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Sample records for neonatal immunotherapy study

  1. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors.

  2. Oral mucosal immunotherapy for allergic rhinitis: A pilot study

    PubMed Central

    Suurna, Maria V.; Rochlin, Kate; Bremberg, Maria G.; Tropper, Guy

    2016-01-01

    Background: The sublingual mucosa has been used for many years to apply allergenic extracts for the purpose of specific immunotherapy (IT). Although sublingual IT (SLIT) is both safe and efficacious, the density of antigen-presenting cells is higher in other regions of the oral cavity and vestibule, which make them a potentially desirable target for IT. Objective: To present the concept of oral mucosal IT (OMIT) and to provide pilot data for this extended application of SLIT. Methods: An open-label, 12-month, prospective study was undertaken as a preliminary step before a full-scale clinical investigation. Twenty-four individuals with allergic rhinitis received IT by applying allergenic extracts daily to either the oral vestibule plus oral cavity mucosa by using a glycerin-based toothpaste or to the sublingual mucosa by using 50% glycerin liquid drops. Adverse events, adherence rates, total combined scores, rhinoconjunctivitis quality-of-life questionnaire scores, changes in skin reactivity, and changes in serum antibody levels were measured for each participant. Results: No severe adverse events occurred in either group. The adherence rate was 80% for the OMIT group and 62% for the SLIT group (p = 0.61). Decreased total combined scores were demonstrated for both the OMIT group (15.6%) and the SLIT group (22.3%), although this decrease did not reach statistical significance in either group. Both groups achieved a meaningful clinical improvement of at least 0.5 points on rhinoconjunctivitis quality-of-life questionnaire. A statistically significant rise in specific immunoglobulin G4 (IgG4) was seen in both groups over the first 6 months of treatment. Conclusion: OMIT and SLIT demonstrated similar safety profiles and adherence rates. Measurements of clinical efficacy improved for both groups, but only changes in IgG4 achieved statistical significance. These pilot data provide enough evidence to proceed with a full-scale investigation to explore the role of OMIT in

  3. Immunotherapy for mold allergy.

    PubMed

    Coop, Christopher A

    2014-12-01

    The objective of this article is to review the available studies regarding mold immunotherapy. A literature search was conducted in MEDLINE to identify peer-reviewed articles related to mold immunotherapy using the following keywords: mold, allergy, asthma, and immunotherapy. In addition, references cited within these articles were also reviewed. Articles were selected based on their relevance to the topic. Allergic responses to inhaled mold antigens are a recognized factor in allergic rhinitis and asthma. There are significant problems with respect to the production of relevant allergen material for the diagnosis and treatment of mold allergy with immunotherapy. Mold allergens contain proteases and should not be mixed with other allergens for immunotherapy. Most of the immunotherapy studies focus on two molds, Alternaria and Cladosporium. There is a lack of randomized placebo-controlled trials when evaluating the efficacy of mold immunotherapy with trials only focusing on immunotherapy to Alternaria and Cladosporium. Additional studies are needed regarding mold allergy and immunotherapy focusing on which molds are important for causing allergic disease.

  4. Immunotherapy for mold allergy.

    PubMed

    Coop, Christopher A

    2014-12-01

    The objective of this article is to review the available studies regarding mold immunotherapy. A literature search was conducted in MEDLINE to identify peer-reviewed articles related to mold immunotherapy using the following keywords: mold, allergy, asthma, and immunotherapy. In addition, references cited within these articles were also reviewed. Articles were selected based on their relevance to the topic. Allergic responses to inhaled mold antigens are a recognized factor in allergic rhinitis and asthma. There are significant problems with respect to the production of relevant allergen material for the diagnosis and treatment of mold allergy with immunotherapy. Mold allergens contain proteases and should not be mixed with other allergens for immunotherapy. Most of the immunotherapy studies focus on two molds, Alternaria and Cladosporium. There is a lack of randomized placebo-controlled trials when evaluating the efficacy of mold immunotherapy with trials only focusing on immunotherapy to Alternaria and Cladosporium. Additional studies are needed regarding mold allergy and immunotherapy focusing on which molds are important for causing allergic disease. PMID:24057512

  5. Peanut immunotherapy

    PubMed Central

    2014-01-01

    Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies, such as egg and milk. Peanut allergy has a significant effect on the quality of life of sufferers and their families, due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication, but a disease- modifying therapy is needed for peanut allergy. Recent developments involve the use of immunotherapy, which has shown promise as an active form of treatment. Various routes of administration are being investigated, including subcutaneous, oral, sublingual and epicutaneous routes. Other forms of treatment, such as the use of vaccines and anti-IgE molecules, are also under investigation. So far, results from immunotherapy studies have shown good efficacy in achieving desensitisation to peanut with a good safety profile. However, the issue of long-term tolerance has not been fully addressed yet and larger, phase III studies are required to further investigate safety and efficacy. An assessment of cost/benefit ratio is also required prior to implementing this form of treatment. The use of immunotherapy for peanut allergy is not currently recommended for routine clinical use and should not be attempted outside specialist allergy units. PMID:25276342

  6. Canine gastrointestinal pythiosis treatment by combined antifungal and immunotherapy and review of published studies.

    PubMed

    Pereira, Daniela I B; Botton, Sônia A; Azevedo, Maria I; Motta, Marco A A; Lobo, Raulene R; Soares, Mauro P; Fonseca, Anelise O S; Jesus, Francielli P K; Alves, Sydney H; Santurio, Janio M

    2013-10-01

    Pythium insidiosum is an oomycete, a fungal like microorganism, which infects mammals, causing pythiosis in animals and humans, especially in tropical and subtropical regions around the world. The treatment for this infection is very difficult, and therapeutic options commonly comprise surgery, immunotherapy and antimicrobial drugs. The present report describes the clinical healing of a dog with gastrointestinal pythiosis by treatment with a combination of antifungals and immunotherapy, as well as reviews the cases reported in the literature that used some type of therapy for canine pythiosis. A 2.5-year-old male beagle initially showed sporadic vomiting episodes, and this symptom became more frequent 5 months after the onset of clinical signs. Celiotomy procedure found thickness of the stomach wall extending to the pylorus and duodenum. A biopsy was performed, and the diagnosis of pythiosis was made by mycological, histopathological analyses and molecular identification. Therapy was based on an association of terbinafine plus itraconazole during 12 months and immunotherapy for 2.5 months. The healing of the dog reported here allows us to propose the use of immunotherapy associated with antifungal therapy to treat canine gastrointestinal pythiosis. However, additional studies should be performed on a larger number of patients to establish a standard treatment protocol for canine pythiosis. PMID:23918089

  7. Immunocompetent murine models for the study of glioblastoma immunotherapy

    PubMed Central

    2014-01-01

    Glioblastoma remains a lethal diagnosis with a 5-year survival rate of less than 10%. (NEJM 352:987-96, 2005) Although immunotherapy-based approaches are capable of inducing detectable immune responses against tumor-specific antigens, improvements in clinical outcomes are modest, in no small part due to tumor-induced immunosuppressive mechanisms that promote immune escape and immuno-resistance. Immunotherapeutic strategies aimed at bolstering the immune response while neutralizing immunosuppression will play a critical role in improving treatment outcomes for glioblastoma patients. In vivo murine models of glioma provide an invaluable resource to achieving that end, and their use is an essential part of the preclinical workup for novel therapeutics that need to be tested in animal models prior to testing experimental therapies in patients. In this article, we review five contemporary immunocompetent mouse models, GL261 (C57BL/6), GL26 (C57BL/6) CT-2A (C57BL/6), SMA-560 (VM/Dk), and 4C8 (B6D2F1), each of which offer a suitable platform for testing novel immunotherapeutic approaches. PMID:24779345

  8. Cancer immunotherapy targeting neoantigens.

    PubMed

    Lu, Yong-Chen; Robbins, Paul F

    2016-02-01

    Neoantigens are antigens encoded by tumor-specific mutated genes. Studies in the past few years have suggested a key role for neoantigens in cancer immunotherapy. Here we review the discoveries of neoantigens in the past two decades and the current advances in neoantigen identification. We also discuss the potential benefits and obstacles to the development of effective cancer immunotherapies targeting neoantigens.

