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Sample records for relapsing polychondritis involving

  1. Relapsing polychondritis: A clinical update.

    PubMed

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

    2016-06-01

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

  2. Callosal Disconnection Syndrome Associated with Relapsing Polychondritis.

    PubMed

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

    2016-01-01

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

  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. PMID:20214060

  4. Relapsing Polychondritis: Inflamed Joints and Ears

    PubMed Central

    Melikoğlu, Meltem Alkan; Şenel, Kazım

    2015-01-01

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

  5. Laryngotracheal stenosis requiring emergency tracheostomy as the first manifestation of childhood-relapsing polychondritis.

    PubMed

    Buscatti, Izabel M; Giacomin, Maria Fernanda A; Silva, Marco Felipe C; Campos, Lúcia M A; Sallum, Adriana M E; Silva, Clovis A

    2013-01-01

    Relapsing polychondritis is a rare childhood disorder of unknown etiology, characterized by inflammatory, recurrent and destructive cartilage lesions. The chondritis could be widespread and involves generally laryngeal and auricular hyaline cartilages. We described a 9 years and 4 months old girl, who presented recurrent acute laryngotracheitis and laryngotracheal stenosis, which were the first manifestations of relapsing polychondritis, and was submitted to emergency tracheostomy. She also had ear condritis and arthritis, being treated with prednisolone and methotrexate. In conclusion, we reported a rare case of relapsing polychondritis that presented a life-threatening laryngo-tracheo-bronchial disorder requiring tracheostomy. We suggest that the diagnosis of relapsing polychondritis should be considered for patients who present recurrent acute laryngotracheitis with other types of condritis, as well as musculoskeletal manifestations. PMID:24149019

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

    PubMed

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

    2016-01-01

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

  7. 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

  8. 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

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

    PubMed Central

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

    2014-01-01

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

  10. A Case of Relapsing Polychondritis Initiating with Unexplained Fever

    PubMed Central

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

    2016-01-01

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

  11. 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

  12. [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

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

    PubMed

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

    1999-10-01

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

  14. 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

  15. A RARE COMPLICATION OF A RARE DISEASE; STROKE DUE TO RELAPSING POLYCHONDRITIS.

    PubMed

    Çoban, Eda Kiliç; Xanmemmedov, Elmir; Çolak, Melek; Soysal, Aysun

    2015-11-30

    Relapsing polychondritis (RP) is an episodic and progressive inflammatory disease of cartilaginous structures. Its diagnosis is based primarily on clinical features such as laboratory parameters, biopsy. Neurological complications occur in 3% of the cases and are classified as an important cause of death. The cranial nerve disorders are most common but hemiplegia, ataxia, myelitis, polyneuritis, seizures, confusion, hallucination and headache can also happen. The aetiology of central nervous system involvement is still unknown. Moreover stroke has rarely reported in these patients. The diagnosis of stroke is challenging because of its rarity among these patients. Perhaps vasculitis is the common underlying mechanism. Also meningitis and encephalitis can occur during the course of RP. A 44 year-old woman was admitted with uncontemplated left hemiparesis, redness, swelling, and tenderness of the metacarpophalangeal and interphalangeal joints of the right hand and the cartilaginous portion. White blood cell count, C-reactive protein and the erythrocyte sedimentation rate were elevated. Vasculitis biomarkers were normal in our patient. Carotid and vertebral artery doppler ultrasonography, cranial and cervical MR Angiography were normal. Echocardiography showed a mild mitral valve prolapse and regurgitation. Our patient had the history of auricular polychondritis but she had not been diagnosed. Hemiparesis was her first neurological manifestation that led her to doctors for diagnosis. Our patient fulfilled the criteria of RP so no biopsy was needed. She was treated with oral prednisolone (80 mg/day) and aspirin (300 mg/day) and now she is on 10 mg prednisolone and 150 mg azathioprine. Two months later her physical and neurological symptoms returned to normal. PMID:26821518

  16. 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

  17. 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

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

    PubMed Central

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

    2014-01-01

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

  19. 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

  20. A Rare Case of Splenic Marginal Zone B-Cell Lymphoma Mimicking Relapsing Polychondritis of the Ear

    PubMed Central

    Huang, Gary J.; Mendes, Bryan; Sheykholeslami, Kianoush

    2014-01-01

    Relapsing polychondritis (RPC) is a poorly understood phenomenon associated with cartilaginous inflammation of the ear, nose, tracheobronchial tree, and peripheral joints. Many cases of RPC respond to anti-inflammatories and resolve with no further complications. However, RPC has also been linked to more insidious conditions such as malignancies, autoimmune disorders, vasculitis, or underlying infections. Given the spectrum of associated disorders, patients with RPC may need to be monitored for more insidious underlying conditions. In this case, we report a unique case of bilateral auricular inflammation and nasal inflammation mimicking RPC as the only presenting symptom of splenic marginal zone B-cell lymphoma and we survey related cases in the literature. PMID:25544924

  1. Critical role of the major histocompatibility complex and IL-10 in matrilin-1-induced relapsing polychondritis in mice.

    PubMed

    Hansson, Ann-Sofie; Johansson, Asa C M; Holmdahl, Rikard

    2004-01-01

    Relapsing polychondritis (RP) is an autoimmune disease that affects extra-articular cartilage. Matrilin-1-induced relapsing polychondritis (MIRP) is a model for RP and is useful for studies of the pathogenic mechanisms in this disease. There are indications that the major histocompatibility complex (MHC) class II plays a major role in RP, since DR4+ patients are more commonly affected than controls. We have now addressed the role of the MHC region, as well as the non-MHC contribution, using congenic mouse strains. Of the MHC congenic strains, B10.Q (H2q) was the most susceptible, the B10.P (H2p) and B10.R (H2r) strains developed mild disease, while B10 strains carrying the v, b, f, or u H2 haplotypes were resistant. A slight variation of susceptibility of H2q strains (B10.Q> C3H.Q> DBA/1) was observed and the (B10.Q x DBA/1)F1 was the most susceptible of all strains. Furthermore, macrophages and CD4+ T cells were the most prominent cell types in inflammatory infiltrates of the tracheal cartilage. Macrophages are the major source of many cytokines, such as interleukin-10 (IL-10), which is currently being tested as a therapeutic agent in several autoimmune diseases. We therefore investigated B10.Q mice devoid of IL-10 through gene deletion and found that they developed a significantly more severe disease, with an earlier onset, than their heterozygous littermates. In conclusion, MHC genes, as well as non-MHC genes, are important for MIRP induction, and IL-10 plays a major suppressive role in cartilage inflammation of the respiratory tract. PMID:15380048

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

    PubMed Central

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

    2014-01-01

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

  4. 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

  5. Tracheobronchial stenosis evaluated by inspiratory and expiratory three-dimensional computed tomography and impulse oscillation with three-dimensional color imaging in a patient with relapsing polychondritis.

    PubMed

    Shimizu, Y; Kamiyoshihara, M; Okajo, J; Ishii, Y; Takise, A

    2014-01-01

    Patients with relapsing polychondritis (RP) and airway stenosis have difficulty performing conventional spirometry that requires maximum forced expiration. We report a patient with RP who showed progressive severe bronchial stenosis on three-dimensional computed tomography (3D-CT) and impulse oscillation (IOS) with 3D color imaging using a Mostgraph®. The forced oscillation technique using IOS allows within-breath evaluation without forced expiration. A 68-year-old man who had RP presented with dyspnea due to stenosis of the trachea and left main bronchus (lt. mb). Stenting was performed twice in two years. Chest 3D-CT revealed a marked difference in the extent of bronchial collapse during expiration compared with inspiration. The forced expiratory volume in 1 second (FEV1.0), reactance at 5Hz (X5), resonant frequency (Fres), and integrated low frequency reactance area (ALX) measured by IOS showed temporary improvement after placement of the first stent, but respiratory resistance at 5Hz (R5) and 20Hz (R20) remained poor. 3D color images of respiratory resistance obtained with a Mostgraph® already showed high values at the time of diagnosis, resembling the features of chronic obstructive disease (COPD). 3D color images were helpful for interpreting the changes of IOS parameters during the clinical course. In conclusion, 3D-CT in inspiration/expiration and noninvasive IOS with 3D color imaging are useful for assessing airway stenosis in RP while reducing the burden of repeated spirometry. PMID:25001664

  6. Cauda equina involvement in acute myeloid leukemia relapse.

    PubMed

    Buakhao, Jitsuda; Tansawet, Amarate

    2011-10-01

    Although central nervous system (CNS) involvement in acute myeloid leukemia has been described in about 2 to 4%, it still represents a major therapeutic problem, particularly cauda eqina involvement that is clinically significant and unusual. Here, a 22-year-old man, with underlying AML (M2-Subtype, FAB classification) and cytogenetic analysis resulted in 45, x, -y, t(8;21) (q22;q22)[15] whose presenting symptoms of low back pain and incontinence, 10 months after first remission, was reported. This was followed by peripheral and bone marrow relapse. The magnetic resonance image (MRI) findings revealed leukemic infiltration at S1-S5 of the spinal cord canal with associated soft tissue component at presacral area encasing bilateral S1-S5 exiting root with heterogeneous enhancement in bone marrow of S2-S4. The therapeutic and prognosis implications of spinal cord involvement by leukemia were discussed. Because of severe morbidity, the patient developed bone marrow failure and died from sepsis. PMID:22145515

  7. 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

  8. Hypothalamic involvement assessed by T1 relaxation time in patients with relapsing-remitting multiple sclerosis.

    PubMed

    Zellini, Francesco; Niepel, Graham; Tench, Christopher R; Constantinescu, Cris S

    2009-12-01

    Recent work in multiple sclerosis, focusing on neuropathological abnormalities, found a frequent and severe hypothalamic involvement. The possible clinical implications are disturbances in sleep and sexual activity, depression, memory impairment and fatigue. Despite this there are no magnetic resonance imaging studies focusing on in vivo hypothalamic pathology in multiple sclerosis. Our objective was to investigate magnetic resonance imaging-detectable abnormalities related to pathological changes in the hypothalamus of patients with multiple sclerosis, and to subsequently explore the relationship with fatigue. We used T1 relaxation time as a sensitive measure of pathology. Using region of interest analysis, median T1 values in the hypothalamus were measured in 44 relapsing-remitting multiple sclerosis patients and in 13 healthy controls. Fatigue was assessed using the Fatigue Severity Scale, and patients were divided in two subgroups, fatigued and non-fatigued, according to Fatigue Severity Scale scores. We found a significantly higher T1 relaxation time in the hypothalamus of multiple sclerosis patients compared with controls (p = 0.027). There was a significant correlation between T1 values and fatigue severity (rho 0.437, p = 0.008), and median T1 values were different among the study groups. Our results show that pathological involvement of the hypothalamus in relapsing-remitting multiple sclerosis is detectable using magnetic resonance imaging, and that the pathology measured by quantitative T1 might reflect fatigue. PMID:19995847

  9. 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

  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. Involvement of the appendix in a relapsed case of primary nasal NK/T-cell lymphoma.

    PubMed

    Tsujimura, H; Takagi, T; Tamaru, J; Sakai, C

    2000-05-01

    We report here a 20-year-old man presenting with primary nasal NK/T-cell lymphoma which showed an aggressive clinical course spreading to the spleen and skin despite various treatments. Eight months after high dose chemotherapy followed by autologous peripheral blood stem cell transplantation, acute appendicitis with perforation occurred and the patient underwent appendectomy. The histopathological diagnosis was NK/T-cell lymphoma of the appendix. Lymphoma of the appendix is extremely rare and the majority of appendiceal lymphomas are of B-cell origin. This is the first report of involvement of appendix by nasal NK/T-cell lymphoma. PMID:11042526

  12. Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis

    PubMed Central

    Sidhu, M; Griffiths, M M; Bradley, D S

    2009-01-01

    Immature dendritic cells (iDCs) have a tolerogenic potential due to low expression of important co-stimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. We report here that injection of iDCs pulsed with chick type II collagen (CII) delayed the onset significantly and suppressed the severity of spontaneous polychondritis (SP) in the human leucocyte antigen (HLA)-DQ6αβ8αβ transgenic mouse model. Bone marrow-derived iDCs were pulsed in vitro with CII and transferred into 6-week-old HLA-DQ6αβ8αβ transgenic mice. Mice receiving CII-pulsed iDCs did not display any clinical signs of disease until 5·5 months of age, indicating the ability of the DC vaccine to delay significantly the onset of SP. Control groups receiving unpulsed iDCs or phosphate-buffered saline (PBS) developed polyarthritis at 3·5 months, as we have reported previously. The severity and incidence of disease was reduced in mice injected with CII-pulsed iDCs. Proinflammatory cytokines were in low to undetectable levels in the serum and tissue in the CII-pulsed iDC mice, correlating with the protection. This is the first evidence of iDC therapy controlling SP and suggests that iDC vaccination may provide a tool to reducing clinical manifestations in human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis. PMID:19664142

  13. Mutations in epigenetic regulators are involved in acute lymphoblastic leukemia relapse following allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Lai, Xiaoyu; Li, Caihua; Shi, Jimin; Tan, Yamin; Fu, Shan; Wang, Yebo; Zhu, Ni; He, Jingsong; Zheng, Weiyan; Yu, Xiaohong; Cai, Zhen; Huang, He

    2016-01-01

    Although steady improvements to chemotherapeutic treatments has helped cure 80% of childhood acute lymphoblastic leukemia (ALL) cases, chemotherapy has proven to be less effective in treating the majority of adult patients, leaving allogeneic hematopoietic stem cell transplantation (allo-HSCT) as the primary adult treatment option. Nevertheless relapse are the leading cause of death following allo-HSCT. The genetic pathogenesis of relapse following allo-HSCT in Philadelphia chromosome- negative ALL (Ph− ALL) remains unexplored. We performed longitudinal whole-exome sequencing analysis in three adult patients with Ph− B-cell ALL (Ph− B-ALL) on samples collected from diagnosis to relapse after allo-HSCT. Based on these data, we performed target gene sequencing on 23 selected genes in 58 adult patients undergoing allo-HSCT with Ph− B-ALL. Our results revealed a significant enrichment of mutations in epigenetic regulators from relapsed samples, with recurrent somatic mutations in SETD2, CREBBP, KDM6A and NR3C1. The relapsed samples were also enriched in signaling factor mutations, including KRAS, PTPN21, MYC and USP54. Furthermore, we are the first to reveal the clonal evolution patterns during leukemia relapse after allo-HSCT. Cells present in relapsed specimens were genetically related to the diagnosed tumor, these cells therefore arose from either an existing subclone that was not eradicated by allo-HSCT therapy, or from the same progenitor that acquired new mutations. In some cases, however, it is possible that leukemia recurrence following allo-HSCT could result from a secondary malignancy with a distinct set of mutations. We identified novel genetic causes of leukemia relapse after allo-HSCT using the largest generated data set to date from adult patients with Ph− B-ALL. PMID:26527318

  14. 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

  15. Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

    SciTech Connect

    Kahn, Shannon; Flowers, Christopher; Xu Zhiheng; Esiashvili, Natia

    2011-09-01

    Purpose: To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Methods and Materials: Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. Results: There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p = 0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p = 0.032) and 0.383 (p = 0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p < 0.001), observed only in patients receiving a busulfan-based conditioning regimen. Conclusion: Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative

  16. [Relapse prevention in drug addicts].

    PubMed

    Rácz, József

    2013-12-01

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

  17. 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

  18. Endocannabinoid regulation of relapse mechanisms.

    PubMed

    Fattore, Liana; Fadda, Paola; Fratta, Walter

    2007-11-01

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

  19. Animal models of fear relapse.

    PubMed

    Goode, Travis D; Maren, Stephen

    2014-01-01

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

  20. [Relapse: causes and consequences].

    PubMed

    Thomas, P

    2013-09-01

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

  1. Late relapses in acute promyelocytic leukaemia.

    PubMed

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

    2007-01-01

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

  2. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  5. 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…

  6. Insomnia, alcoholism and relapse.

    PubMed

    Brower, Kirk J

    2003-12-01

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

  7. 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

  8. 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

  9. 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

  10. 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

  11. [Relapse prevention in anorexia nervosa].

    PubMed

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

    2013-07-01

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

  12. 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 ...

  13. 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

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

    PubMed

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

    2016-02-01

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

  15. Late relapsing childhood lymphoblastic leukemia.

    PubMed

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

    1998-10-01

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

  16. Relapse prevention for addictive behaviors

    PubMed Central

    2011-01-01

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

  17. Relapsing Fever Borreliae in Africa

    PubMed Central

    Elbir, Haitham; Raoult, Didier; Drancourt, Michel

    2013-01-01

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

  18. 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

  19. Novel therapies for relapsed myeloma.

    PubMed

    Stewart, A Keith

    2009-01-01

    Treatment of myeloma relapse needs to be individualized to reflect the effectiveness and toxicities of prior therapies, with consideration given to pragmatic issues such as the tempo of relapse, age of the patient, access to drugs and patient preference. In general, combination therapies have been associated with higher response rates and improved progression-free survival and may be preferable when a rapid response is required. Nevertheless, in a slower-tempo relapse it is unclear at this juncture whether sequencing of drugs or multi-agent combinations offer superior overall survival results. Fortunately, active novel agents that offer further possibilities for some myeloma patients have become available in clinical trials. In this review we will describe the various classes of novel drugs being tested and the pros and cons of preclinical testing, and will particularly focus on two agents with single-agent activity in myeloma: carfilzomib, a proteasome inhibitor, and pomalidomide, a member of the immunomodulatory class of drugs. PMID:20008242

  20. Preventing Relapse Following Smoking Cessation

    PubMed Central

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

    2012-01-01

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

  1. 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

  2. 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

  3. 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…

  4. 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…

  5. Survival After Relapse of Medulloblastoma.

    PubMed

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

    2016-05-01

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

  6. Borrelia hispanica Relapsing Fever, Morocco

    PubMed Central

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

    2009-01-01

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

  7. Borrelia hispanica relapsing fever, Morocco.

    PubMed

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

    2009-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. 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…

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

    PubMed Central

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

    2013-01-01

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

  11. 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

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

    ERIC Educational Resources Information Center

    Goodrick, G. Ken; And Others

    1984-01-01

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

  13. Why do patients with ulcerative colitis relapse?

    PubMed

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

    1990-02-01

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

  14. Lymphoma relapse presenting as neurolymphomatosis

    PubMed Central

    Pham, My; Awad, Mohammed

    2016-01-01

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

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

    PubMed

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

    2010-01-01

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

  16. [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

  17. 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…

  18. Adjuvant steroids and relapse of typhoid fever.

    PubMed

    Cooles, P

    1986-10-01

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

  19. 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…

  20. 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…

  1. Modelling intervention effects after cancer relapses

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. 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

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

    PubMed Central

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

    2010-01-01

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

  6. Improving reporting of multiple sclerosis relapse.

    PubMed

    Roberts, Megan; Lush, Tessa; Pohorely, John

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

  7. 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

  8. 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..

