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Sample records for relapsing polychondritis involving

  1. Relapsing polychondritis.

    PubMed

    Chopra, Ratnesh; Chaudhary, Nida; Kay, Jonathan

    2013-05-01

    Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized by episodic, progressive inflammatory destruction of cartilage. It can occur as an overlap syndrome in patients with other rheumatologic conditions. The disease usually follows an indolent relapsing-remitting course, but occasionally it can progress rapidly and even cause death. Although auricular or nasal chondritis or peripheral arthritis without other significant organ involvement are usually treated with low-dose corticosteroids, other more severe disease manifestations may require treatment with high-dose corticosteroids or other immunosuppressive agents. Biological targeted therapies might prove to be effective treatments of this condition. PMID:23597963

  2. Relapsing polychondritis

    PubMed Central

    Emmungil, Hakan; Aydın, Sibel Zehra

    2015-01-01

    Relapsing polychondritis (RPC) is a unique and rarely observed autoimmune condition regarded as recurrent extensive chondritis of the auricular, nasal, and tracheal cartilages. Moreover, heart, main arteries, skin, and eyes may be involved. Several forms of clinical manifestations may be seen, and the pathogenesis still remains anonymous. A concomitant disease, particularly myelodysplasia or other systemic autoimmune disease can be detected in one-third of the patients with RPC. The treatment of RPC should be considered on personal basis and classified according to disease activity and severity. This study reviews the available data on clinical manifestations, pathogenesis, diagnosis, and therapeutics of the RPC.

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

    PubMed

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

    2009-01-01

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

  4. Clinical characteristics and treatment outcomes of patients with relapsing polychondritis with airway involvement.

    PubMed

    Hong, Goohyeon; Kim, Hojoong

    2013-09-01

    We investigated the clinical characteristics, management modalities, and outcomes in patients with relapsing polychondritis (RP) with airway involvement. The medical records of RP patients with airway involvement seen at Samsung Medical Center from August 2004 to December 2011 were collected. The clinical manifestations were investigated retrospectively, including rheumatologic record, diagnostic tests, treatment modalities, and clinical outcomes. Twelve patients (five females, seven males) with a median age of 48(interquartile range (IQR) 44-60) years were included. All patients had airway involvement, including the trachea (100 %), main bronchi (83 %), and larynx (25 %). Rheumatological manifestations were frequent, including inflammatory arthritis (50 %), auricular chondritis (42 %), keratoconjunctivitis (42 %), nasal chondritis (42 %), saddle nose (25 %), and sensorineural hearing loss (17 %). All patients who had acute exacerbations were treated with high-dose corticosteroids (1,000 mg per day) and were maintained on oral prednisolone (5-40 mg per day), with weekly methotrexate (2.5-15 mg per week) during follow up. One out of 12 patients required mechanical ventilation. Nine patients have survived without ventilator support and eight patients without a tracheostomy. Two patients underwent a tracheostomy with endobronchial stenting. During follow-up (median 24[IQR 7-50] months), the clinical outcome was favorable in nine patients, while three patients died of pneumonia and respiratory failure. High-doses of corticosteroids during an acute exacerbation followed by maintenance prednisolone with methotrexate could be recommended as a therapeutic option in RP patients with airway involvement. Airway intervention by an experienced clinician is sometimes required.

  5. Callosal Disconnection Syndrome Associated with Relapsing Polychondritis.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2009-01-01

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

  7. Pathogenesis of relapsing polychondritis: a 2013 update.

    PubMed

    Arnaud, Laurent; Mathian, Alexis; Haroche, Julien; Gorochov, Guy; Amoura, Zahir

    2014-02-01

    Relapsing polychondritis (RP) is a systemic inflammatory disease primarily affecting not only the cartilaginous structures of the ears, nose and tracheobronchial tree but also the joints, the inner ear, the eyes, and the cardiovascular system. RP is an immune-mediated disease during which target antigens are still unknown, but data from human studies and murine models strongly support a role of both Collagen Type II (CII) and matrilin-1 as potential candidates. RP is likely a Th1-mediated disease as serum levels of interferon (IFN)-γ, interleukin [IL]-12, and IL-2 parallel changes in disease activity, while the levels of Th2 cytokines do not. Serum levels of sTREM-1, interferon-γ, CCL4, vascular endothelial growth factor, and matrix metalloproteinases-3 are significantly higher in RP patients than in healthy donors, with sTREM-1 correlating with disease activity. Patients with active RP also have significantly higher levels of MCP-1, MIP-1β, MIF, and IL-8 than controls. These pro-inflammatory chemokines are involved in the modulation and recruitment of monocytes and neutrophils. Altogether, these data suggest that a complex cytokine network orchestrates the recruitment of infiltrating cells in RP lesions. Cytokine modulation using TNFα blockers, rituximab, anakinra, tocilizumab, and abatacept has recently been shown effective in some RP cases but further data are needed. Better understanding of the repertoire of infiltrating cells may provide interesting clues to further define the putative RP auto-antigens. Study of circulating mononuclear cells during RP flares may also provide crucial information about the ongoing cellular trafficking and recruitment processes involved in this rare disease. PMID:24051104

  8. [Reversible cognitive decline in a patient with relapsing polychondritis].

    PubMed

    Swen, S J; Leonards, D J H; Swen, W A A; de Jonghe, J F M; Kalisvaarte, K J

    2009-10-01

    Patient A, 58 years, is referred by the Rheumatologist to the Geriatrician concerning apathy. History reviews skipping arthritis, reddened and inflamed eyes, apathy and loss of interest. Physical examination revealed red tearing eyes, bradyphrenia and bradykinesia. Laboratory examination showed inflammation markers. The patient develops fever and bilateral reddened and inflamed ears. Diagnosis of relapsing polychondritis is made, the patient is treated with prednisone and the symptoms disappear. Relapsing polychondritis is a chronical disease associated with inflammation and destruction of cartilaginous structures and proteoglycan rich structures. We diagnosed Relapsing Polychondritis with a reversible dementia, probably due to cerebral vasculitis.

  9. Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy

    PubMed Central

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

    2015-01-01

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

  10. Relapsing Polychondritis: an Update on Pathogenesis, Clinical Features, Diagnostic Tools, and Therapeutic Perspectives.

    PubMed

    Vitale, Antonio; Sota, Jurgen; Rigante, Donato; Lopalco, Giuseppe; Molinaro, Francesco; Messina, Mario; Iannone, Florenzo; Cantarini, Luca

    2016-01-01

    Relapsing polychondritis is a rare multisystemic disease widely accepted as a complex autoimmune disorder affecting proteoglycan-rich structures and cartilaginous tissues, especially the auricular pinna, cartilage of the nose, tracheobronchial tree, eyes, and heart's connective components. The clinical spectrum may vary from intermittent inflammatory episodes leading to unesthetic structural deformities to life-threatening cardiopulmonary manifestations, such as airway collapse and valvular regurgitation. The frequent association with other rheumatologic and hematologic disorders has been extensively reported over time, contributing to define its complexity at a diagnostic and also therapeutic level. Diagnosis of relapsing polychondritis is mainly based on clinical clues, while laboratory data have only a supportive contribution. Conversely, radiology is showing a relevant role in estimating the rate of systemic involvement as well as disease activity. The present review is aimed at providing an update on scientific data reported during the last 3 years about relapsing polychondritis in terms of pathogenesis, clinical features, diagnosis, and new treatment options. PMID:26711694

  11. Relapsing polychondritis: bone marrow and circular fibrous nodules in the aorta.

    PubMed Central

    Wilson, G E; Hasleton, P S; Manns, J J; Marks, J S

    1990-01-01

    A case is reported of extensive aortic calcification, bone formation, and haemopoietic tissue in a woman with relapsing polychondritis. An additional feature was 'clock face' nodules of collagen in the aorta. Images PMID:1700671

  12. A Case of Relapsing Polychondritis Initiating with Unexplained Fever.

    PubMed

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

    2016-01-01

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

  13. Optic neuropathy associated with periostitis in relapsing polychondritis.

    PubMed

    Hirunwiwatkul, Parima; Trobe, Jonathan D

    2007-03-01

    Optic neuropathy is an uncommon manifestation of relapsing polychondritis (RPC), a rare systemic disease affecting cartilaginous and proteoglycan-rich structures. The optic neuropathy has been attributed to ischemia, intrinsic inflammation of the optic nerve, or spread of inflammation to the nerve from adjacent intraconal orbital tissues. We report a case of recurrent corticosteroid-responsive optic neuropathy in which MRI did not show ocular, optic nerve, or intraconal orbital abnormalities but did show periosteal thickening and enhancement in the apical orbit and adjacent intracranial space consistent with periostitis. The periostitis, which is a manifestation of a systemic vasculitis or an autoimmune reaction to progenitors of cartilage, probably caused the optic neuropathy by compression or inflammation. It is important to recognize this mechanism of optic neuropathy as its imaging features may be a subtle yet critical clue to an underlying systemic condition that can be life-threatening if not properly managed.

  14. Relapsing polychondritis with different types of ocular inflammations

    PubMed Central

    Furuya, Nana; Oshitari, Toshiyuki; Yotsukura, Jiro; Baba, Takayuki; Yamamoto, Shuichi

    2015-01-01

    We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation. PMID:26425107

  15. [NERVOUS SYSTEM LESIONS ASSOCIATED WITH RELAPSING POLYCHONDRITIS: ANALYSIS OF ORIGINAL OBSERVATIONS].

    PubMed

    Chernyak, V I; Savel'ev A I; Men'shikova, I V; Pogromov, A P

    2016-01-01

    Three clinical cases are described including two of relapsing polychondritis with lesions in the central and peripheral nervous system (one of long-standing aseptic lymphocytic meningitis and one of cranial neuropathy of 2, 5, 7, and 8 pairs) and the third case of the optic nerve lesion with amblyopia. The two former cases were successfully treated with high doses of corticosteroids, the third one with moderate doses of the same medications. The data from the current literature concerning variants of clinical manifestations, methods for diagnostics and treatment of neurologic manifestations of relapsing polychondritis are discussed. PMID:27459759

  16. 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

  17. An uncommon presentation of an uncommon disease: relapsing polychondritis overlap with systemic lupus erythematosus.

    PubMed

    Nguyen, Michelle A; Rahnama-Moghadam, Sahand; Gilson, Robert T

    2016-01-01

    Relapsing polychondritis (RP) is a rare rheumatologic disorder in which recurrent episodes of inflammation result in destruction of cartilage of the ears and nose. The joints, eyes, audio-vestibular system, heart valves, respiratory tract, kidneys, and skin can also be involved. Skin involvement is most frequently linked to concomitant myelodysplastic syndrome and has rarely been associated with systemic lupus erythematosus. A 47-year-old woman presented with violaceous, indurated, tender plaques on the bilateral cartilaginous ears with sparing of the lobes, consistent with RP. Further investigations revealed positive ANA and anti-Smith antibody, oral ulcers, a photo-distributed skin eruption, and biopsy-proven lupus nephritis, leading to a second concomitant diagnosis of systemic lupus erythematosus (SLE). The diagnosis of SLE associated with RP was made and the patient was started on oral prednisone and hydroxychloroquine. This is a rare report of SLE associated with RP. It is unclear whether RP occurring in patients with SLE represents another clinical manifestation of SLE or a coexisting disease. However, a significant ANA titer in a patient with RP strongly suggests the presence of an associated autoimmune disorder. If immunologic abnormalities usually found in SLE are detected in patients with RP, it is important to monitor patients for the development of other manifestations of SLE. PMID:27267190

  18. Efficacy of tocilizumab for psychiatric symptoms associated with relapsing polychondritis: the first case report and review of the literature.

    PubMed

    Liu, Lijun; Liu, Shengyun; Guan, Wenjuan; Zhang, Lei

    2016-08-01

    Relapsing polychondritis (RP) rarely affected the central nervous system (CNS). If the CNS is involved, it can result in psychiatric manifestations. Patients with RP always respond well to glucocorticoids and immunosuppressants. If the therapies fail, biologics can be given, such as tocilizumab, which is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Until now, there have been no randomized clinical trials to test the safety and efficacy of biologics, no reports of RP with psychiatric disorders as initial symptoms, and no reports of tocilizumab used for psychiatric symptoms due to RP. Here, we report a 60-year-old woman with mania, logomania, hallucinations, cognitive disorder, persecutory delusion, and violent tendency as chief complaints. The application of dexamethasone worsened her psychiatric symptoms. After the first infusion of tocilizumab, she achieved complete remission within one week. During the follow-up period, she sustained serological and psychiatric remission. Our case illustrates the safety and efficacy of tocilizumab for psychiatric symptoms of RP. PMID:27260262

  19. Autoantibodies to cartilage and type II collagen in relapsing polychondritis and other rheumatic diseases.

    PubMed Central

    Ebringer, R; Rook, G; Swana, G T; Bottazzo, G F; Doniach, D

    1981-01-01

    Cartilage antibodies were demonstrated by indirect immunofluorescence (IFL) on human fetal cartilage in 6 out of 9 patients with relapsing polychondritis (RPC), in 4 out of 260 patients with rheumatoid arthritis (RA), and in only 1 out of 1016 patients with other disorders. The antibodies were specific for cartilage and evenly stained the whole cartilage matrix. They were predominantly of IgG class and varied in titres from 1:1 to 1:320. Follow-up studies in the RPC patients indicated that higher titres were present during the early acute phase of the disease. Five of the 6 positive cases had developed the disease within the past 12 months, and the 3 negative cases had had the disease for 3 to 7 years when tested. The RA cases showing positive cartilage IFL had no clinical evidence of RPC. Sequential measurements in 2 of the 4 cases showed that these antibodies became detectable some years after the onset of arthritis. Absorption studies with human type II collagen and purified porcine proteoglycan failed to remove the cartilage IFL. Antibodies to human native type II collagen were measured by an enzyme-linked immunosorbent assay. The highest levels were found in the RA sera which also displayed cartilage IFL, but the 2 tests gave discordant results. RPC sera showed the same antibody levels by this method, as did cartilage-IFL-negative RA sera, though both groups had higher mean levels than health controls. The findings that cartilage antibodies are detected in the majority of cases of RPC and only rarely in other diseases suggests these antibodies may play an important role in the pathogenesis of cartilage destruction in RPC. PMID:7030234

  20. Corticosteroid Therapy for a Patient with Relapsing Polychondritis Complicated by IgG4-Related Disease.

    PubMed

    Yamasue, Mari; Nureki, Shin-Ichi; Matsumoto, Hiroyuki; Kan, Takamasa; Hashimoto, Takehiro; Ushijima, Ryoichi; Usagawa, Yuko; Kadota, Jun-Ichi

    2016-01-01

    Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4-RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown. PMID:27396510

  1. Mouth and genital ulcers with inflamed cartilage: MAGIC syndrome. Five patients with features of relapsing polychondritis and Behçet's disease.

    PubMed

    Firestein, G S; Gruber, H E; Weisman, M H; Zvaifler, N J; Barber, J; O'Duffy, J D

    1985-07-01

    Five patients with features of coexistent relapsing polychondritis and Behçet's disease are described. Review of the literature supports the overlap of the clinical manifestations of these two conditions. A common immunologic abnormality is likely, and elastin is cited as a possible target antigen. The "mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome" is the proposed name for this entity.

  2. 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

  3. 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. PMID:24421951

  4. Involving relatives in relapse prevention for bipolar disorder: a multi-perspective qualitative study of value and barriers

    PubMed Central

    2011-01-01

    Background Managing early warning signs is an effective approach to preventing relapse in bipolar disorder. Involving relatives in relapse prevention has been shown to maximize the effectiveness of this approach. However, family-focused intervention research has typically used expert therapists, who are rarely available within routine clinical services. It remains unknown what issues exist when involving relatives in relapse prevention planning delivered by community mental health case managers. This study explored the value and barriers of involving relatives in relapse prevention from the perspectives of service users, relatives and care-coordinators. Methods Qualitative interview study nested within a randomized controlled trial of relapse prevention for individuals with bipolar disorder. The purposive sample of 52 participants comprised service users (n = 21), care coordinators (n = 21) and relatives (n = 10). Data were analyzed using a grounded theory approach. Results All parties identified benefits of involving relatives in relapse prevention: improved understanding of bipolar disorder; relatives gaining a role in illness management; and improved relationships between each party. Nevertheless, relatives were often discouraged from becoming involved. Some staff perceived involving relatives increased the complexity of their own role and workload, and some service users valued the exclusivity of their relationship with their care-coordinator and prioritized taking individual responsibility for their illness over the benefits of involving their relatives. Barriers were heightened when family relationships were poor. Conclusions Whilst involving relatives in relapse prevention has perceived value, it can increase the complexity of managing bipolar disorder for each party. In order to fully realize the benefits of involving relatives in relapse prevention, additional training and support for community care coordinators is needed. Trial registration ISRCTN41352631

  5. 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

  6. 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.

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

    PubMed

    Patel, Shyam A

    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

  8. The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour

    PubMed Central

    Baracz, Sarah Jane; Everett, Nicholas Adams; Cornish, Jennifer Louise

    2015-01-01

    The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol) or co-administration of oxytocin (3.6 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (3 nmol) into the STh (200 nl/side) was examined on METH-primed reinstatement (1 mg/kg; i.p.). We found that local administration of the highest oxytocin dose (3.6 pmol) into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse. PMID:26284529

  9. Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

    PubMed Central

    Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

    2015-01-01

    We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis. PMID:25883816

  10. Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

    PubMed

    Yoo, Sang Woo; Chung, Eun Jin; Kim, Sun Young; Ko, Jeong Hee; Baek, Hey Sung; Lee, Hyun Ju; Oh, Sung Hee; Jeon, Seok Cheol; Lee, Woong Soo; Park, Chan Kum; Lee, Chul Hoon

    2012-06-01

    EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT. PMID:21923886

  11. Extended-Release Naltrexone To Prevent Relapse Among Opioid Dependent, Criminal Justice System Involved Adults: Rationale and Design of a Randomized Controlled Effectiveness Trial

    PubMed Central

    Lee, Joshua D.; Friedmann, Peter D.; Boney, Tamara Y.; Hoskinson, Randall A.; McDonald, Ryan; Gordon, Michael; Fishman, Marc; Chen, Donna T.; Bonnie, Richard J.; Kinlock, Timothy W.; Nunes, Edward V.; Cornish, James W.; O’Brien, Charles P.

    2015-01-01

    Background Extended-release naltrexone (XR-NTX, Vivitrol® Alkermes Inc.) is an injectable monthly sustained-release mu opioid receptor antagonist. XR-NTX is a potentially effective intervention for opioid use disorders and as relapse prevention among criminal justice system (CJS) populations. Methods This 5-site open-label randomized controlled effectiveness trial examines whether XR-NTX reduces opioid relapse compared with treatment as usual (TAU) among community dwelling, non-incarcerated volunteers with current or recent CJS involvement. The XR-NTX arm receives 6 monthly XR-NTX injections at Medical Management visits; the TAU group receives referrals to available community treatment options. Assessments occur every 2 weeks during a 24-week treatment phase and at 12- and 18-month follow-ups. The primary outcome is a relapse event, defined as either self-report or urine toxicology evidence of ≥10 days of opioid use in a 28-day (4 week) period, with a positive or missing urine test counted as 5 days of opioid use. Results We describe the rationale, specific aims, and design of the study. Alternative design considerations and extensive secondary aims and outcomes are discussed. Conclusions XR-NTX is a potentially important treatment and relapse prevention option among persons with opioid dependence and CJS involvement. PMID:25602580

  12. 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

  13. 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

  14. Animal Models of Fear Relapse

    PubMed Central

    Goode, Travis D.; Maren, Stephen

    2014-01-01

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

  15. Animal models of fear relapse.

    PubMed

    Goode, Travis D; Maren, Stephen

    2014-01-01

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

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

    PubMed Central

    Stewart, J

    2000-01-01

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

  17. Mechanism of relapse in pediatric acute lymphoblastic leukemia.

    PubMed

    Henderson, Michelle J; Choi, Seoyeon; Beesley, Alex H; Sutton, Rosemary; Venn, Nicola C; Marshall, Glenn M; Kees, Ursula R; Haber, Michelle; Norris, Murray D

    2008-05-15

    Relapse following initial chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). Recently, to investigate the mechanism of relapse, we analysed clonal populations in 27 pairs of matched diagnosis and relapse ALL samples using PCR-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. In those cases where the new 'relapse clone' could be detected in the diagnosis population, there was a close correlation between length of first remission and quantity of the relapse clone in the diagnosis sample. A shorter length of time to first relapse correlated with a higher quantity of the relapsing clone at diagnosis. This observation, together with demonstrated differential chemosensitivity between sub-clones at diagnosis, indicates that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant sub-clone that is undetectable by routine PCR-based methods. From a clinical perspective, relapse prediction may be improved with strategies to detect minor potentially resistant sub-clones early during treatment, hence allowing intensification of therapy. Together with the availability of relevant in vivo experimental models and powerful technology for detailed analysis of patient specimens, this new information will help shape future experimentation towards targeted therapy for high-risk ALL.

  18. 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…

  19. Relapse Prevention and the Five Rules of Recovery.

    PubMed

    Melemis, Steven M

    2015-09-01

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

  20. Relapse Prevention and the Five Rules of Recovery

    PubMed Central

    Melemis, Steven M.

    2015-01-01

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

  1. 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. PMID:23997924

  2. Extinction, Relapse, and Behavioral Momentum

    PubMed Central

    Podlesnik, Christopher A.; Shahan, Timothy A.

    2010-01-01

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

  3. Extinction, relapse, and behavioral momentum.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2010-05-01

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

  4. 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.

  5. 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

  6. Progressive-Relapsing MS (PRMS)

    MedlinePlus

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

  7. [Relapse prevention in anorexia nervosa].

    PubMed

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

    2013-07-01

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

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

    PubMed Central

    Stone, Emily F.

    2016-01-01

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

  9. 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

  10. 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

  11. Tick-borne relapsing fever.

    PubMed

    Dworkin, Mark S; Schwan, Tom G; Anderson, Donald E; Borchardt, Stephanie M

    2008-09-01

    Each year, many residents of and visitors to endemic regions of the western United States are exposed to the tick vectors of tick-borne relapsing fever (TBRF), Ornithodoros hermsi, Ornithodoros turicata, or Ornithodoros parkeri. This disease is remarkable because the human host is unaware of the tick bite, usually becomes very ill, may experience an exacerbation of symptoms rather than improvement shortly after beginning appropriate treatment, and, despite often high numbers of the etiologic organism in the blood, rarely dies as a result of the illness. Although relapsing fever is acquired in many parts of the world, this article focuses primarily on knowledge about TBRF in North America. PMID:18755384

  12. 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 Central

    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. PMID:24009690

  13. 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…

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

    ERIC Educational Resources Information Center

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

    1998-01-01

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

  15. 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…

  16. Isolated central nervous system relapse of acute lymphoblastic leukemia.

    PubMed

    Sung, Sang-Hyun; Jang, In-Seok

    2014-10-01

    Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and may exhibit central nervous system (CNS) involvement. Advances in chemotherapy and effective CNS prophylaxis have significantly decreased the incidence of CNS relapse of ALL to 5-10%. Here, we report the case of a patient with isolated CNS relapse of standard risk group pre-B-cell type ALL in an 11-year-old girl, relapsed 3 years after successful completion of chemotherapy. An 11-year-old girl visited our hospital complaining of headache, dizziness, vomiting, and visual field defects. Neurological examination revealed left-side homonymous hemianopsia. Brain magnetic resonance imaging showed a large irregular dural-based sulcal hematoma in the right parietal and occipital lobes. Surgery to remove the hematoma revealed the existence of hematopoietic malignancy after pathologic evaluation. Bone marrow biopsy was subsequently performed but showed no evidence of malignancy. PMID:25408936

  17. Randomized trial comparing mindfulness-based relapse prevention with relapse prevention for women offenders at a residential addiction treatment center.

    PubMed

    Witkiewitz, Katie; Warner, Kaitlin; Sully, Betsy; Barricks, Adria; Stauffer, Connie; Thompson, Brian L; Luoma, Jason B

    2014-04-01

    Reincarceration rates are high among substance-involved criminal offenders. This study (conducted during 2010-2011 in an urban area and funded by a Washington State University-Vancouver mini-grant) used a randomized design to examine the effectiveness of mindfulness-based relapse prevention (MBRP) as compared to relapse prevention (RP), as part of a residential addictions treatment program for women referred by the criminal-justice system (N = 105). At 15-week follow up, regression analyses found women in MBRP, compared to RP, reported significantly fewer drug use days and fewer legal and medical problems. Study limitations and future research directions for studying the efficacy of MBRP are discussed.

  18. Isolated Ocular Relapse in Childhood Acute Lymphoblastic Leukemia during Second Interim Maintenance Phase of Chemotherapy: Case Report.

    PubMed

    Monsereenusorn, Chalinee; Rujkijyanont, Piya; Srimanan, Worapot; Traivaree, Chanchai

    2015-11-01

    More than 80% of acute lymphoblastic leukemia (ALL) in pediatric population is curable by using combinations of chemotherapy. However, 20% of the cases still suffer from disease relapse. The most common site of relapse is bone marrow. Relapse of childhood ALL involving the eyeball is rare. However, it occurs in 2.2% of relapsing children. The authors described a 10-year-old Thai boy with underlying ALL on therapy, presented with a one-month history of progressive visual loss of his right eye. The clinical and imaging studies strongly suggested the diagnosis of isolated ocular relapse. In this report, the authors presented the findings from successfully specific treatment consisting of systemic chemotherapy and radiation therapy on the affected eye. From other studies, the outcome was more favorable in cases of ocular relapse off therapy. In our study, one case of isolated ocular relapse ALL was reported.

  19. Late Relapse of Testicular Germ Cell Tumors.

    PubMed

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

    2015-08-01

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

  20. 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)

  1. Geographical variation in Plasmodium vivax relapse

    PubMed Central

    2014-01-01

    Background Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission. Methods A global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse. Results Differences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas. Conclusions The results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to

  2. Diffuse Large B Cell Lymphoma with Extensive Cutaneous Relapse

    PubMed Central

    Malkan, Umit Yavuz; Gunes, Gursel; Yayar, Okan; Demiroglu, Haluk

    2015-01-01

    Herein, we aimed to report a diffuse large B cell lymphoma (DLBCL) case that had extensive cutaneous relapse with no skin involvement previously. A 59-year-old man presented to hospital in April 2014 with fatigue, anorexia, fever, and anemia. Cervical lymph node biopsy revealed CD20+, BCL2+, MUM1+, BCL6+ high grade B lymphoproliferative neoplasm. After FISH investigation, he was diagnosed as DLBCL. He was given 7 cycles of R-CHOP and achieved remission. However, in November 2014, he had emerging skin lesions that cover nearly all of his body. A control PET-CT revealed diffuse cutaneous involvement. CD20+, BCL2+, MUM1+, BCL6+ high grade B cell lymphoma infiltration was detected with skin biopsy. He was diagnosed as relapse lymphoma, so 2 cycles of R-DHAP were given. There was no treatment response; therefore, R-ICE regimen was started. The patient had achieved second complete remission and his skin lesions were completely regressed. The involvement of skin with CD20+ cells after 7 cycles of rituximab therapy favors that there is a rituximab resistant disease which tends to involve the skin. To conclude, DLBCL may relapse extensively with cutaneous involvement and the best treatment option in these patients is salvage chemotherapy followed by autologous peripheral blood stem cell transplantation. PMID:26457084

  3. 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

  4. Amygdala mechanisms of Pavlovian psychostimulant conditioning and relapse.

    PubMed

    Buffalari, Deanne M; See, Ronald E

    2010-01-01

    Psychostimulant addiction often consists of periods of sustained drug abstinence disrupted by periods of relapse and renewed heavy drug use. Prevention of relapse remains the greatest challenge to the successful treatment of drug addiction. Drug-associated cues are a primary trigger for relapse, as they can elicit intense craving for the drug. These cues become associated with the drug reward through Pavlovian learning processes that develop over multiple drug-cue pairings. The amygdala (AMY) is critical for such drug-related learning. Intrinsic and extrinsic circuitry position the AMY to integrate cue and drug-related information and influence drug-seeking and drug-taking behaviors. Animal models of conditioned drug reward, drug use, and relapse have confirmed the necessary role of the AMY for drug conditioned cues to control motivated behavior. Neurons within the AMY are responsive to the primary effects of psychostimulants, and more critically, they also respond to the presentation of drug-associated cues. The mechanisms by which conditioned cues come to influence drug-seeking behavior likely involve long-term plasticity and neuroadaptations within the AMY. A greater understanding of the associative learning mechanisms that depend upon the AMY and related limbic and cortical structures, and the process by which drug cues come to gain control over behavior that maintains the addictive state, will facilitate the development of more effective addiction treatments.

  5. [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.