  9. Engineered human embryonic stem cell-derived lymphocytes to study in vivo trafficking and immunotherapy.

    PubMed

    Knorr, David A; Bock, Allison; Brentjens, Renier J; Kaufman, Dan S

    2013-07-01

    Human embryonic stem cell (hESC)-derived natural killer (NK) cells are a promising source of antitumor lymphocytes for immunotherapeutics. They also provide a genetically tractable platform well suited for the study of antitumor immunotherapies in preclinical models. We have previously demonstrated the potency of hESC-derived NK cells in vivo. Here we use both bioluminescent and fluorescent imaging to demonstrate trafficking of hESC-derived NK cells to tumors in vivo. Our dual-imaging approach allowed us to more specifically define the kinetics of NK cell trafficking to tumor sites. NK cell persistence and trafficking were further evaluated by flow cytometry and immunohistochemistry. This integrated approach provides a unique system to apply the use of human pluripotent stem cells to study the kinetics and biodistribution of adoptively transferred lymphocytes, advances broadly applicable to the field of immunotherapy.

  10. Improvement of QOL and Immunological Function With Lentinula Edodes Mycelia in Patients Undergoing Cancer Immunotherapy: An Open Pilot Study.

    PubMed

    Tanigawa, Keishi; Itoh, Yusuke; Kobayashi, Yasunobu

    2016-07-01

    Context • Combined treatment with an extract of Lentinula edodes mycelia (LEM) and chemotherapy has been reported to improve quality of life (QOL) and immunological function in cancer patients. However, those effects have not been elucidated for patients receiving cancer immunotherapy. Objective • The present study intended to investigate the effects of oral LEM on QOL and immunological function in cancer patients receiving immunotherapy. Design • The research team designed an open-label, single-armed pilot study. Setting • The study took place at Bio-Thera Clinic, a facility associated with Tokyo Women's Medical University in Tokyo, Japan. Participants • The participants were 10 cancer patients undergoing cancer immunotherapy at Bio-Thera Clinic. Intervention • The participants received either dendritic cell (DC)-based cancer vaccine therapy or CD3-activated T-lymphocyte (CAT) therapy as immunotherapy. They received the immunotherapy only for the first 4 wk of the study, and then oral LEM (1800 mg/d) was added for the next 4 wk. Outcome Measures • Preintervention and at 4 and 8 wk after the start of the study, participants completed a QOL survey, and immunological parameters were measured. Results • Participants' QOL symptom scores increased (ie, worsened) by 5.1 ± 1.7 during the first 4 wk of treatment when they were receiving immunotherapy only, but it decreased (ie, improved) by -2.5 ± 1.6 during the next 4 wk when the immunotherapy was combined with the LEM, P < .05. The measurement of the immunological parameters during the 4 wk of immunotherapy combined with LEM showed that the amount of interferon-γ (IFN-γ) produced in the peripheral blood tended to increase as compared with that during the first 4 wk of immunotherapy only. The rise in IFN-γ was correlated with changes in several regulatory T cells (Tregs) (ie, forkhead box P3 [FOXP3]+/cluster of differentiation 4 [CD4]+ and transforming growth factor beta [TGF-β]). Conclusions • The

  11. Systemic Reactions to Dust Mite Subcutaneous Immunotherapy: A 3-Year Follow-up Study

    PubMed Central

    Dong, Xiang; Huang, Nan; Li, Wenjing; Hu, Lintao; Wang, Xiaolong; Wang, Yin; Xiang, Ning; Liu, Guanghui

    2016-01-01

    Purpose The incidence of allergen specific immunotherapy-related systemic reactions (SRs) varies among different studies, and many factors are likely to contribute to SRs. This study aims to investigate the incidence, characteristics, and risk factors of SRs to standardize dust mite-specific subcutaneous immunotherapy (SCIT) in Central China. Methods All patients receiving standardized dust mites (100-100,000 SQ-U/mL; Alutard SQ, Hørsholn, Denmark) immunotherapy were followed up. Recorded data included demographics, diagnosis, patient status, pulmonary function testing results before and after each injection, allergen dosage, and details of SRs. Results From June 2011 to August 2014, a total of 208 patients received 4,369 injections; 27 (13.0%) patients experienced 48 (1.1%) systemic reactions. Most of the SRs were grade 2 reactions (n=30, 62.5%), followed by grade 1 (n=11, 22.9%), grade 3 (n=7, 14.6%), and no fatal reactions occurred. Forty-six SRs (95.8%) occurred within 30 minutes. Higher SR rates were associated with high concentration extracts (100,000 SQ-U/mL), injections with concomitant local reactions (LRs), children, asthma and high sensitivity (skin prick test 3+/4+ and/or sIgE≥17.5 kUA/L) (P<0.05). The estimated odds of SRs increased in children (OR=6.57; 95% CI: 1.88-22.97, P=0.003), asthmatic patients (OR=4.10; 95% CI: 1.72-9.80, P=0.002), and injections with LRs (OR=2.41; 95% CI: 1.33-4.36, P=0.004). Conclusions The incidence of SRs to dust mite SCIT was low, and multiple factors were associated with the increased incidence of SRs. Children, asthmatics and patients with concomitant LR may be prone to develop SRs. PMID:27334780

  12. [Comparative studies of the effectiveness of specific immunotherapy in house dust mite allergy].

    PubMed

    Ebner, H; Neuchrist, C; Havelec, L; Kraft, D

    1989-08-01

    In a prospective study, 60 patients with allergic rhinoconjunctivitis and/or asthma due to house dust mites were chosen for hyposensitization treatment with Migen (M) or Pharmalgen (P). Immunotherapy stretched over a whole year and every 3 months clinical results were evaluated by the patient's symptom score, by results of skin prick and conjunctival provocation tests, as well as by RIA and ELISA regarding the total and specific IgE and also specific IgG and IgG4 levels. Out of 30 patients of the M group, 15 were followed up over the whole therapeutic regimen, 4 of whom showed a very good, 7 a good to moderate clinical outcome and 4 showed no improvement at all. In the P group, 17 out of 30 patients were followed up whereby 9 showed a very good and 8 a good to moderate response. In both groups of patients a statistically significant decrease in skin and conjunctival sensitivity to mite allergens was observed after 12 months of therapy. However, there was no correlation between this observation and the failure or success of immunotherapy. Furthermore, in both groups there was significant increase in total and specific IgE (with a slight decrease after 6 to 12 months) and also in specific IgG and IgG4 (especially in the P group), but again these changes in antibody levels gave no indication of a good or bad clinical outcome. Hence, we believe other reasons than the usually presented thesis of inducing "blocking antibodies" by immunotherapy to be responsible for the well-known effects of hyposensitization.

  13. Local reactions from subcutaneous allergen immunotherapy.

    PubMed

    Coop, Christopher A

    2013-12-01

    Local reactions from subcutaneous allergen immunotherapy are very common during the course of immunotherapy. These local reactions are not bothersome to patients. Local reactions from immunotherapy also do not predict future local or systemic reactions. This review discusses the studies that show that local reactions are not predictive of future reactions and that dose adjustments for local reactions from allergen immunotherapy are unnecessary. The article also focuses on factors that lead to patient noncompliance with immunotherapy and evaluates methods to prevent local reactions from subcutaneous allergen immunotherapy. PMID:24283844

  14. Local reactions from subcutaneous allergen immunotherapy.

    PubMed

    Coop, Christopher A

    2013-12-01

    Local reactions from subcutaneous allergen immunotherapy are very common during the course of immunotherapy. These local reactions are not bothersome to patients. Local reactions from immunotherapy also do not predict future local or systemic reactions. This review discusses the studies that show that local reactions are not predictive of future reactions and that dose adjustments for local reactions from allergen immunotherapy are unnecessary. The article also focuses on factors that lead to patient noncompliance with immunotherapy and evaluates methods to prevent local reactions from subcutaneous allergen immunotherapy.