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

    PubMed

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

    2016-06-15

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

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

    PubMed Central

    Jung, Young-Chul

    2006-01-01

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

  11. 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)

  12. 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

  13. Culture and social class as intervening variables in relapse prevention with chemically dependent women.

    PubMed

    Weiner, H D; Wallen, M C; Zankowski, G L

    1990-01-01

    Craving and relapse are complex, poorly understood phenomena. A distinctive and baffling characteristic of the disease of chemical dependency is the continuing impulse to use alcohol and/or other drugs, even after lengthy periods of sobriety. This article discusses relapse prevention, focusing on public-sector chemically dependent women. Relapse among these women must be seen in the total context of their lives. Poverty and social disorganization do not directly cause relapse, but problems related to daily life under such conditions represent significant risk factors. The Eagleville Hospital treatment model and relapse prevention programs are described, and it is noted that public-sector women typically present with problems related to being raised in addicted households, residing in drug-saturated inner-city environments, deficits in child-rearing skills, destructive (often abusive) relationships with men, social interactions involving other substance abusers, few (if any) work skills, minimal educational achievement, low self-esteem, and poor self-image. A case study illustrates the course of treatment and relapse prevention efforts with a typical public-sector chemically dependent woman. PMID:2374071

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

    PubMed

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

    2015-06-01

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

  15. Quantifying Benefit of Autologous Transplantation for Relapsed Follicular Lymphoma Patients via Instrumental Variable Analysis.

    PubMed

    Oh, Danielle H; Li, Haocheng; Duan, Qiuli; Villa, Diego; Peters, Anthea; Chua, Neil; Owen, Carolyn J; Connors, Joseph M; Stewart, Douglas A

    2016-05-01

    The role of autologous stem cell transplantation (ASCT) in patients with relapsed follicular lymphoma (FL) remains controversial because of a lack of proven overall survival (OS) benefit versus nontransplant strategies. We conducted a comparative effectiveness research study involving 3 tertiary Canadian cancer centers to determine whether the ASCT-based approach used at 1 center improved OS relative to non-ASCT approaches used at the other centers. Of 1082 consecutive patients aged 18 to 60 years and diagnosed with FL from 2001 to 2010, the study population included 355 patients who experienced relapse from chemotherapy (center A = 96, center B = 84, center C = 175). Data were analyzed according to the instrumental variable of treatment center to control for confounding factors. The frequency of using ASCT at first or second relapse was significantly different between the centers (A = 58%, B = 7%, C = 5%, P < .001). With a median follow-up of 69.1 months, the actuarial 5-year OS rates after first chemotherapy relapse were 89%, 60%, and 60% for centers A, B, and C respectively (log rank P < .0001). Based on instrumental variable analysis, the use of ASCT at relapse 1 or 2 significantly decreased the risk of death from first relapse (HR .127, P = .004) and from initial diagnosis (HR .116, P = .004). In conclusion, for FL patients who relapse after chemotherapy, these results strongly support more frequent use of ASCT at first or second relapse. PMID:26785331

  16. Risk of Ovarian Cancer Relapse Score

    PubMed Central

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

    2015-01-01

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

  17. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

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

    2016-01-01

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

  18. Pathological gambling: understanding relapses and dropouts.

    PubMed

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

    2015-02-01

    There is little available information on the factors that influence relapses and dropouts during therapy for pathological gambling (PG). The aim of this study was to determine socio-demographic, clinical, personality, and psychopathological predictors of relapse and dropout in a sample of pathological gamblers seeking treatment. A total of 566 consecutive outpatients diagnosed with PG according to DSM-IV-TR criteria were included. All patients underwent an individualized cognitive-behavioral treatment program. We analyzed predictors of relapse during 6months of treatment and during the subsequent 6months of follow-up, and predictors of dropout over the entire therapeutic program. Eighty patients (14.1%) experienced at least one relapse during the entire follow-up of the study: 50 (8.8%) within the treatment period and 12 (2.1%) during the subsequent 6-month follow-up period. The main predictors of relapse were single marital status, spending less than 100euros/week on gambling, active gambling behavior at treatment inclusion, and high scores on the TCI-R Harm Avoidance personality dimension. One hundred fifty-seven patients (27.8%) missed 3 or more therapeutic sessions over the entire therapeutic program. The main predictors of dropout were single marital status, younger age, and high scores on the TCI-R Novelty Seeking personality dimension. The presence of these factors at inclusion should be taken into account by physicians dealing with PG patients. PMID:25434846

  19. Relapse prevention with intellectually disabled sexual offenders.

    PubMed

    Keeling, Jenny A; Rose, John L

    2005-10-01

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

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

    PubMed Central

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

    2009-01-01

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

  1. 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

  2. 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

  3. 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…

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

    ERIC Educational Resources Information Center

    Fisher, Gary L.; Harrison, Thomas C.

    1993-01-01

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

  5. 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

  6. 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

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

    MedlinePlus

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

  8. Multidisciplinary correction of anterior open bite relapse and upper airway obstruction

    PubMed Central

    Perri, Alessandro; Siviero, Laura; Bonetti, Giulio Alessandri; Cocilovo, Francesco; Stellini, Edoardo

    2015-01-01

    A 27-year-old man presented an anterior open bite relapse. He had low tongue posture positioned anteriorly at rest and during swallowing and reported chronic difficulty in nose breathing. Head cone-beam computed tomography revealed nasal septum deviation, right turbinate hypertrophy, and left maxillary sinus congestion, which were thought to contribute to the breathing problem, encourage the improper tongue posture, and thereby cause the relapse. Multidisciplinary treatment involving an otorhinolaryngologist, an orthodontist, and a periodontist resolved the upper airway obstruction and corrected the malocclusion. The follow-up examination after 3 years 5 months demonstrated stable results. PMID:25667917

  9. Strategies to Reduce Relapse after Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia

    PubMed Central

    Mawad, Raya; Lionberger, Jack M.; Pagel, John M.

    2013-01-01

    The incidence of acute myeloid leukemia (AML) is expected to increase in conjunction with our ageing population. Although it is proving to be a heterogeneous disease process, the only treatment with proven survival benefit for poor risk AML remains allogeneic hematopoietic cell transplant. Although this is presumed to be a curative strategy, many patients relapse after transplant, prompting us to examine various ways that we can improve outcomes. These efforts involve every step of AML diagnostics and therapy, including the intricate processes of conditioning, graft manipulation and immunomodulation. The hope is that improvement in these steps will ultimately improve survival and decrease relapse rates for AML patients after transplant. PMID:23456518

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

    PubMed

    Giebel, S M

    2006-01-01

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

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

    PubMed

    Russo, I; Ferrazzi, A; Alaibac, M

    2016-08-01

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

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

    PubMed

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

    2008-08-01

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

  13. 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

  14. 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

  15. 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

  16. 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…

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

    ERIC Educational Resources Information Center

    Hall, Sharon M.; And Others

    1984-01-01

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

  18. 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…

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

    PubMed

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

    2016-05-01

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

  20. 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.

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

    PubMed

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

    2008-01-01

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

  2. 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

  3. 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

  4. 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

  5. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    PubMed Central

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

    2015-01-01

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

  6. 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

  7. Craving and relapse measurement in alcoholism.

    PubMed

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

    1999-01-01

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

  8. 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

  9. Tick-borne Relapsing Fever in the Pacific Northwest: An Underdiagnosed Illness?

    PubMed Central

    Fihn, Stephan; Larson, Eric B.

    1980-01-01

    Some 30 cases of tick-borne relapsing fever due to Borrelia are known to have occurred between 1965 and 1978 in the Pacific Northwest. This disease was found more frequently in young men with a history of wilderness exposure during the summer months. Recurrent fever was the most common symptom with temperatures reaching higher than 39.5° C (103.1° F) in all cases, and many patients had three or more febrile episodes. Splenomegaly was the second most common finding reported. Diagnosis of relapsing fever was made in 20 cases by identifying spirochetes on peripheral blood smears. In ten remaining cases the diagnosis was made on clinical and epidemiologic grounds. Information regarding therapy was available in 21 cases. Ten patients received a tetracycline drug and all had a prompt response without relapse. Two of the patients died, a 68-year-old woman with possible myocardial involvement and a newborn infant with infection acquired in utero and meningeal involvement. The diagnosis was often delayed in spite of outpatient evaluation and admittance to hospital, probably because borreliosis was not considered in the differential diagnosis. Because tick-borne relapsing fever is eventually a self-limited disease in most patients, it is probably not recognized often enough. Awareness of this disease and examination of the peripheral blood smear for spirochetes will lead to earlier diagnosis. Prompt initiation of tetracycline therapy should reduce morbidity associated with borreliosis. ImagesFigure 3. PMID:7415171

  10. 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

  11. New patterns of relapse in multiple myeloma: a case of "light chain escape" in which FLC predicted relapse earlier than urine and serum immunofixation.

    PubMed

    Caldini, Anna; Nozzoli, Chiara; Terreni, Alessandro; Staderini, Michela; Berardi, Margherita; Biagioli, Tiziana; Brogi, Marco; Bosi, Alberto

    2016-06-01

    Multiple myeloma (MM) is characterized, in about 80% of cases, by the production of monoclonal intact immunoglobulin and more than 95% of them have elevated concentrations of involved (i.e. of the same class of intact immunoglobulin) free light chain (FLC). The introduction of novel therapeutic strategies has changed the natural history of the disease, leading to new manifestations of relapse. Light chain escape (LCE) is a pattern of relapse in which the FLC increase is not accompanied by a concomitant raise of the original monoclonal component (MC). Here we present a case of a 55-year-old man with an IgG kappa MM stage III diagnosed in September 2007. At presentation an IgG kappa MC and urine Bence Jones protein (BJP) kappa were present. Bone marrow biopsy (BMB) showed the presence of 80% monotypic kappa plasma cells (PCs). The patient received bortezomib, thalidomide, dexamethasone before undergoing a double autologous stem cell transplantation (ASCT) in October 2008 and April 2009. In May 2011 he relapsed showing the same pattern of presentation and treatment with lenalidomide and dexamethasone was started. ln May 2013 serum and urine immunofixation and FLC became negative. In September 2014, an increase of kappa FLC was observed, while serum and urine immunofixations remained negative until January 2015, when urine immunofixation became positive. Eventually, in February 2015, serum immunofixation revealed the presence of a free kappa MC. After a new BMB showing 80% of monotypic kappa PCs, a LCE relapse was diagnosed and the patient started the treatment with bendamustine, bortezomib and dexamethasone. In the present case, the increase of kappa FLC has indicated relapse 4 and 5 months earlier than urine and serum IFE, respectively. Our observation confirms that it is advisable to routinely perform FLC or BJP during follow up of MM patients undergoing ASCT and/or treatment with biological drugs to ensure that LCE is not missed. PMID:26581069

  12. 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

  13. 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

  14. Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma.

    PubMed

    Yoon, Harry H; Lewis, Mark A; Foster, Nathan R; Sukov, William R; Khan, Maliha; Sattler, Christopher A; Wiktor, Anne E; Wu, Tsung-Teh; Jenkins, Robert B; Sinicrope, Frank A

    2016-10-01

    Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases. PMID:27198655

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

    PubMed

    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; Rosenquist, Richard

    2016-02-25

    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

  16. Central nervous system relapse in patients with diffuse large B cell lymphoma: analysis of the risk factors and proposal of a new prognostic model.

    PubMed

    Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

    2016-10-01

    Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level <3.2 mg/L, number of extranodal sites >1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P < 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted. PMID:27370993

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

    PubMed

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. PMID:25997994

  18. New Findings on Biological Factors Predicting Addiction Relapse Vulnerability

    PubMed Central

    2013-01-01

    Relapse is a highly prevalent phenomenon in addiction. This paper examines the new research on identifying biological factors that contribute to addiction relapse risk. Prospective studies examining relapse risk are reviewed, and clinical, biological, and neural factors that predict relapse risk are identified. Clinical factors, patient-related factors, and subjective and behavioral measures such as depressive symptoms, stress, and drug craving all predict future relapse risk. Among biological measures, endocrine measures such as cortisol and cortisol/corticotropin (ACTH) ratio as a measure of adrenal sensitivity and serum brain-derived neurotrophic factor were also predictive of future relapse risk. Among neural measures, brain atrophy in the medial frontal regions and hyperreactivity of the anterior cingulate during withdrawal were identified as important in drug withdrawal and relapse risk. Caveats pertaining to specific drug abuse type and phase of addiction are discussed. Finally, significant implications of these findings for clinical practice are presented, with a specific focus on determining biological markers of relapse risk that may be used to identify those individuals who are most at risk of relapse in the clinic. Such markers may then be used to assess treatment response and develop specific treatments that will normalize these neural and biological sequelae so as to significantly improve relapse outcomes. PMID:21792580

  19. Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

    PubMed

    Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

    2011-09-15

    Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

  20. Recent developments in animal models of drug relapse.

    PubMed

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

    2013-08-01

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

  1. 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

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

    PubMed

    Lublin, F D

    1985-01-01

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

  3. Cerebellopontine angle facial schwannoma relapsing towards middle cranial fossa

    PubMed Central

    Nishizaki, Takafumi; Ikeda, Norio; Nakano, Shigeki; Sakakura, Takanori; Abiko, Masaru; Okamura, Tomomi

    2011-01-01

    Facial nerve schwannomas involving posterior and middle fossas are quite rare. Here, we report an unusual case of cerebellopontine angle facial schwannoma that involved the middle cranial fossa, two years after the first operation. A 53-year-old woman presented with a 3-year history of a progressive left side hearing loss and 6-month history of a left facial spasm and palsy. Magnetic resonance imaging (MRI) revealed 4.5 cm diameter of left cerebellopontine angle and small middle fossa tumor. The tumor was subtotally removed via a suboccipital retrosigmoid approach. The tumor relapsed towards middle cranial fossa within a two-year period. By subtemporal approach with zygomatic arch osteotomy, the tumor was subtotally removed except that in the petrous bone involving the facial nerve. In both surgical procedures, intraoperative monitoring identified the facial nerve, resulting in preserved facial function. The tumor in the present case arose from broad segment of facial nerve encompassing cerebellopontine angle, meatus, geniculate/labyrinthine and possibly great petrosal nerve, in view of variable symptoms. Preservation of anatomic continuity of the facial nerve should be attempted, and the staged operation via retrosigmoid and middle fossa approaches using intraoperative facial monitoring, may result in preservation of the facial nerve. PMID:24765294

  4. Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation.

    PubMed

    Dard, Rodolphe; Mignot, Cyril; Durr, Alexandra; Lesca, Gaetan; Sanlaville, Damien; Roze, Emmanuel; Mochel, Fanny

    2015-12-01

    ATP1A3, the gene encoding the α3-subunit of the Na(+) /K(+) -ATPase pump, has been involved in four clinical neurological entities: (1) alternating hemiplegia of childhood (AHC); (2) rapid-onset dystonia parkinsonism (RDP); (3) CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss) syndrome; and (4) early infantile epileptic encephalopathy. Here, we report on a 34-year-old female presenting with a new ATP1A3-related entity involving a relapsing encephalopathy characterized by recurrent episodes of cerebellar ataxia and altered consciousness during febrile illnesses. The term RECA is suggested - relapsing encephalopathy with cerebellar ataxia. The phenotype of this patient, resembling mitochondrial oxidative phosphorylation defects, emphasizes the possible role of brain energy deficiency in patients with ATP1A3 mutations. Rather than multiple overlapping syndromes, ATP1A3-related disorders might be seen as a phenotypic continuum. PMID:26400718

  5. 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

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

    PubMed

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

    2016-05-01

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

  7. Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival.

    PubMed

    January

    2016-04-01

    codynamic interactions are also likely in view of its adverse effect profile. There is no consensus on the treatment of patients with refractory or relapsed mantle cell lymphoma, or for patients with relapsed or possibly refractory chronic lymphocytic leukaemia. Ibrutinib inhibits an enzyme involved in regulating B lymphocyte activity. It has been authorised in the European Union for these conditions. Clinical evaluation of ibrutinib in mantle cell lymphoma is based on a single non-comparative trial in 111 patients, in which the median overall survival time was 22.5 months. Clinical evaluation of ibrutinib in chronic lymphocytic leukaemia is based on two randomised trials. One unblinded trial compared ibrutinib versus ofatumumab and involved 391 patients, most of whom were sufficiently fit to receive anticancer combination therapy. Ibrutinib was more effective than ofatumumab, but the choice of this comparator might not have been appropriate for most of the patients who received it. The other double-blind, placebo-controlled trial involved 578 patients with relapsed or refractory chronic lymphocytic leukaemia. Ibrutinib was added to the bendamustine + rituximab combination. No significant difference in mortality was observed between the two groups. The main adverse effects of ibrutinib were: gastrointestinal disorders such as diarrhoea; life-threatening infections and bleeding disorders; and cardiac disorders, including atrial fibrillation. Ibrutinib carries a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely in view of its adverse effect profile. PMID:27183765

  8. 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.

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  10. Relapse Prevention Needs More Emphasis on Interpersonal Factors

    ERIC Educational Resources Information Center

    Stanton, Mark

    2005-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, G. Alan

    2005-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  14. Power2: Relapse Management with Adolescents Who Stutter.

    ERIC Educational Resources Information Center

    Blood, Gordon W.

    1995-01-01

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

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

    ERIC Educational Resources Information Center

    Brown, Richard A.; And Others

    1984-01-01

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

  16. Graves’ Ophthalmopathy Misdiagnosed as Relapsing Conjunctivitis

    PubMed Central

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

    2010-01-01

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

  17. 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

  18. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

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

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

    PubMed

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

    1998-07-01

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

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  1. 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

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

    PubMed

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

    2010-10-15

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

  3. 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

  4. Interferon beta-1b modulates MCP-1 expression and production in relapsing-remitting multiple sclerosis.

    PubMed

    Iarlori, Carla; Reale, Marcella; De Luca, Giovanna; Di Iorio, Angelo; Feliciani, Claudio; Tulli, Antonio; Conti, Pio; Gambi, Domenico; Lugaresi, Alessandra

    2002-02-01

    Monocyte chemoattractant protein-1 (MCP-1) seems to be involved in the pathogenesis of multiple sclerosis (MS). We found that in unstimulated (PHA(-)) and PHA-stimulated (PHA(+)) peripheral blood mononuclear cells (PBMC), MCP-1 and TNFalpha levels are higher in stable untreated MS patients. Interferon gamma (IFNgamma) is higher in relapsing patients in PHA(-) cultures and in stable patients in PHA(+) cultures. Chronic IFNbeta-1b treatment down-regulates TNFalpha, IFNgamma and MCP-1 production except for TNFalpha in relapsing patients. IFNbeta-1b, in vitro, increases MCP-1, TNFalpha and IFNgamma spontaneous production in all patients. Multivariate analysis suggests that MCP-1 production is dependent from clinical status and not from TNFalpha and IFNgamma production. Logistic regression analysis shows that MCP-1 production is significantly modified by treatment. Further studies are needed to clarify the role of MCP-1 in MS. PMID:11880161

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

    PubMed Central

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

    2016-01-01

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

  6. Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse.