  6. [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. PMID:25817451

  7. Relapse of lymphoma after allogeneic hematopoietic cell transplantation: management strategies and outcome.

    PubMed

    Wudhikarn, Kitsada; Brunstein, Claudio G; Bachanova, Veronika; Burns, Linda J; Cao, Qing; Weisdorf, Daniel J

    2011-10-01

    The outcome and management of relapsed lymphoma after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), reduction of immunosuppression (RIS), chemotherapy, radiation, immunotherapy, second HCT, and experimental treatments, but reported data contrasting the response and efficacy of these salvage treatments are limited. We describe the treatments, response, prognosis, and long-term survival of 72 patients with relapse of lymphoma after allogeneic HCT. Between 1991 and 2007, 227 lymphoma patients underwent allogeneic HCT. Of these, 72 (32%) developed relapse/progression after their HCT at a median of 99 days (0-1898 days); 37 had early (<100 days) post-HCT relapse. Forty-four had non-Hodgkin lymphoma (7 mantle cell, 5 indolent, 15 diffuse large B cell, 4 Burkitt's, and 13 T/Natural Killer cell), and 28 patients had Hodgkin lymphoma. At the time of HCT, 62 patients were in remission (22 in complete [CR] and 40 in partial [PR]), 1 had stable whereas 9 had progressive disease. Seventeen cases received myeloablative and 55 received a reduced-intensity conditioning regimen. At relapse, most patients had generalized lymphadenopathy, extranodal organ involvement, and advanced disease. Five patients received no intervention for the post-HCT relapse. Immunosuppressive treatment was reduced or withdrawn as the first-line therapy in 58 patients (80.5%); 47 were treated using combinations of conventional chemotherapy (n = 22), rituximab (n = 27), interferon (IFN) (n = 1), DLI (n = 7), second HCT (n = 2), local radiation (n = 23), and other therapy (n = 6). Thirty-eight patients had an objective response (CR in 30, PR in 8), and 2 had stable disease (SD). At the post-HCT relapse, favorable prognostic factors for survival after HCT included good ECOG performance status (0-2), normal lactate dehydrogenase (LDH), early stage disease (stage I-III), isolated extranodal organ involvement, and later relapse

  8. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass.

  9. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  10. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Facenda-Lorenzo, María; Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J; Llanos-Gómez, Juan M; Cabello-Rodríguez, Ana I; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called "sanctuaries," are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  11. The cost of relapse and the predictors of relapse in the treatment of schizophrenia

    PubMed Central

    2010-01-01

    Background To assess the direct cost of relapse and the predictors of relapse during the treatment of patients with schizophrenia in the United States. Methods Data were drawn from a prospective, observational, noninterventional study of schizophrenia in the United States (US-SCAP) conducted between 7/1997 and 9/2003. Patients with and without relapse in the prior 6 months were compared on total direct mental health costs and cost components in the following year using propensity score matching method. Baseline predictors of subsequent relapse were also assessed. Results Of 1,557 participants with eligible data, 310 (20%) relapsed during the 6 months prior to the 1-year study period. Costs for patients with prior relapse were about 3 times the costs for patients without prior relapse. Relapse was associated with higher costs for inpatient services as well as for outpatient services and medication. Patients with prior relapse were younger and had onset of illness at earlier ages, poorer medication adherence, more severe symptoms, a higher prevalence of substance use disorder, and worse functional status. Inpatient costs for patients with a relapse during both the prior 6 months and the follow-up year were 5 times the costs for patients with relapse during the follow-up year only. Prior relapse was a robust predictor of subsequent relapse, above and beyond information about patients' functioning and symptom levels. Conclusions Despite the historical decline in utilization of psychiatric inpatient services, relapse remains an important predictor of subsequent relapse and treatment costs for persons with schizophrenia. PMID:20059765

  12. 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. PMID:27077309

  13. 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…

  14. 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…

  15. Relapse Crises and Coping among Dieters.

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; And Others

    1989-01-01

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

  16. Treatment relapse and behavioral momentum theory.

    PubMed

    Pritchard, Duncan; Hoerger, Marguerite; Mace, F Charles

    2014-01-01

    The relapse of problem behavior after apparently successful treatment is an enduring problem for the field of applied behavior analysis. Several theoretical accounts of treatment relapse have emerged over the years. However, one account that has received considerable recent attention is based on behavioral momentum theory (BMT). BMT has shown that behavior is more persistent in contexts that are correlated with higher rates of reinforcers after disruption of the response-reinforcer relation. Accordingly, relapse after successful treatment can be viewed as the persistence of behavior when treatment is compromised in some manner. We review basic BMT research, alternative accounts of treatment relapse, and translational research studies derived from BMT research. The implications for applied behavior analysis in practice are discussed along with potential solutions to the problem of treatment relapse.

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

    PubMed

    Landau, Dan A; Tausch, Eugen; Taylor-Weiner, Amaro N; Stewart, Chip; Reiter, Johannes G; Bahlo, Jasmin; Kluth, Sandra; Bozic, Ivana; Lawrence, Mike; Böttcher, Sebastian; Carter, Scott L; Cibulskis, Kristian; Mertens, Daniel; Sougnez, Carrie L; Rosenberg, Mara; Hess, Julian M; Edelmann, Jennifer; Kless, Sabrina; Kneba, Michael; Ritgen, Matthias; Fink, Anna; Fischer, Kirsten; Gabriel, Stacey; Lander, Eric S; Nowak, Martin A; Döhner, Hartmut; Hallek, Michael; Neuberg, Donna; Getz, Gad; Stilgenbauer, Stephan; Wu, Catherine J

    2015-10-22

    Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome. PMID:26466571

  18. 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.

  19. 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

  20. 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. PMID:26706696

  1. 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.

  2. Management of relapsed ovarian cancer: a review.

    PubMed

    Giornelli, Gonzalo H

    2016-01-01

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

  3. Randomized trial comparing mindfulness-based relapse prevention with relapse prevention for women offenders at a residential addiction treatment center.

    PubMed

    Witkiewitz, Katie; Warner, Kaitlin; Sully, Betsy; Barricks, Adria; Stauffer, Connie; Thompson, Brian L; Luoma, Jason B

    2014-04-01

    Reincarceration rates are high among substance-involved criminal offenders. This study (conducted during 2010-2011 in an urban area and funded by a Washington State University-Vancouver mini-grant) used a randomized design to examine the effectiveness of mindfulness-based relapse prevention (MBRP) as compared to relapse prevention (RP), as part of a residential addictions treatment program for women referred by the criminal-justice system (N = 105). At 15-week follow up, regression analyses found women in MBRP, compared to RP, reported significantly fewer drug use days and fewer legal and medical problems. Study limitations and future research directions for studying the efficacy of MBRP are discussed. PMID:24611849

  4. 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..

  5. Teriflunomide reduces relapses with sequelae and relapses leading to hospitalizations: results from the TOWER study.

    PubMed

    Miller, Aaron E; Macdonell, Richard; Comi, Giancarlo; Freedman, Mark S; Kappos, Ludwig; Mäurer, Mathias; Olsson, Tomas P; Wolinsky, Jerry S; Bozzi, Sylvie; Dive-Pouletty, Catherine; O'Connor, Paul W

    2014-09-01

    Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. This post hoc analysis of the Phase III TOWER study evaluated the effects of teriflunomide treatment on five severe relapse outcomes: relapses with sequelae defined by an increase in Expanded Disability Status Scale (EDSS)/functional system (FS) score (sequelae-EDSS/FS) 30 days post relapse; relapses with sequelae defined by the investigator (sequelae-investigator); relapses leading to hospitalization; relapses treated with intravenous corticosteroids; and intense relapses using the definition of Panitch et al. from the EVIDENCE study based on specified increases in EDSS for severe relapses. Adjusted annualized rates for the five severe relapse outcomes were derived using a Poisson model with robust error variance, with treatment, baseline EDSS strata and region as covariates. Compared with placebo, teriflunomide significantly reduced annualized rates of relapses with sequelae-EDSS/FS [14 mg, 36.6 % (p = 0.0021); 7 mg, 31.3 % (p = 0.0104)] and sequelae-investigator [14 mg only, 53.5 % (p = 0.0004)], relapses leading to hospitalization [14 mg only, 33.6 % (p = 0.0155)], relapses requiring intravenous corticosteroids [14 mg, 35.7 % (p = 0.0002); 7 mg, 21.5 % (p = 0.0337)], and intense relapses [14 mg only, 52.5 % (p = 0.0015)]. Patients treated with teriflunomide 14 mg spent significantly fewer nights in hospital for relapse (p = 0.009) and had lower annualized rates of all hospitalizations (p = 0.030). Taken together, the positive effects of teriflunomide on severe relapses indicate that teriflunomide may reduce relapse-related healthcare costs. PMID:24972678

  6. Relapse after allogeneic stem cell transplantation

    PubMed Central

    Barrett, A John; Battiwalla, Minoo

    2012-01-01

    Since allogeneic stem cell transplantation (SCT) represents an intensive curative treatment for high-risk malignancies, its failure to prevent relapse leaves few options for successful salvage treatment. While many patients have a high early mortality from relapse, some respond and have sustained remissions, and a minority has a second chance of cure with appropriate therapy. The prognosis for relapsed hematological malignancies after SCT depends on four factors: the time elapsed from SCT to relapse (with relapses occurring within 6 months having the worst prognosis), the disease type (with chronic leukemias and some lymphomas having a second possibility of cure with further treatment), the disease burden and site of relapse (with better treatment success if disease is treated early), and the conditions of the first transplant (with superior outcome for patients where there is an opportunity to increase either the alloimmune effect, the specificity of the antileukemia effect with targeted agents or the intensity of the conditioning in a second transplant). These features direct treatments toward either modified second transplants, chemotherapy, targeted antileukemia therapy, immunotherapy or palliative care. PMID:21083034

  7. 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)

  8. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

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

    2016-01-01

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

  9. The Role of Postpartum Intravenous Corticosteroids in the Prevention of Relapses in Multiple Sclerosis

    PubMed Central

    Avila, Mirla; Stosic, Milena; Robles, Liliana; Prieto, Pilar Guillermo; Hutton, George J.; Rivera, Victor M.

    2011-01-01

    Multiple sclerosis (MS) is most prevalent in women of childbearing age. It is well established that the relapse rate decreases during pregnancy but increases significantly during the first postpartum trimester. The objective of this retrospective study was to evaluate the effectiveness of the administration of 1 g of intravenous methylprednisolone (IVMP) after delivery in the prevention of MS relapses. The study involved 47 women with one or more documented pregnancies; each pregnancy was treated as a separate case. There were 50 cases with relapsing-remitting MS and 2 with secondary progressive MS. The cases were divided into two groups: the IVMP group (those who received 1 g of IVMP after delivery) and the no-IVMP group (those who did not receive IVMP after delivery). There were 39 cases in the IVMP group and 13 in the no-IVMP group. During the first postpartum trimester, relapses occurred in 17.9% of the IVMP group, compared with 46.2% of the no-IVMP group (P = .0448). The difference in relapse percentage between the two groups during the second and third postpartum trimesters was not statistically significant. Our study shows a statistically significant benefit of postpartum IVMP administration in reducing MS relapses. PMID:24453710

  10. Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

    PubMed

    Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-10-01

    A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. PMID:27316790

  11. 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.

  12. 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

  13. Peptide YY and ghrelin predict craving and risk for relapse in abstinent smokers.

    PubMed

    al'Absi, Mustafa; Lemieux, Andrine; Nakajima, Motohiro

    2014-11-01

    Appetite hormones are directly involved in regulating satiety, energy expenditure, and food intake, and accumulating evidence suggests their involvement in regulating reward and craving for drugs. This study investigated the ability of peptide YY (PYY) and ghrelin during the initial 24-48 h of a smoking cessation attempt to predict smoking relapse at 4 weeks. Multiple regression analysis indicated that increased PYY was associated with decreased reported craving and increased positive affect. Cox proportional hazard models showed that higher ghrelin levels predicted increased risk of smoking relapse (hazard ratio=2.06, 95% CI=1.30-3.27). These results indicate that circulating PYY may have buffering effects during the early stages of cessation while ghrelin may confer increased risk of smoking relapse. Further investigation of the links between these hormones and nicotine dependence is warranted.

  14. Do hypnozoites cause relapse in malaria?

    PubMed

    Markus, Miles B

    2015-06-01

    The concept that hypnozoites give rise to relapses in Plasmodium vivax and Plasmodium ovale malaria has become dogma. However, it is evident from particular contemporary research findings that hypnozoites are not necessarily the origin of all relapse-like recurrences of malaria caused by these parasites. This is the core opinion presented, and I discuss it fully. The hypnozoite theory of relapse needs to be re-evaluated in view of the recent, increased focus on P. vivax and liver stages of Plasmodium. Hypnozoites have also assumed a new significance because they might, by facilitating ongoing transmission, be a threat to the current (post-2007) goal of eliminating malaria globally. I have suggested some new research directions for finding putative nonhypnozoite sources of recurrent malaria.

  15. An Interpersonal Model of Addiction Relapse

    PubMed Central

    Leach, David; Kranzler, Henry R.

    2012-01-01

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

  16. Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence

    PubMed Central

    Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

    2016-01-01

    ABSTRACT Background: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. Case presentation: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. Discussion: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. Conclusion: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration. PMID:27105248

  17. Immunotoxin Therapy for Relapsed Hairy Cell Leukemia

    Cancer.gov

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

  18. Noncirrhotic hyperammonemia causing relapsing altered mental status

    PubMed Central

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

    2015-01-01

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

  19. Relapsing acute respiratory failure induced by minocycline.

    PubMed

    Oddo, Mauro; Liaudet, Lucas; Lepori, Mattia; Broccard, Alain F; Schaller, Marie-Denise

    2003-06-01

    The antibiotic minocycline, which is used in the treatment of acne, has been associated with various pulmonary complications such as pulmonary lupus and hypersensitivity pneumonitis. We now report a particularly severe case of minocycline-related pulmonary toxicity that was characterized by a relapsing form of hypersensitivity eosinophilic pneumonia complicated by acute respiratory failure.

  20. 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…

  1. 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…

  2. 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…

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

    PubMed

    Giebel, S M

    2006-01-01

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

  4. 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

  5. Development of an acceptance-based coping intervention for alcohol dependence relapse prevention.

    PubMed

    Vieten, Cassandra; Astin, John A; Buscemi, Raymond; Galloway, Gantt P

    2010-04-01

    Both psychological and neurobiological findings lend support to the long-standing clinical observation that negative affect is involved in the development and maintenance of alcohol dependence, and difficulty coping with negative affect is a common precipitant of relapse after treatment. Although many current approaches to relapse prevention emphasize change-based strategies for managing negative cognitions and affect, acceptance-based strategies for preventing relapse to alcohol use are intended to provide methods for coping with distress that are fundamentally different from, though in theory complementary to, approaches that emphasize control and change. This paper describes the development of Acceptance-Based Coping for Relapse Prevention (ABCRP), a new intervention for alcohol-dependent individuals who are within 6 months of having quit drinking. Results of preliminary testing indicate that the intervention is feasible with this population; and a small uncontrolled pilot study (N = 23) showed significant (P < .01) improvements in self-reported negative affect, emotional reactivity, perceived stress, positive affect, psychological well-being, and mindfulness level, as well as a trend (P = .06) toward reduction in craving severity between pre- and postintervention assessments. The authors conclude that this acceptance-based intervention seems feasible and holds promise for improving affect and reducing relapse in alcohol-dependent individuals, warranting further research.

  6. Prospective associations between brain activation to cocaine and no-go cues and cocaine relapse*

    PubMed Central

    Prisciandaro, James J.; Myrick, Hugh; Henderson, Scott; McRae-Clark, Aimee L.; Brady, Kathleen T.

    2013-01-01

    Background The ability to predict potential for relapse to substance use following treatment could be very useful in targeting aftercare strategies. Recently, a number of investigators have focused on using neural activity measured by fMRI to predict relapse propensity. The purpose of the present study was to use fMRI to investigate prospective associations between brain reactivity to cocaine and response inhibition cues and relapse to cocaine use. Methods Thirty cocaine-dependent participants with clean cocaine urine drug screens (UDS) completed a baseline fMRI scan, including a cocaine-cue reactivity task and a go/no-go response inhibition task. After participating in a brief clinical trial of D-cycloserine for the facilitation of cocaine cue extinction, they returned for a one-week follow-up UDS. Associations between baseline activation to cocaine and inhibition cues and relapse to cocaine use were explored. Results Positive cocaine UDS was significantly associated with cocaine cue activation in the right putamen and insula, as well as bilateral occipital regions. Associations between positive cocaine UDS and activation to no-go cues were concentrated in the postcentral gyri, a region involved in response execution. Conclusions Although preliminary, these results suggest that brain imaging may be a useful tool for predicting risk for relapse in cocaine-dependent individuals. Further, larger-scale naturalistic studies are needed to corroborate and extend these findings. PMID:23683790

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

    ERIC Educational Resources Information Center

    Rose-Colley, Mary; Cinelli, Bethann

    1992-01-01

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

  8. 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…

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

    PubMed

    Shaham, Yavin; Hope, Bruce T

    2005-11-01

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

  10. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25239991

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

    PubMed

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

    2014-01-01

    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. PMID:25239991

  13. 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.

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

    PubMed

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

    2016-01-12

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

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

    PubMed

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

    2016-01-01

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

  16. Leptin Influence in Craving and Relapse of Alcoholics and Smokers

    PubMed Central

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

    2013-01-01

    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. PMID:23671541

  17. Management of relapsed mantle cell lymphoma: still a treatment challenge.

    PubMed

    Ruan, Jia; Coleman, Morton; Leonard, John P

    2009-07-01

    Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that remains incurable, and is associated with a median survival of approximately 5 years. Management of patients with relapsed or refractory disease is challenging. The major therapeutic goal in MCL management is to improve survival and quality of life whenever possible. Progress has been made in MCL therapy in the past decade based on clinical experimentation with novel agents and combinations. There is a growing list of conventional and novel agents in our armamentarium, consisting of not only additional chemotherapy combinations including high-dose approaches, but also biologically targeted reagents such as the monoclonal antibody rituximab, the proteasome inhibitor bortezomib, the mTOR inhibitor temsirolimus, immunomodulatory and antiangiogenic agents including thalidomide and lenalidomide, and cyclin-dependent kinase inhibitors, as well as a renewed interest in older compounds such as bendamustine and metronomic regimens. Efficacy evaluations for individual agents and rational combinations are in various stages of development, while treatment selection based on molecular and clinical prognostic scores is yet to be tested. In the absence of evidence demonstrating relative survival advantages of various second-line options, management of relapsed and refractory disease should be individualized. Involvement of a lymphoma center participating in clinical trials of novel MCL treatments is encouraged.

  18. 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

  19. Pseudocyst formation in retroperitoneal fibrosis relapse.

    PubMed

    Jansen, I; Hendriksz, T R; Van Bommel, E F H

    2010-06-01

    We describe a 45-year-old male patient with recurrent retroperitoneal fibrosis (RPF), in whom a pseudocyst in the peri-aortic fibrotic mantle was diagnosed. Without any intervention other than oral treatment with tamoxifen, the pseudocyst showed significant regression. Although rare, pseudocyst formation may sometimes appear in RPF and may mimic other benign and malignant conditions. This is the first paper to describe pseudocyst formation in an RPF relapse.

  20. Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study.

    PubMed

    Sabel, Magnus; Fleischhack, Gudrun; Tippelt, Stephan; Gustafsson, Göran; Doz, François; Kortmann, Rolf; Massimino, Maura; Navajas, Aurora; von Hoff, Katja; Rutkowski, Stefan; Warmuth-Metz, Monika; Clifford, Steven C; Pietsch, Torsten; Pizer, Barry; Lannering, Birgitta

    2016-09-01

    The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 ± 2 % and 78 ± 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. >5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 ± 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour. PMID:27423645

  1. Treatment of relapsed and refractory Hodgkin Lymphoma.

    PubMed

    von Tresckow, Bastian; Moskowitz, Craig H

    2016-07-01

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

  2. 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.

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

    PubMed

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

    2015-01-01

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

  4. A systematic review of relapse measurement in randomized controlled trials of relapse prevention in first-episode psychosis.

    PubMed

    Gleeson, John F M; Alvarez-Jimenez, Mario; Cotton, Sue M; Parker, Alexandra G; Hetrick, Sarah

    2010-06-01

    The prevention of relapse is an important treatment goal in first-episode psychosis. Randomized controlled trials (RCTs) provide the gold standard methodology for evaluating interventions for relapse prevention. Properly designed RCTs which include relapse as a treatment outcome should rigorously operationalize psychotic relapse. The aim of this systematic literature review was to evaluate according to six criteria the operationalization of relapse in RCTs of clinical innovations for the prevention of relapse in first-episode psychosis. Through a systematic literature search of relevant RCTs in first-episode psychosis patients, eight pharmacological and eight non-pharmacological trials, published between 1982 and 2009, were identified. Readmission to a psychiatric hospital was the most common definition of psychotic relapse. Five studies did not measure relapse using any standardized or validated observer-rated instruments. The majority of the studies did not specify a duration criterion for relapse. Only three studies satisfied six criteria for the adequate operationalization of relapse. These results raise concerns regarding the internal and external validity of these research findings. There is an urgent need for a standardized, universally adopted set of criteria for psychotic relapse with appropriate specification of measurement instruments for use in future RCTs. PMID:20347266

  5. Adversity-induced relapse of fear: neural mechanisms and implications for relapse prevention from a study on experimentally induced return-of-fear following fear conditioning and extinction.

    PubMed

    Scharfenort, R; Menz, M; Lonsdorf, T B

    2016-01-01

    The efficacy of current treatments for anxiety disorders is limited by high relapse rates. Relapse of anxiety disorders and addiction can be triggered by exposure to life adversity, but the underlying mechanisms remain unexplored. Seventy-six healthy adults were a priori selected for the presence or absence of adverse experiences during childhood (CA) and recent past (RA; that is, past 12 months). Participants underwent fear conditioning (day 1) and fear extinction and experimental return-of-fear (ROF) induction through reinstatement (a model for adversity-induced relapse; day 2). Ratings, autonomic (skin conductance response) and neuronal activation measures (functional magnetic resonance imaging (fMRI)) were acquired. Individuals exposed to RA showed a generalized (that is, not CS- specific) fear recall and ROF, whereas unexposed individuals showed differential (that is, CS+ specific) fear recall and ROF on an autonomic level despite no group differences during fear acquisition and extinction learning. These group differences in ROF were accompanied by corresponding activation differences in brain areas known to be involved in fear processing and differentiability/generalization of ROF (that is, hippocampus). In addition, dimensional measures of RA, CA and lifetime adversity were negatively correlated with differential skin conductance responses (SCRs) during ROF and hippocampal activation. As discriminating signals of danger and safety, as well as a tendency for overgeneralization, are core features in clinically anxious populations, these deficits may specifically contribute to relapse risk following exposure to adversity, in particular to recent adversity. Hence, our results may provide first and novel insights into the possible mechanisms mediating enhanced relapse risk following exposure to (recent) adversity, which may guide the development of effective pre- and intervention programs. PMID:27434492

  6. 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.

  7. 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. PMID:26786246

  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. Mycophenolate mofetil prevents a clinical relapse in patients with systemic lupus erythematosus at risk

    PubMed Central

    Bijl, M; Horst, G; Bootsma, H; Limburg, P; Kallenberg, C

    2003-01-01

    Background: Systemic lupus erythematosus (SLE) is characterised by the presence of antibodies to double stranded DNA (dsDNA), which are involved in the pathogenesis of SLE. Previous studies showed that at least two thirds of patients develop a clinical relapse within six months after a significant rise in the anti-dsDNA level, and most relapses were prevented by the administration of corticosteroids at the time of the rise. Objective: To determine whether mofetil mycophenolate (MMF) can prevent a clinical relapse without the side effects associated with corticosteroids. Methods: 36 patients with SLE were examined monthly to determine whether a rise in anti-dsDNA level had occurred. A rise was defined as an increase of 25% of the level of the previous sample of at least 15 IU/ml within a four month period. After a rise patients were treated with MMF 2000 mg daily for six months. Patients were monitored monthly for the occurrence of a clinical relapse and to assess the serological activity and state of activation of CD4+, CD8+, and CD19+ lymphocyte subsets. Results: Anti-dsDNA rose in 10 patients. Treatment with MMF was started in all these patients, and after six months no clinical relapse had occurred. Side effects were minimal. Antibodies to dsDNA decreased during the treatment (p<0.001), associated with a decrease in the state of activation of CD19+ lymphocytes. No changes were found in the state of activation of CD4+ or CD8+ lymphocyte subsets. Conclusion: Administration of MMF after a rise in antibodies to dsDNA is well tolerated, decreases anti-dsDNA and B cell activation, and seems to prevent the occurrence of a clinical relapse in patients with SLE. PMID:12759290

  10. Investigation of a Correlation between Thoracic Vertebra Hyperplasia and Relapse in Paroxysmal Atrial FIbrillation Patients Following Extended Pulmonary Vein Isolation.

    PubMed

    Hashida, Tadashi; Yoshioka, Koichiro; Kanda, Shigetaka; Fujibayashi, Daisuke; Amino, Mari; Ikari, Yuji

    2016-01-01

    Pulmonary vein isolation (PVI) with radio-frequency catheter ablation (RFCA) is effective therapy for the patients with paroxysmal atrial fibrillation (pAF). However, it is not easy to predict relapse of pAF. Approximately 70% pAF patients were maintained sinus rhythm for 1 year after PVI in Japan. In this study, all of the cases were underwent chest computed tomography (CT) to check for the morphology and positional relationship of the left atrium. We detected relapse cases that exhibited spur formation in the thoracic vertebrae. Therefore, we conducted an investigation based on the hypothesis that, "Because hyperostosis involves proliferative changes in the synovium or pia mater cells with an inflammatory basis, it is related to the onset of atrial fibrillation." The study sample consisted of 24 sequential cases (males: 20, mean age: 66.2 ± 6.9 years) of drug-resistant pAF that underwent PVI at our hospital between January and May, 2015. When subjects were divided into a relapse group and a non-relapse group and 21 background factors were compared, it was found that the relapse group subjects were older than the non-relapse group subjects (70.3 ± 7.2 vs 64.1 ± 5.7, p = 0.04). The proportion of cases with thoracic vertebra hyperplasia was markedly high in the relapse group (6 cases [75%] vs. 3 cases [18%], p = 0.007). No statistically significant differences were observed between the two groups for any other background factors. Our results suggested that thoracic vertebra hyperplasia could be a marker for predicting relapse after PVI in pAF patients. PMID:27628611

  11. Cardiac Apoptosis in Severe Relapsing Fever Borreliosis

    PubMed Central

    Londoño, Diana; Bai, Yunhong; Zückert, Wolfram R.; Gelderblom, Harald; Cadavid, Diego

    2005-01-01

    Previous studies revealed that the heart suffers significant injury during experimental Lyme and relapsing fever borreliosis when the immune response is impaired (D. Cadavid, Y. Bai, E. Hodzic, K. Narayan, S. W. Barthold, and A. R. Pachner, Lab. Investig. 84:1439-1450, 2004; D. Cadavid, T. O'Neill, H. Schaefer, and A. R. Pachner, Lab. Investig. 80:1043-1054, 2000; and D. Cadavid, D. D. Thomas, R. Crawley, and A. G. Barbour, J. Exp. Med. 179:631-642, 1994). To investigate cardiac injury in borrelia carditis, we used antibody-deficient mice persistently infected with isogenic serotypes of the relapsing fever agent Borrelia turicatae. We studied infection in hearts 1 to 2 months after inoculation by TaqMan reverse transcription-PCR and immunohistochemistry (IHC) and inflammation by hematoxylin and eosin and trichrome staining, IHC, and in situ hybridization (ISH). We studied apoptosis by terminal transferase-mediated DNA nick end labeling assay and measured expression of apoptotic molecules by RNase protection assay, immunofluorescence, and immunoblot. All antibody-deficient mice, but none of the immunocompetent controls, developed persistent infection of the heart. Antibody-deficient mice infected with serotype 2 had more severe cardiac infection and injury than serotype 1-infected mice. The injury was more severe around the base of the heart and pericardium, corresponding to sites of marked infiltration by activated macrophages and upregulation of interleukin-6 (IL-6). Infected hearts showed evidence of apoptosis of macrophages and cardiomyocytes as well as significant upregulation of caspases, most notably caspase-1. We conclude that persistent infection with relapsing fever borrelias causes significant loss of cardiomyocytes associated with prominent infiltration by activated macrophages, upregulation of IL-6, induction of caspase-1, and apoptosis. PMID:16239571

  12. Relapsing Fever Borreliae: A Global Review.

    PubMed

    Cutler, Sally J

    2015-12-01

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

  13. Cortical Thickness, Surface Area and Volume of the Brain Reward System in Alcohol Dependence: Relationships to Relapse and Extended Abstinence

    PubMed Central

    Durazzo, Timothy C.; Tosun, Duygu; Buckley, Shannon; Gazdzinski, Stefan; Mon, Anderson; Fryer, Susanna L.; Meyerhoff, Dieter J.

    2011-01-01

    multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. CONCLUSIONS Results suggest Relapsers demonstrated morphological abnormalities in regions involved in the “top down” regulation/modulation of internal drive states, emotions, reward processing and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an AUD. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in AUD. Results from this report are consistent with previous research implicating plastic neurobiological changes the brain reward system in the maintenance of addictive disorders. PMID:21410483

  14. AML evolution from preleukemia to leukemia and relapse.

    PubMed

    Shlush, Liran I; Mitchell, Amanda

    2015-01-01

    Dismal outcomes of acute myeloid leukemia (AML), especially in the elderly, are mainly associated with leukemia relapse and primary no response to initial therapy. This review will focus on AML relapse, and how a better understanding of the evolutionary stages that lead to relapse might help us improve disease outcome. The fact that the relapse rate for some AMLs is so high indicates that we do not truly understand the biology of relapse or possibly that we are not implementing our current understanding into, clinical practice. Therefore, this review will also aim to explore some of the current understanding of AML relapse biology in order to identify the gaps in our knowledge and translation. Accumulating evidence suggests that the root of relapse evolves even before the time of diagnosis, meaning that the complex clonal structure of AML is created before patients present to the clinic. Some of the clones that exist at diagnosis can survive chemotherapy and give rise to relapse. Accordingly, in order to better understand the mechanisms of relapse, we must consider both early and late steps in AML evolution.