  15. Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy

    PubMed Central

    Ma, Chao; Cheung, Ann F.; Chodon, Thinle; Koya, Richard C.; Wu, Zhongqi; Ng, Charles; Avramis, Earl; Cochran, Alistair J.; Witte, Owen N.; Baltimore, David; Chmielowski, Bartosz; Economou, James S.; Comin-Anduix, Begonya; Ribas, Antoni; Heath, James R.

    2013-01-01

    Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy. SIGNIFICANCE A longitudinal functional study of adoptively transferred TCR–engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma. PMID:23519018

  16. Natal and Neonatal Teeth: A Retrospective Study of 15 Cases

    PubMed Central

    Basavanthappa, Nagaveni N; Kagathur, Umashankara; Basavanthappa, Radhika N; Suryaprakash, Satisha T

    2011-01-01

    Objectives: To present 17 natal/neonatal teeth in 15 patients and describe their clinical characteristics, associated disorders, complications and treatment. Methods: A retrospective study of neonates who visited the Department of Pedodontics and Preventive Dentistry, College of Dental Sciences, Davangere, India, between 2003 and 2006 was carried out. It was a study of clinical data, such as the age and gender of the patients, the history and chief complaints of mothers, the clinical appearance and location of natal/neonatal teeth, and associated complications and treatments. Results: A total of 17 teeth (6 natal, 11 neonatal) were found in 15 patients. No significant gender predilection (8 male, 7 female) was found. Sixteen natal/neonatal teeth were placed in mandibular incisor area (10 on the right side and 6 on the left side) and one tooth in the maxillary incisor area. In 13 patients, the occurrence of natal/neonatal teeth was unilateral, and in 2 patients, it was bilateral. Three cases were associated with enamel hypoplasia, 3 cases with Riga-Fede disease, and 1 case with gingival hyperplasia. One case involved a patient with cleft lip and palate. Radiographic examination confirmed these teeth to be supernumerary, and all teeth exhibited hypermobility. Extraction had been done in all the cases. Eleven of the extracted teeth exhibited only rudimentary roots, and six teeth showed no roots. Conclusions: The occurrence of a natal/neonatal tooth is a rare phenomenon. When it occurs, the teeth have a variety of clinical characteristics and lead to different complications. Knowledge of the management of these structures is essential for the overall well being of a child. PMID:21494384

  17. Effect of Immunotherapy on Seizure Outcome in Patients with Autoimmune Encephalitis: A Prospective Observational Registry Study

    PubMed Central

    Jung, Keun-Hwa; Sunwoo, Jun-Sang; Moon, Jangsup; Lim, Jung-Ah; Lee, Doo Young; Shin, Yong-Won; Kim, Tae-Joon; Lee, Keon-Joo; Lee, Woo-Jin; Lee, Han-Sang; Jun, Jinsun; Kim, Dong-Yub; Kim, Man-Young; Kim, Hyunjin; Kim, Hyeon Jin; Suh, Hong Il; Lee, Yoojin; Kim, Dong Wook; Jeong, Jin Ho; Choi, Woo Chan; Bae, Dae Woong; Shin, Jung-Won; Jeon, Daejong; Park, Kyung-Il; Jung, Ki-Young; Chu, Kon; Lee, Sang Kun

    2016-01-01

    Objective To evaluate the seizure characteristics and outcome after immunotherapy in adult patients with autoimmune encephalitis (AE) and new-onset seizure. Methods Adult (age ≥18 years) patients with AE and new-onset seizure who underwent immunotherapy and were followed-up for at least 6 months were included. Seizure frequency was evaluated at 2–4 weeks and 6 months after the onset of the initial immunotherapy and was categorized as “seizure remission”, “> 50% seizure reduction”, or “no change” based on the degree of its decrease. Results Forty-one AE patients who presented with new-onset seizure were analysed. At 2–4 weeks after the initial immunotherapy, 51.2% of the patients were seizure free, and 24.4% had significant seizure reduction. At 6 months, seizure remission was observed in 73.2% of the patients, although four patients died during hospitalization. Rituximab was used as a second-line immunotherapy in 12 patients who continued to have seizures despite the initial immunotherapy, and additional seizure remission was achieved in 66.6% of them. In particular, those who exhibited partial response to the initial immunotherapy had a better seizure outcome after rituximab, with low adverse events. Conclusion AE frequently presented as seizure, but only 18.9% of the living patients suffered from seizure at 6 months after immunotherapy. Aggressive immunotherapy can improve seizure outcome in patients with AE. PMID:26771547

  18. Allergen Immunotherapy.

    PubMed

    Rael, Efren

    2016-09-01

    Allergies affect a large proportion of the population. Allergies can adversely affect productivity, sleep, and quality of life and can lead to life-threatening reactions. Allergies can spread to affect multiple organ systems. Allergen immunotherapy is the only therapy that can change the natural history of allergic disease. PMID:27545737

  19. Allergen-specific immunotherapy.

    PubMed

    Nelson, Harold S; Norman, Philip S

    2014-01-01

    Specific immunotherapy was introduced for the treatment of grass pollen-induced hay fever in 1911. The treatment was soon extended to other pollens as well as perennial allergens, and to the treatment of bronchial asthma. Definitive studies of its efficacy for both rhinitis and asthma came only many decades later. Understanding gradually emerged of the underlying immunologic mechanisms that include the generation of regulatory T lymphocytes, immune deviation from allergen-specific Th2 to Th1 responses, and a shift in allergen-specific antibody production from immunoglobulin (Ig) E to IgG4. Along with understanding of the immune basis came an appreciation that immunotherapy modifies allergic disease expression, producing protection against disease progression and symptomatic improvement that persists for years after the treatment is discontinued. Recent new directions for immunotherapy include sublingual administration of inhalant allergens and use of the oral route to treat food allergy.

  20. A study of neonatal deaths in the tea gardens of Dibrugarh district of upper Assam.

    PubMed

    Phukan, R K; Mahanta, J

    1998-11-01

    A total of 2432 live births and 46 stillbirths were studied in some of the tea gardens of Dibrugarh district of upper Assam. The neonatal mortality rate was 46.5 per 1000 live births per year. Immaturity (21.2%), fever/sepsis (13.3%), breathing disorder (12.4%), neonatal tetanus (11.5%) and neonatal diarrhoea (8.8%) accounted for most of the neonatal deaths. There were 42.9% low birth weight infants and this was associated with 92.8% of total neonatal deaths and 34.3% of preterm babies were associated with 90.7% of neonatal deaths. The case fatality rate among low birth weight and preterm babies was 9% and 11% respectively. High risk of neonatal deaths had been found among the neonates in case of no maternal immunisation, delivery attended by untrained person and newborn care at home. PMID:10218318

  1. Melanoma immunotherapy.

    PubMed

    Sivendran, Shanthi; Glodny, Bradley; Pan, Michael; Merad, Miriam; Saenger, Yvonne

    2010-01-01

    Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. Adoptive T-cell therapy provides the proof of principle that T cells can attack and eliminate tumors. It has been challenging, however, to adapt this treatment for widespread use. Vaccines have generally yielded poor results, but intratumor pathogen-based strategies have shown encouraging results in recent trials, perhaps due to stronger immune stimulation. A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies.

