scholarly journals Narcolepsy Treatment: Present and Future

2021 ◽  
Author(s):  
Juan José Ortega-Albás ◽  
Raquel López García ◽  
Alfonso Martínez Martínez ◽  
Sonia Carratalá Monfort ◽  
Juan Antonio Royo Prats ◽  
...  

Narcolepsy is a chronic, disabling sleep disorder with a significant diagnostic delay. Nowadays, treatment is focused on managing symptoms that impacts patient’s life, such as at workplace, social events or even at school, but not aimed cure the disease. However, we have pharmacological treatments that effectively help control the main symptoms (excessive daytime sleepiness, cataplexy, fragmentation of nocturnal sleep, sleep paralysis and hypnagogic and hypnopompic hallucinations). On the other hand, pharmacological treatment must be individualised as there are great variations in severity, order of appearance symptoms and development of the disease. We intend to expose the different symptomatic treatments recommended by clinical guidelines and the clinical management from a practical point of view. Future treatments include therapies based on the replacement of hypocretin or the administration of agonist receptors. Other techniques such as hypothalamic stem cell transplantation, gene replacement therapy or immunotherapy are also being investigated.

The investigation of development described in a previous communication was extended by the application of microscopic methods. The fact that both the silver haloid and the resulting silver are distributed through the film in the form of particles of minute but measurable size, allows us in this way to detect finer qualitative differences in, and to draw independent deductions on the processes of exposure and development. The size of the grain is important, both from the practical point of view and from the theoretical: in the one case as bearing on spectroscopical and astronomical photography, in the other on account of the great importance of the degree of surface-extension for heterogeneous systems. The method has been used previously by Abney, Abegg, Kaiserling, Ebert, and others, but by far the most systematic and important inquiry is that of K. Schaum and V. Bellach.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5726-5726
Author(s):  
Daulath Singh ◽  
Patrick Hagen ◽  
Nasheed Hossain ◽  
Scott E. Smith ◽  
Patrick J. Stiff ◽  
...  

Introduction: Liposomal daunorubicin/cytarabine (Vyxeos®) is a dual drug liposomal encapsulation of cytarabine and daunorubicin, delivering drugs at a fixed 5:1 synergistic ratio for a longer therapeutic period. Compared to standard 7+3, liposomal cytarabine/daunorubicin (lipo-cytara/dauno) patients had improved survival and remission rates in a pivotal phase III study of elder adults with high-risk acute myelogenous leukemia (AML). Furthermore, more lipo-cytara/dauno patients went to allogeneic stem cell transplantation (HCT), with lower mortality and improved survival compared to those induced with 7+3. With its enhanced pharmacokinetics, lipo-cytara/dauno may provide a potent bridge to transplant. We report our experience using lipo-cytara/dauno as a bridge to same donor lymphocyte infusion (DLI) or different donor HCT in high-risk AML. Methods: We retrospectively reviewed all patients who received lipo-cytara/dauno at our institution since the FDA approval in August 2017. Of the 21 patients who have been treated, 9 received it as a bridge to cell therapy. All patients received the drug by usual means under the FDA label. Results: The median age of the 9 patients who received lipo-cytara/dauno as a bridge to cell therapy was 59 years. Seven were male, and two were female. Patients had had 1-4 prior lines of chemotherapy (median 2) with 7 of 9 patients having received prior standard 7+3 induction (cytarabine 100-200 mg/m2 x 7 days infusion and daunorubicin 60-90 mg/m2 x 3 days). Most had adverse cytogenetics, and all 9 patients received full lipo-cytara/dauno induction (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 on Days 1, 3, and 5) as outpatient therapy [Table]. Of the 9 patients, 6 had AML with very early relapse after HCT, with median time to relapse of 4 months (range 3 to 7 months). All 6 successfully proceeded to their planned cell infusion: 5 received same donor DLI after melphalan at 140 mg/m2, and 1 underwent second HCT from a different donor with busulfan/fludarabine conditioning at Days 15-40 after lipo-cytara/dauno. Of the remaining 3, two had relapsed AML after an initial remission (one was in first complete remission (CR1) for 3 months after 7+3/midostaurin induction and the other was in CR1 for 7 months after 7+3 induction/high dose cytarabine consolidation) and one had primary refractory disease (PREF) after 7+3 and azacitidine/venetoclax induction regimens. All 3 successfully underwent first HCT at Days 15-100 days after lipo-cytara/dauno bridge. The PREF patient received fludarabine/cyclophosphamide/TBI conditioning followed by matched unrelated donor transplant. Of the 2 with relapsed AML after initial remission, one received busulfan/fludarabine/thiotepa conditioning followed by umbilical cord stem cell transplantation and the other patient received fludarabine/cyclophosphamide/TBI conditioning prior to matched related donor transplant. Six of 9 had Day 14 bone marrow biopsies after lipo-cytara/dauno: 2 were in CR, 2 had >80% cytoreduction, and 2 had similar blast count. Three with persistent disease underwent reinduction with lipo-cytara/dauno (Days 1 and 3) and proceeded straight to cell therapy after. Median days to hospitalization after outpatient lipo-cytara/dauno was 6 days (range 3 to 14 days). Four out of 9 patients remain alive. Two were very early post HCT relapses (relapsed at 3 and 6 months post-HCT), both of which are remarkably in CR at 14 and 17 months after second cell therapy. Interestingly, both had CNS relapse, which were successfully treated, and both remain alive and in remission today. The other two had relapsed AML and PREF AML and underwent first HCT after lipo-cytara/dauno bridge. They remain alive and in remission at 1 and 8 months. Conclusion: In this retrospective study, outpatient lipo-cytara/dauno as a bridge to cell therapy is feasible and effective in very high-risk AML with no other viable options. While preliminary, survival appears favorable to that reported elsewhere at 14-23% at 1 year in this poor risk group, including those with adverse cytogenetic and/or very early post-HCT relapse. Prospective multi-center trials are planned to further evaluate lipo-cytara/dauno as a bridge to DLI/HCT in those with early relapse post-HCT and in those with refractory disease, with therapy to include CNS prophylaxis. Disclosures Stiff: Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding. Tsai:Jazz pharmaceuticals: Speakers Bureau; Jazz pharmaceuticals: Consultancy.