  15. Relapsing and refractory ulcerative colitis in children.

    PubMed

    Turner, Dan

    2014-01-01

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

  16. Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia.

    PubMed

    Kawamata, Norihiko; Ogawa, Seishi; Seeger, Karl; Kirschner-Schwabe, Renate; Huynh, Thien; Chen, John; Megrabian, Nairi; Harbott, Jochen; Zimmermann, Martin; Henze, Günter; Schrappe, Martin; Bartram, Claus R; Koeffler, H Phillip

    2009-06-01

    Acute lymphoblastic leukemia (ALL) cells at relapse are frequently more resistant to treatment than primary clones and this may be caused by further genetic changes in the ALL cells at relapse. These acquired genomic abnormalities have not been fully characterized. To examine the additional genomic alterations of ALL at relapse, we performed single nucleotide polymorphism genomic microarry (SNP-chip) analysis on 14 ALL bone marrow samples at initial diagnosis, remission and relapse. Only two cases at initial diagnosis had a normal appearing genome by SNP-chip. All 14 cases had genomic alterations at relapse; and 10 of these had additional genomic abnormalities not present at diagnosis. Deletion of either the INK4A/ARF gene (2 cases) or the NF2 gene (2 cases) at 22q12.2 was an acquired genomic change at relapse. Loss of heterozygosity with normal copy number [uniparental disomy (UPD)] was detected in 3 cases as an additional genomic change at relapse. Interestingly, several genomic alterations, especially deletions, detected at initial diagnosis, disappeared at relapse, suggesting the ALL cells at relapse were minor clones at initial diagnosis and emerged at relapse. For several cases, trisomy at initial diagnosis changed to either UPD (2 cases) or normal appearing genome (2 cases). Further, we found disruption of PTPRD gene occurring at intron 23 as an additional genomic abnormality in one case. In summary, additional genomic changes are very common events in ALL at relapse; whether these abnormalities are associated with resistance to treatment remains to clarified in further studies.

  17. A double-blind, placebo-controlled trial of the NMDA glycine site antagonist, GW468816, for prevention of relapse to smoking in females.

    PubMed

    Evins, A Eden; Pachas, Gladys; Mischoulon, David; Urbanoski, Karen; Carlini, Sara; Sousa, Jessica; Bentley, Kate; Rigotti, Nancy A; Nino-Gomez, Johanna; Loebl, Tsafrir; Janes, Amy C; Kaufman, Marc J; Fava, Maurizio

    2011-10-01

    Relapse to smoking is common after initial abstinence with pharmacotherapy and behavioral support and represents a major clinical challenge. Although mechanisms underlying relapse to smoking have not been elucidated, preclinical studies suggest that glutamate receptors may be involved. We sought to test a selective antagonist of the glycine coagonist site on the glutamate N-methyl-D-aspartate receptor, GW468816, for prevention of relapse in recently abstinent smokers. To do so, we enrolled 264 healthy female smokers in an open 8-week smoking cessation intervention with behavioral therapy and a standard dose of transdermal nicotine replacement therapy with taper and additional gum or lozenge as needed for nicotine withdrawal symptoms. Ninety-eight participants achieved 7-day point prevalence abstinence and were randomized into a 5-week double-blind, placebo-controlled, relapse-prevention trial of GW468816 (200 mg/d) and then followed for 60 days after randomization. There was no effect of treatment on abstinence rates at the end of treatment (χ² [1, n = 96] = 0.168, P = 0.838), on the rates of relapse (χ² [1, n = 98] = 0.031, P = 1.000) or lapse (χ² [1, n = 62] = 0.802, P = 0.423), or on time to relapse (χ² [1, n = 98) = 0.001, P = 0.972). No significant relationships were detected between plasma GW468816 concentrations and abstinence, time to relapse, or self-reported craving. In conclusion, despite promising preclinical data that support the use of a selective NMDA glycine site antagonist for prevention of relapse to smoking, we observed no effect of GW468816 on relapse or lapse rates, time to relapse, or craving compared to placebo. PMID:21869693

  18. 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.

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

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, G. Alan

    2005-01-01

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

  20. Relapse Prevention Needs More Emphasis on Interpersonal Factors

    ERIC Educational Resources Information Center

    Stanton, Mark

    2005-01-01

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

  1. 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…

  2. 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…

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2016-02-01

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

  5. 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

  6. Tick-borne relapsing fever in children.

    PubMed

    Le, C T

    1980-12-01

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

  7. 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

  8. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    PubMed Central

    2011-01-01

    Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS). Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens) that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus), T-cell activation, T-cell memory, cross-regulation (negative feedback) between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS derives from the emergent

  9. 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

  10. Diffuse Large B-Cell Lymphoma of Maxilla – A Case Report of Late Relapse

    PubMed Central

    Kumar, Medikonda Suresh; Chandragiri, Anuradha; Amarnath, Konda

    2016-01-01

    Diffuse Large B Cell Lymphomas (DLBCL) encompasses a heterogeneous group of tumors that together constitute the commonest of all Non Hodgkin Lymphoma (NHL) and the proclivity of DLBCL to oral cavity is unknown. They mostly arise from soft tissues as asymptomatic lesions, mostly without ‘B’ symptoms and involvement of jaw bones is uncommon. Most studies and case reports of oral DLBCL’s are based on, manifestation of primary extra-nodal disease or a component of a disseminated disease process involving regional lymph nodes. Many investigators have proposed that patients with this cell type who maintain a complete response for 24 consecutive months are cured because late relapses seldom occur. With advances in treatment modalities, many patients with NHL become long-term survivors and the risk of relapses or second tumors are of growing concern. We present a case of DLBCL which relapsed after five years of initial lesion in a 41 year old female patient and presented as a nonspecific bilateral anterior maxillary radiolucency. DLBCL usually express pan-B markers with small percentage expressing T-cell markers. Few rare cases of DLBCL have shown CD3 expression, which is a most sensitive T-cell marker which was focally expressed in the present case. PMID:27190967

  11. Factors associated with prognosis in human breast cancer. III. Estradiol receptors and short term relapse.

    PubMed

    Pascual, M R; Macías, A; Moreno, L; Lage, A

    1983-01-01

    Prognosis in breast cancer is one of the most important subjects currently studied because of the heterogeneity of the disease even inside the same clinical stage. Estrogen receptor determination in human breast cancer has been recognized as a prognostic factor since it is related to the long-term survival and disease-free interval. In a series of papers concerning prognosis in breast cancer this the third one which includes estrogen receptor determination in the multivariate analysis, because of the limitations of the clinical factor to conform stratification groups. We have analyzed the short term probability of relapse in a group of 136 patients treated for breast cancer. Multivariate stratification analysis was performed with the aid of Bintree computer program, which produces binary splits of the population according to the criterion of maximal reduction of variance and generates a binary stratification tree. Lymph node involvement is the most important prognostic factor in the probability of relapse. Patients without nodal involvement lacking estradiol receptor had 25% of relapse. It is therefore evident that estradiol receptor is a factor of prognostic value even inside node negative patients. PMID:6656962

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

    ClinicalTrials.gov

    2016-08-10

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

  13. New strategies in assessing, treating, and relapse prevention of extramarital affairs.

    PubMed

    McCarthy, Barry; Wald, Lana M

    2013-01-01

    Understanding, assessing, treating, and preventing relapse of extra-marital affairs has involved significant changes in the past 10 years. This conceptual/clinical article expands on the groundbreaking work of Snyder, Gordon, and Baucom (2007), and has a special focus placed on the process of sexual recovery from an extra-marital affair. Secondly, this article focuses on the importance of creating a relapse prevention agreement. Both traditional and non-traditional agreements with regard to monogamy are described. Recognizing individual, couple, cultural, and value differences in norms and expectations exhibits a particular challenge in the study and treatment of extra-marital affairs. The clinician honors these complexities and differences by designing a treatment program that meets the needs of each couple.

  14. Prevention of relapse in women who quit smoking during pregnancy.

    PubMed Central

    McBride, C M; Curry, S J; Lando, H A; Pirie, P L; Grothaus, L C; Nelson, J C

    1999-01-01

    OBJECTIVES: This study is an evaluation of relapse prevention interventions for smokers who quit during pregnancy. METHODS: Pregnant smokers at 2 managed care organizations were randomized to receive a self-help booklet only, prepartum relapse prevention, or prepartum and postpartum relapse prevention. Follow-up surveys were conducted at 28 weeks of pregnancy and at 8 weeks, 6 months, and 12 months postpartum. RESULTS: The pre/post intervention delayed but did not prevent postpartum relapse to smoking. Prevalent abstinence was significantly greater for the pre/post intervention group than for the other groups at 8 weeks (booklet group, 30%; prepartum group, 35%; pre/post group, 39%; P = .02 [different superscripts denote differences at P < .05]) and at 6 months (booklet group, 26%, prepartum group, 24%; pre/post group, 33%; P = .04) postpartum. A nonsignificant reduction in relapse among the pre/post group contributed to differences in prevalent abstinence. There was no difference between the groups in prevalent abstinence at 12 months postpartum. CONCLUSIONS: Relapse prevention interventions may need to be increased in duration and potency to prevent post-partum relapse. PMID:10224982

  15. Relapse with Dysphagia in a Case of Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

    PubMed

    Teramoto, Hiroko; Morita, Akihiko; Hara, Makoto; Ninomiya, Satoko; Shigihara, Shuntaro; Kusunoki, Susumu; Kamei, Satoshi

    2015-01-01

    Glossopharyngeal and/or vagus nerve involvement is infrequent in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We herein report the case of a 69-year-old Japanese woman who presented with muscle weakness and numbness of the extremities with dysphagia. The serum anti-ganglioside GM1 immunoglobulin IgM antibody levels were elevated, and treatment with intravenous immunoglobulin (IVIg) resulted in a dramatic improvement; the weakness, numbness and dysphagia all resolved. However, relapse comprising dysphagia alone occurred on hospital day 26, and treatment with IVIg again proved extremely effective. IVIg therapy can be effective against cranial nerve involvement in cases of CIDP.

  16. Dimethyl fumarate for relapsing-remitting multiple sclerosis.

    PubMed

    2014-09-01

    For many years the only drugs licensed for the treatment of multiple sclerosis (MS) were administered by injection (interferon beta, glatiramer and ▼natalizumab). Recently, three oral drugs have become available. We have previously reviewed the use of ▼fingolimod for highly active relapsing-remitting MS1 and ▼teriflunomide for the management of relapsing-remitting MS in adults.2 Here, we review the evidence for ▼dimethyl fumarate (Tecfidera-Biogen Idec Ltd) for the treatment of adults with relapsing-remitting MS. PMID:25213591

  17. Extramedullary relapse of AML with t(9;11)(p22;q23) associated with clonal evolution from trisomy 8 into tetrasomy 8.

    PubMed

    Takahashi, Tohru; Tsukuda, Hiroyuki; Kimura, Hirokazu; Yoshimoto, Mitsuru; Tsujisaki, Masayuki

    2010-01-01

    This report describes a patient with extramedullary relapse of acute myeloid leukemia (AML) without involving bone marrow. A 57-year-old man was diagnosed as having acute monoblastic leukemia with t(9;11)(p22;q23) and trisomy 8. Ten months after achieving complete response (CR) with chemotherapy, masses developed in his left forearm and in the back of his thigh, preceded by enigmatic peripheral neurological symptoms. Aspiration from the forearm showed leukemic relapse, and fluorescence in situ hybridization (FISH) revealed that the majority of the cells had 11q23 anomaly and tetrasomy 8. Bone marrow or meningeal relapse was not observed. To our knowledge, this is the first case report of clonal evolution associated with the development of myeloid sarcoma as a relapse in AML. PMID:20190481

  18. 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

    2016-01-01

    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

  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. 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

  1. 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.

  2. 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.

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

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160747.html Smoking Linked to Higher Relapse Risk After Surgery for ... 1, 2016 THURSDAY, Sept. 1, 2016 (HealthDay News) -- Smoking increases the risk that Crohn's disease patients will ...

  4. Agents for refractory/relapsed acute lymphocytic leukemia in adults.

    PubMed

    Qian, L-R; Fu, W; Shen, J-L

    2014-01-01

    Although treatment results for adult acute lymphoblastic leukemia (ALL) have improved considerably in the past decades, treating adult patients with relapsed/refractory acute lymphocytic leukemia (ALL) is still difficult. Adults with refractory/relapsed acute lymphocytic leukemia (ALL) processed to death rapidly associated with chemotherapy resistance, high mortality by reinduction, etc. Only 20% to 30% of those patients acquired complete remission (CR). Those patients are always of short duration unless an allogeneic stem cell transplant is feasible. Median survival is only ranging from 2 to 12 months. Therapeutic strategy on relapsed/refractory acute lymphocytic leukemia (ALL) is always a major therapeutic challenge bothering hematological researchers. Novel agents and unique therapeutic strategies have been developed in recent years. This review focuses on major clinical advances in the agents for refractory/relapsed ALL.

  5. Is alcohol dependence best viewed as a chronic relapsing disorder?

    PubMed

    Cunningham, John A; McCambridge, Jim

    2012-01-01

    This 'For Debate' paper starts by recognizing the growing trend towards considering alcohol dependence as a chronic relapsing disorder. We argue that the adoption of this model results from focusing on those in treatment for alcohol dependence rather than considering the larger number of people in the general population who meet criteria for alcohol dependence at some point in their lives. The majority of the general population who ever experience alcohol dependence do not behave as though they have a chronic relapsing disorder: they do not seek treatment, resolve their dependence themselves and do not relapse repeatedly. We suggest that caution is therefore needed in using the chronic relapsing disorder label. Our primary concerns are that this formulation privileges biological aspects of dependence to the detriment of psychological and social contributions, it inhibits much-needed developments in understanding alcohol dependence and leads to inefficient distributions of public health and clinical care resources for alcohol dependence. We invite debate on this issue.

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

    PubMed Central

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

    1987-01-01

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

  7. [PROGNOSTIC GROUPS FOR RELAPSE IN STAGE IB1 CERVICAL CANCER].

    PubMed

    Ismail, E; Kornovski, Y; Ivanov, S

    2015-01-01

    Risk factors for relapse in stage IB1 cervical cancer were analized and identified by the following statistical tests-Kaplan-Meier, Cox regression, Log-rank test, Breslow and Tarone-Ware tests. A quantitative analysis of significant factors for relapse in group submitted to surgery and adjuvant radiotherapy(group 1) and group submitted only to surgery (group 2), was done. These methods allow us to difine 3 different prognostic groups, requiring different therapeutic approaches.

  8. Interventricular low-grade oligodendroglioma with multiple parenchymal relapse.

    PubMed

    Akhavan, Ali; Binesh, Fariba; Rakhsha, Afshin; Navabii, Hossein

    2012-06-08

    Oligodendrogliomas can be found anywhere oligodendrocytes exist; however, they mostly occur in frontal lobes. Although intra- and extra central nervous system dissemination of anaplastic oligodendroglioma is a well-known property of this tumour, low-grade oligodendroglioma with intracranial relapse is a very uncommon finding. In this case report, a 37-year-old man with grade II oligodendroglioma relapsed after 18 months with multiple parenchymal masses is presented.

  9. Glatiramer Acetate 40 mg/mL in Relapsing-Remitting Multiple Sclerosis: A Review.

    PubMed

    McKeage, Kate

    2015-05-01

    Glatiramer acetate (Copaxone(®)) is a synthetic analogue of myelin basic protein, which is thought to be involved in the pathogenesis of multiple sclerosis (MS). The therapeutic effects of the drug in the treatment of MS are thought to be via immunomodulation and neuroprotection. Subcutaneous glatiramer acetate 20 mg/mL once daily is approved in several countries for the treatment of relapsing forms of MS. Recently, a high-concentration formulation of glatiramer acetate 40 mg/mL administered three times weekly was approved in the USA and several European countries in the same indication. This article reviews the efficacy and tolerability of the high-concentration regimen. In the randomized, phase III GALA study in patients with relapsing-remitting MS (RRMS), glatiramer acetate 40 mg/mL three times weekly reduced annualized relapse rates significantly more than placebo, and indirect comparisons indicate that the efficacy of the three-times-weekly regimen is similar to that of the 20 mg/mL once-daily regimen. Results of the randomized, phase IIIb GLACIER study in patients with RRMS demonstrated that the three-times-weekly regimen reduced the risk of injection-site reactions by 50 % and was associated with numerically greater patient convenience scores than the once-daily regimen. Thus, in the treatment of RRMS, glatiramer acetate 40 mg/mL three times weekly is effective and provides a better tolerated and possibly more convenient option than the once-daily regimen.

  10. Relapse processes after the extinction of instrumental learning: Renewal, resurgence, and reacquisition

    PubMed Central

    Bouton, Mark E.; Winterbauer, Neil E.; Todd, Travis P.

    2012-01-01

    It is widely recognized that extinction (the procedure in which a Pavlovian conditioned stimulus or an instrumental action is repeatedly presented without its reinforcer) weakens behavior without erasing the original learning. Most of the experiments that support this claim have focused on several “relapse” effects that occur after Pavlovian extinction, which collectively suggest that the original learning is saved through extinction. However, although such effects do occur after instrumental extinction, they have not been explored there in as much detail. This article reviews recent research in our laboratory that has investigated three relapse effects that occur after the extinction of instrumental (operant) learning. In renewal, responding returns after extinction when the behavior is tested in a different context; in resurgence, responding recovers when a second response that has been reinforced during extinction of the first is itself put on extinction; and in rapid reacquisition, extinguished responding returns rapidly when the response is reinforced again. The results provide new insights into extinction and relapse, and are consistent with principles that have been developed to explain extinction and relapse as they occur after Pavlovian conditioning. Extinction of instrumental learning, like Pavlovian learning, involves new learning that is relatively dependent on the context for expression. PMID:22450305

  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. Comparison of Patterns of Relapse in Thymic Carcinoma and Thymoma

    PubMed Central

    Huang, James; Rizk, Nabil P.; Travis, William D.; Riely, Gregory J.; Park, Bernard J.; Bains, Manjit S.; Dycoco, Joseph; Flores, Raja M.; Downey, Robert J.; Rusch, Valerie W.

    2014-01-01

    Objective Thymic carcinomas (TC) are considered to be more aggressive than thymomas and carry a worse prognosis. We reviewed our recent experience with the surgical management of thymic tumors and compared the outcomes and patterns of relapse between TC and thymoma. Methods Single institution retrospective cohort study. Data included patient demographics, stage, treatment, pathologic findings, and postoperative outcomes. Results During the period 1995–2006, 120 patients with thymic tumors underwent surgery, including 23 patients with TC and 97 patients with thymoma by the WHO 2004 histologic classification. The overall 5 year survival was significantly different between TC and thymoma (TC 53%, thymoma 89%, p=0.01). Data on relapse was available for 112 patients. The progression-free 5 year survival was also significantly different between TC and thymoma (TC 36%, thymoma 75%, p<0.01). By multivariate analysis, thymic carcinoma and incomplete resection were found to be independent predictors of progression-free survival. Relapses in TC tended to occur earlier, and occurred signficantly more frequently at distant sites than in thymoma (60% vs. 13%, p=0.01). Conclusions Patterns of relapse differ significantly between TC and thymoma with lower progression-free survival, earlier onset and more distant relapses in TC. Given the greater propensity for distant failures, the inclusion of systemic therapy in the treatment of TC may take on greater importance. Despite significantly higher rates of distant relapse, good overall survival in TC can be achieved. PMID:19577051

  13. Treatment, expressed emotion and relapse in recent onset schizophrenic disorders.

    PubMed

    Linszen, D; Dingemans, P; Van der Does, J W; Nugter, A; Scholte, P; Lenior, R; Goldstein, M J

    1996-03-01

    The effect of in-patient and individual orientated psychosocial intervention (IPI) and in-patient and individual and family orientated intervention (IPFI) across levels of expressed emotion (EE) on relapse was compared in a group of patients with recent onset schizophrenic disorders. Patients were randomly assigned to an individual orientated psychosocial intervention programme or to an identical psychosocial programme plus a behavioural family intervention. Seventy-six patients were studied during a 12 month out-patient treatment period after an in-patient treatment programme in which parents followed a psychoeducational programme. Overall relapse rates during the out-patient interventions were low (16%). Adding family intervention to the psychosocial intervention did not affect the relapse rate. Patients in low EE families relapsed slightly more often during the psychosocial plus family intervention. In-patient treatment with psychoeducation for parents, followed by an out-patient psychosocial intervention programme, has a favourable impact on relapse. Additional family intervention may increase stress in low EE families, thus affecting relapse in their children.

  14. 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

  15. Serum prolactin level in patients with relapsing-remitting multiple sclerosis during relapse.

    PubMed

    Moshirzadeh, Sasan; Ghareghozli, Kourosh; Harandi, Ali Amini; Pakdaman, Hossien

    2012-04-01

    It has been hypothesized that hyperprolactinemia may contribute to the pathogenesis of multiple sclerosis (MS). In a case-control study, 58 patients with definite relapsing-remitting MS (RRMS) during relapse and 58 sex-matched and age-matched healthy controls were assessed for serum prolactin (PRL) concentration. Mean serum PRL levels (± standard deviation) were significantly higher in patients with MS (501.3 ± 232.6 mIU/L) than in healthy control patients (233.3 ± 142.7 mIU/L; p < 0.0001). Furthermore, these differences were consistent in each sex: females with MS (704.4 ± 119.6 mIU/L) compared to female controls (305.5 ± 156.9 mIU/L p < 0.001); and in males with MS (358.0 ± 180.0 mIU/L) compared to male controls (182.3 ± 107.5 mIU/L; p < 0.001). Our findings provided more evidence to support the hypothesis that patients with RRMS, regardless of gender, are in a hyperprolactinemic state. PMID:22341909

  16. 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

  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. PMID

  18. 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.

  19. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

    PubMed

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-07-31

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation.

  20. Varicella-zoster virus at relapses of multiple sclerosis.

    PubMed

    Sotelo, Julio; Ordoñez, Graciela; Pineda, Benjamin

    2007-04-01

    The possible participation of different herpes viruses was studied during exacerbations of multiple sclerosis (MS). We searched for the presence of DNA from the following herpes viruses: varicella zoster virus (VZV), herpes-simplex viruses 1 and 2; Epstein-Barr virus (EBV) and human herpes-virus-6 (HHV6) in mononuclear cells from patients with MS during relapse (n = 40), MS during remission (n = 131) and controls (n = 125). Additionally, immune cells containing viral antigens were quantified by flow cytometry, and VZV load was determined by real time PCR in 2 MS patients at various times during relapse and remission. DNA from VZV was found in 95% of MS patients during relapse and in 17% during remission; all controls were negative; by contrast, DNA from HHV6 was found in 24% of MS patients during relapse and in 2% during remission; DNA from herpes simplex viruses was not found in any subject; and DNA from EBV was found in a similar percentage of subjects from all groups. Sequential quantification of VZV-load showed a curve that increased during relapse and disappeared at remission. Also, VZV antigens were found inside a large number of immune cells from MS patients during relapse as compared with MS patients on remission and controls. In the typical forms of VZV infection, varicella and herpes-zoster, DNA from VZV is found in mononuclear cells exclusively during brief periods at the beginning of the active infection, but not during latency; thus, the conspicuous presence of VZV during relapses of MS may indicate a period of active infection and suggests the participation of VZV in the pathogenesis of MS.

  1. Ocular manifestations of systemic inflammatory diseases.

    PubMed

    Mohsenin, Amir; Huang, John J

    2012-10-01

    Inflammation of the eye is often times seen in association with systemic inflammatory diseases. Understanding the various forms of ocular involvement in these conditions is important as untreated ophthalmic involvement can lead to severe vision loss. In addition to providing a basic framework for diagnosis and treatment, this review will highlight the ocular manifestations of the following systemic inflammatory conditions: rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, Sjögren's syndrome, polyarteritisnodosa, primary antiphospholipid syndrome, Behçet's syndrome, Kawasaki disease, Cogan's syndrome and relapsing polychondritis.

  2. Hepatitis C virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis.

    PubMed

    Tagawa, Asako; Ogawa, Tomoko; Tetsuka, Syuichi; Otsuka, Mieko; Hashimoto, Ritsuo; Kato, Hiroyuki; Ando, Katsuyoshi; Tanabe, Hiroki

    2016-09-01

    We here report a case involving a 38-year-old female with relapsing and remitting multiple sclerosis who developed reactivation of hepatitis C virus (HCV) during administration of fingolimod for 16 months. She had been previously treated for chronic hepatitis C with pegylated interferon and ribavirin, and kept an undetectable HCV-RNA state for more than 4 years before fingolimod starting. Although the increased risk for viral reactivation, for example of herpes zoster virus and varicella-zoster virus, during fingolimod treatment is known, this is, to our knowledge, the first case report of HCV reappearance. PMID:27645365

  3. 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.

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

    PubMed

    Deeks, Emma D

    2016-02-01

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

  5. 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

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

    PubMed

    Moreau, Philippe; Touzeau, Cyrille

    2015-01-01

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

  7. GABRA2 and KIBRA Genotypes Predict Early Relapse to Substance Use

    PubMed Central

    Bauer, L.O.; Covault, J.; Gelernter, J.

    2011-01-01

    Background Numerous single nucleotide polymorphisms (SNPs) within different genes have been associated with alcohol and drug involvement or known risk factors for involvement, such as impaired cognitive control. The ability of these SNPs to predict re-involvement, defined here as abstinence failure during treatment, has not been thoroughly tested. Methods We studied a small sample (n=146; 49% female) of residential substance abuse treatment program patients who had maintained 2–6 months of abstinence. They were followed for 4 months thereafter for the purpose of counting days until the first abstinence violation. The analysis used logistic and Cox regression methods to evaluate the contributions of age; sex; number of intake alcohol, drug use, and depression symptoms; and either GABRA2, CHRM2, ANKK1, BDNF, or KIBRA SNP genotypes to outcome. Results GABRA2 and KIBRA genotypes, as well as the number of intake drug abuse problems and a younger age, were associated with an increased risk of relapse. Importantly, these genotypes were found to add value to relapse prediction: the χ2 statistic evaluating their residual contribution, after age and the number of previous drug use problems were entered, was significant. Conclusions Genetic analyses may add value to outcome prediction. Future studies should evaluate the sensitivity and specificity of GABRA2 and KIBRA genotypes for this purpose in other racial/ethnic groups and treatment settings. PMID:22129841

  8. 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. PMID:25592977

  9. 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.

  10. 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.

  11. 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.

  12. Drugs in development for relapsing multiple sclerosis.

    PubMed

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

    2013-05-01

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

  13. 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.

  14. Relative Efficacy of Mindfulness-Based Relapse Prevention, Standard Relapse Prevention, and Treatment as Usual for Substance Use Disorders

    PubMed Central

    Bowen, Sarah; Witkiewitz, Katie; Clifasefi, Seema L.; Grow, Joel; Chawla, Neharika; Hsu, Sharon H.; Carroll, Haley A.; Harrop, Erin; Collins, Susan E.; Lustyk, M. Kathleen; Larimer, Mary E.

    2015-01-01

    IMPORTANCE Relapse is highly prevalent following substance abuse treatments, highlighting the need for improved aftercare interventions. Mindfulness-based relapse prevention (MBRP), a group-based psychosocial aftercare, integrates evidence-based practices from mindfulness-based interventions and cognitive-behavioral relapse prevention (RP) approaches. OBJECTIVE To evaluate the long-term efficacy of MBRP in reducing relapse compared with RP and treatment as usual (TAU [12-step programming and psychoeducation]) during a 12-month follow-up period. DESIGN, SETTING, AND PARTICIPANTS Between October 2009 and July 2012, a total of 286 eligible individuals who successfully completed initial treatment for substance use disorders at a private, nonprofit treatment facility were randomized to MBRP, RP, or TAU aftercare and monitored for 12 months. Participants medically cleared for continuing care were aged 18 to 70 years; 71.5% were male and 42.1% were of ethnic/racial minority. INTERVENTIONS Participants were randomly assigned to 8 weekly group sessions of MBRP, cognitive-behavioral RP, or TAU. MAIN OUTCOMES AND MEASURES Primary outcomes included relapse to drug use and heavy drinking as well as frequency of substance use in the past 90 days. Variables were assessed at baseline and at 3-, 6-, and 12-month follow-up points. Measures used included self-report of relapse and urinalysis drug and alcohol screenings. RESULTS Compared with TAU, participants assigned to MBRP and RP reported significantly lower risk of relapse to substance use and heavy drinking and, among those who used substances, significantly fewer days of substance use and heavy drinking at the 6-month follow-up. Cognitive-behavioral RP showed an advantage over MBRP in time to first drug use. At the 12-month follow-up, MBRP participants reported significantly fewer days of substance use and significantly decreased heavy drinking compared with RP and TAU. CONCLUSIONS AND RELEVANCE For individuals in aftercare

  15. Tick-borne relapsing fever in North America.

    PubMed

    Dworkin, Mark S; Schwan, Tom G; Anderson, Donald E

    2002-03-01

    Relapsing fever is characterized by recurring episodes of fever and nonspecific symptoms (e.g., headache, myalgia, arthralgia, shaking chills, and abdominal complaints). The illness is caused by an infection from the Borrelia species (spirochetes) that may be acquired through the bite of an infected tick (Ornithodoros species) or contact with the hemolymph of an infected human body louse (Pediculus humanus). In North America, most cases have been acquired in the western United States, southern British Columbia, and few cases have been reported from Mexico. Most cases have been acquired from exposure to rustic tick-infested cabins and caves. This article reviews relapsing fever, especially tick-borne relapsing fever in North America. PMID:11982310

  16. Counseling Women on Smoking Relapse Prevention During Postpartum.

    PubMed

    Feeney, Ann; Britton, Geraldine

    2016-01-01

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

  17. [Polychondritis: a new disease in Swiss Braunvieh?].