  2. Bacteriological study of neonatal sepsis and antibiotic susceptibility pattern of isolates in Kathmandu, Nepal.

    PubMed

    Shrestha, R K; Rai, S K; Khanal, L K; Manda, P K

    2013-03-01

    Bloodstream infections in neonates are life-threatening emergencies. Identification of the common bacteria causing such infections and their susceptibility patterns will provide necessary information for timely intervention. This study was done to determine the prevalence of neonatal septicaemia, identify the bacterial isolates and study their antimicrobial susceptibility pattern in neonates admitted to the neonatal intensive care unit of Nepal Medical College Teaching Hospital (NMCTH), Kathmandu, Nepal. This descriptive-analytical study was conducted in NMCTH from July 2011 to January 2012. Blood culture of all neonates who were suspected for neonatal sepsis was performed. Bacterial isolation, identification and antimicrobial susceptibility testing were done by standard microbiological method. Out of 120 neonates suspected of having neonatal sepsis, 30.8% (37/120) were blood culture positive (i.e. prevalence = 30.8%). The most common causative agents of neonatal sepsis was Staphylococcus aureus (56.8%; 21/37) followed by Klebsiella pneumoniae (21.7%; 8/37), Pseudomonas aeruginosa (13.4%; 5/37) and others. Neonatal sepsis was more frequent in male neonates (32.5%) while (26.5%) in female neonates in the ratio of 1.2:1 (p > 0.05). Neonatal sepsis was significantly higher (58.3%) in low birth weight (LBW) (< 2.5kg) neonates compared with good birth weight (GBW) (23.9%) (< 0.05). Prevalence was higher in preterm neonates (57.8%; 11/19) as compared with term-babies (25.7%) (P = 0.05). Generally, all of the isolates were sensitive to most of the antibiotics used as the first line drugs like amikacin, gentamicin, cefotaxime and ampicillin except Acinetobacter baumannii. This organisms was only sensitive towards cotrimoxazole, azithromicin, cefotaxime and ceftazidime.

  3. Mechanisms of Aeroallergen Immunotherapy: Subcutaneous Immunotherapy and Sublingual Immunotherapy.

    PubMed

    Ozdemir, Cevdet; Kucuksezer, Umut Can; Akdis, Mübeccel; Akdis, Cezmi A

    2016-02-01

    Allergen immunotherapy (AIT) is an effective way to treat allergic disorders, targeting the underlying mechanisms and altering the disease course by inducing a long-lasting clinical and immune tolerance to allergens. Although sublingual and subcutaneous routes are used in daily practice, many novel ways to decrease side effects and duration and increase efficacy have been pursued. Further studies are needed to develop biomarkers for the identification of AIT responder patients and also to use the developed knowledge in allergy prevention studies. Future directions in AIT include treatments for autoimmune diseases, chronic infections, organ transplantation, and breaking immune tolerance to cancer cells.

  4. Preliminary study of cytotoxic effects of photodynamic therapy and immunotherapy on human pancreatic cancer cells

    NASA Astrophysics Data System (ADS)

    Wang, Luowei; Liu, Bolin; Chen, Yang K.; Li, Zhaoshen; Hetzel, Fred W.; Huang, Zheng

    2009-02-01

    Pancreatic cancer is the fourth most common cause of cancer death in the western world. The disease is very resistant to radiotherapy and chemotherapy. One reason for that is the resistance of pancreatic cancer cells to apoptosis. Among the current investigational approaches, targeting human epidermal growth factor receptor (HER-1/EGFR) and interstitial photodynamic therapy (PDT) show promises. When used alone or together, these new approaches might provide an alternative modality to treat pancreatic cancer. This study examined and compared cytotoxic effects of antibody C225 (an anti-HER-1/EGFR monoclonal antibody) and Photofrin-mediated PDT on two human pancreatic cancer cell lines (BxPc-3, HPAF-II). Preliminary in vitro data indicated that these treatments could block various proliferation pathways of pancreatic cancer cells through different mechanisms. For instance, PDT could induce early apoptosis. C225 could induce G1 arrest. These findings might help to design new strategies such as the combination of PDT and immunotherapy for the treatment of pancreatic cancer.

  5. Neonatal bleeding in haemophilia: a European cohort study.

    PubMed

    Richards, M; Lavigne Lissalde, G; Combescure, C; Batorova, A; Dolan, G; Fischer, K; Klamroth, R; Lambert, T; Lopez-Fernandez, M; Pérez, R; Rocino, A; Fijnvandraat, K

    2012-02-01

    Birth is the first haemostatic challenge for a child with haemophilia. Our aim was to examine the association between perinatal risk factors and major neonatal bleeding in infants with haemophilia. This observational cohort study in 12 European haemophilia treatment centres (HTC) incorporated 508 children with haemophilia A or B, born between 1990 and 2008. Risk factors for bleeding were analysed by univariate analysis. Head bleeds occurred in 18 (3·5%) children within the first 28 d of life, including three intraparenchymal bleeds, one subdural haematoma and 14 cephalohaematomas. Intra-cranial bleeds were associated with long-term neurological sequelae in two (0·4%) cases; no deaths occurred. Assisted delivery (forceps/vacuum) was the only risk factor for neonatal head bleeding [Odds Ratio (OR) 8·84: 95% confidence interval (CI) 3·05-25·61]. Mild haemophilia and maternal awareness of her haemophilia carrier status seemed to be protective (OR 0·24; 95%CI 0·05-1·05 and OR 0·34; 95%CI 0·10-1·21, respectively), but due to the low number of events this was not statistically significant. We found no association between neonatal head bleeding and country, maternal age, parity, gestational age or presence of HTC. Maternal awareness of carrier status protected against assisted delivery (unadjusted OR 0·37; 95%CI 0·15-0·90; adjusted OR 0·47 (95%CI 0·18-1·21). PMID:22146054

  6. Mechanism study of tumor-specific immune responses induced by laser immunotherapy

    NASA Astrophysics Data System (ADS)

    Li, Xiaosong; Zhou, Feifan; Le, Henry; Wolf, Roman F.; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2011-03-01

    Laser immunotherapy (LIT) has shown its efficacy against late-stage, metastatic cancers, both in pre-clinical studies and clinical pilot trials. However, the possible mechanism of LIT is still not fully understood. In our previous studies, we have shown that LIT induces tumor-specific antibodies that strongly bind to the target tumors. Tumor resistance in cured animals demonstrated long-term immunological effect of LIT. Successful transfer of adoptive immunity using spleen cells from LIT-cured animals indicated a long-term immunological memory of the host system. In clinical trials for the treatment of late-stage melanoma patients and breast cancer patients, the similar long-term, systemic effects have also been observed. To further study the immunological mechanism of LIT, immuno-histochemical analysis of patient tumor samples has performed before and after LIT treatment. Our results showed strong evidence that LIT significantly increases the infiltration of immune cells in the target tumors. Specifically, LIT appeared to drive the infiltrating immune cell populations in the direction of CD4, CD8 and CD68 T-cells. It is possible that activation and enhancement of both humeral and cellular arms of the host immune system are achievable by the treatment of LIT. These special features of LIT have contributed to the success of patient treatment. The underlying mechanism of LIT appears to be an in-situ autologous whole-cell cancer vaccination, using all components of tumors as sources of tumor antigens. Our preliminary mechanistic studies and future in-depth studies will contribute to the understanding and development of LIT as an effective modality for the treatment of late stage cancer patients who are facing severely limited options.

  7. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    SciTech Connect

    Wada, Satoshi; Harris, Timothy J.; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C.; De Marzo, Angelo M.; and others

    2013-11-15

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

  8. Immunotherapy of allergic contact dermatitis.

    PubMed

    Spiewak, Radoslaw

    2011-08-01

    The term 'immunotherapy' refers to treating diseases by inducing, enhancing or suppressing immune responses. As allergy is an excessive, detrimental immune reaction to otherwise harmless environmental substances, immunotherapy of allergic disease is aimed at the induction of tolerance toward sensitizing antigens. This article focuses on the historical developments, present state and future outlook for immunotherapy with haptens as a therapeutic modality for allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in respiratory allergies, attempts were undertaken at curing allergic contact dermatitis by means of controlled administration of the sensitizing haptens. Animal and human experiments confirmed that tolerance to haptens can be induced most effectively when the induction of tolerance precedes attempted sensitization. In real life, however, therapy is sought by people who are already sensitized and an effective reversal of hypersensitivity seems more difficult to achieve. Decades of research on Rhus hypersensitivity led to a conclusion that immunotherapy can suppress Rhus dermatitis, however, only to a limited degree, for a short period of time, and at a high risk of side effects, which makes this method therapeutically unprofitable. Methodological problems with most available studies of immunotherapy of contact allergy to nickel make any definite conclusions impossible at this stage.