PEDIATRICS ◽  
1957 ◽  
Vol 20 (3) ◽  
pp. 552-556
Author(s):  
Reginald S. Lourie

FROM the viewpoint of the pediatric psychiatrist, the problems of obesity, as seen clinically, can be thought of as having three layers. The first is constitutional, better described as physiologic, which may be broken down into genetic and structural elements. The second is psychologic, consisting of the values that food intake or the obesity itself come to have. The third layer is made of the cultural and social reactions to food and fat. These attitudes encountered inside and outside the home intermesh in their effects with the physiologic and psychologic levels. These, in turn, are also interwoven, until one cannot separate one layer from the other. However, when individual cases are scrutinized they reveal the pathology at one layer or the other to predominate and indicate where efforts to modify the abnormality might best be directed. Incidentally, the same levels operate on the other side of the coin, anorexia. From the practical point of view, let us consider the natural history of obesity and the clinical varieties one sees in practice, and let us see how the three-layer concept fits. First, as pointed out by Gordon, there is a tendency to be complacent or even pleased with obese infants. At level one, the physiologic, such constitutional factors as those present in the neonate born with an excessive quantity of pepsinogen secreted by the gastric mucous membrane could have the effect of producing as Mirsky points out, a relatively intense or even continuous hunger, and make greater demands on its mother for nursing.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5343-5343
Author(s):  
Tomomi Toubai ◽  
Junji Tanaka ◽  
Shuichi Ota ◽  
Junichi Sugita ◽  
Naoko Kato ◽  
...  