    PubMed

    Bleul, U; Stranzinger, G; Sydler, T

    2011-11-01

    Over the last 10 years Swiss Braunvieh cattle with malformations of the pinnae have repeatedly been reported. Endoscopy revealed a shortened and thickened epiglottis and malformations of the arytenoid cartilage in some of these animals. In most cases the elastic cartilage was replaced by fibrocartilage and hyaline cartilage. The direct cause and pathogenesis of the malformations could not be determined.

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

    PubMed

    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.

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

    PubMed

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

    1993-08-01

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

  20. Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse.

    PubMed

    Raffaghello, L; Marimpietri, D; Pagnan, G; Pastorino, F; Cosimo, E; Brignole, C; Ponzoni, M; Montaldo, P G

    2003-07-18

    In spite of the satisfactory frequency of clinical response to first-line therapy in neuroblastoma (NB), complete eradication of NB cells is rarely achieved. As a consequence, the majority of patients with advanced stage NB undergo relapse, which is often resistant to conventional treatment and rapidly overwhelming. Thus, after induction of the apparent remission, new therapeutic strategies are needed to completely eradicate the small number of surviving NB cells and to prevent relapse. We explored the potential of different doses of the anti-GD2 monoclonal antibody (mAb) 14G2a in an experimental metastatic model where a limited number of HTLA-230 human NB cells are injected i.v. into nude mice, leading to extensive metastases and death of animals within 7-8 weeks. Treatment with 14G2a mAb (1-4 mg/kg cumulative dose given as five i.v. daily administrations) dramatically reduced the metastatic spread of NB cells and prolonged the long-term survival of treated mice in a dose-dependent manner. Neither macrophages nor NK cells appeared to contribute to the protective effect of antibody treatment in vivo, suggesting either an involvement of granulocytes or a complement-mediated cytotoxicity towards NB cells. Whatever the effecting mechanism(s) involved, these results strongly support the clinical use of anti-GD2 mAbs after first-line induction regimens.

  1. Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the prevention of neuroblastoma relapse.

    PubMed

    Raffaghello, L; Marimpietri, D; Pagnan, G; Pastorino, F; Cosimo, E; Brignole, C; Ponzoni, M; Montaldo, P G

    2003-07-18

    In spite of the satisfactory frequency of clinical response to first-line therapy in neuroblastoma (NB), complete eradication of NB cells is rarely achieved. As a consequence, the majority of patients with advanced stage NB undergo relapse, which is often resistant to conventional treatment and rapidly overwhelming. Thus, after induction of the apparent remission, new therapeutic strategies are needed to completely eradicate the small number of surviving NB cells and to prevent relapse. We explored the potential of different doses of the anti-GD2 monoclonal antibody (mAb) 14G2a in an experimental metastatic model where a limited number of HTLA-230 human NB cells are injected i.v. into nude mice, leading to extensive metastases and death of animals within 7-8 weeks. Treatment with 14G2a mAb (1-4 mg/kg cumulative dose given as five i.v. daily administrations) dramatically reduced the metastatic spread of NB cells and prolonged the long-term survival of treated mice in a dose-dependent manner. Neither macrophages nor NK cells appeared to contribute to the protective effect of antibody treatment in vivo, suggesting either an involvement of granulocytes or a complement-mediated cytotoxicity towards NB cells. Whatever the effecting mechanism(s) involved, these results strongly support the clinical use of anti-GD2 mAbs after first-line induction regimens. PMID:12880983

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

    PubMed

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

    2016-08-01

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

  3. 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

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. 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…

  7. Does Extended Telephone Callback Counselling Prevent Smoking Relapse?

    ERIC Educational Resources Information Center

    Segan, C. J.; Borland, R.

    2011-01-01

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

  8. 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…

  9. 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

  10. Cluster Subtypes Appropriate for Preventing Postpartum Smoking Relapse

    PubMed Central

    Simonelli, Mary Colleen; Velicer, Wayne F

    2011-01-01

    Objective While the majority of women quit smoking either before or during pregnancy, 60 to 80% relapse in the postpartum period. The objective of this research was to examine postpartum women who quit smoking during their pregnancies and to determine the predictive factors for relapse in the postpartum period by identifying different subgroups that predict risk of relapse. Method One hundred forty four postpartum women who were abstinent at the time of delivery were recruited. Data regarding the Acquisition Stage of Change, Decisional Balance and Situational Temptations to Smoke were assessed in the immediate postpartum period. Based on their intention to remain abstinent, 121 women identified in the acquisition-Precontemplation (aPC) group comprised the study sample. Smoking status was assessed again at 2-months postpartum Results A cluster analysis was performed to idenitfy subgroups of the acquisition-Precontemplation (aPC) group. Four subgroups were identified and were labeled Most Protected, Ambivalent, Risk Denial, and High Risk. Logistic regression was performed to establish external validity of the clusters. The clusters and exclusive breastfeeding were the only statistically significant variables associated with relapse at 2-months postpartum. Conclusions The results confirmed the clusters identified in previous prevention research with both adolescents and postpartum women, The cluster profiles can serve to guide the development of a tailored intervention program. PMID:22136873

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

    PubMed Central

    Citrome, Leslie

    2016-01-01

    When treating persons with schizophrenia, delaying time to relapse is a main goal. Antipsychotic medication has been the primary treatment approach, and there are a variety of different choices available. Lurasidone is a second-generation (atypical) antipsychotic agent that is approved for the treatment of schizophrenia and bipolar depression. Three long-term studies of lurasidone have examined time to relapse in persons with schizophrenia, including a classic placebo-controlled randomized withdrawal study and two 12-month active comparator studies (vs risperidone and vs quetiapine extended-release). Lurasidone 40–80 mg/d evidenced superiority over placebo (number needed to treat [NNT] vs placebo for relapse, 9). Lurasidone 40–160 mg/d was noninferior to quetiapine extended-release 200–800 mg/d on the outcome of relapse, and was superior on the outcome of avoidance of hospitalization (NNT 8) and the outcome of remission (NNT 7). Lurasidone demonstrated a lower risk for long-term weight gain than the active comparators. Demonstrated differences in tolerability profiles among the different choices of antipsychotics make it possible to attempt to match up an individual patient to the best choice for such patient based on past history of tolerability, comorbidities, and personal preferences, potentially improving adherence. PMID:27563237

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

    PubMed

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

    2010-07-01

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

  13. 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.

  14. META-ANALYSIS OF HIGH RISK FACTORS OF RESIDUE OR RELAPSE OF CERVICAL INTRAEPITHELIAL NEOPLASIA AFTER CONIZATION.

    PubMed

    Jin, J; Li, L; Zhang, F

    2015-01-01

    This study assesses the high risk factors of residue or relapse after conization of cervical intraepithelial neoplasia. Literature on high risk factors of residue or relapse after conization of cervical intraepithelial neoplasia from January 2006 to June 2011 were selected from the Pubmed Database, Elsevier Database, Chinese Biomedicine Database and Chinese Journal Full-text Database of China National Knowledge Internet (CNKI). Software RevMan 4. 2 provided by Cochrane collaboration network was used in the statistical analysis of the data. According to the inclusion criteria, 10 essays were retrieved, including 348 cases in case groups and 1,608 cases in control groups. Information about residue or relapse after conization, incisal edge, HIV infection after six months of surgery, age, menopause status was obtained through the above method. Meta-analysis showed that positive surgical margin groups had a higher residual or recurrence rate than negative surgical margin groups after conization; groups where glands were involved had a higher residual or recurrence rate than non-involved glands groups after conization; positive HR-HPV infection after six months of conization groups had higher residual or recurrence rates than negative HR-HPV infection groups; 50 years or older groups had higher residual or recurrence rate than under 50 year-old groups after conization; postmenopausal groups had higher residual or recurrence rate than premenopausal groups. Menopause, 50 years old or older, gland involvement, positive surgical margin and HR-HPV infection after six months are high risk factors of residue or relapse after α - β conization of CIN.

  15. 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

  16. Endemic Foci of the Tick-Borne Relapsing Fever Spirochete Borrelia crocidurae in Mali, West Africa, and the Potential for Human Infection

    PubMed Central

    Schwan, Tom G.; Anderson, Jennifer M.; Lopez, Job E.; Fischer, Robert J.; Raffel, Sandra J.; McCoy, Brandi N.; Safronetz, David; Sogoba, Nafomon; Maïga, Ousmane; Traoré, Sékou F.

    2012-01-01

    Background Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros. Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal. The risk for humans to acquire relapsing fever in Mali is uncertain, as only a few human cases have been identified. Given the high incidence of malaria in Mali, and the potential to confuse the clinical diagnosis of these two diseases, we initiated studies to determine if there were endemic foci of relapsing fever spirochetes that could pose a risk for human infection. Methodology/Principal Findings We investigated 20 villages across southern Mali for the presence of relapsing fever spirochetes. Small mammals were captured, thin blood smears were examined microscopically for spirochetes, and serum samples were tested for antibodies to relapsing fever spirochetes. Ornithodoros sonrai ticks were collected and examined for spirochetal infection. In total, 11.0% of the 663 rodents and 14.3% of the 63 shrews tested were seropositive and 2.2% of the animals had active spirochete infections when captured. In the Bandiagara region, the prevalence of infection was higher with 35% of the animals seropositive and 10% infected. Here also Ornithodoros sonrai were abundant and 17.3% of 278 individual ticks tested were infected with Borrelia crocidurae. Fifteen isolates of B. crocidurae were established and characterized by multi-locus sequence typing. Conclusions/Significance The potential for human tick-borne relapsing fever exists in many areas of southern Mali. PMID:23209863

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

    PubMed

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

    2015-10-01

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

  18. 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.

  19. [Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate].

    PubMed

    Matolcsi, Judit; Rózsa, Csilla

    2015-01-30

    Dimethyl fumarate (DMF) is a novel oral therapy that has recently been approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Dimethyl fumarate shows anti-inflammatory and cytoprotective properties that are thought to be mediated primarily via activation of the nuclear factor (erythroid-derived 2)-like 2- Nrf2 transcriptional pathway, which up-regulates the genes involved in the cellular response to oxidative stress. The drug was evaluated in 2 large, randomized, double-blind, multicentric, multinational, 2-year, phase III clinical trials. The DEFINE and CONFIRM trials, conducted with over 2600 adult patients suffering from RRMS, unequivocally confirmed the efficacy of DMF (2 x 240 mg daily) in reducing the annualized relapse rate (ARR) and reducing the proportion of patients with MS relapse at 2 years. Significantly reduced sustained disability progression was observed with the drug versus placebo in DEFINE, while the same tendency was seen in CONFIRM. The MRI results of the studies were also convincing: DMF significantly reduced the number of new/enlarging T2-hyperintense lesions and the number of Gd-enhancing lesions compared to placebo. Dimethyl fumarate was generally well tolerated and no safety concern has been raised. Adverse events that occurred most frequently included flushing and gastrointestinal events. The long-term efficacy and tolerability of dimethyl fumarate is currently being investigated in the ENDORSE trial, with interim results demonstrating the same results as the two previous studies. In conclusion, although further, mostly comparative data are needed to fully establish the relative efficacy and tolerability of dimethyl fumarate compared with other therapies, dimethyl-fumarate is a valuable addition to the therapeutic options available for RRMS. PMID:25842911

  20. Increased serum carbohydrate antigen 19-9 in relapsed ductal breast carcinoma.

    PubMed

    Papantoniou, Vassilios; Tsiouris, Spyridon; Koutsikos, John; Ptohis, Nikolaos; Lazaris, Dimitrios; Zerva, Cherry

    2006-01-01

    Increased serum carbohydrate antigen (CA) 19-9 is a quite uncommon manifestation of breast cancer both on early disease and on relapse. A 53-year-old woman with invasive ductal breast carcinoma underwent left-sided mastectomy. Two years later she palpated a subcutaneous mass at the mastectomy scar, arousing suspicion of local relapse. Surgery and histopathology revealed infiltration by breast adenocarcinoma and she was treated with chemotherapy. At that time serum tumor markers, carcinoembryonic antigen (CEA) and CA 15-3 were within normal range. Over the next six months she displayed an increase of serum CEA while serum CA 15-3 remained within normal range. In an attempt to search for a second neoplasm possibly of gastrointestinal (GI) origin, abdominal computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography (MRCP), endoscopy of the upper GI tract and colonoscopy were performed, as well as measurement of serum CA 19-9. While no indication of a GI neoplasm was detected, she displayed an over 10-fold increase of serum CA 19-9. The patient had also an X-ray mammography and technetium-99m hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintimammography (SM). Whilst mammography was negative for contralateral disease recurrence, SM was suggestive of axillary lymph node involvement. Axillary lymph node dissection confirmed an extensive metastatic infiltration of these nodes by breast adenocarcinoma. Three months later serum CA 19-9 and CEA became normal. The interest of this case lies on the unexpected high serum CA 19-9 values found in a breast relapsed adenocarcinoma and in the important contribution of SM in diagnosing the axillary lymph node metastatic infiltration. PMID:16617392

  1. 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.

  2. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.

    PubMed

    Kalincik, Tomas; Vivek, Vino; Jokubaitis, Vilija; Lechner-Scott, Jeannette; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Grand'maison, Francois; Hupperts, Raymond; Oreja-Guevara, Celia; Bergamaschi, Roberto; Iuliano, Gerardo; Alroughani, Raed; Van Pesch, Vincent; Amato, Maria Pia; Slee, Mark; Verheul, Freek; Fernandez-Bolanos, Ricardo; Fiol, Marcela; Spitaleri, Daniele La; Cristiano, Edgardo; Gray, Orla; Cabrera-Gomez, Jose Antonio; Shaygannejad, Vahid; Herbert, Joseph; Vucic, Steve; Needham, Merilee; Petkovska-Boskova, Tatjana; Sirbu, Carmen-Adella; Duquette, Pierre; Girard, Marc; Grammond, Pierre; Boz, Cavit; Giuliani, Giorgio; Rio, Maria Edite; Barnett, Michael; Flechter, Shlomo; Moore, Fraser; Singhal, Bhim; Bacile, Elizabeth Alejandra; Saladino, Maria Laura; Shaw, Cameron; Skromne, Eli; Poehlau, Dieter; Vella, Norbert; Spelman, Timothy; Liew, Danny; Kilpatrick, Trevor J; Butzkueven, Helmut

    2013-12-01

    The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration. PMID:24142147

  3. 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

  4. 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…

  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. 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…

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

    ERIC Educational Resources Information Center

    Cantrell, Peggy J.; And Others

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

  8. 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...

  9. Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration.

    PubMed

    Deroche-Gamonet, Véronique; Piat, Frédéric; Le Moal, Michel; Piazza, Pier Vincenzo

    2002-04-01

    Conditioning theories propose that, through a Pavlovian associative process, discrete stimuli acquire the ability to elicit neural states involved in the maintenance and relapse of a drug-taking behaviour. Experimental evidence indicates that drug-related cues play a role in relapse, however, their influence on the development and maintenance of drug self-administration has been poorly investigated. In this report, we analysed the effects of a drug-associated cue light on acquisition, maintenance and reinstatement of intravenous cocaine self-administration. The results show that a cocaine-associated cue light can act as an incentive in absence of the drug, but does not directly modify drug-reinforcing effects. Contingent and non-contingent presentations of a cocaine-associated cue light reinstated an extinguished self-administration behaviour. However, regardless of whether or not a cue light was associated with cocaine infusions, rats acquire cocaine intravenous self-administration reaching the same levels of intake. Furthermore, after self-administration has been acquired in presence of the cue light, the omission of the cue light or its non-contingent presentation did not modify rat behaviour. In conclusion, our work shows that cocaine-associated explicit cues do not directly interfere with the reinforcing effects of the drug.

  10. 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…

  11. Testing the transtheoretical model in predicting smoking relapse among Malaysian adult smokers receiving assistance in quitting.

    PubMed

    Yasin, Siti Munira; Retneswari, Masilamani; Moy, Foong Ming; Taib, Khairul Mizan; Isahak, Marzuki; Koh, David

    2013-01-01

    The role of The Transtheoretical Model (TTM) in predicting relapse is limited. We aimed to assess whether this model can be utilised to predict relapse during the action stage. The participants included 120 smokers who had abstained from smoking for at least 24 hours following two Malaysian universities' smoking cessation programme. The smokers who relapsed perceived significantly greater advantages related to smoking and increasing doubt in their ability to quit. In contrast, former smokers with greater self-liberation and determination to abstain were less likely to relapse. The findings suggest that TTM can be used to predict relapse among quitting smokers.

  12. Relapsing Fever: Diagnosis Thanks to a Vigilant Hematology Laboratory.

    PubMed

    Fuchs, Inbal; Tarabin, Salman; Kafka, Michael

    2015-07-01

    Three cases of relapsing fever from southern Israel were diagnosed promptly thanks to vigilance of the hematology laboratory technicians. In this region of Israel, patients presenting with prolonged fever and leukopenia without localizing symptoms are generally suspected of having brucellosis or a rickettsial disease. Pediatric patients with prolonged fever, cytopenias, and negative aforementioned serologies are often hospitalized for further work-up. Because of the policy of performing a manual blood smear when results of the automated blood count demonstrate severe anemia and abnormal platelet and/or white blood cell counts, a diagnosis of tick-borne relapsing fever was confirmed and promptly relayed to the physician. This routine prevented unnecessary examinations and hospitalization days and provided important information to regional epidemiology and public health authorities.

  13. 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.

  14. Using Conditioned Place Preference to Identify Relapse Prevention Medications

    PubMed Central

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

    2013-01-01

    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. PMID:23680702

  15. 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

  16. Factors associated with immediate relapse among Bahraini heroin abusers.

    PubMed

    Derbas, A N; al-Haddad, M K

    2001-05-01

    Demographic characteristics and factors associated with immediate relapse to heroin use among 40 male Bahraini heroin abusers were studied 1 week after discharge from the Drug and Alcohol Rehabilitation Unit in Bahrain. The mean age of the patients was 32.7 years, the age at which drug abuse began ranged from 12 years to 31 years, and the age range of regular use was 15-37 years. More than half the patients were single, unemployed, unskilled labourers with secondary-school education. The vast majority used heroin intravenously. Negative emotional states and drug-related cues were seen by the majority of the subjects as influential in their immediate relapse after discharge. Findings suggest that the treatment and rehabilitation unit in Bahrain should look into the issues of after-care.

  17. Immune response to racotumomab in a child with relapsed neuroblastoma.

    PubMed

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

    2012-01-01

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

  18. Hippocampal neurogenesis protects against cocaine-primed relapse

    PubMed Central

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

    2012-01-01

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

  19. 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.

  20. Teriflunomide for the treatment of relapsing-remitting multiple sclerosis.

    PubMed

    Miller, Aaron E

    2015-02-01

    Teriflunomide, a once-daily, oral disease-modifying therapy, is a valuable new treatment option for the management of patients with relapsing-remitting multiple sclerosis. This article reviews key efficacy and safety data arising from pivotal teriflunomide studies that demonstrate the utility in treating both treatment-naïve patients and those previously treated with another disease-modifying therapy who, for a variety of reasons, may require an alternative treatment. PMID:25511008

  1. Exercise modifies amphetamine relapse: behavioral and oxidative markers in rats.

    PubMed

    Segat, H J; Kronbauer, M; Roversi, Kr; Schuster, A J; Vey, L T; Roversi, K; Pase, C S; Antoniazzi, C T D; Burger, M E

    2014-04-01

    Exercise has been reported to attenuate rewarding symptoms related to addictive drugs mainly by affecting the brain neuroplasticity and neurotransmission. In this study, we investigated the influence of physical exercise on the behavioral and enzymatic status related to drug relapse in rats. Animals were primarily treated with amphetamine (AMPH; 4.0 mg/kg, i.p.) or vehicle (C; NaCl 0.9% solution) in the conditioned place preference (CPP) paradigm for 14 days. Half of each experimental group was then submitted to swimming sessions (60 min/day, 5 days/week) for 5 weeks. Animals were re-exposed to AMPH- or vehicle-CPP paradigm for another 3 days, in order to observe drug relapse and anxiety-like symptoms, which were observed 24h after AMPH reconditioning in CPP, and elevated plus maze (EPM), respectively, and brain biochemical evaluations were carried out subsequently. While AMPH was related to place preference and anxiety, indicating drug addiction and abstinence symptoms, respectively, physical activity was able to prevent relapse symptoms after AMPH reconditioning, as observed through consecutive decreased CPP and anxiety-like symptoms. In addition, AMPH exposure increased reactive species (RS) generation and protein carbonyl (PC) levels together with decreased activity of catalase- and Na(+)K(+)-ATPase in hippocampus. On the other hand, while all AMPH-induced effects were prevented by physical activity, there was a negative correlation between PC levels (r=0.65; p<0.003) and CAT activity, and a positive correlation between RS generation and PC levels (r=0.54; r=0.52, p<0.05) with AMPH-CPP after exercise. These results indicate that exercise has a clear beneficial influence on the prevention of psychostimulant drug relapse.

  2. 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

  3. [Mechanism of leukemia relapse: novel insights on old problem].

    PubMed

    Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua; Zhu, Xiao-Fan

    2011-06-01

    Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials. PMID:21729521

  4. A comparison of pharmacological tobacco cessation relapse rates.

    PubMed

    McMurry, Timothy B

    2006-01-01

    Tobacco use is the nation's leading preventable cause of chronic illness and injury; it takes the lives of 450,000 of our citizens each year. Currently, there are numerous treatment programs and pharmacological aids that may be obtained with a prescription or purchased over the counter at your local drugstore. The purpose of this study was to compare differences in tobacco cessation relapse rates of military personnel at the 1-, 3-, and 6-month intervals among 4 categories of pharmacological and cognitive regimens used at an outpatient naval treatment facility. A nonprobability convenience sampling plan was used to obtain (a) 10 patient-participant Freedom From Smoking (FFS) course records that utilized Zyban and Nicotine Replacement Therapy, (b) 10 patient-participant FFS course records that utilized Zyban only, (c) 10 patient-participant FFS course records that utilized Nicotine Replacement Therapy only, and (d) 10 patient-participant FFS course records that utilized Nicotine Replacement Therapy and nicotine gum (as needed). Findings revealed no significant difference between relapse and associated pharmacological treatment program. There was, however, a moderate increased cessation effort in Program 4 (nicotine replacement patch and nicotine gum). Results also demonstrated no significant difference between demographic variables and relapse cohorts. A significant positive relation between length of smoking and packs smoked per day was revealed, however. PMID:16445361

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

    PubMed

    Sun, H; Bai, P

    2016-07-01

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

  6. Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse

    PubMed Central

    Ogden, Angela; Rida, Padmashree C.G.; Knudsen, Beatrice; Kucuk, Omer; Aneja, Ritu

    2016-01-01

    Although docetaxel significantly improves survival in a variety of malignancies, its clinical utility is severely restricted by acquired chemoresistance and disease relapse. To uncover the mechanisms underlying these all too common occurrences, an abundance of research has focused on mutations and gene expression patterns; however, these findings are yet to translate into improved outcomes for patients being administered this drug. These analyses have overlooked a promising lead in the quest to discern key mediators of resistance and relapse following docetaxel therapy: polyploidization. This process is manifested following docetaxel-mediated mitotic arrest by the appearance of giant, multinucleated cells, which slipped from mitosis without undergoing cytokinesis. Polyploid cells generally possess supernumerary centrosomes, are chromosomally instable, and resist chemotherapy. We thus suspect that chemoresistance and relapse following treatment with docetaxel might be combated by co-administration of centrosome declustering drugs, which could selectively destroy polyploid cells given that normal cells do not possess amplified centrosomes, an intriguing paradigm that warrants further investigation. PMID:26185000

  7. Assessing and treating alcohol relapse risk in liver transplantation candidates.

    PubMed

    Dom, G; Wojnar, M; Crunelle, C L; Thon, N; Bobes, J; Preuss, U W; Addolorato, G; Seitz, H K; Wurst, F M

    2015-03-01

    In Europe between 30 and 50% of all liver transplantations (LTX) are done within the context of chronic end-stage alcoholic liver disease (ALD). However, post-operatively 20-25% of these patients lapse or relapse into heavy alcohol use. Thus, assessment of alcohol relapse risk before enlisting and therapeutic follow-up during and after LTX is of utmost importance. However, as yet there are enormous differences between European countries and between transplant centers, with regard to the assessment methods and criteria and the implementation of therapeutic follow-up. Only the so-called '6-month abstinence' rule is widely used. However, there are not much scientific data validating its use in predicting relapse. Thus, there is a clear need of a more homogeneous approach, which was the focus of a symposium of the European Federation of Addiction Societies during the 14th conference of the European Society for Biomedical Research on Alcoholism, 2013 (ESBRA), entitled 'Liver transplantation: A European perspective'. In a follow-up on this symposium, the authors aim to sum up the evidence of psychiatric assessment criteria and psychiatric treatment interventions relevant in the context of patient selection and patient follow-up within ALD transplantation procedures. Based upon these findings, we propose elements of a procedure that can serve as a first step toward a model of good practice regarding addiction-specialist input within the pre- and post-transplantation period.

  8. Alemtuzumab in the treatment of relapsing-remitting multiple sclerosis.

    PubMed

    Fox, Edward J

    2010-12-01

    Multiple sclerosis (MS) is an autoimmune disorder characterized by CNS inflammation, demyelination and cellular damage with atrophy. Most patients with MS initially present with a relapsing-remitting course, with periodic episodes of neurologic symptomatology that do not follow a predictable pattern. In order to maintain a stable clinical course, it is felt to be important to control the number and severity of relapses, as disability, at least in part, is a cumulative effect of damage from multiple lesions within the brain and spinal cord. Historically, MS has not been considered curable, because the immune system could not be adequately normalized over the course of a lifetime. Alemtuzumab (Campath-1H; Campath(®), Genzyme, MA, USA) has recently been investigated in a Phase II clinical trial in the treatment of relapsing-remitting MS. The results observed in the study are very encouraging and multiple insights have been made into the nature of autoimmunity in general based on the clinical response to this monoclonal antibody. Enrollment in two pivotal Phase III clinical trials of alemtuzumab in MS is now complete.

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

    PubMed Central

    Lee, Hajeong; Yoo, Kyung Don; Oh, Yun Kyu; Kim, Dong Ki; Oh, Kook-Hwan; Joo, Kwon Wook; Kim, Yon Su; Ahn, Curie; Han, Jin Suk; Lim, Chun Soo

    2016-01-01

    Abstract Minimal change disease (MCD) is a well-known benign primary glomerulonephritis because of its distinct rare tendency to progress to end-stage renal disease. However, factors associated with relapse in adults are not well known. We aimed to identify predictors of relapse in adult-onset MCD patients. A retrospective cohort of 195 patients with adult-onset primary MCD with nephritic syndrome and disease onset between 1979 and 2013 was followed up for >12 months. The number of relapses was counted and predictors of relapse were analyzed. A total of 195 patients were included. Median age at diagnosis was 38 years (IQR, 23–53 years) and 113 (57.9%) were men. During 81 months (IQR, 44–153 months) of follow-up, 92% of patients achieved remission after initial treatment. However, only 60 (32.8%) did not experience a relapse and 11 patients failed to remit. Among the remaining 124 patients, 65 experienced a relapse once or twice and 59 experienced a relapse more than twice. Younger onset age, increased severity of nephrotic features such as lower serum albumin levels and higher cholesterol level were associated with relapse. Interestingly, the grade of mesangial proliferation was lower in patients who experienced a relapse. Initial combined treatment with corticosteroids (CS) and cyclophosphamide reduced the number of relapses. In addition, patients with shorter treatment duration tended to experience relapse more often. Multivariate analysis showed that younger onset age, combined mesangial proliferation, initial treatment regimen, and treatment duration were independent risk factors for relapse. Progression to end-stage renal disease was developed in only a patient. In conclusion, more than two-thirds of adult-onset nephrotic MCD patients experienced relapse, although their renal progression was rare. Younger onset age, CS without cyclophosphamide treatment, and shorter treatment duration were independent risk factors for relapse in adult-onset MCD patients

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

    PubMed

    Lee, Hajeong; Yoo, Kyung Don; Oh, Yun Kyu; Kim, Dong Ki; Oh, Kook-Hwan; Joo, Kwon Wook; Kim, Yon Su; Ahn, Curie; Han, Jin Suk; Lim, Chun Soo

    2016-03-01

    Minimal change disease (MCD) is a well-known benign primary glomerulonephritis because of its distinct rare tendency to progress to end-stage renal disease. However, factors associated with relapse in adults are not well known. We aimed to identify predictors of relapse in adult-onset MCD patients.A retrospective cohort of 195 patients with adult-onset primary MCD with nephritic syndrome and disease onset between 1979 and 2013 was followed up for >12 months. The number of relapses was counted and predictors of relapse were analyzed.A total of 195 patients were included. Median age at diagnosis was 38 years (IQR, 23-53 years) and 113 (57.9%) were men. During 81 months (IQR, 44-153 months) of follow-up, 92% of patients achieved remission after initial treatment. However, only 60 (32.8%) did not experience a relapse and 11 patients failed to remit. Among the remaining 124 patients, 65 experienced a relapse once or twice and 59 experienced a relapse more than twice. Younger onset age, increased severity of nephrotic features such as lower serum albumin levels and higher cholesterol level were associated with relapse. Interestingly, the grade of mesangial proliferation was lower in patients who experienced a relapse. Initial combined treatment with corticosteroids (CS) and cyclophosphamide reduced the number of relapses. In addition, patients with shorter treatment duration tended to experience relapse more often. Multivariate analysis showed that younger onset age, combined mesangial proliferation, initial treatment regimen, and treatment duration were independent risk factors for relapse. Progression to end-stage renal disease was developed in only a patient.In conclusion, more than two-thirds of adult-onset nephrotic MCD patients experienced relapse, although their renal progression was rare. Younger onset age, CS without cyclophosphamide treatment, and shorter treatment duration were independent risk factors for relapse in adult-onset MCD patients.