  9. Possible Prevention of Neonatal Death: A Regional Population-Based Study in Japan

    PubMed Central

    Yanagi, Takahide; Ono, Tetsuo; Tsuji, Shunichiro; Takahashi, Kentaro

    2016-01-01

    Purpose The neonatal mortality rate in Japan has currently been at the lowest level in the world. However, it is unclear whether there are still some potentially preventable neonatal deaths. We, therefore, aimed to examine the backgrounds of neonatal death and the possibilities of prevention in a region of Japan. Materials and Methods This is a population-based study of neonatal death in Shiga Prefecture of Japan. Results The 103 neonatal deaths in our prefecture between 2007 and 2011 were included. After reviewing by a peer-review team, we classified the backgrounds of these neonatal deaths and analyzed end-of-life care approaches associated with prenatal diagnosis. Furthermore, we evaluated the possibilities of preventable neonatal death, suggesting specific recommendations for its prevention. We analyzed 102 (99%) of the neonatal deaths. Congenital malformations and extreme prematurity were the first and the second most common causes of death, respectively. More than half of the congenital abnormalities (59%) including malformations and chromosome abnormality had been diagnosed before births. We had 22 neonates with non-intensive care including eighteen cases with congenital abnormality and four with extreme prematurity. Twenty three cases were judged to have had some possibility of prevention with one having had a strong possibility of prevention. Among specific recommendations of preventable neonatal death, more than half of them were for obstetricians. Conclusion There is room to reduce neonatal deaths in Japan. Prevention of neonatal death requires grater prenatal care by obstetricians before birth rather than improved neonatal care by neonatologists after birth. PMID:26847296

  10. Risk factors of neonatal tetanus in Wenzhou, China: a case-control study

    PubMed Central

    Hong-Ying, Shi; Yi, Xu; Cai-Song, Hu; Xiao-Ming, Zhang; Li-Na, Zhao; Zuo-Kai, Xie

    2015-01-01

    Introduction Neonatal tetanus is a major cause of neonatal mortality in many developing countries and remains a major public health problem. This study aimed to determine risk factors associated with neonatal tetanus in Wenzhou, China. Methodology Medical records of neonatal tetanus cases from 17 hospitals over a 13-year period (2000–2012) were reviewed for potential risk factors. Controls were selected from neonates with diseases other than tetanus who were admitted to the same facility during the same period. The potential risk factors of the neonatal tetanus group were compared with the control group using univariate analysis and an unconditional logistic regression model. Results A total of 246 neonates with tetanus and 257 controls were included in this study. Univariate analysis showed that having untrained birth attendants, home delivery, an unsterile method of delivery and being a migrant to Wenzhou were significantly different between the two groups (P < 0.001). Logistic regression analysis revealed that the odds of having an untrained birth attendant, home delivery and an unsterile method of delivery were significantly higher in the tetanus group than the control group (odds ratio: 1371.0; 95% confidence interval: 206.0, 9123.5). Conclusion This study identified that the main risks of neonatal tetanus in cases from Wenzhou were having an untrained birth attendant, home delivery and an unsterile method of delivery. Preventive measures directed to these risk factors may reduce the occurrence of neonatal tetanus in the studied area. PMID:26668764

  11. A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer

    PubMed Central

    Kershaw, Michael H.; Westwood, Jennifer A.; Parker, Linda L.; Wang, Gang; Eshhar, Zelig; Mavroukakis, Sharon A.; White, Donald E.; Wunderlich, John R.; Canevari, Silvana; Rogers-Freezer, Linda; Chen, Clara C.; Yang, James C.; Rosenberg, Steven A.; Hwu, Patrick

    2007-01-01

    Purpose A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. Experimental Design T cells with reactivity against the ovarian cancer – associated antigen α-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor γ chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells. Results Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111In-labeled adoptively transferred T cells in cohort 1revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells. Conclusions Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to

  12. A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever.

    PubMed

    Van Metre, T E; Adkinson, N F; Lichtenstein, L M; Mardiney, M R; Norman, P S; Rosenberg, G L; Sobotka, A K; Valentine, M D

    1980-04-01

    In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2 + skin test to ragweed AgE at 0.1 microgram /ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance ("optimal dose") for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 micrograms of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 3f the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo

  13. Risk factors associated with neonatal deaths: a matched case–control study in Indonesia

    PubMed Central

    Abdullah, Asnawi; Hort, Krishna; Butu, Yuli; Simpson, Louise

    2016-01-01

    Background Similar to global trends, neonatal mortality has fallen only slightly in Indonesia over the period 1990–2010, with a high proportion of deaths in the first week of life. Objective This study aimed to identify risk factors associated with neonatal deaths of low and normal birthweight infants that were amenable to health service intervention at a community level in a relatively poor province of Indonesia. Design A matched case–control study of neonatal deaths reported from selected community health centres (puskesmas) was conducted over 10 months in 2013. Cases were singleton births, born by vaginal delivery, at home or in a health facility, matched with two controls satisfying the same criteria. Potential variables related to maternal and neonatal risk factors were collected from puskesmas medical records and through home visit interviews. A conditional logistic regression was performed to calculate odds ratios using the clogit procedure in Stata 11. Results Combining all significant variables related to maternal, neonatal, and delivery factors into a single multivariate model, six factors were found to be significantly associated with a higher risk of neonatal death. The factors identified were as follows: neonatal complications during birth; mother noting a health problem during the first 28 days; maternal lack of knowledge of danger signs for neonates; low Apgar score; delivery at home; and history of complications during pregnancy. Three risk factors (neonatal complication at delivery; neonatal health problem noted by mother; and low Apgar score) were significantly associated with early neonatal death at age 0–7 days. For normal birthweight neonates, three factors (complications during delivery; lack of early initiation of breastfeeding; and lack of maternal knowledge of neonatal danger signs) were found to be associated with a higher risk of neonatal death. Conclusion The study identified a number of factors amenable to health service

  14. A comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study.

    PubMed

    Joshi, Jyoti; Malla, Nancy; Kaur, Sukhbir

    2014-08-01

    Visceral leishmaniasis (VL) represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Ninety per cent of VL cases occur in five countries namely Bangladesh, India, Nepal, Sudan and Brazil. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. To combat this situation, immunochemotherapy can provide a solution. In the present study, an attempt has been made to assess the in vivo antileishmanial efficacy of chemotherapy, immunotherapy and immunochemotherapy with the use of a first generation antigen Killed Leishmania donovani (KLD) along with a standard drug sodium stibogluconate (SSG) and a newly tested antileishmanial cisplatin. Inbred BALB/c mice were infected with 10(7) promastigotes/0.1 ml of Leishmania donovani. A month after infection, these animals were given specific immunotherapy (KLD/KLD+MPL-A) or chemotherapy (SSG/cisplatin) or immunochemotherapy (SSG+KLD/SSG+KLD+MPL-A/cisplatin+KLD/cisplatin+KLD+MPL-A). Animals were sacrificed on 1, 15 and 30(th) day post treatment. The efficacy of these combinations was assessed in terms of parasite load and by immunological investigations. Infected mice and normal mice served as controls. Results showed that combination of drug and KLD significantly reduced the parasite burden, enhanced the DTH (Delayed Type Hypersensitivity) responses, showed increased levels of IgG2a and decreased levels of IgG1 as compared to mice given chemotherapy or immunotherapy alone. Further maximum protection was provided by SSG+KLD+MPL-A and it was most effective as depicted by 98.5% reduction in parasite load, a potent increase in IFN-γ levels and a significant decrease in IL-10 and IL-4 levels thus skewing the immune response towards Th1 type. Hence, immunochemotherapy is more effective

  15. Neonatal Intensive Care for Low Birthweight Infants: Costs and Effectiveness. Health Technology Case Study 38.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    After a brief introduction delineating the scope of the case study, chapter 1 summarizes findings and conclusions about the costs and effectiveness of neonatal intensive care in the United States. Chapter 2 inventories the national supply of neonatal intensive care units and describes recent trends in use and costs. Chapter 3 reviews mortality and…

  16. Immunotherapy Not Working? Check Your Microbiota.

    PubMed

    West, Nathan R; Powrie, Fiona

    2015-12-14

    Gut microbes have ascended to prominence as key modulators of host immunity, raising the possibility that they could influence the outcome of cancer immunotherapy. Two recent studies address this question by identifying specific gut-resident bacteria as drivers of checkpoint blockade immunotherapy in pre-clinical tumor models. PMID:26678336

  17. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study.