Abstract Buckgrand. Graft-versus host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT). Macrophage migration inhibitory factor (MIF) plays a pivotal role in systemic as well as local inflammatory and immune responses. Recent reports that MIF expression is up-regulated in the allo-immune reaction during renal transplantation. Otherwise, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein belong to the TNF family. The level of TRAIL expression in T cells as well as NK cells can be markedly up-regulated after cell activations. In this study we report that kinetics of serum level of MIF and TRAIL in GVHD patients before and after HSCT. Patients and Methods. Date randomly obtained from 16 patients (10 males and 6 females) who underwent allo-SCT for treatment of hematological malignancies at Hokkaido University Hospital during the period May 2001 to January 2005. All patients were informed consent of peripheral blood smpling. Eight patients were received conventional transplantation and the others were reduced intensity stem cell transplantation (RIST). Seven patients have HLA identical sibling donor, but the others were received unrelated donor. Twelve of the 16 patients was achieved acute GVHD (aGVHD), gradeIto IIin 8 patients. Twelve patients survived day 100 after allo-SCT, 9 of those 12 patients developed chronic GVHD(cGVHD). Serum MIF and TRAIL concentration were measured at various time points using enzyme-linked immunosorbent assays (ELISAs). Results. Serum MIF concentration analysis by ELISA showed that only patients who developed aGVHD significantly increased (two folds) before and after allo-SCT (avelage, from 7.34 ng/ml before allo-SCT to 14.7 ng/ml after allo-SCT, p=0.018). However, we could not detect any correlation of MIF levels and aGVHD severity, donor sources. On the other hand, serum TRAIL concentration analysis by ELISA showed that patients who developed aGVHD were not associated (avelage, from 458.6 pg/ml before allo-SCT to 484.12 pg/ml after allo-SCT, p=0.632). We could not detect association aGVHD severity, donor sources. However, peak titer in aGVHD patients tends to decrease in unrelated transplantation (related 580.86pg/ml, unrelated 415.59pg/ml, p=0.22). Interestingly, we showed that average serum TRAIL concentration before allo-SCT associated with aGVHD and cGVHD. Serum TRAIL concentration with aGVHD patients (n=12, 458.85pg/ml) was tended to increase than without aGVHD (n=4, 330.45pg/ml, P=0.063) and with cGVHD patients (n=9, 535.21pg/ml) was significantly increase without cGVHD patients (n=3, 282.0 ng/ml, P=0.007). Discussion. The present study demonstrated the kinetics of MIF and TRAIL. Systemic up-regulation of MIF expression is associated with the occurrence of aGVHD. This data suggested that MIF after allo-SCT might play a pathogenetic role in aGVHD. On the other hand, we suggested that high level of TRAIL before allo-SCT associated acute and cGVHD. Maybe we might be to estimate acute and cGVHD in examining TRAIL level before allo-SCT. In conclusion our data are the first to establish an association TRAIL and GVHD in allogeneic stem cell transplantation.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3008-3008
Author(s):  
Francesca F. Patriarca ◽  
Alessandra A. Sperotto ◽  
Barbara B. Bruno ◽  
Andrea A. Bacigalupo ◽  
Alberto A. Bosi ◽  
...  

Abstract Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative treatment for idiopathic myelofibrosis (IM), but it is associated with a high transplantation-related (TRM) mortality rate, especially in advanced and elderly patients. Recently, reduced-intensity conditioning (RIC) regimens were reported to be feasible in these subgroups of patients. Herein, we reported a preliminary analysis of the data of the Gruppo Italiano Trapianto Midollo Osseo (G.I.T.M.O.) Registry regarding a total of 92 patients with IM, who underwent allogeneic HSCT in 25 different Italian Transplant Centres between 1986 and 2005. One Centre performed 26 transplants, 4 Institutions performed between 6 and 10 transplants and the other 20 Centres realized five or less procedures. Ten transplants (11 %) were performed before 1995, 26 (28%) between 1996 and 2000 and 56 (61%) between 2001 and 2005. Sixty patients (65%) were male and median age was 49 years ( range 21–68). Thirty-nine patients (42%) were older than 50 and 8 older than 60 years. Forty-four (48%) received myeloablative conditioning and 48 (52%) a RIC regimen. Myeloablative conditioning was based on cyclophosphamide plus thiotepa ( 42% of the patients) or busulfan (37%) or total body irradiation at the dose of 10–12 Gy (21%). RIC transplants consisted of a combination of fludarabine and 2 Gy TBI (44%) or cyclophosphamide (4%) or busulphan (4%) or an association of thiotepa and cyclophospamide (48%). GVHD prophylaxis included cyclosporin-A and short-course methotrexate, with the association of ATG in 11 patients. Stem cells came from matched sibling donors for 70 patients (76%), missmatched sibling donors for 10 patients (11%) and from matched unrelated donors for the remaining 12 patients (13%). Forty-nine patients (53%) received BM cells and the other 53 cases (47%) PBSC. Seventy-eight out 92 (85%) achieved full engrafment. One-year TRM was 35%. Causes of TRM were as following: GVHD (33% of the patients), infections (36%), bleeding (12%), veno-occlusive disease (3%), thrombotic thrombocytopenic purpura (6%). We observed a trend of higher TRM rate in patients transplanted before 2000 in comparison with those transplanted later (48% vs 33%). However, other potential risk factors for TRM, such as patient age > 50 years, conventional conditioning and unrelated or mismatched donors did not significantly increase TRM rate. There are 43 patients (47%) alive 12 to 156 months after transplantation ( median, 35 months). We conclude that, albeit TRM rate has been lowered in transplants performed in the last 5 years, it still involves one-third of the patients and remains a matter of concern. The ongoing analysis will focus on the impact of the clinical and biological factors at transplant on the outcome of the patient population.