  11. Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and steroid use.

    PubMed

    O'Connor, Paul W; Lublin, Fred D; Wolinsky, Jerry S; Confavreux, Christian; Comi, Giancarlo; Freedman, Mark S; Olsson, Tomas P; Miller, Aaron E; Dive-Pouletty, Catherine; Bégo-Le-Bagousse, Gaëlle; Kappos, Ludwig

    2013-10-01

    Multiple sclerosis (MS) relapses impose a substantial clinical and economic burden. Teriflunomide is a new oral disease-modifying therapy approved for the treatment of relapsing MS. We evaluated the effects of teriflunomide treatment on relapse-related neurological sequelae and healthcare resource use in a post hoc analysis of the Phase III TEMSO study. Confirmed relapses associated with neurological sequelae [defined by an increase in Expanded Disability Status Scale/Functional System (sequelae-EDSS/FS) ≥ 30 days post relapse or by the investigator (sequelae-investigator)] were analyzed in the modified intention-to-treat population (n = 1086). Relapses requiring hospitalization or intravenous (IV) corticosteroids, all hospitalizations, emergency medical facility visits (EMFV), and hospitalized nights for relapse were also assessed. Annualized rates were derived using a Poisson model with treatment, baseline EDSS strata, and region as covariates. Risks of sequelae and hospitalization per relapse were calculated as percentages and groups were compared with a χ(2) test. Compared with placebo, teriflunomide reduced annualized rates of relapses with sequelae-EDSS/FS [7 mg by 32 % (p = 0.0019); 14 mg by 36 % (p = 0.0011)] and sequelae-investigator [25 % (p = 0.071); 53 % (p < 0.0001)], relapses leading to hospitalization [36 % (p = 0.015); 59 % (p < 0.0001)], and relapses requiring IV corticosteroids [29 % (p = 0.001); 34 % (p = 0.0003)]. Teriflunomide-treated patients spent fewer nights in hospital for relapse (p < 0.01). Teriflunomide 14 mg also decreased annualized rates of all hospitalizations (p = 0.01) and EMFV (p = 0.004). The impact of teriflunomide on relapse-related neurological sequelae and relapses requiring healthcare resources may translate into reduced healthcare costs. PMID:23852658

  12. 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.

  13. 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

  14. 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

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

    ClinicalTrials.gov

    2016-08-03

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

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

    PubMed Central

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

    2010-01-01

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

  17. 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.

  18. 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

  19. Lipid peroxidation product acrolein as a predictive biomarker of prostate carcinoma relapse after radical surgery.

    PubMed

    Custovic, Zajim; Zarkovic, Kamelija; Cindric, Marina; Cipak, Ana; Jurkovic, Ilija; Sonicki, Zdenko; Uchida, Koji; Zarkovic, Neven

    2010-05-01

    Cancer recurrence after radical surgery might happen even in the case of patients with localized prostate carcinoma treated by radical prostatectomy. Therefore, identifying predictive markers of tumour recurrence is very important, so this study evaluated the presence of lipid peroxidation product acrolein in primary prostate carcinomas, assuming that acrolein could be involved in prostate carcinogenesis as was recently shown for colon cancer. Samples obtained by radical prostatectomy of 70 patients were analysed, out of which 27 patients suffered afterwards from tumour recurrence, while 43 patients were disease free. Immunohistochemistry using genuine monoclonal antibodies against acrolein-protein adducts revealed the association of acrolein with progression of carcinoma. The logistic regression combining clinical parameters together with the biochemical markers of disease and acrolein immunohistochemistry has shown that the relapse might be predicted with 90% accuracy if tumour-positive surgical margins, stage of disease and the intensity of acrolein presence in tumour stroma were taken together.

  20. 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

  1. Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking.

    PubMed

    Velázquez-Sánchez, Clara; Ferragud, Antonio; Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Canales, Juan J

    2013-07-01

    The treatment of cocaine addiction remains a challenge. The dopamine replacement approach in cocaine addiction involves the use of a competing dopaminergic agonist that might suppress withdrawal and drug craving in abstinent individuals. Although it has long been postulated that such an approach may be therapeutically successful, preclinical or clinical evidence showing its effectiveness to prevent relapse is scant. We used in rats a procedure that involved substitution of the N-substituted benztropine analog 3α-[bis(4'-fluorophenyl)methoxy]-tropane (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. Maintenance treatment was self-administered. After extinction, reinstatement of drug seeking was induced by cocaine priming. We measured the contents of brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. DUI, but not amphetamine, substitution led to extinction of active lever presses, as did saline substitution. DUI substitution significantly reduced cocaine-induced reinstatement of drug-seeking behavior, which was strongly elicited after saline substitution. Rats passively yoked to DUI also showed reduced cocaine-primed reinstatement. Reductions in drug seeking during reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and FADD proteins in the mPFC, which were elevated in relapsing rats. These data indicate that DUI substitution not only leads to extinction of self-administration behavior but also prevents reinstatement of drug seeking induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds with low abuse potential, even if received passively in the context previously paired with drug taking, may provide an effective treatment for stimulant addiction.

  2. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

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

  6. Acamprosate Produces Its Anti-Relapse Effects Via Calcium

    PubMed Central

    Spanagel, Rainer; Vengeliene, Valentina; Jandeleit, Bernd; Fischer, Wolf-Nicolas; Grindstaff, Kent; Zhang, Xuexiang; Gallop, Mark A; Krstew, Elena V; Lawrence, Andrew J; Kiefer, Falk

    2014-01-01

    Alcoholism is one of the most prevalent neuropsychiatric diseases, having an enormous health and socioeconomic impact. Along with a few other medications, acamprosate (Campral—calcium-bis (N-acetylhomotaurinate)) is clinically used in many countries for relapse prevention. Although there is accumulated evidence suggesting that acamprosate interferes with the glutamate system, the molecular mode of action still remains undefined. Here we show that acamprosate does not interact with proposed glutamate receptor mechanisms. In particular, acamprosate does not interact with NMDA receptors or metabotropic glutamate receptor group I. In three different preclinical animal models of either excessive alcohol drinking, alcohol-seeking, or relapse-like drinking behavior, we demonstrate that N-acetylhomotaurinate by itself is not an active psychotropic molecule. Hence, the sodium salt of N-acetylhomotaurinate (i) is ineffective in alcohol-preferring rats to reduce operant responding for ethanol, (ii) is ineffective in alcohol-seeking rats in a cue-induced reinstatement paradigm, (iii) and is ineffective in rats with an alcohol deprivation effect. Surprisingly, calcium salts produce acamprosate-like effects in all three animal models. We conclude that calcium is the active moiety of acamprosate. Indeed, when translating these findings to the human situation, we found that patients with high plasma calcium levels due to acamprosate treatment showed better primary efficacy parameters such as time to relapse and cumulative abstinence. We conclude that N-acetylhomotaurinate is a biologically inactive molecule and that the effects of acamprosate described in more than 450 published original investigations and clinical trials and 1.5 million treated patients can possibly be attributed to calcium. PMID:24081303

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

    PubMed

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

    2014-12-01

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

  8. 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

  9. Teriflunomide: a review of its use in relapsing multiple sclerosis.

    PubMed

    Garnock-Jones, Karly P

    2013-12-01

    Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data

  10. Cognitive reactions to smoking relapse: the reciprocal relation between dissonance and self-esteem.

    PubMed

    Gibbons, F X; Eggleston, T J; Benthin, A C

    1997-01-01

    Perceptions of health risk associated with smoking, commitment to quitting, and self-concept were assessed among smokers before, during, and after their participation in cessation clinics. Consistent with expectations derived from cognitive dissonance theory, results indicated that relapsers' perception of risk declined after they resumed smoking, although the decline was significant only for relapsers with high self-esteem; high self-esteem relapsers experienced a significantly greater decline in commitment to quitting than did low self-esteem relapsers; and decline in risk perception among relapsers was associated with maintenance of self-esteem. The implications of these results for dissonance theory and the study of smoking relapse and cessation are discussed.

  11. Prophylaxis and treatment of acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Chen, Runzhe; Campbell, Jos L; Chen, Baoan

    2015-01-01

    Relapse of acute lymphoblastic leukemia remains a major cause of death in patients following allogeneic hematopoietic stem cell transplantation. Several factors may affect the concurrence and outcome of relapse, which include graft-versus-host disease, minimal residual disease or intrinsic factors of the disease, and transplantation characteristics. The mainstay of relapse prevention and treatment is donor leukocyte infusions, targeted therapies, second transplantation, and other novel therapies. In this review, we mainly focus on addressing the impact of graft-versus-host disease on relapse and the prophylaxis and treatment of acute lymphoblastic leukemia relapse following allogeneic hematopoietic stem cell transplantation. We also make recommendations for critical strategies to prevent relapse after transplantation and challenges that must be addressed to ensure success. PMID:25709473

  12. Biological and Histological Parameters as Predictors of Relapse in Ulcerative Colitis: A Prospective Study

    PubMed Central

    Azad, Sheenam; Sood, Neena; Sood, Ajit

    2011-01-01

    Background/Aim: Ulcerative colitis is a chronic inflammatory disease of unknown etiology characterized by periods of remission and relapses. This study has been carried out in a group of North Indian patients, where the disease has shown an increasing prevalence and frequent relapses. Hence, there is a need to predict relapse for better management and to reduce morbidity. To assess the importance of biological and histological parameters in predicting relapse when the disease is in quiescent phase. Materials and Methods: A prospective study of twenty-six patients with quiescent ulcerative colitis was carried out in Dayanand Medical College and Hospital, Punjab. Only patients with clinical and endoscopic remission at the time of screening visit were included. Hemoglobin, erythrocyte sedimentation rate (ESR), C- reactive protein (CRP) and serum Interleukin-6 (IL-6) levels were measured. The baseline colonoscopic mucosal biopsies were retrieved and studied. Follow-up was conducted for one year at monthly interval or earlier if relapse occurred. Results: Fifteen out of twenty-six patients (57.69%) had evidence of clinical relapse during the follow-up. Hemoglobin, ESR, CRP and IL-6 levels were not found to be significant predictors of relapse. Increased number of eosinophils and neutrophils in the lamina propria were observed to be associated with significantly higher relapse rate. Conclusion: A higher risk of relapse in patients with quiescent colitis can be predicted by the presence of increased number of eosinophils and neutrophils in the lamina propria. PMID:21546723

  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. Stage I malignant lymphoma of Waldeyer's ring: frequent relapse after radiation therapy.

    PubMed

    Takagi, T; Sampi, K; Iida, K

    1992-02-01

    The natural history and therapeutic results of 26 patients with stage I malignant lymphoma of Waldeyer's ring (ML-WR) were analyzed retrospectively. Complete response was achieved in all 26. Relapse occurred in 9 of 21 (43%) patients treated with radiation therapy (RT) alone, while no relapse was seen in those treated with a combination chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP therapy). Relapse occurred within 1 year in 8 of the 9 patients. Relapse-free survival in the patients treated with RT alone was considered suboptimal. PMID:1606083

  15. 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

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

    PubMed Central

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

    2015-01-01

    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; 1–10 mg/kg, subcutaneously [s.c.]; n = 8/dose), LY255582 (LY; 0.03–1 mg/kg, s.c.; n = 8/dose), or vehicle were injected 30 min 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. PMID:21962974

  18. 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.

  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. 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.

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

    PubMed

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

    2015-06-01

    We report the first case of an imported Plasmodium ovale relapse in a Tunisian man who developed malaria three years after leaving sub- Saharan Africa. A 29-year-old Tunisian man consulted in September 2011 because of a fever, myalgia, and headache that had begun eight days earlier and persisted despite treatment with oral antibiotics. On questioning, the patient stated that he had resided three years ago for six months in Ivory Coast, where he acquired malaria. He was treated with artemether-lumefantrine. The patient said he had no recent travel to any other malaria-endemic area and had not received a blood transfusion. A first microscopy of peripheral blood smears was negative for malaria parasites. The diagnosis was established 17 days after onset of symptoms. A repeat microscopic examination of blood smears confirmed the presence of Plasmodium ovale with a parasitemia lower than 0.1%. The patient was treated with artemether lumefantrine, followed by primaquine. This case emphasizes the possibility of relapse of some plasmodial species. It highlights the importance of repeating microscopic examination of blood when the diagnosis of malaria is suspected. PMID:26644094

  2. Clinical translation of animal models of treatment relapse.

    PubMed

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

    2014-05-01

    Behavioral Momentum Theory (BMT) has inspired animal models of treatment relapse. We translated the models of reinstatement and resurgence into clinical procedures to test whether relapse tests would replicate behavior pattern found in basic research. Following multiple schedule baseline reinforcement of a 16-year-old male's problem behavior at equal rates by two therapists, treatment was introduced using a variable-interval, variable-time (VI VT) schedule arrangement with therapists delivering reinforcers at different rates. Despite the differing rates of VI VT reinforcers, the treatment produced comparable reductions in problem behavior. Following successful treatment, the two therapists discontinued treatment and resumed reinforcement of problem behavior at equal rates that constituted a reinstatement of baseline conditions. As predicted by BMT, reinstatement resulted in an immediate return of high rates of problem behavior but was 2.6 times higher for the therapist using the higher rate VI VT treatment. A second treatment phase was implemented followed by a test of resurgence in a single extended extinction session conducted separately for each therapist. The unequal VI VT treatment rates by therapists resulted in 2.1 times greater responding in the resurgence test for the therapist who implemented the higher rate VI VT procedure. These results are consistent with basic research studies and BMT. PMID:24700533

  3. Behavioral momentum and relapse of extinguished operant responding.

    PubMed

    Podlesnik, Christopher A; Shahan, Timothy A

    2009-11-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a stimulus depends on the rate of reinforcement associated with that stimulus, even if some of those reinforcers occur independently of the behavior. We present three experiments examining whether the rate of reinforcement in the presence of a stimulus similarly modulates the relative relapse of operant behavior produced by reinstatement, resurgence, and renewal paradigms. During baseline conditions, pigeons responded for food reinforcement on variable-interval 120-sec schedules in alternating periods of exposure to two stimuli arranged by a multiple schedule. Additional response-independent food presentations were also delivered in the presence of one of the multiple-schedule stimuli. Consistent with previous research, baseline response rates were lower in the presence of the stimulus with the added response-independent reinforcement, and relative resistance to extinction was greater in the presence of that stimulus. In addition, following extinction, the relative relapse of responding produced by reinstatement, resurgence, and renewal paradigms was greater in the presence of the stimulus associated with the higher rate of reinforcement. We suggest that a model of extinction from behavioral momentum theory may be useful for understanding these results. PMID:19815932

  4. 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.

  5. 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

  6. Concurrent hypopituitarism and leukemic retinopathy in a child with B-precursor acute lymphoblastic leukemia and isolated central nervous system relapse

    PubMed Central

    Wu, K.H.; Wu, H.P.; Lin, H.J.; Wang, C.H.; Chen, H.Y.; Weng, T.; Peng, C.T.; Chao, Y.H.

    2016-01-01

    Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse. Concurrent hypopituitarism and leukemic retinopathy were also found. After receiving craniospinal radiotherapy and systemic chemotherapy, her retinopathy and vision improved. She is now in complete remission, and she is still on chemotherapy according to the guideline from the Pediatric Oncology Group. Although rare, hypopituitarism and leukemic retinopathy should be taken into consideration in patients with cns involvement by leukemia. PMID:27536191

  7. Parent Involvement.

    ERIC Educational Resources Information Center

    LaCrosse, Ed

    The paper discusses the rationale and guidelines for parent involvement in HCEEP (Handicapped Children's Early Education Program) projects. Ways of assessing parents' needs are reviewed, as are four types of services to meet the identified needs: parent education, direct participation, parent counseling, and parent provided programs. Materials and…

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

    SciTech Connect

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

    2009-11-15

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

  9. Predictors of Marijuana Relapse in the Human Laboratory: Robust Impact of Tobacco Cigarette Smoking Status

    PubMed Central

    Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D.; Glass, Andrew; Vosburg, Suzanne K.; Comer, Sandra D.; Foltin, Richard W.

    2012-01-01

    Background Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. Study 1: Methods Data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers (n=51; 10 ± 5 marijuana cigarettes/day) were enrolled. Results 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (OR=19, p<0.01). Individuals experiencing more positive subjective effects (i.e. feeling “high”) after marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes (p<0.05). Study 2: Methods To isolate the effects of cigarette smoking, marijuana intoxication, withdrawal and relapse were assessed in daily marijuana and cigarette smokers (n=15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU) and after at least 5 days without cigarettes (Quit). Results Most participants (87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. Conclusions Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse. PMID:22939992

  10. Relapse-related long non-coding RNA signature to improve prognosis prediction of lung adenocarcinoma

    PubMed Central

    Zhao, Hengqiang; Wang, Zhenzhen; Shi, Hongbo; Cheng, Liang; Sun, Jie

    2016-01-01

    Increasing evidence has highlighted the important roles of dysregulated long non-coding RNA (lncRNA) expression in tumorigenesis, tumor progression and metastasis. However, lncRNA expression patterns and their prognostic value for tumor relapse in lung adenocarcinoma (LUAD) patients have not been systematically elucidated. In this study, we evaluated lncRNA expression profiles by repurposing the publicly available microarray expression profiles from a large cohort of LUAD patients and identified specific lncRNA signature closely associated with tumor relapse in LUAD from significantly altered lncRNAs using the weighted voting algorithm and cross-validation strategy, which was able to discriminate between relapsed and non-relapsed LUAD patients with sensitivity of 90.9% and specificity of 81.8%. From the discovery dataset, we developed a risk score model represented by the nine relapse-related lncRNAs for prognosis prediction, which classified patients into high-risk and low-risk subgroups with significantly different recurrence-free survival (HR=45.728, 95% CI=6.241-335.1; p=1.69e-04). The prognostic value of this relapse-related lncRNA signature was confirmed in the testing dataset and other two independent datasets. Multivariable Cox regression analysis and stratified analysis showed that the relapse-related lncRNA signature was independent of other clinical variables. Integrative in silico functional analysis suggested that these nine relapse-related lncRNAs revealed biological relevance to disease relapse, such as cell cycle, DNA repair and damage and cell death. Our study demonstrated that the relapse-related lncRNA signature may not only help to identify LUAD patients at high risk of relapse benefiting from adjuvant therapy but also could provide novel insights into the understanding of molecular mechanism of recurrent disease. PMID:27105492

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

    PubMed Central

    HU, WANGQIANG; WANG, XIAOXIA; YANG, RONGRONG

    2016-01-01

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

  12. Total cost comparison in relapsed/refractory multiple myeloma

    PubMed Central

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

    2013-01-01

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

  13. 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

  14. 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

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

    2016-08-01

    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

  15. 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

  16. The Orexin-1 Receptor Antagonist SB-334867 Reduces Alcohol Relapse Drinking, but not Alcohol-Seeking, in Alcohol-Preferring (P) Rats

    PubMed Central

    Dhaher, Ronnie; Hauser, Sheketha R.; Getachew, Bruk; Bell, Richard L.; McBride, William J.; McKinzie, David L.; Rodd, Zachary A.

    2010-01-01

    Principle The orexin system has been hypothesized to regulate drug-seeking and drug self-administration behaviors, including ethanol (EtOH) seeking and consumption. However, studies on the effects of orexin receptor antagonists have not been conducted on robust alcohol-relapse behavior. Objectives This study assessed the effects of the orexin-1 receptor antagonist, SB-334867, on alcohol-seeking behavior and responding for alcohol under relapse conditions. Methods Adult alcohol-preferring (P) rats self-trained in 2-lever operant chambers to administer 15% EtOH (vol/vol) on a fixed-ratio-5 and water on a fixed-ratio-1 schedule of reinforcement. After 10 weeks, rats underwent extinction training for 7 sessions. Animals were then maintained in their home cages for 2 weeks before being tested for Pavlovian Spontaneous Recovery (PSR; a measure of alcohol seeking) for 4 sessions. Rats were then allowed a week in their home cages before being returned to the operant chamber with access to EtOH and water (relapse). Thirty minutes before the PSR and relapse test sessions, rats received 0, 10, or 20 mg/kg SB-334867. Results Responses on the EtOH lever during the 1st PSR test session were ~70 presses/session (3-fold higher than baseline); SB-334867 did not alter responses on the EtOH lever. Under relapse conditions, P rats increased responding on the EtOH lever from 250 (at baseline) to 350 responses/session; both doses of SD-334867 prevented this increase. Conclusions The results of this study suggest that activation of orexin-1 receptors is not involved in intrinsically initiated EtOH seeking, but may regulate the consummatory behavior of EtOH consumption. PMID:20871792

  17. 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

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

    2016-08-01

    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

  18. 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.…

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

    PubMed

    Mitra, Abhisek; Mishra, Lopa; Li, Shulin

    2015-05-10

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

  20. 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…

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

    PubMed

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

    2012-05-01

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

  2. 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…

  3. 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

  4. 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…

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

    ERIC Educational Resources Information Center

    Marlatt, G. Alan

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

  6. 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…

  7. 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…

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

    PubMed Central

    Brower, Kirk J.; Perron, Brian E.

    2009-01-01

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

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

    ERIC Educational Resources Information Center

    Wadsworth, Rick; And Others

    1995-01-01

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

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

    PubMed Central

    Mitra, Abhisek; Mishra, Lopa; Li, Shulin

    2015-01-01

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

  11. 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

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

    PubMed Central

    Wolford, Larry M

    2014-01-01

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

  13. 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.

  14. 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.

  15. 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. PMID:23537484

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

    PubMed

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

    1998-08-01

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

  17. Tickborne Relapsing Fever Diagnosis Obscured by Malaria, Togo

    PubMed Central

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

    2007-01-01

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

  18. Novel Agents for Relapsing Forms of Multiple Sclerosis.

    PubMed

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

    2016-01-01

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

  19. Contemporary treatment options for relapsing-remitting multiple sclerosis.

    PubMed

    Salhofer-Polanyi, S; Leutmezer, F

    2014-05-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, encompassing both neuroinflammatory as well as prominent neurodegenerative aspects. A significant proportion of MS patients will develop neurological disability over time and up until recently licensed drugs could not satisfactorily halt this process. However, in the last years MS treatment has raised a stage of rapid progress. Several new drugs with significantly improved efficacy have entered the therapeutic field and several others are currently undergoing phase III clinical trials. In this review, we will summarize efficacy data as well as safety and tolerability issues of currently licensed drugs for relapsing-remitting MS and will give a short update on new drugs currently undergoing late-stage clinical trials. PMID:24918837

  20. Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

    SciTech Connect

    Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej; Rapalino, Otto; Caruso, Paul; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

    2014-03-01

    Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for

  1. 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

  2. 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.

  3. Treatment of relapsing Clostridium difficile infection using fecal microbiota transplantation

    PubMed Central

    Pathak, Rahul; Enuh, Hill Ambrose; Patel, Anish; Wickremesinghe, Prasanna

    2014-01-01

    Background Clostridium difficile infection (CDI) has become a global concern over the last decade. In the United States, CDI escalated in incidence from 1996 to 2005 from 31 to 64/100,000. In 2010, there were 500,000 cases of CDI with an estimated mortality up to 20,000 cases a year. The significance of this problem is evident from the hospital costs of over 3 billion dollars annually. Fecal microbiota transplant (FMT) was first described in 1958 and since then about 500 cases have been published in literature in various small series and case reports. This procedure has been reported mainly from centers outside of the United States and acceptance of the practice has been difficult. Recently the US Food and Drug Administration (FDA) labeled FMT as a biological drug; as a result, guidelines will soon be required to help establish it as a mainstream treatment. More US experience needs to be reported to popularize this procedure here and form guidelines. Method We did a retrospective review of our series of patients with relapsing CDI who were treated with FMT over a 3-year period. We present our experience with FMT at a community hospital as a retrospective review and describe our procedure. Results There were a total of 12 patients who underwent FMT for relapsing C. difficile. Only one patient failed to respond and required a second FMT. There were no complications associated with the transplant and all patients had resolution of symptoms within 48 hours of FMT. Conclusion FMT is a cheap, easily available, effective therapy for recurrent CDI; it can be safely performed in a community hospital setting with similar results. PMID:24421645

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

    PubMed Central

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

    2008-01-01

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

  5. 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.

  6. 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. PMID:23008521

  7. 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

  8. Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse

    PubMed Central

    Lin, Jessica T.; Hathaway, Nicholas J.; Saunders, David L.; Lon, Chanthap; Balasubramanian, Sujata; Kharabora, Oksana; Gosi, Panita; Sriwichai, Sabaithip; Kartchner, Laurel; Chuor, Char Meng; Satharath, Prom; Lanteri, Charlotte; Bailey, Jeffrey A.; Juliano, Jonathan J.

    2015-01-01

    Plasmodium vivax infections often recur due to relapse of hypnozoites from the liver. In malaria-endemic areas, tools to distinguish relapse from reinfection are needed. We applied amplicon deep sequencing to P. vivax isolates from 78 Cambodian volunteers, nearly one-third of whom suffered recurrence at a median of 68 days. Deep sequencing at a highly variable region of the P. vivax merozoite surface protein 1 gene revealed impressive diversity—generating 67 unique haplotypes and detecting on average 3.6 cocirculating parasite clones within individuals, compared to 2.1 clones detected by a combination of 3 microsatellite markers. This diversity enabled a scheme to classify over half of recurrences as probable relapses based on the low probability of reinfection by multiple recurring variants. In areas of high P. vivax diversity, targeted deep sequencing can help detect genetic signatures of relapse, key to evaluating antivivax interventions and achieving a better understanding of relapse-reinfection epidemiology. PMID:25748326

  9. Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse.

    PubMed

    Lin, Jessica T; Hathaway, Nicholas J; Saunders, David L; Lon, Chanthap; Balasubramanian, Sujata; Kharabora, Oksana; Gosi, Panita; Sriwichai, Sabaithip; Kartchner, Laurel; Chuor, Char Meng; Satharath, Prom; Lanteri, Charlotte; Bailey, Jeffrey A; Juliano, Jonathan J

    2015-09-15

    Plasmodium vivax infections often recur due to relapse of hypnozoites from the liver. In malaria-endemic areas, tools to distinguish relapse from reinfection are needed. We applied amplicon deep sequencing to P. vivax isolates from 78 Cambodian volunteers, nearly one-third of whom suffered recurrence at a median of 68 days. Deep sequencing at a highly variable region of the P. vivax merozoite surface protein 1 gene revealed impressive diversity-generating 67 unique haplotypes and detecting on average 3.6 cocirculating parasite clones within individuals, compared to 2.1 clones detected by a combination of 3 microsatellite markers. This diversity enabled a scheme to classify over half of recurrences as probable relapses based on the low probability of reinfection by multiple recurring variants. In areas of high P. vivax diversity, targeted deep sequencing can help detect genetic signatures of relapse, key to evaluating antivivax interventions and achieving a better understanding of relapse-reinfection epidemiology.

  10. Gut microbiota composition and relapse risk in pediatric MS: A pilot study.

    PubMed

    Tremlett, Helen; Fadrosh, Douglas W; Faruqi, Ali A; Hart, Janace; Roalstad, Shelly; Graves, Jennifer; Lynch, Susan; Waubant, Emmanuelle

    2016-04-15

    We explored the association between baseline gut microbiota (16S rRNA biomarker sequencing of stool samples) in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. From the Kaplan-Meier curve, 25% relapsed within an estimated 166 days from baseline. A shorter time to relapse was associated with Fusobacteria depletion (p=0.001 log-rank test), expansion of the Firmicutes (p=0.003), and presence of the Archaea Euryarchaeota (p=0.037). After covariate adjustments for age and immunomodulatory drug exposure, only absence (vs. presence) of Fusobacteria was associated with relapse risk (hazard ratio=3.2 (95% CI: 1.2-9.0), p=0.024). Further investigation is warranted. Findings could offer new targets to alter the MS disease course.

  11. 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.

  12. 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

  13. Behçet Disease With Vascular Involvement

    PubMed Central

    Alibaz-Oner, Fatma; Karadeniz, Aslı; Yılmaz, Sema; Balkarlı, Ayşe; Kimyon, Gezmiş; Yazıcı, Ayten; Çınar, Muhammet; Yılmaz, Sedat; Yıldız, Fatih; Bilge, Şule Yaşar; Bilgin, Emre; Coskun, Belkis Nihan; Omma, Ahmet; Çetin, Gözde Yıldırım; Çağatay, Yonca; Karaaslan, Yaşar; Sayarlıoğlu, Mehmet; Pehlivan, Yavuz; Kalyoncu, Umut; Karadağ, Ömer; Kaşifoğlu, Timuçin; Erken, Eren; Pay, Salih; Çefle, Ayşe; Kısacık, Bünyamin; Onat, Ahmet Mesut; Çobankara, Veli; Direskeneli, Haner

    2015-01-01

    Abstract Vascular involvement is one of the major causes of mortality and morbidity in Behçet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively. Patients with BD (n = 936, female/male: 347/589, mean age: 37.6 ± 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired. VBD was observed in 27.7% (n = 260) of the patients during follow-up. In 57.3% of the VBD patients, vascular involvement was the presenting sign of the disease. After the first vascular event, ISs were given to 88.8% and AC treatment to 59.8% of the patients. Median duration of AC treatment was 13 months (1–204) and ISs, 22 months (1–204). Minor hemorrhage related to AC treatment was observed in 7 (4.7%) patients. A second vascular event developed in 32.9% (n = 86) of the patients. The vascular relapse rate was similar between patients taking only ISs and AC plus IS treatments after the first vascular event (29.1% vs 22.4%, P = 0.28) and was significantly higher in group taking only ACs than taking only ISs (91.6% vs 29.1%, P < 0.001). During follow-up, a third vascular event developed in 17 (n = 6.5%) patients. The relapse rate was also similar between the patients taking only ISs and AC plus IS treatments after second vascular event (25.3% vs 20.8%, P = 0.93). When multivariate analysis was performed, development of vascular relapse negatively correlated with only IS treatments. We did not find any additional positive

  14. An Analysis of Relapse Rates and Predictors of Relapse in 2 Randomized, Placebo-Controlled Trials of Desvenlafaxine for Major Depressive Disorder

    PubMed Central

    Fayyad, Rana S.; Guico-Pabia, Christine J.