    PubMed

    Fustolo-Gunnink, S F; Vlug, R D; Smits-Wintjens, V E H J; Heckman, E J; Te Pas, A B; Fijnvandraat, K; Lopriore, E

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x109/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis. PMID:27177157

  18. Immunotherapy and tumor microenvironment.

    PubMed

    Tang, Haidong; Qiao, Jian; Fu, Yang-Xin

    2016-01-01

    Recent exciting progress in cancer immunotherapy has ushered in a new era of cancer treatment. Immunotherapy can elicit unprecedented durable responses in advanced cancer patients that are much greater than conventional chemotherapy. However, such responses only occur in a relatively small fraction of patients. A positive response to immunotherapy usually relies on dynamic interactions between tumor cells and immunomodulators inside the tumor microenvironment (TME). Depending on the context of these interactions, the TME may play important roles to either dampen or enhance immune responses. Understanding the interactions between immunotherapy and the TME is not only critical to dissect the mechanisms of action but also important to provide new approaches in improving the efficiency of current immunotherapies. In this review, we will highlight recent work on how the TME can influence the efficacy of immunotherapy as well as how manipulating the TME can improve current immunotherapy regimens in some cases.

  19. Hypoallergenic molecules for subcutaneous immunotherapy.

    PubMed

    Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K

    2016-01-01

    Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field.

  20. Hypoallergenic molecules for subcutaneous immunotherapy.

    PubMed

    Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K

    2016-01-01

    Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field. PMID:26558320

  1. New directions in immunotherapy.

    PubMed

    Cox, Linda; Compalati, Enrico; Kundig, Thomas; Larche, Mark

    2013-04-01

    Allergen immunotherapy (AIT) is effective in reducing the clinical symptoms associated with allergic rhinitis, asthma and venom-induced anaphylaxis. Subcutaneous (SCIT) and sublingual immunotherapy (SLIT) with unmodified allergen extracts are the most widely prescribed AIT regimens. The efficacy of these 2 routes appears comparable, but the safety profile with SLIT is more favorable allowing for home administration and requiring less patient time. However, both require that the treatment is taken regularly over several years, e.g., monthly in a supervised medical setting with SCIT and daily at home with SLIT. Despite the difference in treatment settings, poor adherence has been reported with both routes. Emerging evidence suggests that AIT may be effective in other allergic conditions such as atopic dermatitis, venom sting-induced large local reactions, and food allergy. Research with oral immunotherapy (OIT) for food allergies suggest that many patients can be desensitized during treatment, but questions remain about whether this can produce long term tolerance. Further studies are needed to identify appropriate patients and treatment regimens with these conditions. Efforts to develop safer and more effective AIT for inhalant allergies have led to investigations with modified allergens and alternate routes. Intralymphatic (ILIT) has been shown to produce long-lasting clinical benefits after three injections comparable to a 3-year course of SCIT. Epicutaneous (EPIT) has demonstrated promising results for food and inhalant allergies. Vaccine modifications, such as T cell epitopes or the use of viral-like particles as an adjuvant, have been shown to provide sustained clinical benefits after a relatively short course of treatment compared to the currently available AIT treatments, SLIT and SCIT. These newer approaches may increase the utilization and adherence to AIT because the multi-year treatment requirement of currently available AIT is a likely deterrent for

  2. Facility Delivery, Postnatal Care and Neonatal Deaths in India: Nationally-Representative Case-Control Studies

    PubMed Central

    Fadel, Shaza A.; Ram, Usha; Morris, Shaun K.; Begum, Rehana; Shet, Anita; Jotkar, Raju; Jha, Prabhat

    2015-01-01

    Objective Clinical studies demonstrate the efficacy of interventions to reduce neonatal deaths, but there are fewer studies of their real-life effectiveness. In India, women often seek facility delivery after complications arise, rather than to avoid complications. Our objective was to quantify the association of facility delivery and postnatal checkups with neonatal mortality while examining the “reverse causality” in which the mothers deliver at a health facility due to adverse perinatal events. Methods We conducted nationally representative case-control studies of about 300,000 live births and 4,000 neonatal deaths to examine the effect of, place of delivery and postnatal checkup on neonatal mortality. We compared neonatal deaths to all live births and to a subset of live births reporting excessive bleeding or obstructed labour that were more comparable to cases in seeking care. Findings In the larger study of 2004–8 births, facility delivery without postnatal checkup was associated with an increased odds of neonatal death (Odds ratio = 2.5; 99% CI 2.2–2.9), especially for early versus late neonatal deaths. However, use of more comparable controls showed marked attenuation (Odds ratio = 0.5; 0.4–0.5). Facility delivery with postnatal checkup was associated with reduced odds of neonatal death. Excess risks were attenuated in the earlier study of 2001–4 births. Conclusion The combined effect of facility deliveries with postnatal checks ups is substantially higher than just facility delivery alone. Evaluation of the real-life effectiveness of interventions to reduce child and maternal deaths need to consider reverse causality. If these associations are causal, facility delivery with postnatal check up could avoid about 1/3 of all neonatal deaths in India (~100,000/year). PMID:26479476

  3. Trends in use of neonatal CPAP: a population-based study

    PubMed Central

    2011-01-01

    Background Continuous positive airway pressure (CPAP) is used widely to provide respiratory support for neonates, and is often the first treatment choice in tertiary centres. Recent trials have demonstrated that CPAP reduces need for intubation and ventilation for infants born at 25-28 weeks gestation, and at > 32weeks, in non-tertiary hospitals, CPAP reduces need for transfer to NICU. The aim of this study was to examine recent population trends in the use of neonatal continuous positive airway pressure. Methods We undertook a population-based cohort study of all 696,816 liveborn neonates ≥24 weeks gestation in New South Wales (NSW) Australia, 2001-2008. Data were obtained from linked birth and hospitalizations records, including neonatal transfers. The primary outcome was CPAP without mechanical ventilation (via endotracheal intubation) between birth and discharge from the hospital system. Analyses were stratified by age ≤32 and > 32 weeks gestation. Results Neonates receiving any ventilatory support increased from 1,480 (17.9/1000) in 2001 to 2,486 (26.9/1000) in 2008, including 461 (5.6/1000) to 1,465 (15.8/1000) neonates who received CPAP alone. There was a concurrent decrease in mechanical ventilation use from 12.3 to 11.0/1000. The increase in CPAP use was greater among neonates > 32 weeks (from 3.2 to 11.8/1000) compared with neonates ≤32 weeks (from 18.1 to 32.7/1000). The proportion of CPAP > 32 weeks initiated in non-tertiary hospitals increased from 6% to 30%. Conclusions The use of neonatal CPAP is increasing, especially > 32 weeks gestation and among non-tertiary hospitals. Recommendations are required regarding which infants should be considered for CPAP, resources necessary for a unit to offer CPAP and monitoring of longer term outcomes. PMID:21999325

  4. Adherence to Sublingual Immunotherapy.

    PubMed

    Incorvaia, Cristoforo; Mauro, Marina; Leo, Gualtiero; Ridolo, Erminia

    2016-02-01

    Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13% of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment. PMID:26758865