    PubMed

    Pu, Yang; Xu, Meng; Liang, Yong; Yang, Kaiting; Guo, Yajun; Yang, Xuanming; Fu, Yang-Xin

    2016-04-01

    Surgical and medical androgen deprivation therapy (ADT) is a cornerstone for prostate cancer treatment, but relapse usually occurs. We herein show that orchiectomy synergizes with immunotherapy, whereas the more widely used treatment of medical ADT involving androgen receptor (AR) antagonists suppresses immunotherapy. Furthermore, we observed that the use of medical ADT could unexpectedly impair the adaptive immune responses through interference with initial T cell priming rather than in the reactivation or expansion phases. Mechanistically, we have revealed that inadvertent immunosuppression might be potentially mediated by a receptor shared with γ-aminobutyric acid. Our data demonstrate that the timing and dosing of antiandrogens are critical to maximizing the antitumor effects of combination therapy. This study highlights an underappreciated mechanism of AR antagonist-mediated immunosuppression and provides a new strategy to enhance immune response and prevent the relapse of advanced prostate cancer. PMID:27053771

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

    PubMed

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

    2016-08-01

    Glioblastoma is an uncommon and aggressive primary brain tumor with incidence of 3 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within threeyears of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development. PMID:26970935

  8. 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

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

    SciTech Connect

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

    1984-10-01

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

  10. Late Isolated Central Nervous System Relapse from Ovarian Serous Adenocarcinoma: A Case Report and Literature Review

    PubMed Central

    de Castria, Tiago Biachi; Rodrigues, Sylvia Regina Quintanilha; Diz, Maria del Pilar Estevez

    2014-01-01

    Central nervous system involvement by ovarian serous adenocarcinoma is rare. We report a case of a 60-year-old woman that developed brain metastasis as isolated site of relapse 4.5 years after a complete resection and adjuvant chemotherapy for a stage Ic disease. She proceeded to a craniotomy with resection of the lesion and, subsequently, to a whole brain radiotherapy. Nineteen months later, she developed carcinomatous meningitis as isolated site of recurrence. Patient was submitted to intrathecal chemotherapy with methotrexate; however, she died from progressive neurologic involvement disease few weeks later. PMID:25506007

  11. [A case of anti-aquaporin 4 antibody-positive Sjögren syndrome associated with a relapsed myelitis in pregnancy].

    PubMed

    Tsugawa, Jun; Tsuboi, Yoshio; Inoue, Hirosato; Baba, Yasuhiko; Yamada, Tatsuo

    2010-01-01

    It is known that pregnancy influences the relapsing rate of multiple sclerosis (MS); however, interaction between pregnancy and relapse of neuromyelitis optica (NMO), a distinct disease from MS, remains unclear. A 34-year-old woman who 1 year previously had clinical history of Sjögren syndrome complicated by myelitis with the presence of anti-AQP4 antibody in her serum, although there was no optic neuritis involvement, was neurologically normal at time of becoming pregnant. In the 22nd week of her pregnancy, however, she developed abdominal belt-shaped numbness and sensory impairment followed by weakness of bilateral lower limb leading to difficulty of her gait. MR imaging revealed hyperintense lesions within the spinal cord extending from C2 to T2 vertebral level with marked spinal cord swelling, indicating relapse of myelitis associated with anti-AQP4 antibody. She was treated with intravenous corticosteroid with marked benefits for her neurological status; she was able to walk without assistance after the treatment. However, in the 30th week she relapsed with myelitis at T2 to T9 vertebral level on MR imaging. Intravenous steroid administration again elicited improvement. She delivered a baby via Caesarean section at 34 weeks of pregnancy. After delivery, she started taking oral corticosteroid as preventive therapy for further relapse of myelitis; thus far she has had no relapse at 7 months of follow-up. There are few reports regarding the influence of pregnancy on anti-AQP4 antibody-positive myelitis. Although further investigation should be done to clarify the difference of immunological changes during pregnancy between NMO and conventional MS, our case together with previous reports indicate increased risk of relapse during pregnancy in NMO. It is necessary to remain vigilant against possible risk of relapse during pregnancy in patients with NMO and/or positive anti-AQP4 antibody. Intravenous steroid administration seems safe and effective against relapse of

  12. 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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. 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.

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

    PubMed Central

    Jona, Adam; Younes, Anas

    2011-01-01

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

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

    PubMed

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

    2013-06-01

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

  18. 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.

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

    PubMed

    Brasseur, D

    1985-09-01

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

  20. Recrudescence and relapse of meningococcal meningitis and septicaemia.

    PubMed

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

    1995-03-01

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

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

    PubMed

    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

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

    PubMed

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

    2016-01-01

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

  3. 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

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

    PubMed

    Schooler, Nina R

    2003-01-01

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

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

    PubMed

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

    2015-08-01

    The majority of patients with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas showed clonal evolution from the diagnostic tumor, with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK pathway. Seven of these events were detected only in the relapse tumor, whereas the others showed clonal enrichment. In neuroblastoma cell lines, we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18; 61%), and these lesions predicted sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastomas and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease. PMID:26121087

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

    PubMed Central

    Preston, Kenzie L

    2005-01-01

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

  7. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations

    PubMed Central

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

    2016-01-01

    The majority of neuroblastoma patients have tumors that initially respond to chemotherapy, but a large proportion of patients will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole genome sequencing of 23 paired diagnostic and relapsed neuroblastomas showed clonal evolution from the diagnostic tumor with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK signaling pathway. Seven events were detected only in the relapse tumor while the others showed clonal enrichment. In neuroblastoma cell lines we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18, 61%) and these lesions predicted for sensitivity to MEK inhibition in vitro and in vivo. Our findings provide the rationale for genetic characterization of relapse neuroblastoma and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease. PMID:26121087

  8. Aggressive chemotherapy for acute leukemia relapsed after transplantation.

    PubMed

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

    1994-09-01

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

  9. Adoptive transfer of murine relapsing experimental allergic encephalomyelitis.

    PubMed

    Lublin, F D

    1985-02-01

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

  10. Connective Tissue Disorder-Associated Vasculitis.

    PubMed

    Sharma, Aman; Dhooria, Aadhaar; Aggarwal, Ashish; Rathi, Manish; Chandran, Vinod

    2016-06-01

    Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years. PMID:27097818

  11. High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

    PubMed

    Cocorocchio, E; Peccatori, F; Vanazzi, A; Piperno, G; Calabrese, L; Botteri, E; Travaini, L; Preda, L; Martinelli, G

    2013-03-01

    High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL. PMID:22473680

  12. The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine

    PubMed Central

    Kupchik, Yonatan M.; Moussawi, Khaled; Tang, Xing-Chun; Wang, Xiusong; Kalivas, Benjamin C.; Kolokithas, Rosalia; Ogburn, Katelyn B.; Kalivas, Peter W.

    2011-01-01

    Background Relapse to cocaine-seeking has been linked with low glutamate in the nucleus accumbens core (NAcore) causing potentiation of synaptic glutamate transmission from prefrontal cortex (PFC) afferents. Systemic N-acetylcysteine (NAC) has been shown to restore glutamate homeostasis, reduce relapse to cocaine-seeking and depotentiate PFC-NAcore synapses. Here we examine the effects of NAC applied directly to the NAcore on relapse and neurotransmission in PFC-NAcore synapses, as well as the involvement of the metabotropic glutamate receptors (mGluRs) mGluR2/3 and mGluR5. Methods Rats were trained to self-administer cocaine for 2 weeks and following extinction received either intra-accumbens NAC or systemic NAC 30 or 120 minutes, respectively, prior to inducing reinstatement with a conditioned cue or a combined cue and cocaine injection. We also recorded postsynaptic currents using in vitro whole cell recordings in acute slices and measured cystine and glutamate uptake in primary glial cultures. Results NAC microinjection into the NAcore inhibited the reinstatement of cocaine-seeking. In slices, a low concentration of NAC reduced the amplitude of evoked glutamatergic synaptic currents in the NAcore in a mGluR2/3-dependent manner, while high doses of NAC increased amplitude in a mGluR5-dependent manner. Both effects depended on NAC uptake through cysteine transporters and activity of the cysteine/glutamate exchanger. Finally, we showed that by blocking mGluR5 the inhibition of cocaine-seeking by NAC was potentiated. Conclusions The effect of NAC on relapse to cocaine-seeking depends on the balance between stimulating mGluR2/3 and mGluR5 in the NAcore, and the efficacy of NAC can be improved by simultaneously inhibiting mGluR5. PMID:22137594

  13. 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

  14. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

    PubMed Central

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

    2015-01-01

    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-1hiTIM-3+ cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1hiTIM-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-1hiTIM-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. PMID:26230954

  15. Identifying patients with a high risk of relapse in quiescent Crohn's disease. The GETAID Group. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.

    PubMed Central

    Sahmoud, T; Hoctin-Boes, G; Modigliani, R; Bitoun, A; Colombel, J F; Soule, J C; Florent, C; Gendre, J P; Lerebours, E; Sylvester, R

    1995-01-01

    No reliable identification of quiescent Crohn's disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) > or = 200, a CDAI > or = 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age < or = 25 years, interval since first symptoms > 5 years, interval since previous relapse < or = 6 months, and colonic involvement (p < 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p < 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse. PMID:8537053

  16. 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

    2015-01-01

    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. PMID:26230954

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

    PubMed

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

    1999-01-01

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

  18. 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

  19. 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

  20. Natural History of CNS Relapse in Patients With Aggressive Non-Hodgkin's Lymphoma: A 20-Year Follow-Up Analysis of SWOG 8516—The Southwest Oncology Group

    PubMed Central

    Bernstein, Steven H.; Unger, Joseph M.; LeBlanc, Michael; Friedberg, Jonathan; Miller, Thomas P.; Fisher, Richard I.

    2009-01-01

    Purpose To investigate the incidence, natural history, and risk factors predictive of CNS relapse in patients with de novo aggressive lymphomas and to evaluate the efficacy of CNS prophylaxis in patients with initial bone marrow (BM) involvement. Patients and Methods We conducted an analysis of CNS events from 20-year follow-up data on 899 eligible patients with aggressive lymphoma treated on Southwest Oncology Group protocol 8516, a randomized trial of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), ProMACE (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide)-CytaBOM (cytarabine, bleomycin, vincristine, methotrexate), and m-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide). Patients with BM involvement randomly assigned to receive ProMACE-CytaBOM (63 patients) or m-BACOD (58 patients) were to receive CNS prophylaxis, whereas those randomly assigned to receive CHOP or MACOP-B did not. Results CNS relapse is uncommon (25 of 899 patients), with a cumulative incidence of 2.8%. CNS relapse occurs early (median time to relapse, 5.4 months from diagnosis). Indeed, 20 of 25 patients with CNS relapse relapsed during chemotherapy, or within 6 months of completion. The number of extranodal sites and the International Prognostic Index were predictive of CNS relapse. There was no significant benefit of CNS prophylaxis in patients with BM involvement at diagnosis; however, given the small number of events, the power of this analysis is limited. Conclusion The early occurrence of CNS events suggests that these patients had subclinical disease at initial diagnosis. As such, strategies to better detect and treat patients with subclinical CNS disease at diagnosis would be anticipated to result in a decrease in the incidence of CNS relapse, without subjecting those patients not destined for CNS relapse to unnecessary and potentially toxic

  1. 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. PMID:26744591

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

    PubMed Central

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

    2015-01-01

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

  3. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1994-04-01

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

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

    PubMed

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

    2014-02-01

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

  7. 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

  8. A focus group study of predictors of relapse in electronic gaming machine problem gambling, part 1: factors that 'push' towards relapse.

    PubMed

    Oakes, J; Pols, R; Battersby, M; Lawn, S; Pulvirenti, M; Smith, D

    2012-09-01

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

  9. 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

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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…

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

    PubMed

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

    2002-05-01

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

  18. An Ecological Momentary Assessment of Relapse Crises in Dieting

    ERIC Educational Resources Information Center

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

    2004-01-01

    Much of the research on relapse crises in dieting has focused on isolated lapse events and relied heavily on retrospective self-report data. The present study sought to overcome these limitations by using ecological momentary assessment (EMA) techniques to examine situations of dietary temptation and lapse with a sample of obese, formerly…

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

    PubMed

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

    2015-09-01

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

  20. 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

  1. 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

  2. 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…

  3. 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…

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

    PubMed Central

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

    2014-01-01

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

  5. 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.

  6. Social Resource Characteristics and Adolescent Substance Abuse Relapse.

    ERIC Educational Resources Information Center

    Vik, Peter W.; And Others

    1992-01-01

    Examined social resource network characteristics of adolescent substance abusers (n=19). Perceived similarity to one's social network emerged as important moderator of whether social network provided support to remain abstinent or elevated risk for relapse. Increased perceived support predicted continued posttreatment abstinence when recovering…

  7. Couples Relapse Prevention Sessions as a Maintenance Strategy for Alcoholics.

    ERIC Educational Resources Information Center

    Cutter, Henry S. G.; And Others

    This study evaluated whether alcoholics who receive relapse prevention (RP) sessions in the year after a short-term behavioral marital therapy (BMT) do better at long-term follow-up than do those not receiving the additional RP. Sixty couples with an alcoholic husband, after participating in 10 weekly BMT couples group sessions, were assigned…

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

    PubMed

    Citrome, Leslie

    2016-01-01

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

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

    PubMed

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

    2016-07-01

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

  10. 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

  11. 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

  12. [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

  13. African Relapsing Fever Borreliae Genomospecies Revealed by Comparative Genomics

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-08-01

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

  15. 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.

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

    PubMed

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

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

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

    PubMed

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

    2013-12-01

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

  18. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations | Office of Cancer Genomics

    Cancer.gov

    The majority of patients with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas showed clonal evolution from the diagnostic tumor, with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK pathway.

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

    PubMed

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

    2011-12-01

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

  20. 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

  1. 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

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

    2015-02-01

    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

  2. Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao

    ERIC Educational Resources Information Center

    Witkiewitz, Katie; Marlatt, Alan G.

    2004-01-01

    Relapse prevention, based on the cognitive-behavioral model of relapse, has become an adjunct to the treatment of numerous psychological problems, including (but not limited to) substance abuse, depression, sexual offending, and schizophrenia. This article provides an overview of the efficacy and effectiveness of relapse prevention in the…

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  4. Comparison of PR3-ANCA and MPO-ANCA Epitope Specificity upon Disease Relapse

    EPA Science Inventory

    BACKGROUND Relapse is a major clinical problem in ANCA vasculitis that causes increased morbidity and mortality. Compared to MPO-ANCA patients, patients with PR3-ANCA run a significantly increased risk of experiencing relapses. We hypothesized that a relapsing patient is produ...

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

    ERIC Educational Resources Information Center

    Gintner, Gary G.

    1988-01-01

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

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

    ERIC Educational Resources Information Center

    Hodgins, David C.; el-Guebaly, Nady

    2004-01-01

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

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

    ERIC Educational Resources Information Center

    Cantrell, Peggy J.; And Others

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  10. A focus group study of predictors of relapse in electronic gaming machine problem gambling, part 2: factors that 'pull' the gambler away from relapse.

    PubMed

    Oakes, J; Pols, R; Battersby, M; Lawn, S; Pulvirenti, M; Smith, D

    2012-09-01

    This study aimed to develop an empirically based description of relapse in Electronic Gaming Machine (EGM) problem gambling (PG) by describing the processes and factors that 'pull' the problem gambler away from relapse contrasted with the 'push' towards relapse. These conceptualisations describe two opposing, interacting emotional processes occurring within the problem gambler during any relapse episode. Each relapse episode comprises a complex set of psychological and social behaviours where many factors interact sequentially and simultaneously within the problem gambler to produce a series of mental and behaviour events that end (1) with relapse where 'push' overcomes 'pull' or (2) continued abstinence where 'pull' overcomes 'push'. Four focus groups comprising thirty participants who were EGM problem gamblers, gamblers' significant others, therapists and counsellors described their experiences and understanding of relapse. The groups were recorded, recordings were then transcribed and analysed using thematic textual analysis. It was established that vigilance, motivation to commit to change, positive social support, cognitive strategies such as remembering past gambling harms or distraction techniques to avoid thinking about gambling to enable gamblers to manage the urge to gamble and urge extinction were key factors that protected against relapse. Three complementary theories emerged from the analysis. Firstly, a process of reappraisal of personal gambling behaviour pulls the gambler away from relapse. This results in a commitment to change that develops over time and affects but is independent of each episode of relapse. Secondly, relapse may be halted by interacting factors that 'pull' the problem gambler away from the sequence of mental and behavioural events, which follow the triggering of the urge and cognitions to gamble. Thirdly, urge extinction and apparent 'cure' is possible for EGM gambling. This study provides a qualitative, empirical model for

  11. Extramedullary relapse after allogeneic bone marrow transplantation plus buffy-coat in two high risk patients.

    PubMed

    Salutari, P; Sica, S; Micciulli, G; Rutella, S; Di Mario, A; Leone, G

    1996-01-01

    In order to obtain an additional graft versus leukemia effect (GVL) and rapid engraftment, donor leukocyte infusion (DLI) was added to unseparated, sex-mismatched allogeneic bone marrow transplantation in two male patients (age 21, 26) affected by high risk hematological malignancies (refractory T-ALL, refractory B-LBL in leukemic phase). Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone. DLI were obtained after G-CSF 16 ug/kg/day sc. A total of 2.36 and 5.8 x 10(6)/kg MNC, 5.4 and 11 x 10(6)/kg CD34+ cells, 1.3 and 1.3 x 10(6)/kg CD3+ lymphocytes, respectively, were infused. Hemopoietic recovery occurred promptly. Complete chimerism was detected by cytogenetic examination. One patient developed an extramedullary relapse that first involved the cranial nerves, and then the testes, soft tissue and skin; the other patient developed central nervous system disease and then bilateral paravertebral masses with progressive paraplegia. Despite complete medullary remission with normal female karyotype, both patients died from extramedullary progression of their disease. Our observation shows that, at least in high risk patients, no additional GVHD or GVL effect was evident after donor leukocyte infusion. Extramedullary relapse was not prevented despite good control of medullary disease. PMID:8641654

  12. Indoleamine 2,3 Dioxygenase (IDO) Expression and Activity in Relapsing- Remitting Multiple Sclerosis

    PubMed Central

    Mancuso, Roberta; Hernis, Ambra; Agostini, Simone; Rovaris, Marco; Caputo, Domenico; Fuchs, Dietmar; Clerici, Mario