    2015-01-01

    Objective: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of desvenlafaxine for major depressive disorder (MDD). Method: Study 1: week 8 responders to open-label desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. Results: Overall relapse rates for all definitions were significantly lower for desvenlafaxine versus placebo for both studies (all P ≤ .002). In study 1, rates were significantly lower for desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P < .0001–.002). Hazard ratios were similar at months 1, 2, and 3 and overall for both studies (0.382–0.639). Conclusions: Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. Trial Registration: ClinicalTrials.gov identifiers

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

    PubMed Central

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

    2015-01-01

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

  16. Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time.

    PubMed

    Gu, Bobby; Magil, Alex B; Barbour, Sean J

    2016-10-01

    Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody-positive flares with pulmonary and renal involvement, and anti-GBM antibody-negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over time. Disease severity paralleled the detection of anti-GBM antibodies but was independent of IgG subtype staining along the GBM. This case suggests a role for changing subpopulations of pathogenic antibodies as an explanation for variation in disease phenotype and anti-GBM antibody results. PMID:27679711

  17. Frequently relapsing anti-glomerular basement membrane antibody disease with changing clinical phenotype and antibody characteristics over time

    PubMed Central

    Gu, Bobby; Magil, Alex B.; Barbour, Sean J.

    2016-01-01

    Anti-glomerular basement membrane (GBM) antibody disease is a typically monophasic autoimmune disease with severe pulmonary and renal involvement. We report an atypical case of frequently relapsing anti-GBM antibody disease with both anti-GBM antibody–positive flares with pulmonary and renal involvement, and anti-GBM antibody–negative flares that were pulmonary limited with no histologic renal disease. This is the first report of alternating disease phenotype and anti-GBM antibody status over time. Disease severity paralleled the detection of anti-GBM antibodies but was independent of IgG subtype staining along the GBM. This case suggests a role for changing subpopulations of pathogenic antibodies as an explanation for variation in disease phenotype and anti-GBM antibody results.

  18. 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. PMID:26586462

  19. 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

  20. 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.

  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. 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.

  3. Relapse prevention in serious and enduring mental illness: a pilot study.

    PubMed

    Foster, J H; Jumnoodoo, R

    2008-09-01

    The purpose of the research was to ascertain whether coping knowledge and relapse outcomes are enhanced after 12 months following a programme of community-based relapse prevention (RP). Relapse to mental illness has high societal costs and this programme aims to lessen the likelihood of relapse by equipping service users with greater coping mechanisms by employing a quasi-experimental design with some controls. Participants are recruited from a day hospital in London. There are two groups: (1) experimental group (n = 10) and (2) control group (n = 10). The experimental group is given an 8-week RP programme, and the control group receives routine care. Both groups are then followed up at 1, 2 and 12 months. The research hypothesis was participants undergoing a programme of RP will have greater 12-month knowledge and superior relapse outcomes. The 52-week follow-up rates are 80% for experimental group and 70% for control group. There are no differences in the two groups in terms of relapse outcomes. Knowledge between baseline and 52 weeks is improved in the experimental group though most of the changes are observed during the first 12 weeks. We conclude that an 8-week RP programme resulted in improved knowledge but not relapse outcomes at 52 weeks. A randomized controlled trial should now be conducted to assess whether these results are replicated.

  4. Predictors of relapse among smokers: transtheoretical effort variables, demographics, and smoking severity.

    PubMed

    Gökbayrak, N S; Paiva, A L; Blissmer, B J; Prochaska, J O

    2015-03-01

    The present longitudinal study investigates baseline assessments of static and dynamic variables, including demographic characteristics, smoking severity, and Transtheoretical Model of Behavior Change (TTM) effort variables (Decisional Balance (i.e. Pros and Cons), Situational Temptations, and Processes of Change) of relapse among individuals who were abstinent at 12months. The study sample (N=521) was derived from an integrated dataset of four population-based smoking cessation interventions. Several key findings included: Participants who were aged 25-44 and 45-64 (OR=.43, p=.01 and OR=.40, p=.01, respectively) compared to being aged 18-24 were less likely to relapse at follow-up. Participants in the control group were more than twice as likely to relapse (OR=2.17, p=.00) at follow-up compared to participants in the treatment group. Participants who reported higher Habit Strength scores were more likely to relapse (OR=1.05, p=.02). Participants who had higher scores of Reinforcement Management (OR=1.05, p=.04) and Self-Reevaluation (OR=1.08, p=.01) were more likely to relapse. Findings add to one assumption that relapsers tend to relapse not solely due to smoking addiction severity, but due to immediate precursor factors such as emotional distress. One approach would be to provide additional expert guidance on how smokers can manage stress effectively when they enroll in treatment at any stage of change. PMID:25481450

  5. 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

  6. 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.

  7. [Risk factors for relapse in drug-dependent patients after hospital detoxification].

    PubMed

    Grau-López, Lara; Roncero, Carlos; Daigre, Constanza; Gonzalvo, Begoña; Bachiller, Diana; Rodriguez-Cintas, Laia; Egido, Ángel; Casas, Miquel

    2012-01-01

    This work describes the profile of patients with relapse after hospital detoxification at six months of outpatient follow-up. An observational and prospective study was carried out in patients with substance-dependence disorder who were in the Detoxification Unit of the Vall d'Hebron University Hospital (Barcelona) between June 2009 and October 2010. Demographic, clinical, diagnostic and therapeutic variables were assessed. The criterion for relapse was a return to use of the substance that had led to hospitalization, and relapse was assessed by means of anamnesis, breathalyzer and/or urine analysis. Study variables were compared between patients who relapsed and those who did not. Of the 165 patients included, 108 patients finished the study (75% males, age 37.7 ± 9.5 years). A total of 72.2% had relapsed at the 6-month follow-up. Profile of patients who relapsed was: hospitalized for heroin detoxification (91.7% vs 8.3%, p = .038), polyconsumers (71.4% vs 32%, p = .05), high substance use in the hours prior to admission as a "farewell" (61.5% vs 39.5%, p = .04), patients with comorbidity (44.9% vs 23.3%, p = .04) and patients with affective disorders (19.5% vs 3.2%, p = .005). Detoxification from opiates and use in the hours prior to admission were associated independently with relapse at 6 months. There is a high percentage of relapses after hospital detoxification. Patients most likely to relapse are those dependent on opiates and those with compulsive use immediately prior to hospitalization. PMID:22648314

  8. 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

  9. 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

  10. 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

  11. 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

  12. Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

    PubMed

    Havermans, Remco C; Jansen, Anita T M

    2003-07-01

    Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

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

    PubMed

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

    2011-01-01

    The objective of this study was to determine whether there are gender-specific associations between trauma exposure and alcohol or drug relapse in alcohol-dependent adults. Participants were 51 men (n = 24) and women (n = 27) with alcohol dependence, 22 (43.1%) of whom relapsed during study participation. Severity of childhood trauma; number of lifetime events evoking fear, helplessness, or horror; and current trauma symptoms all predicted relapse in women, but not in men. These findings highlight the importance of assessing trauma history and providing treatment of trauma-related symptoms for individuals with alcohol and drug dependence, and for women in particular. PMID:21679261

  14. Progression-free survival of two cases of high-risk neuroblastoma with refractory/relapsed disease following surgery alone.

    PubMed

    Sokol, Elizabeth; Haut, Paul R; Gosiengfiao, Yasmin; Feinstein, Kate; Pytel, Peter; Cohn, Susan L

    2013-03-01

    Outcome for the vast majority of high-risk neuroblastoma patients with refractory or relapsed disease is dismal. We report two high-risk patients who remain progression-free for more than 113 and 18 months following the diagnosis of refractory/relapsed disease who were treated with surgery alone. Complete resolution of a refractory thoracic mass and relapsed liver nodules was observed in one patient. The refractory/relapsed disease in the second patient has remained stable. In both cases, the tumor showed histologic evidence of neuroblastoma maturation. These cases demonstrate that refractory/relapsed neuroblastoma is clinically heterogeneous and highlight the need for better biomarkers to optimize patient care.

  15. The spectrum of relapsing fever in the Rocky Mountains.

    PubMed

    Horton, J M; Blaser, M J

    1985-05-01

    Between 1940 and 1976, two cases of tick-borne relapsing fever were reported in Colorado, but since 1977, 23 confirmed cases have occurred. All patients had fever, with a mean of 2.8 febrile episodes (range, one to six). Complications included thrombocytopenia, endophthalmitis, meningitis, abortion, in utero infection, and erythema multiforme. All treated patients were eventually cured with antibiotics, although two pregnant patients failed to be cured by their initial courses of antibiotics. Seven of 21 treated patients had Jarisch-Herxheimer reactions, three of whom required intensive care. Five of nine patients who received tetracycline at an initial dose of 5 mg/kg or more had reactions v none of four patients treated with lower doses. Possible causes of the recent increased incidence include increased physician awareness and reporting, improved diagnostic techniques, and an actual increase due to a larger population at risk. Because summertime visits to the Rocky Mountains are becoming increasingly popular, physicians elsewhere should know how to recognize and treat this condition. PMID:3994463

  16. An apparent idiopathic case of relapsing acute pancreatitis.

    PubMed

    Nocente, R; Silveri, N G; Gasbarrini, A; Cicconi, V; Caminiti, G; Mutignani, M; Manfredi, R; Gasbarrini, G

    2001-01-01

    We describe a case of relapsing acute pancreatitis apparently idiopathic in a 55-year-old man. The patient did not smoke and was a modest and irregular drinker of wine. Endoscopic retrograde cholangiopancreatography showed an initial dilatation of secondary ducts like a chronic pancreatitis of class I of Cremer. Ultrasound and computed tomography resulted negative for pancreatic lesions. In the follow-up however, magnetic resonance cholangiopancreatography detected the presence of an intraductal mucin-hypersecreting neoplasm, a duct-ectatic mucinous cystic tumor of the pancreas, in the uncinate process. This is a benign lesion clearly recognized nowadays by magnetic resonance cholangiopancreatography, because this radiological technique shows the grape-like clusters of cystic lesions in secondary ducts communicating with the main duct on the same plane. The radiological picture above excludes a malignant lesion and a biopsy specimen is not required. Furthermore, an intraductal mucin-hypersecreting neoplasm of the pancreas does not require an immediate surgical resection because of its slow evolution and can be followed-up. Conversely cystoadenocarcinoma spreads in peripheral ducts and does not communicate with the Wirsung duct. It requires both surgical resection and a biopsy specimen for histological diagnosis. In the last episode of acute pancreatitis, a sphincterotomy was performed at endoscopic retrograde cholangiopancreatography and our patient had no more pain for one year.

  17. Varicella zoster virus and relapsing remitting multiple sclerosis.

    PubMed

    Sotelo, Julio; Corona, Teresa

    2011-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS.

  18. Advances in the treatment of relapsing-remitting multiple sclerosis.

    PubMed

    Tanasescu, Radu; Ionete, Carolina; Chou, I-Jun; Constantinescu, Cris S

    2014-01-01

    This article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS) that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone). The place of each drug in the therapeutic algorithm is dependent on its specific risk-benefit profile. Patients' clinical and paraclinical phenotypes and biomarker profile may help to elucidate disease subtypes and response to therapy in the future, thus allowing treatment individualization. PMID:24732658

  19. Reoperative sentinel lymph node biopsy in ipsilateral breast cancer relapse.

    PubMed

    Tasevski, R; Gogos, A J; Mann, G B

    2009-10-01

    Sentinel lymph node biopsy (SLNB) is controversial following ipsilateral breast tumour relapse (IBTR) and previous axillary surgery. We retrospectively assessed the feasibility, outcomes and utility of this procedure. Eighteen patients with IBTR who underwent reoperative SLNB were identified. Fifteen women had previously undergone axillary lymph node dissection and three SLNB for breast cancer. Twelve of 16 patients underwent successful lymphoscintigraphy (LSG). Lymphatic drainage patterns varied widely - ipsilateral axilla (5), contralateral axilla (5), and ipsilateral internal mammary (5). Two patients had drainage to more than one nodal basin. Nine of 12 patients demonstrated drainage outside of the ipsilateral axilla. Reoperative SLNB was successful in 12/18 of patients - 4 ipsilateral axilla, 1 ipsilateral internal mammary, 1 ipsilateral intramammary, 4 contralateral axilla. Two patients had sentinel nodes in multiple nodal basins. Positive sentinel node was found in one successful case (contralateral axilla) and isolated tumour cells in two (1 contralateral axilla, 1 ipsilateral internal mammary). In conclusion, reoperative SLNB is feasible. Lymphatic drainage patterns vary widely and preoperative LSG is vital to facilitate identification of sentinel nodes in unusual sites. Its prognostic and therapeutic significance warrants further study. PMID:19819141

  20. 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

  1. 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

  2. Deep grey matter MRI abnormalities and cognitive function in relapsing-remitting multiple sclerosis.

    PubMed

    Debernard, Laëtitia; Melzer, Tracy R; Alla, Sridhar; Eagle, Jane; Van Stockum, Saskia; Graham, Charlotte; Osborne, Jonathan R; Dalrymple-Alford, John C; Miller, David H; Mason, Deborah F

    2015-12-30

    Although deep grey matter (GM) involvement in multiple sclerosis (MS) is well documented, in-vivo multi-parameter magnetic resonance imaging (MRI) studies and association with detailed cognitive measures are limited. We investigated volumetric, diffusion and perfusion metrics in thalamus, hippocampus, putamen, caudate nucleus and globus pallidum, and neuropsychological measures, spanning 4 cognitive domains, in 60 relapsing-remitting MS patients (RRMS) (mean disease duration of 5.1 years, median EDSS of 1.5) and 30 healthy controls. There was significantly reduced volume of thalamus, hippocampus and putamen in the RRMS patients, but no diffusion or perfusion changes in these structures. Decreased volume in these deep GM volumes in RRMS patients was associated with a modest reduction in cognitive performance, particularly information processing speed, consistent with a subtle disruption of distributed networks, that subserve cognition, in these patients. Future longitudinal studies are needed to elucidate the influence of deep GM changes on the evolution of cognitive deficits in MS. PMID:26602610

  3. 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

  4. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis.

  5. “Identifying the neural circuitry of alcohol craving and relapse vulnerability”

    PubMed Central

    Heinz, A.; Beck, A.; Grüsser, S.M.; Grace, A. A.; Wrase, J.

    2010-01-01

    Summary With no further intervention, relapse rates in detoxified alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of alcohol and to alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified alcoholics. Current brain imaging studies indicate that dysfunction of dopaminergic, glutamatergic, and opioidergic neurotransmission in the brain reward system (ventral striatum including the nucleus accumbens) can be associated with alcohol craving and functional brain activation in neuronal systems that process attentional relevant stimuli, reward expectancy and experience. Increased functional brain activation elicited by such alcohol-associated cues predicted an increased relapse risk, while high brain activity elicited by affectively positive stimuli may represent a protective factor and was correlated with a decreased prospective relapse risk. These findings are discussed with respect to psychotherapeutic and pharmacological treatment options. PMID:18855799

  6. 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.

  7. How does cognitive therapy prevent depressive relapse and why should attentional control (mindfulness) training help?

    PubMed

    Teasdale, J D; Segal, Z; Williams, J M

    1995-01-01

    There is encouraging evidence that structured psychological treatments for depression, in particular cognitive therapy, can reduce subsequent relapse after the period of initial treatment has been completed. However, there is a continuing need for prophylactic psychological approaches that can be administered to recovered patients in euthymic mood. An information-processing analysis of depressive maintenance and relapse is used to define the requirements for effective prevention, and to propose mechanisms through which cognitive therapy achieves its prophylactic effects. This analysis suggests that similar effects can be achieved using techniques of stress-reduction based on the skills of attentional control taught in mindfulness meditation. An information-processing analysis is presented of mindfulness and mindlessness, and of their relevance to preventing depressive relapse. This analysis provides the basis for the development of Attentional Control Training, a new approach to preventing relapse that integrates features of cognitive therapy and mindfulness training and is applicable to recovered depressed patients.

  8. Risk factors for relapse after allogeneic transplantation in acute myeloid leukemia

    PubMed Central

    Ossenkoppele, Gert J.; Janssen, Jeroen J.W.M.; van de Loosdrecht, Arjan A.

    2016-01-01

    Acute myeloid leukemia is a clonal neoplasm derived from myeloid progenitor cells with a varying outcome. The initial goal of treatment is the achievement of complete remission, defined for over 40 years by morphology. However, without additional post-remission treatment the majority of patients relapse. In many cases of acute myeloid leukemia, allogeneic stem cell transplantation offers the best prospects of cure. In 2013, 5608 stem cell transplantations in acute myeloid leukemia were performed in Europe (5228 allogeneic and 380 autologous stem cell transplantations). Most stem cell transplantations are performed in first complete remission. However, despite a considerable reduction in the chance of relapse, in most studies, overall survival benefit of allogeneic stem cell transplantation is modest due to substantial non-relapse mortality. Here we discuss the many factors related to the risk of relapse after allogeneic stem cell transplantation. PMID:26721801

  9. 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

  10. Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study

    PubMed Central

    Gooskens, S L; Furtwängler, R; Spreafico, F; van Tinteren, H; de Kraker, J; Vujanic, G M; Leuschner, I; Coulomb-L'Herminé, A; Godzinski, J; Schleiermacher, G; Stoneham, S; Bergeron, C; Pritchard-Jones, K; Graf, N; van den Heuvel-Eibrink, M M

    2014-01-01

    Background: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. Patients and methods: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. Results: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%–32%), and 5-year overall survival (OS) was 26% (95% CI: 10%–42%). Conclusions: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required. PMID:24937667

  11. Additional follow-up telephone counselling and initial smoking relapse: a longitudinal, controlled study

    PubMed Central

    Wu, Lei; He, Yao; Jiang, Bin; Zuo, Fang; Liu, Qinghui; Zhang, Li; Zhou, Changxi

    2016-01-01

    Objectives Smoking cessation services can help smokers to quit; however, many smoking relapse cases occur over time. Initial relapse prevention should play an important role in achieving the goal of long-term smoking cessation. Several studies have focused on the effect of extended telephone support in relapse prevention, but the conclusions remain conflicting. Design and setting From October 2008 to August 2013, a longitudinal, controlled study was performed in a large general hospital of Beijing. Participants The smokers who sought treatment at our smoking cessation clinic were non-randomised and divided into 2 groups: face-to-face individual counselling group (FC group), and face-to-face individual counselling plus telephone follow-up counselling group (FCF group). No pharmacotherapy was offered. Outcomes The timing of initial smoking relapse was compared between FC and FCF groups. Predictors of initial relapse were investigated during the first 180 days, using the Cox proportional hazards model. Results Of 547 eligible male smokers who volunteered to participate, 457 participants (117 in FC group and 340 in FCF group) achieved at least 24 h abstinence. The majority of the lapse episodes occurred during the first 2 weeks after the quit date. Smokers who did not receive the follow-up telephone counselling (FC group) tended to relapse to smoking earlier than those smokers who received the additional follow-up telephone counselling (FCF group), and the log-rank test was statistically significant (p=0.003). A Cox regression model showed that, in the FCF group, being married, and having a lower Fagerström test score, normal body mass index and doctor-diagnosed tobacco-related chronic diseases, were significantly independent protective predictors of smoking relapse. Conclusions Within the limitations of this study, it can be concluded that additional follow-up telephone counselling might be an effective strategy in preventing relapse. Further research is still

  12. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse.

    PubMed

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M; De Bont, Evelina S J M; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valérie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J L

    2014-09-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n = 198) of relapsed non-French-American-British M3, non-Down syndrome AML patients that received similar relapse treatment. We correlated molecular aberrations with clinical and biological factors and studied their prognostic relevance. Hotspot mutations in the analysed genes were detected in 92 out of 198 patients (46·5%). In 72 of these 92 patients (78%), molecular aberrations were mutually exclusive for the currently analysed genes. FLT3-internal tandem repeat (ITD) (18% of total group) mutations were most frequent, followed by NRAS (10·2%), KRAS (8%), WT1 (8%), KIT (8%), NPM1 (5%) and FLT3-tyrosine kinase domain (3%) mutations. Presence of a WT1 aberration was an independent risk factor for second relapse (Hazard Ratio [HR] = 2·74, P = 0·013). In patients who achieved second complete remission (70·2%), WT1 and FLT3-ITD aberrations were independent risk factors for poor overall survival (HR = 2·32, P = 0·038 and HR = 1·89, P = 0·045 respectively). These data show that molecular aberrations at first relapse are of prognostic relevance and potentially useful for risk group stratification of paediatric relapsed AML and for identification of patients eligible for personalized treatment. PMID:24962064

  13. Louse-borne relapsing fever (Borrelia recurrentis) in an Eritrean refugee arriving in Switzerland, August 2015.

    PubMed

    Goldenberger, D; Claas, G J; Bloch-Infanger, C; Breidthardt, T; Suter, B; Martínez, M; Neumayr, A; Blaich, A; Egli, A; Osthoff, M

    2015-08-13

    We report an imported case of louse-borne relapsing fever in a young adult Eritrean refugee who presented with fever shortly after arriving in Switzerland. Analysis of blood smears revealed spirochetes identified as Borrelia recurrentis by 16S rRNA gene sequencing. We believe that louse-borne relapsing fever may be seen more frequently in Europe as a consequence of a recent increase in refugees from East Africa travelling to Europe under poor hygienic conditions in confined spaces.

  14. Delay discounting rates: A strong prognostic indicator of relapse to smoking

    PubMed Central

    Sheffer, Christine E.; Christensen, Darren R; Landes, Reid; Carter, Larry P.; Jackson, Lisa; Bickel, Warren K.

    2014-01-01

    Recent evidence suggests that several dimensions of impulsivity and locus of control are likely to be significant prognostic indicators of relapse. We compared the relative strengths of associations among delay discounting rates, dimensions of trait impulsiveness from the Barratt Impulsiveness Scale - 11, locus of control, nicotine dependence, and stress level with days to relapse among smokers after an intensive multicomponent cognitive-behavioral treatment for tobacco dependence. We used Cox proportional hazard regressions to model days to relapse with each of the following: delay discounting of $100, delay discounting of $1,000, six subscales of the Barratt Impulsiveness Scale (BIS), Rotter’s Locus of Control (RLOC), Fagerstrom Test for Nicotine Dependence (FTND), and the Perceived Stress Scale (PSS). Standardized regression coefficients and hazard ratios (HRs) were used to assess the relative strength and direction of the associations along with a bootstrap method to determine 95% confidence intervals. We then examined the extent to which the measures retained associations with days to relapse while accounting for nicotine dependence and stress level. Our findings indicate that the $100 delay discounting rate had the strongest association with days to relapse, but was only significantly stronger than nicotine dependence. Discounting rates maintained significant associations with days to relapse when combined with the FTND and the PSS, but the BIS subscales and the RLOC did not. These findings indicate that delay discounting is independently associated with relapse and adds to what is already accounted for by nicotine dependence and stress level. These findings signify that delay discounting is a productive new target for enhancing treatment for tobacco dependence. Adding an intervention designed to decrease discounting rates to a comprehensive treatment for tobacco dependence has the potential to decrease relapse rates. PMID:24878037

  15. IMPULSIVE SUICIDE ATTEMPTS PREDICT POST-TREATMENT RELAPSE IN ALCOHOL DEPENDENT PATIENTS

    PubMed Central

    Wojnar, Marcin; Ilgen, Mark A.; Jakubczyk, Andrzej; Wnorowska, Anna; Klimkiewicz, Anna; Brower, Kirk J.

    2010-01-01

    Background The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined. Methods A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months. Results Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, df=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95%C.I. = 1.13–6.95, p=0.026) and time to relapse (OR=2.10, 95% C.I. = 1.18–3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity. Conclusions This study is the first to document the relationship between pre-treatment impulsive suicide attempts and higher likelihood of post-treatment relapse in alcohol-dependent patents. Clinicians should routinely conduct an assessment for previous suicide attempts in patients with alcohol use disorders, and when impulsive suicidality is reported, they should recognize the increased risk for relapse and formulate their patients' treatment plans accordingly with the goals of reducing both alcoholic relapse and suicide rates. PMID:18556146

  16. Evaluation of prognostic factors in patients with relapsed AML: Clonal evolution versus residual disease

    PubMed Central

    Kim, Hyojeong; Seol, Young Mi; Song, Moo-Kon; Choi, Young Jin; Shin, Ho-Jin; Park, Sang Hyuk; Lee, Eun Yup

    2016-01-01

    Background It is widely known that the prognosis of acute myeloid leukemia (AML) depends on chromosomal abnormalities. The majority of AML patients relapse and experience a dismal disease course despite initial remission. Methods We reviewed the medical records and laboratory findings of 55 AML patients who had relapsed between 2004 and 2013 and who had been treated at the Division of Hematology of the Pusan National University Hospital. Results The event-free survival (EFS) was related to prognostic karyotype classification at the time of diagnosis and relapse (unfavorable vs. favorable or intermediate karyotypes at diagnosis, 8.2 vs. 11.9 mo, P=0.003; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.2 vs. 11.9 mo, P=0.009). The overall survival (OS) was significantly correlated with karyotype classification only at diagnosis (unfavorable vs. favorable or intermediate vs. karyotypes at diagnosis, 8.5 vs. 21.8 mo, P=0.001; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.5 vs. 21.2 mo, P=0.136). A change in karyotype between diagnosis and relapse, which is regarded as a factor of resistance against treatment, was not a significant prognostic factor for OS, EFS, and post-relapse survival (PRS). A Cox proportional hazards model showed that the combined use of fludarabine, cytosine arabinoside, and granulocyte colony-stimulating factor (FLAG) as a salvage regimen, was a significant prognostic factor for OS (hazard ratio=0.399, P=0.010) and the PRS (hazard ratio=0.447, P=0.031). Conclusion The karyotype classification at diagnosis predicts survival including PRS in relapsed AML patients as well as in treatment-naïve patients. We suggest that presently, administration of salvage FLAG could be a better treatment option. PMID:27722128

  17. Cocaine Influences Alcohol-Seeking Behavior and Relapse Drinking in Alcohol-Preferring (P) Rats

    PubMed Central

    Hauser, Sheketha R.; Wilden, Jessica A.; Deehan, Gerald A.; McBride, William J.; Rodd, Zachary A.

    2014-01-01

    Background The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for one drug can be enhanced by exposure to another drug of abuse. The objective of the current study was to assess the time-course effects of acute cocaine administration on alcohol seeking and relapse. Methods Alcohol-Preferring (P) rats were allowed to self-administer 15% ethanol (EtOH) and water. EtOH-seeking was assessed through use of the Pavlovian Spontaneous Recovery (PSR) model, while relapse EtOH drinking was assessed through use of the alcohol deprivation effect. Results Cocaine (0, 1 or 10 mg/kg), injected immediately, 30 min, or 4 hr prior to the 1st PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hr prior to the relapse session markedly enhanced EtOH responding compared to saline. Conclusion The enhanced expression of EtOH-seeking and relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate) and priming of relapse/seeking (4 hour delay). PMID:25346508

  18. Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis.

    PubMed

    Magliozzi, Roberta; Columba-Cabezas, Sandra; Serafini, Barbara; Aloisi, Francesca

    2004-03-01

    Given the abnormalities in B-cell activity occurring in the central nervous system (CNS) of patients with multiple sclerosis (MS), we have explored the possibility that CNS inflammation induced in mouse models of experimental autoimmune encephalomyelitis (EAE) triggers expression of molecules that control the development and functional organization of lymphoid follicles, the sites where B-cell responses are initiated. By reverse transcription-polymerase chain reaction (RT-PCR), we find that gene expression of CXCL13, a chemokine involved in B-cell recruitment into lymphoid follicles, and BAFF, a key regulator of B-cell survival, is markedly and persistently upregulated in the CNS of mice with relapsing-remitting and chronic-relapsing EAE. Using immunohistochemical techniques, we also show the presence of lymphoid follicle-like structures containing B cells and a reticulum of CXCL13+ and FDC-M1+ follicular dendritic cells within the meninges of several mice undergoing progressive relapsing EAE. These observations indicate that, under chronic inflammatory conditions, the less immunoprivileged meningeal compartment is the site where ectopic lymphoid follicles preferentially develop and where pathogenic B-cell responses could be sustained in autoimmune disorders of the CNS.

  19. No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses

    PubMed Central

    Joyner, Chester; Barnwell, John W.; Galinski, Mary R.