2012 ◽  
Vol 504-506 ◽  
pp. 1383-1388 ◽  
Author(s):  
Piotr Sędek ◽  
Marek Stanisław Węglowski

The application of mechanical vibration has been known for many years, but some controversy still exists. According to some ideas the mechanical vibration reduces the technological stresses by summation of technological stress and stress from external loads (vibration). But on the other hand, the mechanical vibration causes more complicated phenomena (micro-relaxation) resulting in dimensional stability close to natural seasoning effects. In the present study authors present results of research into mechanical vibration from the experimental and practical point of view, proving that this process can be used to obtain dimensional stability. The results has also indicated that the reduction of the technological stresses is highly questionable.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5812-5812
Author(s):  
Brenda Lizeth Lizeth Acosta-Maldonado ◽  
Liliana Rivera-Fong. ◽  
Juan Francisco Zazueta Pozos. ◽  
Jaime Eduardo Dulón Tarqui. ◽  
José Guadalupe Ríos. ◽  
...  

Abstract Introduction Autologous hematopoietic stem cell transplantation (ASCT) is a treatment option for long-term remission in patients with multiple myeloma and recurrent non-Hodgkin´s lymphoma (NHL). The eligibility for ASCT is based on a risk-benefit assesssment of the disease, age has not been considered an exclusion criteria for ASCT where treatment related mortality are relatively low. The treatment-related morbidity is associated with toxicity of condition regimen and infections associated with the degree of immune deficiency. Outcome in elderly patients with multiple myeloma and recurrence of Hodgkin´s lymphomas with chemosensitive illness in ≥ 60 years patients undergo ASCT are limited and contradictory. For this reason the aims of the present study was to reviewed to identify patient with multiple myeloma and non-Hodgkin lymphoma undergoing ASCT at 60 or greater and describe the clinical data and outcome. Method: This work was a retrospective transversal study, 24 patients older than 60 years was enrolled and all of them were undergo ASCT al Instituto Nacional de Cancerologia, Mexico from 2005 to 2015. We assessed previous comorbidities, treatment lines, response prior to transplantation, treatment response, relapse free-survived and global survival, it was considered from the transplantation day until last visit at the hospital. Results Twenty-four patients were assessed, all were ≥60 years at the transplant moment. 16 of them had diagnostic of multiple myeloma and 8 with Non-Hodgkin's lymphoma (NHL). For the multiple myeloma group the median of age was 66 years (60-70 years), the 81% was male. At the transplant moment, two people in that group had hypertension, one had diagnosis of Diabetes Mellitus Diabetes II and the another did not have any other illness. At the transplant moment 62.5% of the patients had been treated with only one line treatment and 37.5% had been received two treatment lines. On the other hand, at the transplant moment 50% of the patients had completed response, 12% had partial response, 31.26% had very good partial responses and 6.25% had illness progression. Multiple myeloma patient was conditioned with melphalan 200mg/m2 in 95%. Neutrophils recovery was at 12 days. Fourty-three percent of the patient required transfusion. Neutropenic fever was presented in 43% of the patient. Fifty percent got completed response after ASCT and 20% with progression disease. Relapse disease was in 31% and mortality was 6.25%, there was not mortality associated with the process and 44% is alive without illness (Table 1). In patients with multiple myeloma the OS at two year was 100% and at three years 86%; for NHL patients OS at one year was 67% and at two years 33%. . For the NHL group the median of age was 67 years (61-72 years), the 50% was male, one person in that group had HTA at transplant moment, another one had diagnosis of MDII, another one had rheumatology disease and another one had long disease, and the other four did not have any other diseases. At the transplant moment 37.5% of the