  5. Legal and ethical issues in neonatal nursing: a case study.

    PubMed

    Hagger, Victoria; Ellis, Catherine; Strumidlo, Laura

    2016-06-29

    Neonatal nurses regularly face complex legal and ethical dilemmas. This article discusses the hypothetical case of Jack, a two-day-old infant diagnosed with trisomy 13 (syndrome), a life-limiting condition. Jack's prognosis is poor, and he is not expected to live past two weeks of age. The legal and ethical perspectives of withholding life-sustaining treatment in infants and children will be explored through the application of ethical frameworks, as well as statute and case law relevant to children and adolescent nursing. The article also discusses the neonatal nurse's role, with reference to local and national guidelines. PMID:27353936

  6. A Qualitative Study of Physician Perspectives on Prognostication in Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Rasmussen, Lisa Anne; Bell, Emily; Racine, Eric

    2016-10-01

    Hypoxic ischemic encephalopathy is the most frequent cause of neonatal encephalopathy and yields a great degree of morbidity and mortality. From an ethical and clinical standpoint, neurological prognosis is fundamental in the care of neonates with hypoxic ischemic encephalopathy. This qualitative study explores physician perspectives about neurological prognosis in neonatal hypoxic ischemic encephalopathy. This study aimed, through semistructured interviews with neonatologists and pediatric neurologists, to understand the practice of prognostication. Qualitative thematic content analysis was used for data analysis. The authors report 2 main findings: (1) neurological prognosis remains fundamental to quality-of-life predictions and considerations of best interest, and (2) magnetic resonance imaging is presented to parents with a greater degree of certainty than actually exists. Further research is needed to explore both the parental perspective and, prospectively, the impact of different clinical approaches and styles to prognostication for neonatal hypoxic ischemic encephalopathy.

  7. Potentiality of immunotherapy against hepatocellular carcinoma.

    PubMed

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-09-28

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the new-found field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future.

  8. Epidemiology of Neonatal Sepsis and Implicated Pathogens: A Study from Egypt.

    PubMed

    Shehab El-Din, Eman M Rabie; El-Sokkary, Mohamed M Adel; Bassiouny, Mohamed Reda; Hassan, Ramadan

    2015-01-01

    Prospective analytic study was conducted in NICUs of three Egyptian Neonatal Network (EGNN) participants in Mansoura Hospitals in Egypt over a period of 18 months from March 2011 to August 2012. By using EGNN 28-day discharge form, all demographic, clinical, and laboratory data were recorded and studied. During the study period, 357 neonates were diagnosed as suspected sepsis with an incidence of 45.9% (357/778) among the admitted neonates at the three neonatal intensive care units. 344 neonates (sex ratio = 1.3:1) were enrolled in the study in which 152 (44.2%) were classified as early onset sepsis EOS (≤72 hr) and 192 (55.8%) as late onset sepsis LOS (>72 hr). Among the LOS cases, 33.9% (65/192) were caused by nosocomial infections. In 40.7% (140/344), sepsis was confirmed by positive blood culture. The total mortality rate for the proven neonatal sepsis was 51% (25/49) and 42.9% (39/91) for EOS and LOS, respectively. Coagulase negative staphylococci were predominant isolates in both EOS and LOS, followed by Klebsiella pneumoniae. Most of the bacterial isolates had low sensitivity to the commonly used empiric antibiotics. However, 70.1% (89/127) exhibited multidrug resistance. Best sensitivities among Gram-positive isolates were found against imipenem, ciprofloxacin, vancomycin, and amikacin. PMID:26146621

  9. Epidemiology of Neonatal Sepsis and Implicated Pathogens: A Study from Egypt.

    PubMed

    Shehab El-Din, Eman M Rabie; El-Sokkary, Mohamed M Adel; Bassiouny, Mohamed Reda; Hassan, Ramadan

    2015-01-01

    Prospective analytic study was conducted in NICUs of three Egyptian Neonatal Network (EGNN) participants in Mansoura Hospitals in Egypt over a period of 18 months from March 2011 to August 2012. By using EGNN 28-day discharge form, all demographic, clinical, and laboratory data were recorded and studied. During the study period, 357 neonates were diagnosed as suspected sepsis with an incidence of 45.9% (357/778) among the admitted neonates at the three neonatal intensive care units. 344 neonates (sex ratio = 1.3:1) were enrolled in the study in which 152 (44.2%) were classified as early onset sepsis EOS (≤72 hr) and 192 (55.8%) as late onset sepsis LOS (>72 hr). Among the LOS cases, 33.9% (65/192) were caused by nosocomial infections. In 40.7% (140/344), sepsis was confirmed by positive blood culture. The total mortality rate for the proven neonatal sepsis was 51% (25/49) and 42.9% (39/91) for EOS and LOS, respectively. Coagulase negative staphylococci were predominant isolates in both EOS and LOS, followed by Klebsiella pneumoniae. Most of the bacterial isolates had low sensitivity to the commonly used empiric antibiotics. However, 70.1% (89/127) exhibited multidrug resistance. Best sensitivities among Gram-positive isolates were found against imipenem, ciprofloxacin, vancomycin, and amikacin.

  10. Classification of current anticancer immunotherapies.

    PubMed

    Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, José-Manuel; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P; Coussens, Lisa; Dhodapkar, Madhav V; Eggermont, Alexander M; Fearon, Douglas T; Fridman, Wolf H; Fučíková, Jitka; Gabrilovich, Dmitry I; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M; Klein, Eva; Knuth, Alexander; Lewis, Claire E; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J; Mittendorf, Elizabeth A; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E; Pienta, Kenneth J; Porgador, Angel; Prendergast, George C; Rabinovich, Gabriel A; Restifo, Nicholas P; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J; Speiser, Daniel E; Spisek, Radek; Srivastava, Pramod K; Talmadge, James E; Tartour, Eric; Van Der Burg, Sjoerd H; Van Den Eynde, Benoît J; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S; Whiteside, Theresa L; Wolchok, Jedd D; Zitvogel, Laurence; Zou, Weiping; Kroemer, Guido

    2014-12-30

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.

  11. Classification of current anticancer immunotherapies

    PubMed Central

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  12. Classification of current anticancer immunotherapies.

    PubMed

    Galluzzi, Lorenzo; Vacchelli, Erika; Bravo-San Pedro, José-Manuel; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P; Coussens, Lisa; Dhodapkar, Madhav V; Eggermont, Alexander M; Fearon, Douglas T; Fridman, Wolf H; Fučíková, Jitka; Gabrilovich, Dmitry I; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M; Klein, Eva; Knuth, Alexander; Lewis, Claire E; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J; Mittendorf, Elizabeth A; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E; Pienta, Kenneth J; Porgador, Angel; Prendergast, George C; Rabinovich, Gabriel A; Restifo, Nicholas P; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J; Speiser, Daniel E; Spisek, Radek; Srivastava, Pramod K; Talmadge, James E; Tartour, Eric; Van Der Burg, Sjoerd H; Van Den Eynde, Benoît J; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S; Whiteside, Theresa L; Wolchok, Jedd D; Zitvogel, Laurence; Zou, Weiping; Kroemer, Guido

    2014-12-30

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  13. [Immunotherapy of malignant diseases].

    PubMed

    Dorval, T; Michon, J; Tartour, E; Fridman, W H

    1995-01-01

    Cancer immunotherapy has been carried out since the early fifties and first involved nonspecific system (BCG, Corynebacterium parvum, levamisole...). More recently, the production of cytokines as interferons or interleukin 2, the introduction of monoclonal antibodies have allowed a new development to cancer immunotherapy. Nevertheless, these new approaches have to be considered as a step in the biological therapy of cancer.

  14. [Immunotherapy of malignant diseases].

    PubMed

    Dorval, T; Michon, J; Tartour, E; Fridman, W H

    1995-01-01

    Cancer immunotherapy has been carried out since the early fifties and first involved nonspecific system (BCG, Corynebacterium parvum, levamisole...). More recently, the production of cytokines as interferons or interleukin 2, the introduction of monoclonal antibodies have allowed a new development to cancer immunotherapy. Nevertheless, these new approaches have to be considered as a step in the biological therapy of cancer. PMID:7542946

  15. [Neonatal deafness screening with the evoked otoacoustic emissions technique. Study of 320 newborns at the neonatal resuscitation service of the Amiens neonatal care unit].