    2015-01-01

    Background Interferon gamma (IFN-γ) production induces the transcription of indoleamine 2,3 dioxygenase (IDO) resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS) patients. Methods IDO and interferon-γ (IFN-γ) gene expression, serum IDO activity (Kynurenine/Tryptophan ratio) and serum neopterin concentration – a protein released by macrophages upon IFN-γ stimulation – were measured in 51 individuals: 36 relapsing remitting (RR)-MS patients (21 in acute phase -AMS, 15 in stable phase -SMS) and 15 healthy controls (HC). PBMCs samples in AMS patients were collected before (BT-AMS) and during glucocorticoids-based therapy (DT-AMS). Results IDO expression was increased and IFN-γ was decreased (p<0.001) in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001). Serum neopterin concentration followed the same trend as IDO expression and activity. Conclusions Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS. PMID:26110930

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

    PubMed

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

    1992-01-01

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

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

    PubMed

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

    2004-04-01

    Much of the research on relapse crises in dieting has focused on isolated lapse events and relied heavily on retrospective self-report data. The present study sought to overcome these limitations by using ecological momentary assessment (EMA) techniques to examine situations of dietary temptation and lapse with a sample of obese, formerly sedentary, postmenopausal women (N = 37) during the final week of a weight-loss intervention. Mood was associated with reports of dietary lapse. Abstinence-violation effects were more strongly associated with dietary lapses than temptations. Finally, coping responses distinguished dietary temptations from lapses. Education on the factors associated with relapse crises in dieting may be imperative for weight loss success and maintenance. PMID:15065966

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

    PubMed

    Fuchs, Inbal; Tarabin, Salman; Kafka, Michael

    2015-07-01

    Three cases of relapsing fever from southern Israel were diagnosed promptly thanks to vigilance of the hematology laboratory technicians. In this region of Israel, patients presenting with prolonged fever and leukopenia without localizing symptoms are generally suspected of having brucellosis or a rickettsial disease. Pediatric patients with prolonged fever, cytopenias, and negative aforementioned serologies are often hospitalized for further work-up. Because of the policy of performing a manual blood smear when results of the automated blood count demonstrate severe anemia and abnormal platelet and/or white blood cell counts, a diagnosis of tick-borne relapsing fever was confirmed and promptly relayed to the physician. This routine prevented unnecessary examinations and hospitalization days and provided important information to regional epidemiology and public health authorities. PMID:26186517

  16. 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

  17. 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

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Melkert, P W

    1988-10-01

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

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

    PubMed

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

    2000-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1987-01-01

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

  4. 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

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

    PubMed

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

    2014-01-01

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

  6. 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

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

    PubMed Central

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

    2011-01-01

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

  8. [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

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

    PubMed

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

    2000-05-01

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

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

    PubMed

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

    2011-03-01

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

  11. Bevacizumab is safe in acute relapses of neuromyelitis optica

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

    We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected from 13 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 years after initial radical nephrectomy. One hundred fifty-one patients were included in this analysis. Among them, MSKCC risk score was favorable in 68 %, intermediate in 29 %, and poor in 3 %. Fifty-six patients (37 %) had NLR ≥3 at the start of VEGFR-TKI therapy (group A), while 95 had lower NLR (63 %, group B). The median overall survival (OS) was 28.8 months in group A and 68.7 months (95 % confidence interval (CI) 45.3-NA) in group B (p < 0.001). The median progression-free survival (PFS) was 15.8 months in group A and 25.1 months in group B (p = 0.03). At multivariate analysis, MSKCC risk group and NLR were independent prognostic factors for both OS and PFS. Pretreatment NLR is an independent prognostic factor for patients with late relapsing mRCC treated with first-line VEGFR-TKIs. A better characterization of baseline immunological impairment may optimize the management of this RCC subpopulation. PMID:25559290

  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. The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low Side-Effect Profile.

    PubMed

    Vengeliene, Valentina; Moeller, Achim; Meinhardt, Marcus W; Beardsley, Patrick M; Sommer, Wolfgang H; Spanagel, Rainer; Bespalov, Anton

    2016-03-01

    Preclinical studies revealed contribution of N-methyl-D-aspartate receptors (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but development of NMDAR antagonists for therapeutic use has been a challenge, in part due to severe side effects. One of the key intracellular events resulting from stimulation of NMDAR is activation of calpains-calcium-dependent cysteine proteases. Here we studied whether inhibition of calpains would produce therapeutic-like effects of NMDAR antagonists but without their NMDAR-mediated side-effect profile. The calpain inhibitor A-705253 (3-10 mg/kg) was tested in a model of cue-induced reinstatement of alcohol-seeking behavior in post-dependent Wistar rats and in an alcohol deprivation effect (ADE) model in long-term alcohol drinking Wistar rats, two behavioral models for alcohol-seeking and relapse, respectively. We also tested the effect of A-705253 on the saccharine deprivation effect (SDE) as a selectivity measure. Acute treatment with A-705253 dose-dependently reduced cue-induced reinstatement of alcohol-seeking behavior. Repeated administration of A-705253 caused significant reductions of relapse-like excessive alcohol intake during the post-abstinence drinking days, an effect that persisted during two more successive drug-free drinking weeks, which was selective for the ADE as the SDE was unaffected. However, A-705253 did not produce psychostimulant, cognition impairing (delayed-matching-to-position), or psychotomimetic effects (specifically, phencyclidine discriminative stimulus effects). Taken together, these results demonstrate the involvement of calpains in alcohol-seeking and relapse and present a rationale for a novel pharmacological intervention that may reduce craving and relapse with minimal side effects in alcohol-dependent patients. PMID:26216521

  17. 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

  18. Primary synovial sarcoma of the thyroid with locally repeated relapses in short periods: A case report

    PubMed Central

    SHI, RONG-LIANG; QU, NING; GAO, LI-LI; LU, ZHONG-WU; SUN, GUO-HUA; JI, QING-HAI

    2016-01-01

    The primary occurrence of synovial sarcoma (SS) in the thyroid is quite rare. As other SS arise from the head and neck structure, it tends to present poor biological behaviors and is generally treated as a high-grade sarcoma. The present study reports the case of a 31-year-old male who presented a neck mass, involving the thyroid, as shown by ultrasonography. The tumor was resected by total thyroidectomy and diagnosed as SS by histopathology. However, the initial surgery was considered as incomplete (R2) and no adjuvant protocol was followed. At the follow-up, neck recurrences within local lymph nodes were found repeatedly. The tumor grade increased for the metastatic lesions, indicating poorer differentiations with repeated relapses. The accurate evaluations of the primary tumor facilitated it to tailor the initial treatments, otherwise, the prognosis may be deteriorated by inappropriate management. PMID:27330751

  19. 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

  20. Neural substrates of cue reactivity: association with treatment outcomes and relapse.

    PubMed

    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

  1. 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

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

    PubMed

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

    2013-01-01

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

  3. 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.

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

    SciTech Connect

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

    1991-06-01

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

  5. 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…

  6. 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

  7. 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

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

    PubMed

    Anis, Saar; Achiron, Anat

    2014-11-01

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

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

    PubMed

    Delval, Arnaud; Stojkovic, Tanya; Vermersch, Patrick

    2006-02-01

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

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

    PubMed Central

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

    2010-01-01

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

  11. 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

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

    PubMed

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

    2003-01-01

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

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

    PubMed

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

    2013-04-01

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

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

    PubMed

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

    2012-01-26

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

    Tuliao, Antover P; Liwag, Maria Emma Concepcion D

    2011-01-01

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

  17. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-11

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

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

    PubMed

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

    2016-06-01

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

  19. 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

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

    PubMed

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

    2016-05-01

    Statins are drugs that have been used for decades in humans for the treatment of hypercholesterolemia. More recently, several lines of evidence demonstrate that statins, in addition to their peripheral effects, produce a wide variety of effects in the brain and may be beneficial in neurological and psychiatric conditions. In this study, we allowed rats to self-administer cocaine for several weeks and, at the end of self-administration training, we treated them with low doses of statins daily for a 21-day period of abstinence. Chronic administration of brain-penetrating statins, simvastatin (1 mg/kg) and atorvastatin (1 mg/kg), reduced cocaine seeking compared with vehicle, whereas administration of pravastatin (2 mg/kg), a statin with low brain penetrability, did not. Importantly, the effects of brain-penetrating statins persisted even after discontinuation of the treatment and were specific for drug seeking because drug taking was not altered by simvastatin treatment. Finally, the effects of simvastatin were found to generalize to another drug of abuse such as nicotine, but not to food reward, and to reinstatement of cocaine seeking induced by stress. These results demonstrate that brain-penetrating statins can reduce risks of relapse to addiction. Given their well-known safety profile in humans, statins could be a novel effective treatment for relapse to cocaine and nicotine addiction and their use could be implemented in clinical settings without major health risks. PMID:26466819

  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. Lenalidomide for the treatment of relapsed and refractory multiple myeloma

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    1984-01-01

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

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

    PubMed

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

    2000-01-01

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

  7. 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

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

    PubMed

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

    2006-04-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5 +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease. PMID:16612466

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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.

  14. [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

  15. 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

  16. 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

  17. 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

  18. 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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  20. 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…

  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. PMID:22246158

  2. 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…

  3. 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…

  4. 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

  5. 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.…

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

    PubMed

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

    2016-07-01

    Many patients with schizophrenia will relapse despite uninterrupted antipsychotic (AP) long-acting therapy (LAT). This exploratory analysis examined variables associated with relapse despite ensured adherence to LAT. This was a post-hoc exploratory analysis of a 1-year study of risperidone long-acting injection in patients with stable schizophrenia or schizoaffective disorder (NCT00297388; N=323). Patients were discontinued from previous oral APs and randomly assigned to biweekly intramuscular injections of risperidone long-acting injectable 50 (n=163) or 25 mg (n=161) for 52 weeks. Cox proportional hazards regression models examined variables putatively associated with relapse. A total of 59/323 (18.3%) patients relapsed over 12 months despite continuous AP LAT. Variables associated with the risk of relapse included illness duration (6.0% increase each year; P=0.0003) and country (Canada vs. USA, 4.7-fold risk increase; P=0.0008). When illness duration was further categorized as ≤5, 6-10, and >10 years, patients with an illness duration of >10 versus ≤5 years were at greatest risk of relapse (>10 vs. ≤5 years associated with a 4.4-fold increase in the risk of relapse; P=0.0181). Findings suggest that patients with more chronic illness have a greater risk of relapse despite ensured treatment adherence, supporting the need for early intervention to prevent the deleterious effects of chronicity. PMID:26974214

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

    ERIC Educational Resources Information Center

    Sussman, Steve; And Others

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

  9. 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…

  10. 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)

  11. 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

  12. 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

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

    PubMed Central

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

    2012-01-01

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

  14. 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

  15. 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

  16. 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.

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

    PubMed

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

    2007-06-01

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

  18. 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

  19. 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

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

    PubMed

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

    2014-10-01

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

  1. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia

    PubMed Central

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

    2014-01-01

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

  2. Decreased dopamine activity predicts relapse in methamphetamine abusers

    SciTech Connect

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

    2011-01-20

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2002-06-15

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2015-12-01

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

  7. 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

  8. 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.

  9. Drug-induced plasticity contributing to heightened relapse susceptibility: neurochemical changes and augmented reinstatement in high-intake rats.

    PubMed

    Madayag, Aric; Kau, Kristen S; Lobner, Doug; Mantsch, John R; Wisniewski, Samantha; Baker, David A

    2010-01-01

    A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for cocaine-induced reinstatement. In this report, we examined whether drug-induced adaptations that are necessary to generate cocaine-induced reinstatement also determine relapse vulnerability. To do this, rats were assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5 mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug intake since these manipulations produce groups of rats exhibiting differences in the magnitude of cocaine-induced reinstatement. Approximately 19 d after the last session, cocaine-induced drug seeking and extracellular levels of glutamate and dopamine in the NAcc were measured. Contrary to our hypothesis, high-intake rats exhibited a more robust cocaine-induced increase in extracellular levels of dopamine but not glutamate. Further, increased reinstatement in high-intake rats was no longer observed when the D(1) receptor antagonist SCH-23390 was infused into the NAcc. The sensitized dopamine response to cocaine in high-intake rats may involve blunted cystine-glutamate exchange by system x(c(-)). Reduced (14)C-cystine uptake through system x(c(-)) was evident in NAcc tissue slices obtained from high-intake rats, and the augmented dopamine response in these rats was no longer observed when subjects received the cysteine prodrug N-acetyl cysteine. These data reveal a role for drug-induced NAcc dopamine in heightened relapse vulnerability observed in rats with a history of high levels of drug intake. PMID:20053903

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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.

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

    PubMed

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

    2015-11-01

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

  15. 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.

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

    PubMed

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

    2015-02-01

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

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

    SciTech Connect

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

    1990-01-01

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

  18. 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

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

    PubMed Central

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

    2015-01-01

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

  20. 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

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

    PubMed Central

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

    2007-01-01

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

  2. 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

  3. 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

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

    PubMed

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

    2016-09-01

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

  5. Constitutive NF-κB Activation Underlines Major Mechanism of Drug Resistance in Relapsed Refractory Diffuse Large B Cell Lymphoma

    PubMed Central

    2015-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common subtype of B cell non-Hodgkin's lymphoma (NHL), encompassing 30–40% of the estimated 70,000 cases of NHL in 2014 in the USA. Despite major improvements with immune-chemotherapy, the fraction of patients who still succumb to a refractory or relapsed disease remains high. This review addresses whether the better understanding of the biology of DLBCL defines new therapeutic avenues that may overcome the emerging resistance of this disease to traditional immune-chemotherapy, such as rituximab in combination with traditional chemotherapy agents. Emerging targeted therapy for relapsed refractory DLBCL encompasses more complex molecular abnormalities involving signaling pathways other than NF-κB as mechanism of resistance to immune-chemotherapy. Our review suggests that NF-κB pathway is an important crossroad where other pathways converge as phenotype of resistance that emerges in patients who fail frontline and salvage immune-chemotherapy. Future efforts should aim at targeting the role of NF-κB resistance in clinical trials, where novel agents like lenalidomide and proteasome inhibitors with established activity in this perspective will be an important component in combination therapy, along with new monoclonal antibody, BTK-inhibitors, and other novel therapy agents. PMID:25984532

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2009-02-24

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

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

    PubMed

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

    2015-11-01

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

  13. 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

  14. Conversion of a linear to a circular plasmid in the relapsing fever agent Borrelia hermsii.

    PubMed Central

    Ferdows, M S; Serwer, P; Griess, G A; Norris, S J; Barbour, A G

    1996-01-01

    Spirochetes of the genus Borrelia have genomes composed of both linear and circular replicons. We characterized the genomic organization of B. burgdorferi, B. hermsii, B. turicatae, and B. anserina with pulsed-field gel electrophoresis. All four species contained a linear chromosome approximately 1 Mb in size and multiple linear plasmids in the 16- to 200-kb size range. Plasmids 180 and 170 kb in size, present in the relapsing fever agents B. hermsii and B. turicatae but not in the other two species, behaved as linear duplex DNA molecules under different electrophoretic conditions. A variant of strain HSI of B. hermsii had a 180-kb circular instead of linear plasmid. There were no detectable differences in the growth rates or in the expression of cellular proteins between cells bearing linear forms and those bearing circular forms of the plasmid. The conversion to a circular conformation of monomeric length was demonstrated by the introduction of strand breaks with irradiation, restriction endonuclease analysis, and direct observation of the DNA molecules by fluorescent microscopy. Consideration of different models for the replication of linear DNA suggests that circular intermediates may be involved in the replication of linear replicons in Borrelia spp. PMID:8550515

  15. 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

  16. Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma.

    PubMed

    Moreau, Philippe; Facon, Thierry; Touzeau, Cyrille; Benboubker, Lotfi; Delain, Martine; Badamo-Dotzis, Julie; Phelps, Charles; Doty, Christopher; Smit, Hans; Fourneau, Nele; Forslund, Ann; Hellemans, Peter; Leleu, Xavier

    2016-07-01

    The maximum tolerated dose (MTD) of quisinostat + bortezomib + dexamethasone in patients with relapsed multiple myeloma was evaluated in a phase-1b, open-label, multicenter, '3 + 3' dose-escalation study. Patients received escalating doses of oral quisinostat (6 mg [n = 3], 8 mg [n = 3], 10 mg [n = 6], and 12 mg [n = 6] on days 1, 3, and 5/week) plus subcutaneous bortezomib (1.3 mg/m(2)) and oral dexamethasone (20 mg) in cycles of 21 (cycles 1-8) or 35 d (cycles 9-11) until MTD was determined. No dose-limiting toxicities were reported in 6/8 mg groups except ventricular fibrillation (Grade 4 cardiac arrest, n = 1 [10 mg] cycle 6) and clinically significant cardiac toxicities (Grade 3 QTc prolongation, Grade 3 atrial fibrillation, n = 2 [12 mg]). Thrombocytopenia (n = 11), asthenia (n = 10), and diarrhea (n = 12) were most common adverse events. Overall, 88.2% patients achieved treatment response, median duration of response, and median progression-free survival were 9.4 and 8.2 months, respectively. The MTD of quisinostat was established as 10 mg thrice weekly oral dose with bortezomib + dexamethasone. PMID:26758913

  17. Cerebellar information processing in relapsing-remitting multiple sclerosis (RRMS).

    PubMed

    Lesage, E; Apps, M A J; Hayter, A L; Beckmann, C F; Barnes, D; Langdon, D W; Ramnani, N

    2010-01-01

    Recent research has characterized the anatomical connectivity of the cortico-cerebellar system - a large and important fibre system in the primate brain. Within this system, there are reciprocal projections between the prefrontal cortex and Crus II of the cerebellar cortex, which both play important roles in the acquisition and execution of cognitive skills. Here, we propose that this system also plays a particular role in sustaining skilled cognitive performance in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), in whom advancing neuropathology causes increasingly inefficient information processing. We scanned RRMS patients and closely matched healthy subjects while they performed the Paced Auditory Serial Addition Test (PASAT), a demanding test of information processing speed, and a control task. This enabled us to localize differences between conditions that change as a function of group (group-by-condition interactions). Hemodynamic activity in some patient populations with CNS pathology are not well understood and may be atypical, so we avoided analysis strategies that rely exclusively on models of hemodynamic activity derived from the healthy brain, using instead an approach that combined a 'model-free' analysis technique (Tensor Independent Component Analysis, TICA) that was relatively free of such assumptions, with a post-hoc 'model-based' approach (General Linear Model, GLM). Our results showed group-by-condition interactions in cerebellar cortical Crus II. We suggest that this area may have in role maintaining performance in working memory tasks by compensating for inefficient data transfer associated with white matter lesions in MS. PMID:20714060

  18. Copy number alteration burden predicts prostate cancer relapse

    PubMed Central

    Hieronymus, Haley; Schultz, Nikolaus; Gopalan, Anuradha; Carver, Brett S.; Chang, Matthew T.; Xiao, Yonghong; Heguy, Adriana; Huberman, Kety; Bernstein, Melanie; Assel, Melissa; Murali, Rajmohan; Vickers, Andrew; Scardino, Peter T.; Sander, Chris; Reuter, Victor; Taylor, Barry S.; Sawyers, Charles L.