patients had been treated with only one line treatment, 37.5% had been received two treatment lines and 25% had been received three treatment lines. On the other hand, at the transplant moment 87.5% of the patients had completed response and 12.5% had partial response. NHL patients were conditioned with PEAM (cisplatin, etoposide, cytosine arabinoside and melphalan) 25%, Rituximab-PEAM in 62.5% and one patient with fludarabine with cyclophosphamide (FLUCY). Neutrophils recovery was at 12 days. Fourty-three percent of the patient required transfusion. Neutropenic fever was presented in 43% of the patient. Fifty percent got completed response after ASCT and 20% with progression disease. Relapse disease was in 31% and mortality was 6.25%, there was not mortality associated with the process and 44% is alive without illness (Table 1) For lymphoma, the relapse-free survival at one year 48.6%. For patients with multiple myeloma, the free illness survival at one year was 85.7%, at two years 77.9% and at four year 58.4%. Conclusion Autologous stem cell transplantion in older people is a good option for treatment without mortality asociated at process. The complications like neutropenic fever and transfusional requirement are similar with younger patients. In our population, age is not a limit to offer a treatment with high dose of chemotherapy and autologous. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 980-980
Author(s):  
Christoph Schliemann ◽  
Katrin Gutbrodt ◽  
Andrea Kerkhoff ◽  
Michele Pohlen ◽  
Stefanie Wiebe ◽  
...  

Abstract The tumor-directed delivery of therapeutics using monoclonal antibodies specific to a tumor-associated antigen promises to accumulate large doses of the delivered payload at the tumor site while sparing healthy organs. The antibody-based delivery of interleukin-2 (IL-2) to extracellular targets expressed in the easily accessible tumor vasculature has shown promising results in animal models of solid tumors and hematological malignancies. In xenograft and immunocompetent murine models of acute myeloid leukemia (AML), IL-2-based vascular targeting antibody fusions have recently demonstrated potent anti-leukemic activity, especially when used in combination with cytarabine. Here, we report our experiences in four patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, consisting of a human monoclonal antibody specific to spliced large isoforms of tenascin-C fused to human IL-2, in combination with very low dose cytarabine (5 mg subcutaneously twice daily for 10 days). Clinical evidence of anti-leukemia efficacy was shown in all patients. One patient with rapidly progressing disseminated extramedullary AML lesions achieved a complete metabolic response in PET/CT, which lasted three months. Two out of three patients with bone marrow relapse achieved a blast reduction with transient molecular negativity (NPM1). One of the two enjoyed a short complete remission before AML relapse occurred two months after the first infusion of F16-IL2. The other patient did not regenerate neutrophil and thrombocyte counts and showed progressive disease after completion of the first cycle. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells (natural killer cells, CD8+ T cells, γδ T cells) in the bone marrow. Grade 2 fevers were the only non-hematological side effects in two patients. Grade 3 cytokine-release syndrome developed in the other two patients, required hospitalization, but was manageable in both cases with systemic glucocorticoids. No non-hematological grade 4 toxicities were observed. The concept of specifically targeting IL-2 to the leukemia-associated stroma using armed antibodies deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. Disclosures Off Label Use: In this report, the antibody-cytokine fusion protein F16-IL2 has been used in a compassionate use setting in individual patients presenting with AML relapse after allogeneic stem cell transplantation. F16-IL2 is currently being evaluated in phase I/II studies in patients with solid cancer.. Neri:Philogen SpA: Employment, Equity Ownership.


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