for understanding and treating addiction. We first review constitutive corticostriatal adaptations that are elicited by and shared between all abused drugs from the perspective of tetrapartite synapses, and integrate recent discoveries regarding ce