    2015-01-01

    Plasmodium vivax is a human malaria parasite responsible for significant morbidity worldwide and potentially death. This parasite possesses formidable liver-stage biology that involves the formation of dormant parasites known as hypnozoites. Hypnozoites are capable of activating weeks, months, or years after a primary blood-stage infection causing relapsing bouts of illness. Elimination of this dormant parasitic reservoir will be critical for global malaria eradication. Although hypnozoites were first discovered in 1982, few advancements have been made to understand their composition and biology. Until recently, in vitro models did not exist to study these forms and studying them from human ex vivo samples was virtually impossible. Today, non-human primate (NHP) models and modern systems biology approaches are poised as tools to enable the in-depth study of P. vivax liver-stage biology, including hypnozoites and relapses. NHP liver-stage model systems for P. vivax and the related simian malaria species P. cynomolgi are discussed along with perspectives regarding metabolite biomarker discovery, putative roles of extracellular vesicles, and relapse immunobiology. PMID:25859242

  20. 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.

  1. Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

    PubMed Central

    Malagola, Michele; Skert, Cristina; Ruggeri, Giuseppina; Ribolla, Rossella; Bernardi, Simona; Borlenghi, Erika; Pagani, Chiara; Rossi, Giuseppe; Caimi, Luigi; Russo, Domenico

    2014-01-01

    To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43) and at the 6th month (71% versus 20%; P = 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P = 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk. PMID:25202702

  2. Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system.

    PubMed

    Kushner, B H; Kramer, K; Modak, S; Kernan, N A; Reich, L M; Danis, K; Cheung, N-K V

    2006-02-01

    We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m2/day, x 4 days; thiotepa 300 mg/m2/day, x 3 days; and carboplatin approximately 500 mg/m2/day, x 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cis-retinoic acid, +/-oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.+/-8%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day +9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.

  3. 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. PMID:26710887

  4. Dysfunctional Default Mode Network in Methadone Treated Patients Who Have a Higher Heroin Relapse Risk

    PubMed Central

    Li, Wei; Li, Qiang; Wang, Defeng; Xiao, Wei; Liu, Kai; Shi, Lin; Zhu, Jia; Li, Yongbin; Yan, Xuejiao; Chen, Jiajie; Ye, Jianjun; Li, Zhe; Wang, Yarong; Wang, Wei

    2015-01-01

    The purpose of this study was to identify whether heroin relapse is associated with changes in the functional connectivity of the default mode network (DMN) during methadone maintenance treatment (MMT). Resting-state functional magnetic resonance imaging (fMRI) data of chronic heroin relapsers (HR) (12 males, 1 female, age: 36.1 ± 6.9 years) and abstainers (HA) (11males, 2 female; age: 42.1 ± 8.1 years) were investigated with an independent component analysis to address the functional connectivity of their DMN. Group comparison was then performed between the relapsers and abstainers. Our study found that the left inferior temporal gyrus and the right superior occipital gyrus associated with DMN showed decreased functional connectivity in HR when compared with HA, while the left precuneus and the right middle cingulum had increased functional connectivity. Mean intensity signal, extracted from left inferior temporal gyrus of HR patients, showed a significant negative correlation corresponding to the degree of heroin relapse. These findings suggest that altered functional connectivity of DMN may contribute to the potential neurobiological mechanism(s) of heroin relapse and have a predictive value concerning heroin relapse under MMT. PMID:26469876

  5. Successful long-term jejunostomy feedings in relapsing pancreatitis: a case report.

    PubMed

    Sanchez-Fermin, Patricia; Ukleja, Andrew; Cruz-Correa, Marcia

    2006-01-01

    Relapsing pancreatitis is characterized by repeated episodes of acute inflammation of the pancreas, with either a localized or a systemic organic response that may progress to chronic pancreatitis. Enteral jejunal feedings have been shown to be effective in the management of acute pancreatitis, but long-term use of jejunal feedings as treatment of relapsing pancreatitis has not been reported. We describe the case of a young patient treated with long-term jejunal feedings to induce remission and prevent recurrence of acute relapsing pancreatitis. An 18-year-old Hispanic man had well-documented recurrent episodes of acute pancreatitis. Multiple studies were performed as part of the diagnostic workup of the patient's relapsing pancreatitis, including endoscopic ultrasound, endoscopic retrograde cholangiopancreatography with biliary sphincterotomy, and laparoscopic cholecystectomy. Despite medical therapy, endoscopic and surgical procedures, the patient continued having episodes of pancreatitis on a monthly basis, with over 13 distinct documented episodes of pancreatitis during a 15-month period. A jejunostomy tube was inserted surgically, and long-term jejunal feedings were instituted, with excellent control of the patient's symptoms. There was only 1 episode of pancreatitis in the ensuing 24 months associated with the resumption of oral feedings and a weight gain of 20 pounds during this time period. Chronic jejunal feedings seem to be an effective alternative for treatment and prevention of acute relapsing pancreatitis. To our knowledge, this is the first report of long-term enteral feedings in acute relapsing pancreatitis.

  6. Compliance with buprenorphine medication-assisted treatment and relapse to opioid use.

    PubMed

    Tkacz, Joseph; Severt, Jamie; Cacciola, John; Ruetsch, Charles

    2012-01-01

    Opioid dependence (OD), often characterized as a chronic relapsing disorder, affects millions of people worldwide. The purpose of this study was to examine the effect of compliance with buprenorphine on reducing relapse among a sample of patients in treatment for OD. Patients new to buprenorphine (N = 703) completed the Addiction Severity Index (ASI) at baseline, and at 1, 2, and 3 months postbaseline. The ASI is a semistructured interview designed to measure problem severity in seven functional areas known to be affected by alcohol and drug dependence. Compliance was defined as taking buprenorphine medication on at least 22 of the past 28 days (80%), while relapse classification was based on resumed use of opioids during the follow-up period (months 2 and 3). Relapse was regressed onto demographic indicators, baseline ASI composite scores, and compliance with buprenorphine. Noncompliant patients were over 10 times more likely to relapse than those who were compliant (exp β= 10.55; p < .001). Neither demographics nor baseline ASI composite scores were predictive of relapse (p's > .05). Compliance with medication-assisted treatment supports abstinence, essential for patient recovery. Understanding the factors that drive treatment compliance and noncompliance may assist providers in supporting patient compliance and recovery. 

  7. Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

    PubMed Central

    Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

    2015-01-01

    Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

  8. THE NEURAL CIRCUITRY UNDERLYING REINSTATEMENT OF HEROIN-SEEKING BEHAVIOR IN AN ANIMAL MODEL OF RELAPSE

    PubMed Central

    ROGERS, J.L.; GHEE, S.; SEE, R.E.

    2008-01-01

    Reinstatement of extinguished drug-seeking has been utilized in the study of the neural substrates of relapse to drugs of abuse, particularly cocaine. However, limited studies have examined the circuitry that drives the reinstatement of heroin-seeking behavior in the presence of conditioned cues, or by heroin itself. In order to test the hypothesis that the circuitry underlying reinstatement in heroin-experienced animals would show overlapping, yet distinct differences from cocaine-experienced animals, we used transient inhibition of several cortical, striatal, and limbic brain regions during reinstatement of heroin-seeking produced by heroin-paired cues, or by a single priming dose of heroin. Rats lever pressed for i.v. heroin discretely paired with a conditioned stimulus (CS) during daily 3-hr sessions for a period of 2 weeks, followed by daily extinction of lever responding. Subsequent reinstatement of heroin-seeking was measured as lever responding in the absence of heroin reinforcement. The first set of reinstatement tests involved response-contingent CS presentations following bilateral intracranial infusion of either a combination of GABA receptor agonists (baclofen-muscimol, B/M) or vehicle (saline) into one of thirteen different brain regions. The second set of reinstatement tests involved a single heroin injection (0.25 mg/kg, s.c.) following either B/M or vehicle infusions. Our results showed that vehicle infused animals reinstated to both CS presentations and a priming injection of heroin, while B/M inactivation of several areas known to be important for the reinstatement of cocaine-seeking also attenuated heroin-seeking in response to CS presentations and/or a priming dose of heroin. However, as predicted, inactivation of areas previously shown to not affect cocaine-seeking significantly attenuated heroin-seeking, supporting the hypothesis that the circuitry underlying the reinstatement of heroin-seeking is more diffusely distributed than that for

  9. 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.

  10. 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

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

    PubMed

    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.

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

    PubMed

    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

  13. Incidence and outcome of lung involvement in IgG4-related autoimmune pancreatitis.

    PubMed

    Ogoshi, Takaaki; Kido, Takashi; Yatera, Kazuhiro; Oda, Keishi; Nishida, Chinatsu; Yamasaki, Kei; Orihashi, Takeshi; Kawanami, Yukiko; Ishimoto, Hiroshi; Taguchi, Masashi; Harada, Masaru; Mukae, Hiroshi

    2015-10-01

    We evaluated the incidence and outcome of lung involvement in 35 patients with autoimmune pancreatitis (AIP). Our results indicate that lung involvement is commonly observed in AIP (40%). In addition, corticosteroid treatment improved the lung lesions and appeared to reduce the probability of relapse compared with pancreatic lesions (0% vs 36%). This is the first report to assess the long-term outcome of lung involvement in AIP (52 ± 33 months).

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

    PubMed

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

    2015-05-01

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

  15. 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

  16. Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

    PubMed Central

    Gulati, Rohit; Alkhatib, Yaser; Donthireddy, Vijayalakshmi; Felicella, Michelle Madden; Menon, Madhu P.; Inamdar, Kedar V.

    2015-01-01

    Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation. PMID:26819793

  17. Continuation Electroconvulsive Therapy vs Pharmacotherapy for Relapse Prevention in Major Depression

    PubMed Central

    Kellner, Charles H.; Knapp, Rebecca G.; Petrides, Georgios; Rummans, Teresa A.; Husain, Mustafa M.; Rasmussen, Keith; Mueller, Martina; Bernstein, Hilary J.; O’Connor, Kevin; Smith, Glenn; Biggs, Melanie; Bailine, Samuel H.; Malur, Chitra; Yim, Eunsil; McClintock, Shawn; Sampson, Shirlene; Fink, Max

    2013-01-01

    Background Although electroconvulsive therapy (ECT) has been shown to be extremely effective for the acute treatment of major depression, it has never been systematically assessed as a strategy for relapse prevention. Objective To evaluate the comparative efficacy of continuation ECT (C-ECT) and the combination of lithium carbonate plus nortriptyline hydrochloride (C-Pharm) in the prevention of depressive relapse. Design Multisite, randomized, parallel design, 6-month trial performed from 1997 to 2004. Setting Five academic medical centers and their outpatient psychiatry clinics. Patients Two hundred one patients with Structured Clinical Interview for DSM-IV–diagnosed unipolar depression who had remitted with a course of bilateral ECT. Interventions Random assignment to 2 treatment groups receiving either C-ECT (10 treatments) or C-Pharm for 6 months. Main Outcome Measure Relapse of depression, compared between the C-ECT and C-Pharm groups. Results In the C-ECT group, 37.1% experienced disease relapse, 46.1% continued to have disease remission at the study end, and 16.8% dropped out of the study. In the C-Pharm group, 31.6% experienced disease relapse, 46.3% continued to have disease remission, and 22.1% dropped out of the study. Both Kaplan-Meier and Cox proportional hazards regression analyses indicated no statistically significant differences in overall survival curves and time to relapse for the groups. Mean±SD time to relapse for the C-ECT group was 9.1±7.0 weeks compared with 6.7±4.6 weeks for the C-Pharm group (P=.13). Both groups had relapse proportions significantly lower than a historical placebo control from a similarly designed study. Conclusions Both C-ECT and C-Pharm were shown to be superior to a historical placebo control, but both had limited efficacy, with more than half of patients either experiencing disease relapse or dropping out of the study. Even more effective strategies for relapse prevention in mood disorders are urgently needed

  18. Etiologies and prognostic factors of leukocytoclastic vasculitis with skin involvement: A retrospective study in 112 patients.

    PubMed

    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

    2016-07-01

    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 survival rates were

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

    PubMed

    Garg, Manoj; 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

    2015-11-26

    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.

  20. 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.

  1. 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

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

    PubMed Central

    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. PMID:24194642

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

    PubMed

    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

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

    PubMed

    Garg, Manoj; 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

    2015-11-26

    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

  5. Cardiovascular involvement in Behçet's disease.

    PubMed

    Sezen, Yusuf; Buyukhatipoglu, Hakan; Buyukatipoglu, Hakan; Kucukdurmaz, Zekeriya; Geyik, Ramazan

    2010-01-01

    Behçet's disease is a chronic relapsing systemic vasculitis that can involve almost every organ and systems in the body with extremely different diverse manifestations. Cardiovascular involvement is one of these manifestations, the involvement of which might present in various patterns in itself. Cardiovascular involvement is relatively uncommon in Behçet's disease; however, Behçet's disease is relatively rather common in certain parts of the world. Therefore, especially in these locations recognizing such miscellaneous presentations are of critical importance, since cardiovascular involvements exceed other presentation in mortality and morbidity rates. Based on these facts, in this review, we summarized the cardiovascular involvements and its different manifestations in Behçet's disease. PMID:19830382

  6. [A study on relapse of schizophrenic patients--10-year-follow-up investigation after initial admission].

    PubMed

    Uchida, S

    1996-01-01

    Ten year prognosis of schizophrenic patients after their initial admission was studied. The subjects of the present investigation were 106 schizophrenic patients who fulfilled the criteria for schizophrenia of DSM-III-R and were initially admitted to a hospital between January 1979 and December 1984. They were classified into following five groups: 1) a discontinuing group (39 patients who could not be followed up because of changing the hospital or ceasing outpatient treatment), 2) an unrelapsing group (29 patients who had no relapse in continuing medication), 3) an A group (13 patients who relapsed in spite of continuing medication), 4) a B group (22 patients who relapsed only after discontinuing medication), and 5) a C group (3 patients who relapsed in continuing medication as well as after discontinuing medication). These groups were compared in multiple domains such as age at onset, age on initial admission, duration from onset to initial admission, etc. The average age at onset was significantly older in the unrelapsing group (29.0 years) than in the A group (22.1 years) (p < 0.05). The average age on initial admission was significantly older in the unrelapsing group (35.2 years) than in the A group (25.0 years) (p < 0.01). Furthermore the average duration from onset to initial admission was significantly longer in the unrelapsing group (70.9 months) than in the A group (23.8 months) (p < 0.05). Assuming theoretical groups considered in points of tendency of relapse and the effect of neuroleptics on the prevention in each patient, as well as theoretical subgroups considered in points of biological pathology and nonbiological pathology as factors of relapse, the following two subgroups were abstracted from the groups of this study: a subgroup with a high effect of medication on the prevention of relapse and the other with a low effect. There were significant differences in the average age at onset, age on initial admission, duration from onset to initial

  7. Inhibition of the Casein-Kinase-1-Epsilon/Delta Prevents Relapse-Like Alcohol Drinking

    PubMed Central

    Perreau-Lenz, Stéphanie; Vengeliene, Valentina; Noori, Hamid R; Merlo-Pich, Emilio V; Corsi, Mauro A; Corti, Corrado; Spanagel, Rainer

    2012-01-01

    During the past decade, it has been shown that circadian clock genes have more than a simple circadian time-keeping role. Clock genes also modulate motivational processes and have been implicated in the development of psychiatric disorders such as drug addiction. Recent studies indicate that casein-kinase 1ɛ/δ (CK1ɛ/δ)—one of the components of the circadian molecular clockwork—might be involved in the etiology of addictive behavior. The present study was initiated to study the specific role of CK1ɛ/δ in alcohol relapse-like drinking using the ‘Alcohol Deprivation Effect' model. The effect of CK1ɛ/δ inhibition was tested on alcohol consumption in long-term alcohol-drinking rats upon re-exposure to alcohol after deprivation using a four-bottle free-choice paradigm with water, 5%, 10%, and 20% ethanol solutions, as well as on saccharin preference in alcohol-naive rats. The inhibition of CK1ɛ/δ with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats. The impact of the treatment was further characterized using nonlinear regression analyses on the daily profiles of drinking and locomotor activity. We reveal that CK1ɛ/δ inhibition blunted the high daytime alcohol intake typically observed upon alcohol re-exposure, and induced a phase shift of locomotor activity toward daytime. Only the highest dose of PF-670462 shifted the saccharin intake daily rhythm toward daytime during treatment, and decreased saccharin preference after treatment. Our data suggest that CK1 inhibitors may be candidates for drug treatment development for alcoholism. PMID:22549116

  8. Close or Positive Margins After Mastectomy for DCIS: Pattern of Relapse and Potential Indications for Radiotherapy

    SciTech Connect

    Rashtian, Afshin Iganej, Shawn; Amy Liu, In-Lu; Natarajan, Sathima

    2008-11-15

    Purpose: Mastectomies result in very high local control rates for pure ductal carcinoma in situ; however, close or involved tumor margins are occasionally encountered. Data regarding the patterns of relapse in this setting are limited. Methods and Materials: Between 1994 and 2002, the pathology reports of 574 patients who had undergone mastectomy at our institution for pure ductal carcinoma in situ were retrospectively reviewed. Of the 574 patients, 84 were found to have margins of <10 mm. Of the 84 patients, 4 underwent postoperative radiotherapy and were excluded, leaving 80 patients for this analysis. Of the 80 patients, 31 had margins <2 mm and 49 had margins of 2.1-10 mm. High-grade disease was observed in 47 patients; 45 patients had comedonecrosis; and 30 had multifocal disease. Of the 80 patients, 51 were <60 years of age. Results: With a median follow-up of 61 months, 6 (7.5%) of the 80 patients developed local recurrence. Of the 31 patients with a margin of {<=}2 mm, 5 (16%) developed local recurrence vs. only 1 (2%) of 49 patients with a margin of 2.1-10 mm (p = 0.0356). Of the 6 patients with local recurrence, 5 had high-grade disease and/or comedonecrosis. All six recurrences were noted in patients <60 years old. Conclusion: The findings of this review suggest that patients with pure ductal carcinoma in situ who undergo mastectomy with a margin of <2 mm have a greater-than-expected incidence of local recurrence. Patients with additional unfavorable features such as high-grade disease, comedonecrosis, and age <60 years are particularly at risk of local recurrence. These patients might benefit from postmastectomy radiotherapy.

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

    PubMed

    Dimidjian, Sona; Goodman, Sherryl H

    2014-03-01

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

  10. A longitudinal study of clinical and immunological findings in 52 patients with relapsing retinal vasculitis.

    PubMed Central

    Stanford, M R; Graham, E; Kasp, E; Sanders, M D; Dumonde, D C

    1988-01-01

    Fifty-two patients with retinal vasculitis--26 with idiopathic disease and 26 with associated systemic inflammatory disease--were followed up for periods ranging from six months to 12 years. The aim of the study was to determine the relationship between relapse of uveitis, visual outcome, and the occurrence of circulating immune complexes (CIC) and antiretinal antibodies. In a total of 69 relapses, CIC were increased in one-third of patients and antiretinal antibodies in one-half. In those 34 patients who expressed antiretinal antibodies 27 (79%) of the relapses were characterised by antiretinal antibodies in the absence of raised CIC levels (p less than 0.01). These findings support our previous hypothesis that CIC may have a protective role in autoimmune retinal vasculitis and that antiretinal autoimmunity is of pathogenetic importance in relapse. In individual patients the visual outcome was not related to the number of relapses or to the CIC-autoantibody pattern, suggesting the operation of additional features which merit identification. PMID:3390420

  11. 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. PMID:26822355

  12. Defining the Survival Benchmark for Breast Cancer Patients with Systemic Relapse

    PubMed Central

    Zeichner, Simon B; Ambros, Tadeu; Zaravinos, John; Montero, Alberto J; Mahtani, Reshma L; Ahn, Eugene R; Mani, Aruna; Markward, Nathan J; Vogel, Charles L

    2015-01-01

    BACKGROUND Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. METHODS Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients. RESULTS Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of local-regional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades. CONCLUSION The new benchmark for MSFSR approaches 3 years. PMID:25922577

  13. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    PubMed

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

  14. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning

    PubMed Central

    Kahl, Christoph; Storer, Barry E.; Sandmaier, Brenda M.; Mielcarek, Marco; Maris, Michael B.; Blume, Karl G.; Niederwieser, Dietger; Chauncey, Thomas R.; Forman, Stephen J.; Agura, Edward; Leis, Jose F.; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A.; McSweeney, Peter A.; Wade, James C.; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A.; Maloney, David G.

    2007-01-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m2; n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT. PMID:17595333

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

    PubMed Central

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

    2012-01-01

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

  16. 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

  17. 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.

  18. 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. PMID:26445390

  19. The burden of Plasmodium vivax relapses in an Amerindian village in French Guiana.

    PubMed

    Nacher, Mathieu; Stefani, Aurelia; Basurko, Celia; Lemonnier, Delphine; Djossou, Félix; Demar, Magalie; Elenga, Narcisse; Brousse, Paul; Ville, Muriel; Carme, Bernard

    2013-10-24

    Malaria is a public health problem in French Guiana. Plasmodium vivax is the most frequent parasite. The objective of this analysis was to estimate the proportion of relapses in the burden of vivax malaria using the statistical rule stating that any case of vivax malaria occurring less than 90 days following a first episode is a relapse.A total of 622 subjects were followed for 2,9 years with 336 first single episodes of P. vivax malaria, and a total of 1,226 episodes of vivax malaria among which 559 were relapses (45.5%). For 194 patients having had falciparum malaria followed by vivax malaria it was estimated that 19% of the vivax episodes occurred less than 90 days following the falciparum episode and thus were possibly relapses due to the activation of latent hypnozoites. Despite the number of vivax cases and the number of relapses, there were only 28 recorded primaquine prescriptions (3.4% of vivax episodes, 4.5% of subjects).The present study points out that despite the fact that nearly half of the P. vivax cases, many of which in children, are caused by latent hypnozoites, only a minority of them benefit from primaquine radical cure. The obstacles to this are discussed and suggestions are made to reduce the burden of vivax malaria in Camopi and other remote health centres in French Guiana.

  20. Relapse Coping Strategies in Young Adults Addicts: A Quantitative Study in Iran

    PubMed Central

    Shafiei, Ebrahim; Hoseini, Agha Fatemeh; Parsaeian, Farnaz; Heidarinejad, Ali; Azmal, Mohammad

    2016-01-01

    Background: Cognitive-behavioral coping approach is known as an effective strategy to preventing relapse. Its goal is to forget incompatible behaviors and replaces them with the compatible answers. Objectives: This study examines relapse coping strategies in young adults in selected substance abuse treatment centers in Iran. Patients and Methods: The present is a descriptive cross-sectional study. The sample consisted of 70 self-referred young addicts (18-24 years). Adolescence Relapse Coping Questionnaire was used to assess relapse coping strategies. Descriptive statistics was used to analyze the data. Results: The findings revealed that 71.2% have experienced a relapse totally. It was hard to control the hypothetical high risk situation and they greatly wanted to use the substance (mean 7.39 of 10). Addicts have used of all three coping skills in “definitely would do” level. Conclusion: Enhancing self-efficacy through training coping skills, especially abstinence - focused coping skills to react properly in high risk situation can be useful. PMID:27011402

  1. Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

    PubMed

    Uderzo, C; Grazia Zurlo, M; Adamoli, L; Zanesco, L; Aricò, M; Calculli, G; Comelli, A; Cordero di Montezemolo, L; Di Tullio, M T; Guazzelli, C

    1990-04-01

    Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

  2. Late relapse of testicular cancer: Recurrence after 24 years and treatment with chemotherapy alone.

    PubMed

    Akar, Emre; Tural, Deniz; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Yıldız, Özcan

    2015-01-01

    Late relapse of testicular cancer, defined as >2 years interval between initial treatment and recurrence, is a rare disease with the incidence rate of 2.6%. Due to its chemoresistant features, treatment options of late relapses are controversial while surgical approach and cisplatin-based chemotherapies can be considered. We report here a patient with nonseminomatous germ cell tumor who experienced relapse 24 years after his first diagnosis. After detecting left supraclavicular lymphadenopathy and absence of any other malignant lesion in positron emission tomography-computerized tomography, patient was treated with three cycles of VeIP regimen (vinblastine/ifosfamide/cisplatin). Second complete response to this treatment was achieved with chemotherapy alone.

  3. Role of Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Hodgkin Lymphoma

    PubMed Central

    Carella, Angelo Michele

    2012-01-01

    Hodgkin lymphoma is one of the most curable human tumors. Despite this, about 30% of these patients relapsed or are primary refractory to the first line treatment. Autografting is generally considered the standard of care for these patients. Alternative salvage strategies have been evaluated such as high dose sequential and tandem autografting strategies. In younger patients, refractory or early relapsed after autografting, allogeneic stem cell transplantation has been employed but this approach has been followed by significant concerns since the treatment related mortality, often exceeded 40–50%, and relapses were not uncommon. It is clear that patient selection remains an issue in all allografting reports. At the end, new drugs and novel treatment strategies, that are based on our understanding of the disease biology and signaling pathways, are needed to improve treatment outcome for these patients. The two leading compounds Brentuximab Vedotin and Panobinostat, are currently under evaluation in several clinical trials. PMID:23170188

  4. 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.

  5. The mitochondrial genetic landscape in neuroblastoma from tumor initiation to relapse

    PubMed Central

    Riehl, Lara M.; Schulte, Johannes H.; Mulaw, Medhanie A.; Dahlhaus, Meike; Fischer, Matthias; Schramm, Alexander; Eggert, Angelika; Debatin, Klaus-Michael; Beltinger, Christian

    2016-01-01

    Little is known about changes within the mitochondrial (mt) genome during tumor progression in general and during initiation and progression of neuroblastoma (NB) in particular. Whole exome sequencing of corresponding healthy tissue, primary tumor and relapsed tumor from 16 patients with NB revealed that most NB harbor tumor-specific mitochondrial variants. In relapsed tumors, the status of mt variants changed in parallel to the status of nuclear variants, as shown by increased number and spatio-temporal differences of tumor-specific variants, and by a concomitant decrease of germline variants. As mt variants are present in most NB patients, change during relapse and have a higher copy number compared to nuclear variants, they represent a promising new source of biomarkers for monitoring and phylogenetic analysis of NB. PMID:26735174

  6. NK cell immunotherapy for high-risk neuroblastoma relapse after haploidentical HSCT.

    PubMed

    Kanold, Justyna; Paillard, Catherine; Tchirkov, Andrei; Lang, Peter; Kelly, Antony; Halle, Pascale; Isfan, Florentina; Merlin, Etienne; Marabelle, Aurelien; Rochette, Emmanuelle; Deméocq, François

    2012-10-01

    Little is known on strategies to prevent or to treat relapses occurring after haploidentical stem cell transplantation (haplo-HSCT) performed for the high-risk neuroblastoma (NB). We describe a 6-year-old male with refractory NB who relapsed 22 months after haplo-HSCT. A complete remission was obtained with a combination of immuno-chemotherapy based on donor NK cells transplants, IL2 infusions and temozolomide/topotecan. This case is an incentive to explore both the immediate therapeutic effect of haplo-graft provided via haplo-NK cells and the immunogenic platform that haplo-HSCT offers for future treatment. Our post-relapse strategy shows that chemo- and bio-treatment should be viewed as complementary therapeutic options.

  7. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

  8. Late relapse of testicular cancer: Recurrence after 24 years and treatment with chemotherapy alone.

    PubMed

    Akar, Emre; Tural, Deniz; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Yıldız, Özcan

    2015-01-01

    Late relapse of testicular cancer, defined as >2 years interval between initial treatment and recurrence, is a rare disease with the incidence rate of 2.6%. Due to its chemoresistant features, treatment options of late relapses are controversial while surgical approach and cisplatin-based chemotherapies can be considered. We report here a patient with nonseminomatous germ cell tumor who experienced relapse 24 years after his first diagnosis. After detecting left supraclavicular lymphadenopathy and absence of any other malignant lesion in positron emission tomography-computerized tomography, patient was treated with three cycles of VeIP regimen (vinblastine/ifosfamide/cisplatin). Second complete response to this treatment was achieved with chemotherapy alone. PMID:26458676

  9. α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15

    PubMed Central

    Kume, Kohei; Ikeda, Miyuki; Miura, Sawako; Ito, Kohei; Sato, Kei A.; Ohmori, Yukimi; Endo, Fumitaka; Katagiri, Hirokatsu; Ishida, Kaoru; Ito, Chie; Iwaya, Takeshi; Nishizuka, Satoshi S.

    2016-01-01

    Cancer relapse occurs with substantial frequency even after treatment with curative intent. Here we studied drug-tolerant colonies (DTCs), which are subpopulations of cancer cells that survive in the presence of drugs. Proteomic characterization of DTCs identified stemness- and epithelial-dominant subpopulations, but functional screening suggested that DTC formation was regulated at the transcriptional level independent from protein expression patterns. We consistently found that α-amanitin, an RNA polymerase II (RNAPII) inhibitor, effectively inhibited DTCs by suppressing TAF15 expression, which binds to RNA to modulate transcription and RNA processing. Sequential administration of α-amanitin and cisplatin extended overall survival in a cancer-relapse mouse model, namely peritonitis carcinomatosa. Therefore, post-treatment cancer relapse may occur through non-distinct subpopulations and may be effectively prevented by α-amanitin to disrupt transcriptional machinery, including TAF15. PMID:27181033

  10. 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. PMID:23862404

  11. Relapse induced by cues predicting cocaine depends on rapid, transient synaptic potentiation

    PubMed Central

    Gipson, Cassandra D.; Kupchik, Yonatan M.; Shen, Haowei; Reissner, Kathryn J.; Thomas, Charles A.; Kalivas, Peter W.