    2014-01-01

    Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input whole-genome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts. PMID:25024180

  19. Relationship of marital structure and interactions to opiate abuse relapse.

    PubMed

    Kosten, T R; Jalali, B; Steidl, J H; Kleber, H D

    1987-01-01

    Several aspects of marital functioning were associated with subsequent relapse to opiate abuse in 17 married addicts. The addicts and spouses were evaluated in a task-oriented interview and rated using the Beavers Timberlawn Family Assessment instrument. The global health-pathology ratings on this instrument indicated that most couples had rigid patterns of interacting, rather than a chaotic lack of structure or a flexible, negotiated partnership. Within this range of rigid functioning, higher ratings were associated with longer times drug-free (up to 18 months with a mean of 7 months). On the seven subscales of the Beavers', five were significantly correlated with the time drug-free: effective and clear leadership, closeness between the spouses, a nonhostile mood, empathy, and efficient negotiation and problem solving. The subscales associated with drug abstinence were quite different for a group of seven single ex-addicts participating in the same outpatient program, but living with their parents. For these single ex-addicts three subscales were correlated with the time drug-free: parental reaction to separation strivings, the open expression of thoughts and feelings, and empathy. This difference in the subscales associated with abstinence for married versus single addicts suggested some specificity in the characteristics of family structure and interaction that may be related to drug abstinence. PMID:3687898

  20. 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

  1. Perceived Relapse Risk and Desire for Medication Assisted Treatment among Persons Seeking Inpatient Opiate Detoxification

    PubMed Central

    Bailey, Genie L; Herman, Debra S.; Stein, Michael D.

    2016-01-01

    Most patients with opioid addiction do not receive medication at the time of discharge from brief inpatient detoxification programs despite the high risk of relapse and the availability of three FDA-approved medications. We surveyed 164 inpatient opioid detoxification patients to assess desire for pharmacotherapy following detoxification program discharge. Participants were predominantly male (71.3%) and 80% had detoxed in the past. Reporting on their most recent previous inpatient detoxification, 27% had relapsed the day they were discharged, 65% within a month of discharge, and 90% within a year of discharge. 63% reported they wanted medication-assisted treatment (MAT) after discharge from the current admission. The odds of desiring a treatment medication increased by a factor of 1.02 for every 1% increase in perceived relapse risk (p < .01). These data suggest patient preference discussions including relapse risk could increase post-detox abstinence. PMID:23786852

  2. [Molecular remission induced by gemtuzumab ozogamicin in an elderly patient with relapsed acute promyelocytic leukemia].

    PubMed

    Yago, Kazuhiro; Aono, Maki; Shimada, Hideto

    2010-04-01

    A 79-year-old female with acute promyelocytic leukemia (APL) presented with second hematological relapse. She had been treated previously with modified AIDA protocol as the front-line therapy and had achieved complete remission. During ATRA maintenance therapy, the first hematological relapse occurred and she was treated with arsenic trioxide (ATO), achieving the second complete remission. After four courses of consolidation therapy of ATO, the second hematological relapse occurred. At this time, except for a transient effect of tamibarotene, neither arsenic trioxide nor combination chemotherapy was effective. The patient was then treated with two courses of gemtuzumab ozogamicin (GO) and achieved the third complete remission. At present, she is maintaining molecular remission more than one year after GO treatment. GO is considered to be a promising agent for elderly patients with relapsed acute promyelocytic leukemia resistant to arsenic trioxide. PMID:20467227

  3. Treatment of relapsed classical Hodgkin lymphoma in the brentuximab vedotin era

    PubMed Central

    Graf, Solomon A.; Gopal, Ajay K.

    2015-01-01

    Classical Hodgkin lymphoma (HL) relapses after or is refractory to upfront multiagent chemotherapy in 20%–30% of patients. Effective salvage therapy for relapsed or refractory HL is limited, and advancements are needed. Brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate, has demonstrated significant activity and manageable toxicities in advanced HL. Currently approved as a monotherapy for patients with HL that is relapsed or refractory to multiple lines of chemotherapy or autologous stem cell transplantation, BV is now being evaluated earlier in the course of disease and in combination with other therapies. This review discusses the successful translation of BV from its conception to the clinical setting and highlights ongoing trials that may ultimately expand its role in relapsed or refractory HL and improve outcomes for patients. PMID:25696848

  4. Dynamic self-efficacy and outcome expectancies: prediction of smoking lapse and relapse.

    PubMed

    Gwaltney, Chad J; Shiffman, Saul; Balabanis, Mark H; Paty, Jean A

    2005-11-01

    According to social learning models of drug relapse, decreases in abstinence self-efficacy (ASE) and increases in positive smoking outcome expectancies (POEs) should foreshadow lapses and relapse. In this study, the authors examined this hypothesis by using ecological momentary assessment data from 305 smokers who achieved initial abstinence from smoking and monitored their smoking and their ASE and POEs by using palmtop computers. Daily ASE and POEs predicted the occurrence of a 1st lapse on the following day. Following a lapse, variations in daily ASE predicted the onset of relapse, even after controlling for concurrent smoking. ASE and POEs generally neither mediated nor moderated each other's effects. These data emphasize the role of dynamic factors in the relapse process. PMID:16351387

  5. Perceived relapse risk and desire for medication assisted treatment among persons seeking inpatient opiate detoxification.

    PubMed

    Bailey, Genie L; Herman, Debra S; Stein, Michael D

    2013-09-01

    Most patients with opioid addiction do not receive medication at the time of discharge from brief inpatient detoxification programs despite the high risk of relapse and the availability of three FDA-approved medications. We surveyed 164 inpatient opioid detoxification patients to assess desire for pharmacotherapy following detoxification program discharge. Participants were predominantly male (71.3%) and 80% had detoxed in the past. Reporting on their most recent previous inpatient detoxification, 27% had relapsed the day they were discharged, 65% within a month of discharge, and 90% within a year of discharge. 63% reported they wanted medication-assisted treatment (MAT) after discharge from the current admission. The odds of desiring a treatment medication increased by a factor of 1.02 for every 1% increase in perceived relapse risk (p<.01). These data suggest patient preference discussions including relapse risk could increase post-detox abstinence. PMID:23786852

  6. 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

  7. 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

  8. Relapse from safer sex: the next challenge for AIDS prevention efforts.

    PubMed

    Stall, R; Ekstrand, M; Pollack, L; McKusick, L; Coates, T J

    1990-01-01

    Prevention campaigns to reduce sexual transmission of human immunodeficiency virus (HIV) typically emphasize the initial adoption of safer sex techniques. We present data from a 5-year prospective study to show that the vast majority of resident gay men in San Francisco have made these initial risk reductions. Rather, relapse from safer sex techniques is now the predominant predominant kind of high-risk sex, accounting for approximately two thirds of all prevalent high-risk sex in the 1988 wave of data collection. Predictors of relapse from safer sex are identified, and these are discussed in terms of their implications for preventing relapse from the exclusive practice of safe sex. In communities that have already manifested widespread behavioral risk reductions and in which HIV infection is highly prevalent, finding ways to prevent relapse of behavioral risk reductions will be the next important challenge in the fight against acquired immune deficiency syndrome. PMID:2243318

  9. 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

  10. Kinetics of relapse after pegylated interferon and ribavirin therapy for chronic hepatitis C.

    PubMed

    Brochot, Etienne; Riachi, Ghassan; Plantier, Jean-Christophe; Guillemard, Catherine; Vabret, Astrid; Mathurin, Philippe; Nguyen-Khac, Eric; Duverlie, Gilles

    2013-07-01

    To optimize standard treatment of chronic hepatitis C in responder patients who have achieved undetectable viral load, a prospective study was conducted to determine the factors and kinetics of virologic relapse. Responder patients were monitored 2, 4, 8, 12, 16, and 24 weeks after the end of treatment with pegylated interferon and ribavirin. Forty-seven of the 154 patients (30.5%) relapsed. Relapse was significantly associated with absence of rapid virologic response (RVR), retreatment, higher baseline viral load, older age, and lower weight-based dose of pegylated interferon. Relapse was more frequent in patients failing to achieve a RVR after receiving pegylated interferon alpha 2a < 2.5 µg/week or alpha 2b < 1.5 µg/week (P = 0.002). Among patients infected with hepatitis C virus (HCV) genotype 1 with non-CC IL-28B polymorphism (rs12979860), viral decay during treatment was lower in relapsers (P = 0.003 at week 4). Relapse was detected at weeks 2, 4, 8, and 12 after the end of treatment for 5, 8, 10, and 6 patients infected with HCV genotype 1, respectively. Positive predictive values for sustained virologic response were 70.9%, 80.2%, 91.9%, and 98.8% at weeks 2, 4, 8, and 12, respectively. Only one patient relapsed beyond 24 weeks. Closer follow-up and treatment adaptation in patients failing to achieve RVR may decrease the relapse rate in slower responders and heavier patients. Monitoring viral load as early as 1 month after the end of treatment could be useful to assess virologic response. PMID:23918537

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

    PubMed Central

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

    2015-01-01

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

  12. Evaluation of factors associated with relapse in telaprevir-based triple therapy for chronic hepatitis C

    PubMed Central

    Kondo, C; Atsukawa, M; Tsubota, A; Shimada, N; Abe, H; Aizawa, Y

    2016-01-01

    Background and Rationale: Most patients with chronic hepatitis C show virological response to telaprevir-based triple therapy, and achieve an end-of-treatment response (ETR). However, some patients showing ETR develop virological relapse. This study was carried out to evaluate factors associated with relapse after triple therapy. Materials and Methods: A prospective, multicentric study was conducted in chronic hepatitis C patients who received telaprevir-based triple therapy. We evaluated independent variables such as age, with or without cirrhosis, prior treatment response to interferon (IFN) therapy, IL28B genotype, core amino acid (aa) 70 mutation, drug adherence, white blood cell counts, hemoglobin level, and serum low-density lipoprotein (LDL) cholesterol level. The characteristics of the patients who relapsed after achieving ETR were compared with those who did not. Results: Among 168 patients, 157 patients achieved ETR (93.5%) and 11 discontinued. Of these 157 patients, relapse occurred in 21 patients (13.4%). Nineteen patients (90.5%) of 21 relapsed patients had the IL28B non-TT genotype (P = 1.79 × 10-9). Multivariate analysis identified core amino acid 70 [P = 0.018, crude odds ratio (OR): 6.927] and the IL28B genotype (P = 3.758 × 10-5, crude OR: 39.311) as significantly independent factors that influenced the relapse-related variables. Among the 49 patients with the IL28B non-TT, 18 patients had core aa70 mutation and 31 patients had core aa70 wild-type. In addition, 66.7% (12/18) of those with core aa70 mutation and 22.6% (7/31) of those with core aa70 wild-type developed relapse (P = 0.005). Discussion: Core aa70 mutation and the IL28B non-TT genotype were identified as independent factors that influenced relapse after achievement of ETR for telaprevir-based triple therapy. PMID:26732192

  13. 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

  14. Error processing and gender-shared and -specific neural predictors of relapse in cocaine dependence.

    PubMed

    Luo, Xi; Zhang, Sheng; Hu, Sien; Bednarski, Sarah R; Erdman, Emily; Farr, Olivia M; Hong, Kwang-Ik; Sinha, Rajita; Mazure, Carolyn M; Li, Chiang-Shan R

    2013-04-01

    Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were associated with relapse to drug use, were not clear. In a prospective study, we recruited 97 treatment-seeking individuals with cocaine dependence to perform the stop signal task during functional magnetic resonance imaging and participate in follow-up assessments for 3 months, during which time cocaine use was evaluated with timeline follow back and ascertained by urine toxicology tests. Functional magnetic resonance imaging data were analysed using general linear models as implemented in Statistical Parametric Mapping 8, with the contrast 'stop error greater than stop success trials' to index error processing. Using voxelwise analysis with logistic and Cox regressions, we identified brain activations of error processing that predict relapse and time to relapse. In females, decreased error-related activations of the thalamus and dorsal anterior cingulate cortex predicted relapse and an earlier time to relapse. In males, decreased error-related activations of the dorsal anterior cingulate cortex and left insula predicted relapse and an earlier time to relapse. These regional activations were validated with data resampling and predicted relapse with an average area under the curve of 0.849 in receiver operating characteristic analyses. These findings provide direct evidence linking deficits in cognitive control to clinical outcome in a moderate-sized cohort of cocaine-dependent individuals. These results may provide a useful basis for future studies to examine how psychosocial factors interact with cognitive control to determine drug use and to evaluate the efficacy of pharmacological or behavioural treatment in remediating

  15. 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

  16. Association of ITPA Genotype with Event-Free Survival and Relapse Rates in Children with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy

    PubMed Central

    Smid, Alenka; Karas-Kuzelicki, Natasa; Milek, Miha; Jazbec, Janez; Mlinaric-Rascan, Irena

    2014-01-01

    Although the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over recent decades, failure due to treatment-related toxicities and relapse of the disease still occur in about 20% of patients. This retrospective study included 308 pediatric ALL patients undergoing maintenance therapy and investigated the effects of genetic variants of enzymes involved in the 6-mercaptopurine (6-MP) metabolism and folate pathway on survival and relapse rates. The presence of at least one of the non-functional ITPA alleles (94C>A and/or IVS2+21A>C variant) was associated with longer event-free survival compared to patients with the wild-type ITPA genotype (p = 0.033). Furthermore, patients carrying at least one non-functional ITPA allele were shown to be at a lower risk of suffering early (p = 0.003) and/or bone marrow relapse (p = 0.017). In conclusion, the ITPA genotype may serve as a genetic marker for the improvement of risk stratification and therapy individualization for patients with ALL. PMID:25303517

  17. 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. PMID:26246443

  18. CNS involvement in small noncleaved-cell lymphoma: is CNS disease per se a poor prognostic sign?

    PubMed

    Haddy, T B; Adde, M A; Magrath, I T

    1991-11-01

    Of 120 patients with small noncleaved-cell lymphoma who were entered sequentially on four National Cancer Institute (NCI) protocols, 29 (24%) had CNS involvement at some time in their clinical course. Seventeen had initial CNS involvement, and 12 developed CNS involvement at the time of first relapse. All 29 patients had extensive disease at presentation. The median serum lactate dehydrogenase (LDH) levels at presentation were 1,150 IU/L for patients with initial CNS involvement and 1,083 IU/L for patients with CNS involvement at relapse. CNS disease was significantly associated with serum LDH levels (P less than .0001), bone marrow involvement (P less than .0001), and jaw involvement (P = .018), but not involvement of the abdomen. There were nine long-term survivors among the 29 patients (31%). CNS disease did not appear to confer a worse prognosis on these patients than on patients without CNS involvement who had similar degrees of serum LDH elevation or who had bone marrow involvement, suggesting that extensive disease rather than CNS involvement was responsible for the poor prognosis. Event-free survival for patients with serum LDH levels above 500 IU/L was not different whether CNS disease was present or not (P = .29), nor was event-free survival different for patients with stage IV disease, whether CNS disease was present or not (P = .92). Although some patients had CNS radiation, there was no evidence that this was of therapeutic benefit. Intrathecal (IT) chemoprophylaxis effectively prevented spread to the CNS in patients without initial CNS involvement. Five of 18 patients (28%) who received no IT prophylaxis had CNS relapse (four isolated to the CNS), but only seven of the 85 patients (8%) who received IT prophylaxis had CNS relapse (two isolated to the CNS). The differences in overall and isolated CNS relapse rates were statistically significant (P = .034 and P = .008, respectively). PMID:1941056

  19. The neural circuitry underlying reinstatement of heroin-seeking behavior in an animal model of relapse.

    PubMed

    Rogers, J L; Ghee, S; See, R E

    2008-01-24

    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-h 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 13 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 cocaine

  20. 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

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

    PubMed

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

    2015-08-26

    The identification of early-stage breast cancer patients at high risk of relapse would allow tailoring of adjuvant therapy approaches. We assessed whether analysis of circulating tumor DNA (ctDNA) in plasma can be used to monitor for minimal residual disease (MRD) in breast cancer. In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment-either at a single postsurgical time point or with serial follow-up plasma samples-predicted metastatic relapse with high accuracy [hazard ratio, 25.1 (confidence interval, 4.08 to 130.5; log-rank P < 0.0001) or 12.0 (confidence interval, 3.36 to 43.07; log-rank P < 0.0001), respectively]. Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse. We further demonstrated that targeted capture sequencing analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. Mutation tracking can therefore identify early breast cancer patients at high risk of relapse. Subsequent adjuvant therapeutic interventions could be tailored to the genetic events present in the MRD, a therapeutic approach that could in part combat the challenge posed by intratumor genetic heterogeneity. PMID:26311728

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

    PubMed Central

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

    2015-01-01

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

  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. 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.  PMID:22211347

  6. Headache in relapse and remission phases of multiple sclerosis: A case-control study

    PubMed Central

    Togha, Mansoureh; Abbasi Khoshsirat, Nahid; Moghadasi, Abdorreza Naser; Mousavinia, Faezeh; Mozafari, Mohammad; Neishaboury, Mohamadreza; Mousavi, Seyed Mahmood

    2016-01-01

    Background: Headaches are one of the most frequent reasons for pain in multiple sclerosis (MS) individuals. Characterization of headaches and delineating possible relationships with MS-related determinants can ultimately circumvent headaches. Methods: In a prospective case-control study, 65 Iranian relapsing-remitting MS (RRMS) patients and 65 healthy controls were recruited during patients’ admission for attack-period treatment and asked about characteristics and co-symptoms of headaches they experienced in the preceding week and usage of disease modifying drugs (DMDs) and types of MS attacks were also inquired. The same questions were asked from the same patients 3 months later in a follow-up visit. Results: A total of 57 patients and 57 controls were included in the final analyses. In total, 26 (45.6%) patients in relapse, 18 (27.7%) controls, and 22 (38.6%) patients in remission reported headaches and only significant difference existed between relapse patients and controls (P = 0.036). In headache prevalence was higher in patients in relapse phase having MS < 3 years compared to relapse patients with more than 3 years of MS (68 vs. 28.1%; P = 0.004). Other variables of interest did not differ among the three groups. Conclusion: The RRMS patients in relapse phase suffer from headaches more than healthy people do. PMID:27141270

  7. GlpQ: an antigen for serological discrimination between relapsing fever and Lyme borreliosis.

    PubMed Central

    Schwan, T G; Schrumpf, M E; Hinnebusch, B J; Anderson, D E; Konkel, M E

    1996-01-01

    Tick-borne relapsing fever is caused by numerous Borrelia species maintained in nature by Ornithodoros tick-mammal cycles. Serological confirmation is based on either an immunofluorescence assay or an enzyme-linked immunosorbent assay using whole cells or sonicated Borrelia hermsii as the antigen. However, antigenic variability of this bacterium's outer surface proteins and antigens shared with the Lyme disease spirochete (B. burgdorferi), may cause both false-negative and false-positive results when testing sera of patients suspected to have either relapsing fever or Lyme disease. To develop a specific serological test for relapsing fever, we created a genomic DNA library of B. hermsii, screened transformed Escherichia coli cells for immunoreactivity with high-titered (> or = 1:2,048) human anti-B. hermsii antiserum, and selected an immunoreactive clone (pSPR75) expressing a 39-kDa protein. DNA sequencing, subcloning, and serum adsorption experiments identified the immunoreactive protein as a homolog of GlpQ, a glycerophosphodiester phosphodiesterase identified previously in E. coli, Haemophilus influenzae, and Bacillus subtilis. Serum samples from humans and mice infected with B. hermsii or other species of relapsing fever spirochetes contained antibodies recognizing GlpQ, whereas serum samples from Lyme disease and syphilis patients were nonreactive. Serologic tests based on this antigen will identify people exposed previously to relapsing fever spirochetes and help clarify the distribution of relapsing fever and Lyme disease in situations in which the occurrence of their causative agents is uncertain. PMID:8880505

  8. Multiple Sclerosis, Relapses, and the Mechanism of Action of Adrenocorticotropic Hormone

    PubMed Central

    Ross, Amy Perrin; Ben-Zacharia, Aliza; Harris, Colleen; Smrtka, Jennifer

    2013-01-01

    Relapses in multiple sclerosis (MS) are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the hypothalamic-pituitary-adrenal axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH) gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides [ACTH and α-, β-, γ-melanocyte-stimulating hormones (MSH)] and their receptors (Melanocortin receptors, MCRs) exert multiple actions, including modulation of inflammatory and immune mediator production. MCRs are widely distributed within the central nervous system and in peripheral tissues including immune cells (e.g., macrophages). This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management. PMID:23482896

  9. Testing Social Cognitive Theory as a theoretical framework to predict smoking relapse among daily smoking adolescents.