    2013-01-01

    Summary Cocaine addiction is characterized by long-lasting vulnerability to relapse arising because neutral environmental stimuli become associated with drug use and then act as cues that induce relapse. It is not known how cues elicit cocaine seeking, and why cocaine seeking is more difficult to regulate than seeking a natural reward. We found that cocaine-associated cues initiate cocaine seeking by inducing a rapid, transient increase in dendritic spine size and synaptic strength in the nucleus accumbens. These changes required neural activity in the prefrontal cortex. This is not the case when identical cues were associated with obtaining sucrose, which did not elicit changes in spine size or synaptic strength. The marked cue-induced synaptic changes in the accumbens were correlated with the intensity of cocaine, but not sucrose seeking, and may explain the difficulty addicts experience in managing relapse to cocaine use. PMID:23473317

  12. An unusual case of chronic relapsing tetanus associated with mandibular osteomyelitis.

    PubMed

    Wakasaya, Yasuhito; Watanabe, Mitsunori; Tomiyama, Masahiko; Suzuki, Chieko; Jackson, Mandy; Fujimuro, Masahiro; Kimura, Tamaki; Seino, Yusuke; Kawarabayashi, Takeshi; Yamamoto-Watanabe, Yukiko; Matsubara, Etsuro; Shirahama, Ikumi; Takamura, Ayumi; Nakahata, Naoko; Shoji, Mikio

    2009-01-01

    A 55-year-old man underwent radiation therapy due to malignant lymphoma of the neck. Eight years after the therapy he developed tetanus. It appears that the radiation therapy resulted in mandibular necrosis, and that this lesion may have been the infectious focus of tetanus. Treatment with penicillin G was very effective in the acute stage, and chronic administration of metronidazole prevented relapse of the disease. However in spite of injections of tetanus toxoid, symptoms of tetanus returned when the administration of metronidazole was discontinued because the infectious focus could not be completely removed. This is the first report of chronic relapsing tetanus associated with radiation-induced mandibular osteomyelitis, and demonstrates that tetanus can occur due to mandibular focus but the chronic administration of metronidazole can prevent relapse.

  13. 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

  14. 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.

  15. Brain-Specific Inactivation of the Crhr1 Gene Inhibits Post-Dependent and Stress-Induced Alcohol Intake, but Does Not Affect Relapse-Like Drinking

    PubMed Central

    Molander, Anna; Vengeliene, Valentina; Heilig, Markus; Wurst, Wolfgang; Deussing, Jan M; Spanagel, Rainer

    2012-01-01

    Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic–pituitary–adrenal (HPA) axis activity might be involved as well. Here we examined the role of CRHR1 in various drinking conditions in relation to HPA and extra-HPA sites, and studied relapse-like drinking behavior in the alcohol deprivation model (ADE). To dissect CRH/CRHR1 extra-HPA and HPA signaling on a molecular level, a conditional brain-specific Crhr1-knockout (Crhr1NestinCre) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1 antagonists in the ADE model. Stress-induced augmentation of alcohol intake was lower in Crhr1NestinCre mice as compared with control animals. Crhr1NestinCre mice were also resistant to escalation of alcohol intake in the post-dependent state. Contrarily, global Crhr1 knockouts showed enhanced stress-induced alcohol consumption and a more pronounced escalation of intake in the post-dependent state than their control littermates. Basal intake and deprivation-induced intake were unaltered in both knockout models when compared with their respective controls. In line with these findings, CRHR1 antagonists did not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load. PMID:22113086

  16. Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking.

    PubMed

    Molander, Anna; Vengeliene, Valentina; Heilig, Markus; Wurst, Wolfgang; Deussing, Jan M; Spanagel, Rainer

    2012-03-01

    Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA) axis activity might be involved as well. Here we examined the role of CRHR1 in various drinking conditions in relation to HPA and extra-HPA sites, and studied relapse-like drinking behavior in the alcohol deprivation model (ADE). To dissect CRH/CRHR1 extra-HPA and HPA signaling on a molecular level, a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1 antagonists in the ADE model. Stress-induced augmentation of alcohol intake was lower in Crhr1(NestinCre) mice as compared with control animals. Crhr1(NestinCre) mice were also resistant to escalation of alcohol intake in the post-dependent state. Contrarily, global Crhr1 knockouts showed enhanced stress-induced alcohol consumption and a more pronounced escalation of intake in the post-dependent state than their control littermates. Basal intake and deprivation-induced intake were unaltered in both knockout models when compared with their respective controls. In line with these findings, CRHR1 antagonists did not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.

  17. Current Role of Autologous and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma

    PubMed Central

    Castagna, Luca; Carlo-Stella, Carmelo; Mazza, Rita; Santoro, Armando

    2015-01-01

    Classical Hodgkin lymphoma (cHL) is a relatively rare disease, with approximately 9,200 estimated new cases and 1,200 estimated deaths per year in the United States. First-line chemo-radiotherapy leads to cure rates approaching 80% in patients with advanced-stage disease. However, 25 to 30% of these patients are not cured with chemotherapy alone (i.e., the ABVD regimen) and show either primary refractoriness to chemotherapy, early disease relapse or late disease relapse. Second-line salvage high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) have an established role in the management of refractory/relapsed cHL, leading to durable responses in approximately 50% of relapsed patients and a minority of refractory patients. However, due to the poor responses to second-line salvage chemotherapy and dismal long-term disease control of primary refractory and early relapsed patients, their treatment represents an unmet medical need. Allogeneic SCT represents, by far, the only strategy with a curative potential for these patients; however, as discussed in this review, it’s role in cHL remains controversial. Despite a general consensus that early relapsed and primary refractory patients represent a clinical challenge requiring effective treatments to achieve long-term disease control, there has been no consensus on the optimal therapy that should be offered to these patients. This review will briefly discuss the clinical results and the main issues regarding autologous SCT as well as the current role of allogeneic SCT. PMID:25745542

  18. 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.

  19. 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

  20. Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

    SciTech Connect

    Foote, Matthew; Harvey, Jennifer; Porceddu, Sandro

    2010-07-01

    Purpose: To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). Patients and Methods: This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. Results: Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%) were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving {>=}50Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). Conclusion: This study indicates a dose-response for subclinical and gross MCC. Doses of {>=}50Gy for subclinical disease and {>=}55Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.

  1. 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

  2. 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. PMID:25673130

  3. Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma

    PubMed Central

    2014-01-01

    Background Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations. Methods Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses. Results Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1–2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles. Conclusions This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic

  4. Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency.

    PubMed

    Thompson, S A; Calvin, J; Hogg, S; Ferdinandusse, S; Wanders, R J A; Barker, R A

    2008-04-01

    Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies.

  5. Tick-borne relapsing fever in Colorado. Historical review and report of cases.

    PubMed

    Edell, T A; Emerson, J K; Maupin, G O; Barnes, A M; Vernon, T M

    1979-05-25

    Since 1915 the front range of the Colorado Rocky Mountains has been postulated as a focus of endemic tick-borne relapsing fever. However, the disease has rarely been identified: only two cases have been reported in Colorado since 1944. Three sporadic cases in 1977--tightly grouped geographically and temporally--prompted an epidemiologic review. Tick-borne relapsing fever should be considered in the differential diagnosis of recurrent paroxysmal fever--with or without known presence of ticks--whenever exposure in an endemic area is part of a patient's history. PMID:374757

  6. 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

  7. Factors in Successful Relapse Prevention among Hong Kong Drug Addicts

    ERIC Educational Resources Information Center

    Cheung, Chau-Kiu; Lee, Tak-Yan; Lee, Chak-Man

    2003-01-01

    This article reports on the findings of a study involving intensive interviews with 21 former drug addicts who had successfully maintained abstinence for periods ranging from one-and-a-half to four years. They were among the 74 successful former drug addicts out of a pool of more than 2,000 participating in a major rehabilitation program in Hong…

  8. 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

  9. 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…

  10. Risk Factors and Timing of Relapse after Allogeneic Transplantation in Pediatric ALL: For Whom and When should Interventions be Tested?

    PubMed Central

    Pulsipher, Michael A.; Langholz, Bryan; Wall, Donna A.; Schultz, Kirk R.; Bunin, Nancy; Carroll, William; Raetz, Elizabeth; Gardner, Sharon; Goyal, Rakesh K.; Gastier-Foster, Julie; Borowitz, Michael; Teachey, David; Grupp, Stephan A.

    2015-01-01

    We previously showed that minimal residual disease (MRD) detection pre- hematopoietic cell transplant (HCT) and acute graft versus host disease (aGVHD) independently predicted risk of relapse in pediatric ALL. In this study we further define risk by assessing timing of relapse and the effects of leukemia risk category and post-HCT MRD. By multivariate analysis, pre-HCT MRD < 0.1% and aGVHD by day +55 were associated with decreased relapse and improved EFS. Intermediate leukemia risk status predicted decreased relapse, and improved EFS and OS. Patients with pre-HCT MRD ≥ 0.1% who did not develop aGVHD compared to those with MRD <0.1% who did develop aGVHD had much worse survival (2yr EFS 18 vs. 71%; p=0.001, 2yr OS 46 vs. 74%; p=0.04). Patients with pre-HCT MRD <0.1% who did not experience aGVHD had higher rates of relapse if they did not develop aGVHD (40% vs 13%; p= 0.008). Post-HCT MRD led to a substantial increase in relapse risk (HR=4.5, p<0.01). Patients at high risk of relapse can be defined after transplant using leukemia risk category, presence of MRD pre- or post-HCT, and occurrence of aGVHD. An optimal window to initiate intervention to prevent relapse occurs between day +55 and +200 after HCT. PMID:25961775

  11. 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"…

  12. 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…

  13. Rates and Predictors of Renewed Quitting After Relapse During a One-Year Follow-Up Among Primary Care Patients

    PubMed Central

    Bold, Krysten W.; Rasheed, Abdullah S.; McCarthy, Danielle E.; Jackson, Thomas C.; Fiore, Michael C.; Baker, Timothy B.

    2014-01-01

    Background Most people who quit smoking relapse within a year of quitting. Little is known about what prompts renewed quitting after relapse or how often this results in abstinence. Purpose To identify rates, efficacy, and predictors of renewed quit attempts after relapse during a one-year follow-up. Methods Primary care patients in a comparative effectiveness trial of smoking cessation pharmacotherapies reported daily smoking every 6–12 weeks for 12 months to determine relapse, renewed quitting, and 12-month abstinence rates. Results Of 894 known relapsers, 291 (33%) renewed quitting for at least 24 hours and 99 (34%) of these were abstinent at follow-up. The average latency to renewed quitting was 106 days and longer latencies predicted greater success. Renewed quitting was more likely for older, male, less dependent smokers, and later abstinence was predicted by fewer depressive symptoms and longer past abstinence. Conclusions Renewed quitting is common and produces meaningful levels of cessation. PMID:24796541

  14. Single Agent Lenalidomide Activity in Multiple Myeloma Relapse Evidenced Uniquely by CT/PET

    PubMed Central

    Gozzetti, Alessandro; Rossi, Vania; Cerase, Alfonso; Papini, Giulia; Defina, Marzia; Bocchia, Monica

    2012-01-01

    A 71 year old female with multiple myeloma presented with back pain seven year after autologous stem cell transplant. Skeletal bone survey and magnetic resonance imaging did not show a relapse that was evidenced by CT/PET. Lenalidomide as single agent induced a complete disappearance of the lesions 6 months later and confirmed after one year at CT/PET. PMID:22811790

  15. 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)

  16. 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…

  17. Knowledge Mapping: A Psychoeducational Tool in Drug Abuse Relapse Prevention Training.

    ERIC Educational Resources Information Center

    Knight, Kevin; And Others

    1994-01-01

    Examined effectiveness of relapse prevention training (RPT), part of outpatient-drug education program for 83 drug addicted probationers, with special attention to knowledge maps as supplemental instructional materials. Found that program participation improved during use of RPT. Participants who successfully completed RPT sessions had lower rates…

  18. 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…

  19. Louse-borne relapsing fever among East African refugees in Europe.

    PubMed

    Antinori, Spinello; Mediannikov, Oleg; Corbellino, Mario; Raoult, Didier

    2016-01-01

    Louse-borne relapsing fever a neglected and forgotten disease by western physicians has recently re-emerged among East African migrants seeking asylum in Europe. We review here the cases observed so far together with a critical reappraisal of several issues regarding clinical presentation, diagnosis and treatment. PMID:26872415

  20. Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse.

    PubMed

    Meye, Frank J; Soiza-Reilly, Mariano; Smit, Tamar; Diana, Marco A; Schwarz, Martin K; Mameli, Manuel

    2016-08-01

    Cocaine withdrawal produces aversive states and vulnerability to relapse, hallmarks of addiction. The lateral habenula (LHb) encodes negative stimuli and contributes to aversive withdrawal symptoms. However, it remains unclear which inputs to LHb promote this and what the consequences are for relapse susceptibility. We report, using rabies-based retrolabeling and optogenetic mapping, that the entopeduncular nucleus (EPN, the mouse equivalent of the globus pallidus interna) projects to an LHb neuronal subset innervating aversion-encoding midbrain GABA neurons. EPN-to-LHb excitatory signaling is limited by GABAergic cotransmission. This inhibitory component decreases during cocaine withdrawal as a result of reduced presynaptic vesicular GABA transporter (VGAT). This shifts the EPN-to-LHb GABA/glutamate balance, disinhibiting EPN-driven LHb activity. Selective virally mediated VGAT overexpression at EPN-to-LHb terminals during withdrawal normalizes GABAergic neurotransmission. This intervention rescues cocaine-evoked aversive states and prevents stress-induced reinstatement, used to model relapse. This identifies diminished inhibitory transmission at EPN-to-LHb GABA/glutamate synapses as a mechanism contributing to the relapsing feature of addictive behavior. PMID:27348214

  1. 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…

  2. 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. PMID:27100471

  3. 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…

  4. 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

  5. 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),…

  6. 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. PMID:27282331

  7. Evaluation of a Web-Phone Intervention System on Preventing Smoking Relapse

    ERIC Educational Resources Information Center

    Peng, Wu-Der

    2010-01-01

    This randomized-controlled-trial aimed to evaluate the effectiveness of a web-phone intervention system in preventing smoking relapse. The intervention was based on the Transtheoretical Model (TTM), incorporated with Motivational Interviewing strategies, and the Two-phase Model. One hundred and sixteen volunteer subjects were recruited from the…

  8. Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy.

    PubMed

    Morgenstern, Daniel A; Baruchel, Sylvain; Irwin, Meredith S

    2013-07-01

    More than half of the patients with high-risk neuroblastoma (NB) will relapse despite intensive multimodal therapy, with an additional 10% to 20% refractory to induction chemotherapy. Management of these patients is challenging, given disease heterogeneity, resistance, and organ toxicity including poor hematological reserve. This review will discuss the current treatment options and consider novel therapies on the horizon. Cytotoxic chemotherapy regimens for relapse and refractory NB typically center on the use of the camptothecins, topotecan and irinotecan, in combination with agents such as cyclophosphamide and temozolomide, with objective responses but poor long-term survival. I-meta-iodobenzylguanidine therapy is also effective for relapsed patients with meta-iodobenzylguanidine-avid disease, with objective responses in a third of cases. Immunotherapy with anti-GD2 has recently been incorporated into upfront therapy, but its role in the relapse setting remains uncertain, especially for patients with bulky disease. Future cell-based immunotherapies and other approaches may be able to overcome this limitation. Finally, many novel molecularly targeted agents are in development, some of which show specific promise for NB. Successful incorporation of these agents will require combinations with conventional cytotoxic chemotherapies, as well as the development of predictive biomarkers, to ultimately personalize approaches to patients with "targetable" molecular abnormalities.

  9. Altered T cell phenotypes associated with clinical relapse of multiple sclerosis patients receiving fingolimod therapy

    PubMed Central

    Fujii, Chihiro; Kondo, Takayuki; Ochi, Hirofumi; Okada, Yoichiro; Hashi, Yuichiro; Adachi, Tetsuya; Shin-Ya, Masaharu; Matsumoto, Sadayuki; Takahashi, Ryosuke; Nakagawa, Masanori; Mizuno, Toshiki

    2016-01-01

    Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7+ central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects. The frequency of CD56+ T cells and granzyme B-, perforin-, and Fas ligand-positive T cells significantly increased during fingolimod treatment. Each T cell subpopulation further increased during relapse. Interestingly, T cells from fingolimod-treated patients exhibited interferon-γ biased production, and more myelin basic protein-reactive cells was noted in CD56+ than in CD56− T cells. It is likely that the altered T cell phenotypes play a role in MS relapse in fingolimod-treated patients. Further clinical studies are necessary to investigate whether altered T cell phenotypes are a biomarker for relapse under fingolimod therapy. PMID:27752051

  10. 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)…

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

    PubMed

    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 CD56(bright) 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

  12. 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

  13. 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.

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. Stress as a Trigger for Relapses in IBD: A Case-Crossover Study

    PubMed Central

    Jaghult, Susanna; Saboonchi, Fredrik; Moller, Jette; Johansson, Unn-Britt; Wredling, Regina; Kapraali, Marjo

    2013-01-01

    Background It is important to identify factors that influence the risk of relapses in inflammatory bowel disease. Few studies have been conducted and with limited methodology. This prospective case-crossover study, aims to examine whether perceived stress has a short-term acute effect, namely whether it acts as a trigger, on the risk of relapse in inflammatory bowel disease. Methods Sixty patients with inflammatory bowel disease and in remission were included. The case-crossover design was employed, which is an epidemiological design developed to study triggers for acute events and diseases. To collect information regarding symptoms and potential trigger factors, such as perceived stress, a structured diary was constructed. The participants were instructed to fill in the diary daily during six months. Fifty patients completed the study. Results The analysis showed an effect for high level of perceived stress. Being exposed to “quite a lot” of stress, yield an increase in risk for relapse during the forthcoming day (OR = 4.8, 95% CI 1.09 - 21.10). No statistically increased risk for lower levels of perceived stress was found, although elevated effect estimates were found for “some” stress. Conclusion This study supports earlier findings regarding perceived stress as an important factor in triggering relapses in IBD. However, this is the first case-crossover study performed to explore the trigger risk of stress in this population. Further investigations with larger patient samples are needed to confirm the findings. PMID:27785220

  19. 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.

  20. 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. PMID:27356309

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

    PubMed

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

    2013-09-01

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

  2. 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

  3. Extending Prednisolone Treatment Does Not Reduce Relapses in Childhood Nephrotic Syndrome

    PubMed Central

    Kist-van Holthe, Joana E.; van Rijswijk, Nienske; de Mos, Nienke I.; Hop, Wim C.J.; Wetzels, Jack F.M.; van der Heijden, Albert J.; Nauta, Jeroen

    2012-01-01

    Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m2). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration. PMID:23274956

  4. 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.

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

    PubMed Central

    Cohan, Stanley

    2016-01-01

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

  6. 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.

  7. 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. PMID:21099400

  8. The Use of Art Therapy as a Predictor of Relapse in Chemical Dependency Treatment.

    ERIC Educational Resources Information Center

    Dickman, Sara Brizdle; Dunn, Jonathan E.; Wolf, Abraham W.

    1996-01-01

    Based on five years observations, three items were more likely to appear in drawings of patients who relapsed within three months: (1) presence of psychoactive substances or drug paraphernalia; (2) lack of a figure representing the self or any detailed figure; (3) notable use of abstract or geometric drawing style. (LSR)

  9. [Outpatient reinduction therapy with gemcitabine, dexamethasone, Cisplatin (GDP) for patients with relapsed and refractory lymphoma].

    PubMed

    Aota, Yasuo; Tanaka, Masaru; Watanabe, Naoki; Tomomatu, Jyunichi; Gotoh, Akihiko; Komatu, Norio

    2015-01-01

    For younger patients with relapsed or refractory lymphomas who respond to salvage therapy, autologous stem cell trans- plantation(ASCT)is the standard of care. Recently, it was demonstrated that the gemcitabine/dexamethasone/cisplatin (GDP) regimen for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) prior to ASCT was not inferior to the standard dexamethasone/cytarabine/cisplatin (DHAP) regimen for patients with relapsed and refractory aggressive lymphoma. In Japan, most patients who receive CDDP-containing regimens are hospitalized because of the substantial transfusions required for preventing renal dysfunction. We initiated GDP therapy combined with a short period of hydration and the administration of a magnesium agent and mannitol for 5 patients with relapsed and refractory aggressive lymphoma. In 4 cases, GDP was safely administered on an outpatient basis. Furthermore, peripheral blood stem cells were successfully collected in 2 patients. After stem cell harvest, ASCT was performed in a patient with diffuse large B-cell lymphoma, with the patient remaining in complete remission (CR) after ASCT.

  10. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis. PMID:26725353

  11. A Markov model for sequences of ordinal data from a relapsing-remitting disease.

    PubMed

    Albert, P S

    1994-03-01

    Many chronic diseases follow a course with multiple relapses into periods with severe symptoms alternating with periods of remission; experimental allergic encephalomyelitis, the animal model for multiple sclerosis, is an example of such a disease. A finite Markov chain is proposed as a model for analyzing sequences of ordinal data from a relapsing-remitting disease. The proposed model is one in which the state space is expanded to include information about the relapsing-remitting status as well as the ordinal severity score, and a reparameterization is suggested that reduces the number of parameters needed to be estimated. The Markov model allows for a wide range of relapsing-remitting behavior, provides an understanding of the stochastic nature of the disease process, and allows for efficient estimation of important characteristics of the disease course (such as mean first passage times, occupation times, and steady-state probabilities). These methods are applied to data from a study of the effect of a treatment (transforming growth factor-beta 1) on experimental allergic encephalomyelitis. PMID:8086615

  12. Teriflunomide in Patients with Relapsing-Remitting Forms of Multiple Sclerosis.

    PubMed

    Chan, Andrew; de Seze, Jérôme; Comabella, Manuel

    2016-01-01

    Teriflunomide is a once-daily oral agent that has been licensed in the EU since August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). More recently (September 2014), the EU summary of product characteristics (SmPC) was updated to include data from patients with a first clinical demyelinating event. This review examines the EU SmPC for teriflunomide, with reference to key clinical and safety outcomes and practical considerations for prescribing physicians. In two phase III trials (TEMSO and TOWER) in patients with relapsing forms of MS, teriflunomide 14 mg significantly reduced the annualized relapse rate and the risk of confirmed disability progression sustained for at least 12 weeks. Magnetic resonance imaging (MRI) total lesion volume, gadolinium-enhancing lesions, and unique active lesions were reduced with teriflunomide treatment in TEMSO. In the TOPIC study, in patients with a first clinical demyelinating event, teriflunomide treatment significantly reduced the time to a second clinical episode (relapse). Across the clinical studies, teriflunomide was generally well tolerated; adverse events reported in ≥ 10% of teriflunomide-treated patients were diarrhea, nausea, increased alanine aminotransferase, and alopecia. Data from the clinical development program support the use of teriflunomide in a broad spectrum of patients with RRMS. PMID:26758290

  13. Fatal toxic epidermal necrolysis in a patient on teriflunomide treatment for relapsing multiple sclerosis.

    PubMed

    Gerschenfeld, Gaspard; Servy, Amandine; Valeyrie-Allanore, Laurence; de Prost, Nicolas; Cecchini, Jérôme

    2015-10-01

    We report a case of toxic epidermal necrolysis in a 46-year-old woman on teriflunomide treatment. Such a severe adverse cutaneous drug reaction with this new therapy for relapsing forms of multiple sclerosis should be early recognized in order to ensure the rapid withdrawal of the drug. PMID:26199352

  14. 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

  15. Microgeographical differences of Plasmodium vivax relapse and re-infection in the Peruvian Amazon.

    PubMed

    Chuquiyauri, Raul; Peñataro, Pablo; Brouwer, Kimberly C; Fasabi, Manuel; Calderon, Maritza; Torres, Sonia; Gilman, Robert H; Kosek, Margaret; Vinetz, Joseph M

    2013-08-01

    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.

  16. Louse-borne relapsing fever among East African refugees in Europe.

    PubMed

    Antinori, Spinello; Mediannikov, Oleg; Corbellino, Mario; Raoult, Didier

    2016-01-01

    Louse-borne relapsing fever a neglected and forgotten disease by western physicians has recently re-emerged among East African migrants seeking asylum in Europe. We review here the cases observed so far together with a critical reappraisal of several issues regarding clinical presentation, diagnosis and treatment.

  17. 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…

  18. Factors associated with the risk of relapse in schizophrenic patients after a response to electroconvulsive therapy: a retrospective study

    PubMed Central

    Shibasaki, Chiyo; Takebayashi, Minoru; Fujita, Yasutaka; Yamawaki, Shigeto

    2015-01-01

    Purpose Electroconvulsive therapy (ECT) is an effective treatment for depression and schizophrenia. However, there is a high rate of relapse after an initial response to ECT, even with antidepressant or antipsychotic maintenance therapy. This study was carried out to examine the factors that influence the risk of relapse in schizophrenic patients after a response to ECT. Patients and methods We retrospectively reviewed the records of 43 patients with schizophrenia who received and responded to an acute ECT course. We analyzed the associated clinical variables and relapse after response to the acute ECT. Relapse was defined as a Clinical Global Impressions Improvement score ≥6 or a psychiatric rehospitalization. Results All patients were treated with neuroleptic medication after the acute ECT course. The relapse-free rate of all 43 patients at 1 year was 57.3%, and the median relapse-free period was 21.5 months. Multivariate analysis showed that the number of ECT sessions was associated with a significant increase in the risk of relapse (hazard ratio: 1.159; P=0.033). Patients who were treated with adjunctive mood stabilizers as maintenance pharmacotherapy after the response to the acute ECT course were at a lower risk of relapse than were those treated without mood stabilizers (hazard ratio: 0.257; P=0.047). Conclusion Our study on the recurrence of schizophrenia after a response to an acute ECT course suggests that the number of ECT sessions might be related to the risk of relapse and that adjunctive mood stabilizers might be effective in preventing relapse. PMID:25609968

  19. Cardiotrophin-1: A new predictor of atrial fibrillation relapses after successful cardioversion

    PubMed Central

    Altun, Ibrahim; Pamukcu, Burak; Yildiz, Cenk Eray; Arkaya, Selda Can; Guz, Goksel; Yilmaz, Akar; Bilge, Ahmet Kaya; Turkoglu, Umit Mutlu; Adalet, Kamil

    2015-01-01

    We aimed to investigate whether or not cardiotrophin-1 (CT-1) can be used as a predictor of sinus rhythm constancy in patients with atrial fibrillation (AF) converted to sinus rhythm. Thirty two patients with AF (48-78 years), without any structural heart disease were enrolled for the study. The control group consisted of 32, age and gender matched healthy persons. Measurements of CT-1 were made after transthoracic and transesophageal echocardiography prior to cardioversion (CV). Relapses of AF were investigated by monthly electrocardiograms (ECGs) and ambulatory ECGs at 1st, 3rd, and 6th month. At the end of 6th month, measurements of CT-1 were repeated. At the beginning patients with AF had increased CT-1 levels when compared to controls (0.94 ± 0.32 pg/mL vs. 0.30 ± 0.12 pg/mL, [p < 0.001]). At the end of follow-up of the 32 patients, 17 (53%) had AF relapse. Age, initial duration of AF, left ventricle diameters, ejection fraction, left atrium appendix flow rates were similar among patients with and without AF relapse. However, basal left atrium diameter (4.24 ± 0.14 cm vs. 4.04 ± 0.22 cm, p = 0.005), pulmonary artery pressure (32.82 ± 5 vs. 28.60 ± 6.23 mmHg, p = 0.004) and CT-1 values (1.08 ± 0.37 vs. 0.82 ± 0.16 pg/mL, p = 0.02) were significantly increased in patients with AF relapse. Furthermore, patients with relapsed AF had higher CT-1 levels at 6th month when compared to those in sinus rhythm (1.00 ± 0.40 vs. 0.71 ± 0.23 pg/mL). We conclude that post-CV, AF relapses are more frequent among patients with increased baseline CT-1 levels, and CT-1 may be a potential predictor of AF relapse. PMID:26295297

  20. Ex Vivo Innate Immune Cytokine Signature of Enhanced Risk of Relapsing Brucellosis

    PubMed Central

    Feldman, Kristyn E.; Loriaux, Paul M.; Saito, Mayuko; Tuero, Iskra; Villaverde, Homarh; Siva, Tenaya; Gotuzzo, Eduardo; Gilman, Robert H.; Hoffmann, Alexander; Vinetz, Joseph M.

    2013-01-01

    Background Brucellosis, a zoonotic infection caused by one of the Gram-negative intracellular bacteria of the Brucella genus, is an ongoing public health problem in Perú. While most patients who receive standard antibiotic treatment recover, 5–40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis. Methodology/Principal Findings Blood was taken from healthy control donors, patients with a history of acute brucellosis, or patients with a history of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and remained in culture without stimulation or were stimulated with a panel of toll-like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate immune cytokine gene expression and protein secretion were measured by quantitative real-time polymerase chain reaction and a multiplex bead-based immunoassay, respectively. Acute and relapse patients demonstrated consistently elevated cytokine gene expression and secretion levels compared to controls. Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF-α, and IFN-γ in response to LPS and HKBM; basal secretion of IL-6, IL-8, and TNF-α; and HKBM or Rev1-induced secretion of IL-1β, IL-2, GM-CSF, IFN-Υ, and TNF-α. Although acute and relapse patients were largely indistinguishable by their cytokine gene expression profiles, we identified a robust cytokine secretion signature that accurately discriminates acute from relapse patients. This signature consists of basal IL-6 secretion, IL-1β, IL-2, and TNF-α secretion in response to LPS and HKBM, and IFN-γ secretion in response to HKBM. Conclusions/Significance This work demonstrates that informative cytokine variations in brucellosis patients can be detected using an ex vivo assay system and used to identify patients with differing infection histories. Targeted diagnosis of this signature may