    PubMed

    Van Zundert, Rinka M P; Nijhof, Linda M; Engels, Rutger C M E

    2009-03-01

    Predictors of adolescent smoking relapse are largely unknown, since studies either focus on relapse among adults, or address (long-term) smoking cessation but not relapse. In the present study, Social Cognitive Theory (SCT) was used as a theoretical framework to examine the first and second lapses, as well as mild and heavy relapse into smoking among 135 daily smoking adolescents who embarked on a serious quit attempt. Baseline predictors were pros of smoking, pros of quitting, self-efficacy, and intensity of smoking. Using an ecological momentary assessment (EMA) study design, participants were monitored three times a day during 4 weeks. A follow-up was administered 2 months after the monitoring period. Perceiving many pros of smoking, reporting a low self-efficacy to quit, and high levels of baseline smoking significantly predicted relapse within 3 weeks after quitting. The effects of pros of smoking and self-efficacy on relapse, however, appeared to be accounted for by differences in intensity of smoking. Besides that pros of quitting showed a marginal effect on abstinence at the 2-month follow-up, no long-term effects were detected. PMID:19059732

  10. 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

  11. Implementation of the High-Risk Alcoholism Relapse Scale in a Liver Transplant Clinic.

    PubMed

    Zhou, Min; Wagner, Laura M; Diflo, Thomas; Naegle, Madeline

    2015-01-01

    Because of the high prevalence of alcohol relapse after liver transplantation, transplant programs are challenged to evaluate alcoholism among liver transplant patients. Relapse after liver transplantation can have detrimental outcomes such as organ rejection, medical and social resource exhaustion, financial burden to the family and society, and negative public perception of organ transplantation. The purpose of this project was to improve post-liver transplant assessment for the risk of relapse to heavy alcohol use by implementing a protocol using the High-Risk Alcoholism Relapse (HRAR) scale (DiMartini et al., 2000; Yates et al., 1993). The project was conducted in an urban organ transplant center's outpatient post liver transplant clinic. Chart reviews assessed the process of patients identified as being at high risk and the transplant providers' completion of the HRAR scale. Eleven percent of patients assessed were identified as being at high risk for relapse of heavy alcohol use and 85% of providers used the HRAR scale in their clinic interviews. This project demonstrates that further refinements in techniques of predicting the risks of relapse are necessary, and nurses are in ideal positions to screen patients for alcohol use. PMID:26626033

  12. Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.

    PubMed

    Nocentini, U; Pasqualetti, P; Bonavita, S; Buccafusca, M; De Caro, M F; Farina, D; Girlanda, P; Le Pira, F; Lugaresi, A; Quattrone, A; Reggio, A; Salemi, G; Savettieri, G; Tedeschi, G; Trojano, M; Valentino, P; Caltagirone, C

    2006-02-01

    Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients. PMID:16459723

  13. 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

  14. 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

  15. Heterogeneity in the therapeutic approach to relapsed elderly patients with acute myeloid leukaemia: a survey from the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Acute Leukaemia Working Party.

    PubMed

    Ferrara, Felicetto; Fazi, Paola; Venditti, Adriano; Pagano, Livio; Amadori, Sergio; Mandelli, Franco

    2008-06-01

    The percentage of long-term survivors in acute myeloid leukaemia (AML) in the elderly does not exceed 10-15% of patients enrolled into clinical trials because of lower complete remission (CR) rates and higher incidence of relapse. However, few data are available as the treatment of elderly patients with relapsed disease is concerned. The aim of this study was of collecting data on criteria adopted for the treatment of these patients. A questionnaire was e-mailed to 32 haematologic institutions involved in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group. Questions to be addressed regarded: (1) per cent of relapsed elderly patients treated with aggressive salvage chemotherapy; (2) the selection criteria adopted for inclusion into intensive reinduction; (3) the specific treatment adopted; (4) the treatment given to patients not eligible for intensive salvage. Per cent of patients enrolled into aggressive salvage regimens varied from 10 to 80% (median 50%). The most frequent factor influencing the therapeutic choice was performance status (97%). Additional factors were age >70 years (44%) and duration of first CR (53%). Fludarabine including regimens were most frequently used as aggressive salvage therapy (59%), while gemtuzumab ozogamicin was adopted in various combinations at 11 out of 32 institutions (34%). For patients not eligible to aggressive therapy, the most frequent approach included hydroxyurea (59%). Low dose ARA-C (LDARA-C) was adopted at five centres: as single agent (n = 1), with 6-thioguanine (n = 1), with vitamin D3 and all-trans retinoic acid (ATRA) (n = 2), or with ATRA alone (n = 1). The FLT3 inhibitor CEP-701 was used at one centre. We conclude that the treatment of AML in elderly relapsed patients is extremely heterogeneous. A marked selection is operated as to inclusion into aggressive salvage regimens and only a small minority of patients are offered experimental approaches. PMID:18271064

  16. 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

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

    PubMed Central

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

    2015-01-01

    High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18–30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone. PMID:25917266

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

    PubMed

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

    2015-08-01

    High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone. PMID:25917266

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-05-01

    In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. PMID:25828702

  1. 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.

  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. Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance

    PubMed Central

    Chung, Peter; Daugaard, Gedske; Tyldesley, Scott; Atenafu, Eshetu G; Panzarella, Tony; Kollmannsberger, Christian; Warde, Padraig

    2015-01-01

    A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1–10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making. PMID:25236854

  4. Diversity in relapse prevention needs: gender and race comparisons among substance abuse treatment patients.

    PubMed

    Walton, M A; Blow, F C; Booth, B M

    2001-05-01

    Attempts to address high relapse rates following substance abuse treatment have focused on identifying relapse prevention needs and development of subsequent relapse prevention programs. Few studies have examined whether women and African-Americans have unique relapse prevention needs. Research in this area could provide an initial basis for the development of alternative relapse prevention approaches that could be more appropriate for this pop ulation. This study examined gender and race differences in psychosocial concerns among patients recruited from substance abuse treatment as potential indicators of relapse prevention needs. Participants (N = 331) completed several questionnaires during their first month of substance abuse treatment. Assessment packets included measures of coping, self-efficacy, resource needs, cravings, social influences, exposure, and leisure activities. Analyses focused on gender and race differences in these variables before and after controlling for background characteristics (i.e., age, marital status, income, polysubstance use, treatment type, and problem severity). Gender differences found were that men reported poorer coping skills and more negative social influences and exposure to substances than women; these differences remained significant when controlling for background characteristics. Significant race differences were found on all scales except negative social influences. After controlling for background characteristics, African-Americans reported significantly greater coping skills and self-efficacy than did Caucasians; however, African-Americans also reported greater resource needs in comparison to Caucasians. Results highlight the diversity in psychosocial issues among substance abusers in treatment, particularly between Caucasians and African-Americans. Implications for developing alternative relapse prevention approaches to address this diversity are discussed. PMID:11417937

  5. 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

  6. 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

  7. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.

    PubMed

    Hutchinson, Michael; Kappos, Ludwig; Calabresi, Peter A; Confavreux, Christian; Giovannoni, Gavin; Galetta, Steven L; Havrdova, Eva; Lublin, Fred D; Miller, David H; O'Connor, Paul W; Phillips, J Theodore; Polman, Chris H; Radue, Ernst-Wilhelm; Rudick, Richard A; Stuart, William H; Wajgt, Andrzej; Weinstock-Guttman, Bianca; Wynn, Daniel R; Lynn, Frances; Panzara, Michael A

    2009-03-01

    The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease. PMID:19308305

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

    PubMed Central

    Fotso Fotso, Aurélien; Drancourt, Michel

    2015-01-01

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

  9. Predicting relapse of Graves' disease following treatment with antithyroid drugs

    PubMed Central

    LIU, LIN; LU, HONGWEN; LIU, YANG; LIU, CHANGSHAN; XUN, CHU

    2016-01-01

    The aim of the present study was to monitor long term antithyroid drug treatments and to identify prognostic factors for Graves' disease (GD). A total of 306 patients with GD who were referred to the Endocrinology Clinic at Weifang People's Hospital (Weifang, China) between August 2005 and June 2009 and treated with methimazole were included in the present study. Following treatment, patients were divided into non-remission, including recurrence and constant treatment subgroups, and remission groups. Various prognosis factors were analyzed and compared, including: Patient age, gender, size of thyroid prior to and following treatment, thyroid hormone levels, disease relapse, hypothyroidism and drug side-effects, and states of thyrotropin suppression were observed at 3, 6 and 12 months post-treatment. Sixty-five patients (21.2%) were male, and 241 patients (78.8%) were female. The mean age was 42±11 years, and the follow-up was 31.5±6.8 months. Following long-term treatment, 141 patients (46%) demonstrated remission of hyperthyroidism with a mean duration of 18.7±1.9 months. The average age at diagnosis was 45.6±10.3 years in the remission group, as compared with 36.4±8.8 years in the non-remission group (t=3.152; P=0.002). Free thyroxine (FT)3 levels were demonstrated to be 25.2±8.9 and 18.7±9.4 pmol/l in the non-remission and remission groups, respectively (t=3.326, P=0.001). The FT3/FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were both significantly higher in the non-remission group (t=3.331, 3.389, P=0.001), as compared with the remission group. Logistic regression analysis demonstrated that elevated thyroid size, FT3/FT4 ratio and TRAb at diagnosis were associated with poor outcomes. The ratio of continued thyrotropin suppression in the recurrent subgroup was significantly increased, as compared with the remission group (P=0.001), as thyroid function reached euthyroid state at 3, 6 and 12 months post-treatment. Patients with GD exhibiting

  10. Low-Dose Involved-Field Radiotherapy as Alternative Treatment of Nodular Lymphocyte Predominance Hodgkin's Lymphoma

    SciTech Connect

    Haas, Rick L.M. Girinsky, Theo; Aleman, Berthe; Henry-Amar, Michel; Boer, Jan-Paul de; Jong, Daphne de

    2009-07-15

    Purpose: Nodular lymphocyte predominance Hodgkin's lymphoma is a very rare disease, characterized by an indolent clinical course, with sometimes very late relapses occurring in a minority of all patients. Considerable discussion is ongoing on the treatment of primary and relapsed disease. Patients and Methods: A group of 9 patients were irradiated to a dose of 4 Gy on involved areas only. Results: After a median follow-up of 37 months (range, 6-66), the overall response rate was 89%. Six patients had complete remission (67%), two had partial remission (22%), and one had stable disease (11%). Of 8 patients, 5 developed local relapse 9-57 months after radiotherapy. No toxicity was noted. Conclusion: In nodular lymphocyte predominance Hodgkin's lymphoma, low-dose radiotherapy provided excellent response rates and lasting remissions without significant toxicity.

  11. Autologous tandem transplantation in patients with primary progressive or relapsed/refractory lymphoma.

    PubMed

    Glossmann, Jan-Peter; Staak, Jan Oliver; Nogova, Lucia; Diehl, Volker; Scheid, Christoph; Kisro, Jens; Reis, Hans-Edgar; Peter, Norma; Engert, Andreas; Josting, Andreas

    2005-08-01

    Patients with primary progressive or refractory Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL) have a particularly poor prognosis. Here we report the results of autologous tandem transplantation in these patients. Patients aged 18-55 years with primary progressive or refractory relapsed HD and aggressive NHL were included. Patients received high-dose etoposide (2000 mg/m(2)) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m(2)), mitoxantrone (40 mg/m(2)), and carboplatin (990 mg/m(2)). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m(2)), etoposide (1200 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)). Patients with bulky disease (>5 cm) or residual lymphoma received involved field radiotherapy. Twenty-five patients were included (HD=10, NHL=15, median age 34 years). Two patients with HD achieved a CR and five patients a PR [response rate (RR) 70%]. Three patients (30%) experienced treatment failure including two deaths due to peritransplant complications. Five patients with aggressive NHL were in CR and two patients in PR (RR 46%). Of the eight patients (56%) with treatment failure, three had progressive disease and five died from peritransplant complications. Freedom from treatment failure (FFTF) and overall survival (OS) for all patients after 12 months was 28% and 40%, respectively. Tandem HDCT followed by autologous stem cell transplantation (ASCT) offers a chance of cure in these poor prognostic patients, but is associated with risks. PMID:15759115

  12. 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

  13. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia

    PubMed Central

    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

    2015-01-01

    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 PMID:26001791

  14. UNRELATED DONOR REDUCED INTENSITY ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR RELAPSED AND REFRACTORY HODGKIN LYMPHOMA

    PubMed Central

    Devetten, Marcel P.; Hari, Parameswaran N.; Carreras, Jeanette; Logan, Brent R.; van Besien, Koen; Bredeson, Christopher N.; Freytes, César O.; Peter Gale, Robert; Gibson, John; Giralt, Sergio A.; Goldstein, Steven C.; Gupta, Vikas; Marks, David I.; Maziarz, Richard T.; Vose, Julie M.; Lazarus, Hillard M.; Anderlini, Paolo

    2010-01-01

    Myeloablative allogeneic hematopoietic cell transplantation (HCT) may cure patients with relapsed or refractory Hodgkin Lymphoma (HL), but is associated with a high treatment-related mortality (TRM). Reduced intensity and nonmyeloablative (RIC/NST) conditioning regimens aim to lower TRM. We analyzed the outcomes of 143 patients undergoing unrelated donor RIC/NST HCT for relapsed and refractory HL between 1999 and 2004 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients were heavily pretreated, including autologous HCT in 89%. With a median follow-up of 25 months, the probability of TRM at day 100 and 2 years was 15% (95% CI 10-21%) and 33% (95% CI 25-41%) respectively. The probabilities of progression free survival (PFS) and overall survival (OS) were 30% and 56% at 1 year and 20% and 37% at 2 years. The presence of extranodal disease and KPS < 90 were significant risk factors for TRM, PFS and OS, whereas chemosensitivity at transplantation was not. Dose intensity of the conditioning regimen (RIC vs NST) did not impact outcomes. Unrelated donor HCT with RIC/NST can salvage some patients with relapsed/refractory HL, but relapse remains a common reason for treatment failure. Clinical studies should be aimed at reducing the incidence of acute Graft-versus-Host Disease and relapse. PMID:19135949

  15. 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

  16. Posterior Reversible Encephalopathy Syndrome due to High Dose Corticosteroids for an MS Relapse.

    PubMed

    Morrow, Sarah A; Rana, Robina; Lee, Donald; Paul, Terri; Mahon, Jeffrey L

    2015-01-01

    Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse. PMID:26101676

  17. Plasmapheresis and immunoadsorption in patients with steroid refractory multiple sclerosis relapses.

    PubMed

    Faissner, Simon; Nikolayczik, Johanna; Chan, Andrew; Hellwig, Kerstin; Gold, Ralf; Yoon, Min-Suk; Haghikia, Aiden

    2016-06-01

    Patients suffering from multiple sclerosis (MS) are treated with high-dose intravenous steroids during acute relapses. In case of steroid refractory relapses, patients are treated with plasmapheresis or immunoadsorption. Until now data concerning the efficacy of both procedures are scarce. Visual evoked potentials (VEP), visual acuity and degree of remission of deficits caused by a relapse that had led to admission in MS patients (n = 48) treated with PLEX, IA or both in a single university centre setting were evaluated retrospectively. In a grouped analysis of patients treated with combined PLEX/IA, PLEX or IA alone, patients in all groups profited as assessed by VEP. Visual acuity also showed a trend towards a better performance, but lacked significance. In a subgroup analysis only concerning patients with initially pathological VEP there was a significant beneficial effect in the groups treated with PLEX/IA as well as in the group summarizing all patients. The combination of PLEX and IA provides a valid treatment option in steroid-refractory MS-relapses, and IA should be considered in acute relapses especially in patients with side effect of PLEX. PMID:27039388

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

    PubMed

    Dimidjian, Sona; Goodman, Sherryl H

    2014-03-01

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

  19. 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

  20. HLA mismatching as a strategy to reduce relapse after alternative donor transplantation.

    PubMed

    Fleischhauer, Katharina; Beelen, Dietrich W

    2016-04-01

    Human leukocyte antigen (HLA) mismatches are targets of alloreactive T cells, mediators of graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) after alternative donor transplantation. Exploitation of HLA mismatching in order to reduce relapse is hampered by necessary interventions aimed at controlling GvHD on the one hand, and by the possibility of immune escape through selective loss of mismatched HLA in relapsing leukemia on the other. Retrospective studies reporting the impact of HLA mismatches on post-transplant relapse need to be interpreted with caution, due to many confounding factors, including disease and use of T-cell depletion, and to be constantly updated to the rapidly changing clinical protocols. Current evidence suggests similar relapse rates for 8/8, 7/8 HLA-matched unrelated, T-cell-replete haploidentical and umbilical cord blood transplantation; however, investigations of locus-specific effects are still scarce in the latter two settings. In unrelated transplantation, a specific role for mismatches at HLA-C and HLA-DPB1, and therein of permissive mismatches defined on the basis of T-cell alloreactivity and/or expression levels, in reducing relapse has been demonstrated in independent studies. This observation suggests new approaches to utilize HLA matching in unrelated donor searches, and the need for further research in the field. PMID:27000727

  1. Serum uric acid level in patients with relapsing-remitting multiple sclerosis.

    PubMed

    Ashtari, Fereshteh; Bahar, Mohammadali; Aghaei, Maryam; Zahed, Arash

    2013-05-01

    Uric acid (UA) is a hydrophilic antioxidant product associated with multiple sclerosis (MS). We conducted a randomized case-control study to evaluate the serum level of UA in different phases of MS in comparison with levels in a healthy control population. Serum UA was checked in 130 patients with relapsing-remitting MS (85 patients in remitting and 45 patients in relapsing phase) and 50 age-matched controls using a quantitative enzyme-linked immunosorbent assay (ELISA). The mean concentrations of UA in serum was 6.41(±3.18)mg/dL in patients with remitting MS, 4.76(±1.66)mg/dL in patients with relapsing MS and 6.33(±2.94)mg/dL in controls. There was a significant difference between mean UA concentration in relapsing MS and remitting MS (p<0.001), and between patients with relapsing MS and controls (p=0.002); however, the difference between levels for patients in the remitting phase of MS and the control group was not significant (p=0.87). It seems probable that UA has a role in the prevention of disease activity in MS. PMID:23528410

  2. ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases.

    PubMed

    Aoe, Michinori; Shimada, Akira; Muraoka, Michiko; Washio, Kana; Nakamura, Yoshimi; Takahashi, Takahide; Imada, Masahide; Watanabe, Toshiyuki; Okada, Ken; Nishiuchi, Ritsuo; Miyamura, Takako; Chayama, Kosuke; Shibakura, Misako; Oda, Megumi; Morishima, Tsuneo

    2014-01-01

    The tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) revolutionized the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL), which had showed poor prognosis before the dawn of IM treatment. However, if Ph-ALL patients showed IM resistance due to ABL kinase mutation, second-generation TKI, dasatinib or nilotinib, was recommended. We treated 4 pediatric Ph-ALL patients with both IM and bone marrow transplantation (BMT); however, 3 relapsed. We retrospectively examined the existence of ABL kinase mutation using PCR and direct sequencing methods, but there was no such mutation in all 4 diagnostic samples. Interestingly, two relapsed samples from patients who were not treated with IM before relapse did not show ABL kinase mutation and IM was still effective even after relapse. On the other hand, one patient who showed resistance to 3 TKI acquired dual ABL kinase mutations, F359C at the IM-resistant phase and F317I at the dasatinib-resistant phase, simultaneously. In summary, Ph-ALL patients relapsed with or without ABL kinase mutation. Furthermore, ABL kinase mutation was only found after IM treatment, so an IM-resistant clone might have been selected during the IM treatment and intensive chemotherapy. The appropriate combination of TKI and BMT must be discussed to cure Ph-ALL patients. PMID:24652384

  3. 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

  4. Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation.

    PubMed

    Solh, M; Zhang, X; Connor, K; Brown, S; Solomon, S R; Morris, L E; Holland, H K; Bashey, A

    2016-07-01

    Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post-relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N=48), MUDT (N=87) and MRDT (N=102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P=0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P<0.05). In a multivariate analysis, time to relapse (<3 vs >3 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival. PMID:26999464

  5. 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

  6. 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

  7. Update on Salvage Options in Relapsed/Refractory Hodgkin Lymphoma after Autotransplant

    PubMed Central

    Kumar, Lalit; Iqbal, Naveed

    2014-01-01

    Despite a high clinical success, relapse in Hodgkin lymphoma occurs in 10–30% of cases and 5–10% patients are nonresponsive to initial chemotherapy. The standard management of these patients includes high-dose chemotherapy followed by autologous stem cell transplant. However, 50% of patients ultimately relapse after autotransplant which poses a big challenge. Allogeneic stem cell transplantation offers the only chance of cure in these patients. For patients who are not candidates for allogeneic stem cell transplantation, achieving cure with other possible options is highly unlikely, and thus the treatment plan becomes noncurative. Various novel agents have shown promising results but the duration of response is short lived. A standard approach to deliver the most effective treatment for these patients is still lacking. This review focuses on the treatment options currently available for relapsed and refractory disease after autotransplant. PMID:25006506

  8. 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

  9. 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

  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. Complications of pregnancy and transplacental transmission of relapsing-fever borreliosis.

    PubMed

    Larsson, Christer; Andersson, Marie; Guo, Betty P; Nordstrand, Annika; Hagerstrand, Inga; Carlsson, Sara; Bergstrom, Sven

    2006-11-15

    Relapsing-fever borreliosis caused by Borrelia duttonii is a common cause of complications of pregnancy, miscarriage, and neonatal death in sub-Saharan Africa. We established a murine model of gestational relapsing fever infection for the study of the pathological development of these complications. We demonstrate that B. duttonii infection during pregnancy results in intrauterine growth retardation, as well as placental damage and inflammation, impaired fetal circulation, and decreased maternal hemoglobin levels. We show that spirochetes frequently cross the maternal-fetal barrier, resulting in congenital infection. Furthermore, we compared the severity of infection in pregnant and nonpregnant mice and show that pregnancy has a protective effect. This model closely parallels the consequences of human gestational infection, and our results provide insight into the mechanisms behind the complications of pregnancy that have been reported in human relapsing-fever infection. PMID:17054065

  12. On statistical relationship between ADRA2A expression and the risk of breast cancer relapse.

    PubMed

    Shkurnikov, M Yu; Galatenko, V V; Lebedev, A E; Podol'skii, V E; Tonevitskii, E A; Mal'tseva, D V

    2014-08-01

    The search for novel parameters to predict the risk of relapse in breast cancer was conducted. Significant correlation between the risk of relapse and α-2A adrenergic receptor (ADRA2A) expression was revealed using public microarray datasets. This relationship was confirmed by validation on independent microarray dataset. It was found that when assessing the risk of BC relapse, the accuracy of prediction based solely on the expression of ADRA2A gene is close to that made using OncotypeDX and MammaPrint test systems. In this case, addition of only one or two supplemental prognostic markers (for instance, expression of SQLE gene or SQLE and DSCC1genes) to ADRA2A ensures the accuracy of prediction not inferior to reliability of these test systems. PMID:25110082

  13. 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

  14. Multiple myeloma: Updates for pharmacists in the treatment of relapsed and refractory disease.

    PubMed

    Ashjian, Emily; Redic, Kimberly

    2016-04-01

    There have been a number of recent advances in the treatment of patients with relapsed and refractory multiple myeloma. However, despite additional FDA-approved therapies including carfilzomib and pomalidomide as well as clinical trials investigating new combinations of existing treatments, multiple myeloma remains an incurable disease. New therapies currently in the drug development pipeline for relapsed and refractory disease include additional proteasome inhibitors (oprozomib, marizomib, ixazomib), histone deacetylase inhibitors (panobinostat, ricolinostat, quisinostat), monoclonal antibodies (daratumumab, elotuzumab, SAR650984), Bruton's tyrosine kinase inhibitors (ibrutinib), a selective inhibitor of nuclear export, and others. This review will focus on these newly developing therapies as well as the ever expanding role of the pharmacist in supportive care for patients with relapsed and refractory multiple myeloma. PMID:25694345

  15. Overlooking Evolution: A Systematic Analysis of Cancer Relapse and Therapeutic Resistance Research

    PubMed Central

    Aktipis, C. Athena; Kwan, Virginia S. Y.; Johnson, Kathryn A.; Neuberg, Steven L.; Maley, Carlo C.

    2011-01-01

    Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms in abstracts has remained at about 1% since the 1980s. However, detailed coding of 22 recent papers revealed a higher proportion of papers using evolutionary methods or evolutionary theory, although this number is still less than 10%. Despite the fact that relapse and therapeutic resistance is essentially an evolutionary process, it appears that this framework has not permeated research. This represents an unrealized opportunity for advances in research on therapeutic resistance. PMID:22125594

  16. Acthar gel treatment suppresses acute exacerbations in a murine model of relapsing-remitting multiple sclerosis.

    PubMed

    Cusick, Matthew F; Libbey, Jane E; Oh, Luke; Jordan, Shaun; Fujinami, Robert S

    2015-06-01

    Acthar gel is indicated for the treatment of acute exacerbations of multiple sclerosis (MS) in adults. Its effects on immune cells during a relapse are unknown. This study investigated the effects of Acthar in an animal model of relapsing-remitting MS, using SJL/J mice sensitized with myelin peptide. All animal studies were reviewed and approved by the University of Utah Institutional Animal Care and Use Committee and conducted in accordance with the guidelines prepared by the Committee on Care and Use of Laboratory Animals, Institute of Laboratory Animals Resources, National Research Council. Mice injected with Acthar to treat the second attack had a significantly lower mean clinical score during relapse and a significantly reduced cumulative disease burden compared to Placebo gel-treated mice. Furthermore, Acthar treatment ameliorated inflammation/demyelination in the spinal cord and markedly suppressed ex vivo myelin peptide-induced CD4(+) T cell proliferation. PMID:25410153

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

    PubMed

    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

  18. 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

  19. A Simple PSA-Based Computational Approach Predicts the Timing of Cancer Relapse in Prostatectomized Patients.

    PubMed

    Stura, Ilaria; Gabriele, Domenico; Guiot, Caterina

    2016-09-01

    Recurrences of prostate cancer affect approximately one quarter of patients who have undergone radical prostatectomy. Reliable factors to predict time to relapse in specific individuals are lacking. Here, we present a mathematical model that evaluates a biologically sensible parameter (α) that can be estimated by the available follow-up data, in particular by the PSA series. This parameter is robust and highly predictive for the time to relapse, also after administration of adjuvant androgen deprivation therapies. We present a practical computational method based on the collection of only four postsurgical PSA values. This study offers a simple tool to predict prostate cancer relapse. Cancer Res; 76(17); 4941-7. ©2016 AACR. PMID:27587651

  20. Relapsing peritonitis with Bacillus cereus in a patient on continuous ambulatory peritoneal dialysis.

    PubMed

    Magnussen, Eyð Tausen; Vang, Amanda Gratton; Á Steig, Torkil; Gaini, Shahin

    2016-01-01

    We present a case where Bacillus cereus was determined to be the causative agent of relapsing peritonitis in a patient on continuous ambulatory peritoneal dialysis (CAPD). The patient, a 70-year-old man from the Faroe Islands, was admitted with relapsing peritonitis four times over a 3-month period. Peritoneal cultures were positive for growth of B. cereus, a rare bacterial cause of peritonitis. The cultures demonstrated susceptibility to vancomycin, and therefore the patient was treated with intraperitoneal vancomycin, intraperitoneal gentamycin and oral ciprofloxacin. As a result of the relapsing B. cereus peritonitis diagnosis and a CT scan showing contraction of the peritoneum after longstanding inflammation, the peritoneal catheter was removed and the patient converted to haemodialysis. To date, the patient has not been readmitted due to peritonitis. A lack of proper hygiene when changing the dialysis bag was the suspected source of infection with B. cereus. PMID:27118739

  1. Remission With Donor Lymphocyte Infusion in a Child With Marrow Relapse After Haploidentical Stem Cell Transplantation for Relapsed Stage 4 Neuroblastoma.

    PubMed

    Liu, A P Y; Leung, R Y Y; Cheuk, K L; Lee, P P W; Chiang, A K S; Ha, S Y; Chan, G C F

    2016-08-01

    A 7-year-old male with Stage 4 neuroblastoma was treated with chemotherapy and autologous hematopoietic stem cell transplantation (HSCT), resulting in partial response with residual bone and marrow disease. He proceeded to haploidentical-HSCT with his mother as donor and achieved remission. The patient developed marrow relapse 2 years after haploidentical-HSCT with cytopenia and dropping donor chimerism. Donor lymphocyte infusion (DLI) using mother's whole blood was given resulting in clearance of marrow disease, resolution of cytopenia, and full donor chimerism. This is the first report of successful treatment for neuroblastoma relapse after haploidentical-HSCT using DLI alone, supporting the role of adoptive cell therapy post-HSCT in neuroblastoma. PMID:27100283

  2. Predictors of Smoking Relapse in Patients with Thoracic Cancer or Head and Neck Cancer

    PubMed Central

    Simmons, Vani Nath; Litvin, Erika B.; Jacobsen, Paul B.; Patel, Riddhi D.; McCaffrey, Judith C.; Oliver, Jason A.; Sutton, Steven K.; Brandon, Thomas H.

    2012-01-01

    Background Cancer patients who continue smoking are at increased risk for adverse outcomes including reduced treatment efficacy and poorer survival rates. Many patients spontaneously quit smoking after diagnosis; however, relapse is understudied. The goal of this study was to evaluate smoking-related, affective, cognitive, and physical variables as predictors of smoking after surgical treatment among lung and head/neck cancer patients. Methods A longitudinal study was conducted with 154 patients (57% male) who recently quit smoking. Predictor variables were measured at baseline (i.e., time of surgery); smoking behavior was assessed at 2, 4, 6, and 12 months post-surgery. Analyses of 7-day point prevalence were performed using a Generalized Estimating Equations (GEE) approach. Results Relapse rates varied significantly depending on pre-surgery smoking status. At 12-months post-surgery, 60% of patients who smoked during the week prior to surgery had resumed smoking, versus only 13% who were abstinent prior to surgery. Smoking rates among both groups were relatively stable across the 4 follow-ups. For patients smoking pre-surgery (N = 101), predictors of smoking relapse included lower quitting self-efficacy, higher depression proneness, and greater fears about cancer recurrence. For patients abstinent pre-surgery (N = 53), higher perceived difficulty quitting and lower cancer-related risk perceptions predicted smoking relapse. Conclusion Efforts to encourage early cessation at diagnosis, and increased smoking relapse-prevention efforts in the acute period following surgery, may promote long-term abstinence. Several modifiable variables are identified to target in future smoking relapse-prevention interventions for cancer patients. PMID:23280005

  3. High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.

    PubMed

    Aurer, Igor; Nemet, Damir; Mitrović, Zdravko; Dujmović, Dino; Bašić-Kinda, Sandra; Radman, Ivo; Sertić, Dubravka; Šantek, Fedor; Kralik, Marko; Dotlić, Snježana; Mazić, Sanja; Labar, Boris

    2016-06-01

    Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options. PMID:27103009

  4. 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

  5. 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…

  6. Cue exposure and relapse prevention in the treatment of addictive behaviors.

    PubMed

    Marlatt, G A

    1990-01-01

    Cue exposure techniques have been increasingly applied in the treatment of addictive behaviors. The role of cue exposure in a comprehensive approach to relapse prevention is considered from several theoretical perspectives. Issues discussed include the optimal definition of both cue and response variables in cue exposure, the relation between exposure to drug-taking cues and elicitation of outcome expectancies, and the combination of extinction-based cue exposure methods and skill training in relapse prevention programs. Whether cue exposure effects are mediated by extinction of appetitive craving responses and/or by the modification of efficacy and outcome expectancies is discussed. PMID:2248112

  7. 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

  8. Cryptococcal meningoencephalitis relapse after an eight-year delay: an interplay of infection and immune reconstitution.

    PubMed

    Katchanov, Juri; Blechschmidt, Cristiane; Nielsen, Kirsten; Branding, Gordian; Arastéh, Keikawus; Tintelnot, Kathrin; Meintjes, Graeme; Boulware, David R; Stocker, Hartmut

    2015-10-01

    We report a case of a symptomatic relapse of HIV-related cryptococcal meningoencephalitis eight years after the first diagnosis on the background of immune reconstitution. The findings as well as the clinical course suggests a combination of smouldering localised infection and enhanced inflammatory reaction related to immune restoration due to antiretroviral therapy. A combination of antifungal and anti-inflammatory therapy resulted in clinical and radiological improvement. Our case challenges the concept that immune reconstitution inflammatory syndrome and microbiological relapse are dichotomous entities. PMID:25505049

  9. Baseline Stage, Severity, and Effort Effects Differentiate Stable Smokers from Maintainers and Relapsers

    PubMed Central

    Redding, Colleen A.; Prochaska, James O.; Paiva, Andrea; Rossi, Joseph S.; Velicer, Wayne; Blissmer, Bryan J.; Greene, Geoffrey W.; Robbins, Mark L.; Sun, Xiaowu

    2011-01-01

    This cross-sectional study (N = 4,144) compared three longitudinal dynatypes (Maintainers, Relapsers, and Stable Smokers) of smokers on baseline demographics, stage, addiction severity, and transtheoretical model effort effect variables. There were significant small-to-medium-sized differences between the Stable Smokers and the other two groups on stage, severity, and effort effect variables in both treatment and control groups. There were few significant, very small differences on baseline effort variables between Maintainers and Relapsers in the control, but not the treatment group. The ability to identify Stable Smokers at baseline could permit enhanced tailored treatments that could improve population cessation rates. PMID:21449711

  10. Hematologic Response to Vorinostat Treatment in Relapsed Myeloid Leukemia of Down Syndrome.

    PubMed

    Scheer, Carina; Kratz, Christian; Witt, Olaf; Creutzig, Ursula; Reinhardt, Dirk; Klusmann, Jan-Henning

    2016-09-01

    Children with Down syndrome are at high risk to develop myeloid leukemia (ML-DS). Despite their excellent prognosis, children with ML-DS particularly suffer from severe therapy-related toxicities and for relapsed ML-DS the cure rates are very poor. Here we report the clinical course of one child with ML-DS treated with the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid) after second relapse. The child had previously received conventional chemotherapy and stem cell transplantation, yet showed a remarkable clinical and hematologic response. Thus, HDAC inhibitor may represent an effective class of drugs for the treatment of ML-DS. PMID:27191354

  11. Successful adoptive immunotherapy for relapse of AML 9 years after T-cell-depleted BMT.

    PubMed

    Bertz, H; Kunzman, R; Bunjes, D; Finke, J

    1998-11-01

    Relapse is one of the main problems which can occur following allogeneic transplantation for haematological malignancies. In this situation the enhancement of the graft-versus-leukaemia effect by transfusion of donor buffy coats with or without cytokines may lead to complete remission especially in myeloid leukaemias. FISH (fluorescence in situ hybridization) is a sensitive method to monitor chimaerism in gender-different transplantation. We report a case of successful buffy coat transfer therapy > 9 years after bone marrow transplantation. This is the longest interval reported, to our knowledge, between transplantation to relapse, which was treated by adoptive immunotherapy. Complete donor chimaerism was confirmed by FISH. PMID:9827936

  12. Radical Resection of a Late-Relapsed Testicular Germ Cell Tumour: Hepatectomy, Cavotomy, and Thrombectomy

    PubMed Central

    Ní Leidhin, C.; Redmond, C. E.; Cahalane, A. M.; Heneghan, H. M.; Motyer, R.; Ryan, E. R.; Hoti, E.

    2014-01-01

    Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation. PMID:25587480

  13. Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy, cavotomy, and thrombectomy.

    PubMed

    Ní Leidhin, C; Redmond, C E; Cahalane, A M; Heneghan, H M; Motyer, R; Ryan, E R; Hoti, E

    2014-01-01

    Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation. PMID:25587480

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

    PubMed

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

    1991-02-01

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

  15. Clofarabine-based combination chemotherapy for relapse and refractory childhood acute lymphoblastic leukemia.

    PubMed

    Arakawa, Yuki; Koh, Katsuyoshi; Aoki, Takahiro; Kubota, Yasuo; Oyama, Ryo; Mori, Makiko; Hayashi, Mayumi; Hanada, Ryoji

    2014-11-01

    Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required. PMID:25501414

  16. Analyzing diaries for analytical relapse prevention using natural induction: a method and preliminary results.

    PubMed

    Wojtusiak, Janusz; Michalski, Ryszard S

    2008-01-01

    This article briefly describes natural induction approach to knowledge discovery, and then applies it to the problem of bad habit relapse prevention by analyzing patients' diaries. Natural induction seeks patterns in data that are in forms easy to understand and interpret, because they resemble those in which humans represent knowledge, such as natural language descriptions and visual forms. The application of natural induction to the problem of bad habit relapse has produced patterns easy to understand, in some cases of surprising simplicity. PMID:18204380

  17. An international, multicenter, prospective, observational study of neutropenia in patients being treated with lenalidomide + dexamethasone for relapsed or relapsed/refractory multiple myeloma (RR-MM).

    PubMed

    Leleu, Xavier; Terpos, Evangelos; Sanz, Ramón García; Cooney, Julian; O'Gorman, Peter; Minarik, Jiri; Greil, Richard; Williams, Catherine; Gray, Diep; Szabo, Zsolt

    2016-08-01

    Neutropenia is a well-known dose-limiting toxicity associated with lenalidomide plus dexamethasone treatment in patients with multiple myeloma; however, little is known about its management and associated outcomes in the real world setting. The present prospective, multicenter, observational study evaluated the incidence, management, and outcomes of grade 3/4 neutropenia in patients with relapsed or relapsed/refractory multiple myeloma who initiated treatment with lenalidomide plus dexamethasone. Of 198 patients, 62 (31%, 95% CI: 25, 38) experienced grade 3/4 neutropenia, and half of these patients experienced 3 or more events during the 12-month observational period. Grade 3/4 neutropenia occurred throughout lenalidomide treatment, with a median time to first event of 8.8 weeks (Q1, Q3: 5.9, 17.3). In a multivariate analysis, diagnosis of relapsed and refractory disease was associated with grade 3/4 neutropenia. Lenalidomide exposure reduction, use of G-CSF, unplanned hospitalization, and outpatient clinic visits were more common in patients who experienced grade 3/4 neutropenia than in those who did not. In conclusion, grade 3/4 neutropenia is a common toxicity and patients are at continued risk throughout treatment with lenalidomide and dexamethasone. Further efforts should be made to improve the recommendations for neutropenia management in this population. Am. J. Hematol. 91:806-811, 2016. © 2016 Wiley Periodicals, Inc. PMID:27169523

  18. 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

  19. Biotherapies in large vessel vasculitis.

    PubMed

    Ferfar, Y; Mirault, T; Desbois, A C; Comarmond, C; Messas, E; Savey, L; Domont, F; Cacoub, P; Saadoun, D

    2016-06-01

    Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV. PMID:26883459

  20. Current imaging follow-up of non-Hodgkin lymphoma exposes patients to significant radiation but does not detect asymptomatic relapses.

    PubMed

    Riva, Eloisa; Oliver, Carolina; Pérez, Maria Del Carmen; Telis, Osmar; Díaz, Lilian; Mikhael, Joseph R

    2016-06-01

    The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6-12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL. PMID:26374395

  1. miR-27a and miR-214 exert opposite regulatory roles in Th17 differentiation via mediating different signaling pathways in peripheral blood CD4+ T lymphocytes of patients with relapsing-remitting multiple sclerosis.

    PubMed

    Ahmadian-Elmi, Maryam; Bidmeshki Pour, Ali; Naghavian, Reza; Ghaedi, Kamran; Tanhaei, Somayeh; Izadi, Tayebeh; Nasr-Esfahani, Mohammad Hossein

    2016-01-01

    Multiple sclerosis (MS) is one of the most prevalent autoimmune diseases, which involves the central nervous system. In this illness, Treg/Th17 cell imbalance causes the defect. Several studies revealed that T helper 17 (Th17) cells play a crucial role in pathogenesis, inflammation, and autoimmunity of several autoimmune diseases such as MS. In the present study, we assessed transcript levels of miR-27a and miR-214, in purified CD4+ T cells of MS patients, during relapsing and remitting phases in inducing differentiation of T naïve cells to Th17 cells. Forty RR-MS patient samples including those in relapsing (n=20) and remitting (n=20) phases were participated in this study. In addition, transcript levels of IL-17A, RORγt, IL-23R, Foxp3, and TGF-β in purified CD4+ T cells of patients in relapsing and remitting phases of RRMS patients were compared to healthy controls. Expression levels of miR-27a and miR-214 were measured by RT-qPCR and compared to healthy control group (n=10). Data indicated upregulation of miR27a in relapsing phase of multiple sclerosis compared to remitting phase and healthy volunteers while miR-214 downregulated in relapsing phase of MS compared to remitting phase and healthy volunteers. In silico studies demonstrated pathways which miR-27a and miR-214 could effect on CD4+ T cell lineage fate including TGF-β and mTOR signaling, respectively. Our data suggest that miR-27a may probably inhibit negative regulators of Th17 cell differentiation, thus promoting its differentiation while miR-214 has an adverse effect. PMID:26563334

  2. 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…

  3. Re-Training the Addicted Brain: A Review of Hypothesized Neurobiological Mechanisms of Mindfulness-Based Relapse Prevention

    PubMed Central

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

    2013-01-01

    Addiction has generally been characterized as a chronic relapsing condition. Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, Mindfulness-Based Relapse Prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting “automatically.” A recent efficacy trial found that those randomized to MBRP, as compared to those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. Importantly, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive behavior relapse. PMID:22775773

  4. Reducing Relapse and Recurrence in Unipolar Depression: A Comparative Meta-Analysis of Cognitive-Behavioral Therapy's Effects

    ERIC Educational Resources Information Center

    Vittengl, Jeffrey R.; Clark, Lee Anna; Dunn, Todd W.; Jarrett, Robin B.

    2007-01-01

    Relapse and recurrence following response to acute-phase treatment for major depressive disorder (MDD) are prevalent and costly. In a meta-analysis of 28 studies including 1,880 adults, the authors reviewed the world's published literature on cognitive-behavioral therapies (CT) aimed at preventing relapse-recurrence in MDD. Results indicate that…

  5. 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"…

  6. 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…

  7. Predictors of Initial Smoking Cessation and Relapse through the First 2 Years of the Lung Health Study.

    ERIC Educational Resources Information Center

    Nides, Mitchell; And Others

    1995-01-01

    Analyzed predictors of end-of-treatment (4 months) smoking cessation and subsequent relapse at 12 and 24 months among 3,923 participants enrolled in a 12-week cognitive-behavioral group smoking-cessation program. Men were more likely than women to quit smoking initially, but relapse rates were similar for both genders. Clinical implications are…

  8. Do animal models provide a valid analogue for human drug lapse and relapse? Comment on Leri and Stewart (2002).

    PubMed

    Marlatt, G Alan

    2002-11-01

    Prior research on animal models of drug relapse has demonstrated that passive exposure to an addictive substance following acquisition and extinction of drug self-administration has a "priming effect" on subsequent drug use. The validity of this animal analogue of human relapse can be criticized, however, because most human drug relapses are precipitated by the user's voluntary self-administration of a substance. The results of the present study by F. Leri and J. Stewart (2002) clearly show that if the initial heroin lapse is self-administered by rats, subsequent heroin seeking during the relapse test is significantly greater than if the heroin is externally administered. These results help bridge the gap between animal and human models of drug use and highlight the significance of both behavioral and environmental determinants of relapse. PMID:12498331

  9. A clofarabine-based bridging regimen in patients with relapsed ALL and persistent minimal residual disease (MRD).

    PubMed

    Gossai, N; Verneris, M R; Karras, N A; Gorman, M F; Patel, N J; Burke, M J

    2014-03-01

    In patients with relapsed ALL, minimal residual disease (MRD) identified prior to allogeneic hematopoietic cell transplantation (HCT) is a strong predictor of relapse. We report our experience using a combination of reduced-dosing clofarabine, CY and etoposide as a 'bridge' to HCT in eight patients with high risk or relapsed ALL and pre-HCT MRD. All patients had detectable MRD (>0.01%, flow cytometry) at the start of therapy with all eight achieving MRD reduction following one cycle. The regimen was well tolerated with seven grade 3/4 toxicities occurring among four of the eight patients. Five patients (62.5%) are alive, one died from relapse (12.5%) and two from transplant-related mortality (25%). The combination of reduced-dose clofarabine, CY and etoposide as bridging therapy appears to be well tolerated in patients with relapsed ALL and is effective in reducing pre-HCT MRD. PMID:24317126

  10. Successful treatment of ctx-m ESBL producing Escherichia coli relapsing pyelonephritis with long term pivmecillinam.

    PubMed

    Nicolle, Lindsay E; Mulvey, Michael R

    2007-01-01

    Oral therapy options for pyelonephritis caused by ESBL producing E. coli are limited. We describe a woman with relapsing pyelonephritis due to a CTX-M ESBL E. coli who was cured with a prolonged course of pivmecillinam. This suggests pivmecillinam may be effective treatment for selected patients with pyelonephritis with these organisms. PMID:17654359

  11. Schizophrenia relapse after stopping olanzapine treatment during pregnancy: a case report

    PubMed Central

    Ifteni, Petru; Moga, Marius A; Burtea, Victoria; Correll, Christoph U

    2014-01-01

    Women with schizophrenia have a high risk for symptom exacerbation or relapse during pregnancy and thereafter. Relapses are more frequent when antipsychotics are discontinued. This paper describes the case of a 28-year old woman with schizophrenia who continued treatment with olanzapine during the first trimester. Olanzapine, a second-generation antipsychotic, was administered at a therapeutic dose from week 1 of gestation until week 13 when she reported the pregnancy to her psychiatrist. Despite the psychiatrist’s recommendation to continue treatment, the patient stopped olanzapine at 20 weeks. She was hospitalized at week 36 for a schizophrenia relapse and was transferred to the obstetrics department where she gave birth by Cesarean section to a normal child. This case is important, illustrating the perils of unplanned pregnancy during antipsychotic treatment and abrupt discontinuation. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother in terms of symptom exacerbation and relapse if antipsychotic treatment is discontinued, and the potential risk to the fetus regarding possible teratogenic effects of continued antipsychotic treatment. PMID:25364259

  12. 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

  13. Meningitis following relapsing painful ophthalmoplegia in aspergillus sphenoidal sinusitis: a case report.

    PubMed

    Botturi, A; Salmaggi, A; Pollo, B; Lamperti, E; Erbetta, A; Boiardi, A

    2006-09-01

    We report the case of a 58-year-old woman in whom relapsing painful ophthalmoplegia related to a mycetoma of the sphenoid sinus gave origin to meningitis with markedly depressed glucose levels in the cerebrospinal fluid. Surgical exeresis of the mycetoma allowed aetiological diagnosis (aspergillosis) and--together with antimycotic therapy--led to durable clinical response. PMID:16998735

  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. Sudden Gains in Cognitive Therapy of Depression and Depression Relapse/Recurrence

    ERIC Educational Resources Information Center

    Tang, Tony Z.; DeRubeis, Robert J.; Hollon, Steven D.; Amsterdam, Jay; Shelton, Richard

    2007-01-01

    Cognitive therapy (CT) may have significant advantages over antidepressants in preventing depression relapses. Many CT patients experience sudden gains: large symptom improvement in 1 between-session interval. Past studies have associated CT sudden gains with in-session cognitive changes but not with life events. This study examined sudden gains…

  16. Chronic myeloid leukemia relapsing ten years after allogenic bone marrow transplantation.

    PubMed

    Hino, Yutaro; Doki, Noriko; Yamamoto, Keita; Senoo, Yasushi; Sasajima, Satoshi; Sakaguchi, Masahiro; Hattori, Keiichiro; Kaito, Satoshi; Kurosawa, Shuhei; Harada, Kaito; Ikegawa, Shuntaro; Watanabe, Daisuke; Hagino, Takeshi; Yoshioka, Kosuke; Watakabe, Kyoko; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2016-05-01

    A 58-year-old female was diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis (BC) in 2004. The patient received imatinib, which quickly induced molecular remission, and subsequently underwent bone marrow transplantation (BMT) from an unrelated human leukocyte antigen (HLA)-identical donor. The post-transplant clinical course was essentially uneventful. In 2014, ten years after the BMT, the patient was admitted to our hospital complaining of lymphadenopathy, and blasts were observed in peripheral blood. The patient was diagnosed as having a CML relapse in myeloid BC, with leukemic infiltration in lymph nodes, and was treated with dasatinib. Subsequently, pleural effusion developed and nilotinib was administered, which induced normal blood counts without blasts and partial cytogenetic remission, one month after administration. Six months after the relapse, this patient underwent a second BMT from an HLA-matched unrelated donor. Recent studies have demonstrated the cumulative incidence of CML relapse more than five years after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to be higher than in acute myeloid leukemia. Although rare, the possibility of late relapse should be considered in patients diagnosed with CML after allo-HSCT. PMID:27263786

  17. Relapsed and refractory Hodgkin lymphoma: transplantation strategies and novel therapeutic options.

    PubMed

    David, Kevin A; Mauro, Lauren; Evens, Andrew M

    2007-10-01

    Many patients with Hodgkin lymphoma are cured with initial therapy, although a portion of patients will experience primary induction failure or disease relapse. Pathologic confirmation of refractory or relapsed Hodgkin lymphoma is important. Following two to four cycles of non-cross-resistant salvage chemotherapy, the standard of care is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), which is associated with long-term event-free survival rates of 45-68%. Of note, survival rates for studies integrating total lymphoid irradiation into the autologous HSCT-conditioning regimen are among the highest reported for relapsed/refractory Hodgkin lymphoma. Further treatment options are available for patients not fit to proceed to HSCT, for relapsed disease after autologous HSCT, and for 'high-risk' Hodgkin lymphoma including chemotherapy-resistant disease. Allogeneic HSCT is a valid treatment option, as a graft-vs.-Hodgkin-lymphoma effect has been demonstrated. In addition, novel targeted treatments are being investigated such as receptor-specific antibodies, radiolabeled antibodies, antiapoptotic agents including inhibitors of the nuclear factor-kappaB complex or X-linked inhibitor of apoptosis proteins, transcription pathway modulators such as histone deacetylase and mTOR inhibitors, and Epstein-Barr virus-directed therapy. Continued translational and collaborative prospective clinical research efforts are needed in order to continue to increase the survival rates for Hodgkin lymphoma and to lessen the toxicities associated with lymphoma-related therapy. PMID:18214690

  18. 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…

  19. Multiplex Real-Time PCR Diagnostic of Relapsing Fevers in Africa

    PubMed Central

    Elbir, Haitham; Henry, Mireille; Diatta, Georges; Mediannikov, Oleg; Sokhna, Cheikh; Tall, Adama; Socolovschi, Cristina; Cutler, Sally J.; Bilcha, Kassahum D.; Ali, Jemal; Campelo, Dayana; Barker, Steven C.; Raoult, Didier; Drancourt, Michel

    2013-01-01

    Background In Africa, relapsing fever borreliae are neglected arthropod-borne pathogens causing mild to deadly septicemia and miscarriage. The closely related Borrelia crocidurae, Borrelia duttonii, Borrelia recurrentis and Borrelia hispanica are rarely diagnosed at the species level, hampering refined epidemiological and clinical knowledge of the relapsing fevers. It would be hugely beneficial to have simultaneous detection and identification of Borrelia to species level directly from clinical samples. Methodology/Principal Findings We designed a multiplex real-time PCR protocol targeting the 16S rRNA gene detecting all four Borrelia, the glpQ gene specifically detecting B. crocidurae, the recN gene specifically detecting B. duttonii/B. recurrentis and the recC gene specifically detecting B. hispanica. Compared to combined 16S rRNA gene and flaB gene sequencing as the gold standard, multiplex real-time PCR analyses of 171 Borrelia-positive and 101 Borrelia-negative control blood specimens yielded 100% sensitivity and specificity for B. duttonii/B. recurrentis and B. hispanica and 99% sensitivity and specificity for B. crocidurae. Conclusions/Significance The multiplex real-time PCR developed in this study is a rapid technique for both molecular detection and speciation of relapsing fever borreliae from blood in Africa. It could be incorporated in point-of-care laboratory to confirm diagnosis and provide evidence of the burden of infection attributed to different species of known or potentially novel relapsing fever borreliae. PMID:23390560

  20. Mediastinal Single Nodal Relapse of a Nasal Nk/T cell Lymphoma

    PubMed Central

    Rhee, Kyoung Hoon; Hong, Seok Chan; An, Jeong Min; Huh, Jooryung; Sook, Ryu Jin; Lee, Jin Seong

    2007-01-01

    A nasal NK/T cell lymphoma is a very aggressive form of lymphoma. Patterns of relapse after treatment have not been systematically evaluated, and mediastinal nodal relapse at a primary site has never been documented. We describe here a 40-year old man who presented with a nasal obstruction caused by a protruding mass that was identified as a nasal NK/T cell lymphoma. The initial work-up, including chest and abdominopelvic computed tomography (CT) and positron emission tomography (PET), showed no regional or distant metastasis. A CT scan performed following three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) showed that the mass had nearly disappeared. Radiation therapy undertaken following chemotherapy was given to the primary site. However, PET performed following radiotherapy revealed a single mediastinal lymphadenopathy, with no evidence of residual tumor in the nasal cavity. A biopsy using video-assisted thoracoscopy (VATS) showed the presence of a recurrent NK/T cell lymphoma with an immunophenotype identical to that of the primary nasal lymphoma. An additional three cycles of CHOP chemotherapy were administered, and the patient remains alive, with no evidence of disease 30 months after the initial relapse. These findings indicate that early detection with PET and prompt surgical excision with the use of VATS can lead to successful treatment of a relapsed nasal NK/T cell lymphoma. PMID:17939339