    PubMed

    Ayache, S; Kolski, C; Stramandinoli, E; Leke, A; Krim, G; Strunski, V

    2001-04-01

    Between January 1997 and June 1999, we screened for hearing loss using evoked otoacoustic emissions in 320 newborns in the neonate intensive care unit at the Amiens University Hospital. The purpose of this study was to search for correlations between deafness and one of the hearing loss risk factors identified by the Joint Committee on Infant Screening. Three risk factors were found to be significant: craniofacial abnormalities, low birth weight (less than 1500 g) and a familial history of hearing loss. Unfortunately a large proportion of the infants were lost to follow-up. Evoked otoacoustic emission provide an excellent screening technique for hearing loss in newborns. Such screening implies however the creation of networks to assure patient follow-up.

  16. Neonatal ECMO Study of Temperature (NEST) - a randomised controlled trial

    PubMed Central

    2010-01-01

    Background Existing evidence indicates that once mature neonates with severe cardio-respiratory failure become eligible for Extra Corporeal Membrane Oxygenation (ECMO) their chances of intact survival are doubled if they actually receive ECMO. However, significant numbers survive with disability. NEST is a multi-centre randomised controlled trial designed to test whether, in neonates requiring ECMO, cooling to 34°C for the first 48 to 72 hours of their ECMO course leads to improved later health status. Infants allocated to the control group will receive ECMO at 37°C throughout their course, which is currently standard practice around the world. Health status of both groups will be assessed formally at 2 years corrected age. Methods/Design All infants recruited to the study will be cared for in one of the four United Kingdom (UK) ECMO centres. Babies who are thought to be eligible will be assessed by the treating clinician who will confirm eligibility, ensure that consent has been obtained and then randomise the baby using a web based system, based at the National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit. Trial registration. Babies allocated ECMO without cooling will receive ECMO at 37°C ± 0.2°C. Babies allocated ECMO with cooling will be managed at 34°C ± 0.2°C for up to 72 hours from the start of their ECMO run. The minimum duration of cooling will be 48 hours. Rewarming (to 37°C) will occur at a rate of no more than 0.5°C per hour. All other aspects of ECMO management will be identical. Primary outcome: Cognitive score from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) at age of 2 years (24 - 27 months). Discussion For the primary analysis, children will be analysed in the groups to which they are assigned, comparing the outcome of all babies allocated to "ECMO with cooling" with all those allocated to "ECMO" alone, regardless of deviation from the protocol or treatment received. For the primary outcome the

  17. The Impact of Recycled Neonatal Incubators in Nigeria: A 6-Year Follow-Up Study

    PubMed Central

    Amadi, Hippolite Onyejiaka; Azubuike, Jonathan C.; Etawo, Uriah S.; Offiong, Uduak R.; Ezeaka, Chinyere; Olateju, Eyinade; Adimora, Gilbert N.; Osibogun, Akin; Ibeziako, Ngozi; Iroha, Edna O.; Dutse, Abdulhameed I.; Chukwu, Christian O.; Okpere, Eugene E.; Kawuwa, Mohammed B.; El-Nafaty, Aliyu U.; Kuranga, Sulyman A.; Mokuolu, Olugbenga Ayodeji

    2010-01-01

    Nigeria has a record of high newborn mortality as an estimated 778 babies die daily, accounting for a ratio of 48 deaths per 1000 live births. The aim of this paper was to show how a deteriorating neonatal delivery system in Nigeria may have, in part, been improved by the application of a novel recycled incubator technique (RIT). Retrospective assessment of clinical, technical, and human factors in 15 Nigerian neonatal centres was carried out to investigate how the application of RIT impacted these factors. Pre-RIT and post-RIT neonatal mortalities were compared by studying case files. Effect on neonatal nursing was studied through questionnaires that were completed by 79 nurses from 9 centres across the country. Technical performance was assessed based on 10-indices scores from clinicians and nurses. The results showed an increase in neonatal survival, nursing enthusiasm, and practice confidence. Appropriately recycled incubators are good substitutes to the less affordable modern incubators in boosting neonatal practice outcome in low-income countries. PMID:21331375

  18. Timing of Caffeine Therapy and Neonatal Outcomes in Preterm Infants: A Retrospective Study.

    PubMed

    Hand, Ivan; Zaghloul, Nahla; Barash, Lily; Parris, Rudolph; Aden, Ulrika; Li, Hsiu-Ling

    2016-01-01

    Background. Caffeine is widely used to treat apnea of prematurity. Here, we evaluated the efficacy of early caffeine (1-2 DOL) in decreasing the incidence of adverse neonatal outcomes. Methods. A retrospective cohort was used to compare the neonatal morbidity of 150 preterm neonates with gestational age ≤29 weeks. Infants were divided into 3 groups based on the initiation timing of caffeine therapy; (1) early caffeine (1-2 DOL), (2) late caffeine (3-7 DOL), and (3) very late caffeine (≥8 DOL). Results. The neonatal outcomes of early caffeine were comparable with those of the late caffeine group. Moreover, when comparing the neonatal morbidity of the very late caffeine group with that of the early caffeine group, multivariable logistic regression analyses were performed. We found that the timing of caffeine did not influence the risk of BPD (OR, 0.393; CI, 0.126-1.223; p = 0.107), but birthweight did (OR, 0.996; CI, 0.993-0.999; p = 0.018) in these infants. Conclusion. Neonatal outcomes of preterm infants were comparable whether caffeine was administered early or late in the first 7 DOL. The risk of BPD in infants receiving caffeine after 8 DOL was irrespective of delayed treatment with caffeine. Our results clearly demonstrate the need for further studies before caffeine prophylaxis can be universally recommended.

  19. Timing of Caffeine Therapy and Neonatal Outcomes in Preterm Infants: A Retrospective Study

    PubMed Central

    Hand, Ivan; Zaghloul, Nahla; Barash, Lily; Parris, Rudolph; Aden, Ulrika; Li, Hsiu-Ling

    2016-01-01

    Background. Caffeine is widely used to treat apnea of prematurity. Here, we evaluated the efficacy of early caffeine (1-2 DOL) in decreasing the incidence of adverse neonatal outcomes. Methods. A retrospective cohort was used to compare the neonatal morbidity of 150 preterm neonates with gestational age ≤29 weeks. Infants were divided into 3 groups based on the initiation timing of caffeine therapy; (1) early caffeine (1-2 DOL), (2) late caffeine (3–7 DOL), and (3) very late caffeine (≥8 DOL). Results. The neonatal outcomes of early caffeine were comparable with those of the late caffeine group. Moreover, when comparing the neonatal morbidity of the very late caffeine group with that of the early caffeine group, multivariable logistic regression analyses were performed. We found that the timing of caffeine did not influence the risk of BPD (OR, 0.393; CI, 0.126–1.223; p = 0.107), but birthweight did (OR, 0.996; CI, 0.993–0.999; p = 0.018) in these infants. Conclusion. Neonatal outcomes of preterm infants were comparable whether caffeine was administered early or late in the first 7 DOL. The risk of BPD in infants receiving caffeine after 8 DOL was irrespective of delayed treatment with caffeine. Our results clearly demonstrate the need for further studies before caffeine prophylaxis can be universally recommended. PMID:27242907

  20. Neonatal catecholamine levels and neurodevelopmental outcome: a cohort study

    PubMed Central

    Evans, D; MacGregor, R; Dean, H; Levene, M

    2001-01-01

    AIMS—To determine whether neonatal plasma catecholamine concentrations can be used to predict (a) death plus disability and (b) motor and cognitive impairment at 5 years of age.
METHODS—A cohort comprised 136 preterm infants from two randomised controlled trials of neonatal sedation (1989-1992). Adrenaline (epinephrine) and noradrenaline (norepinephrine) were measured at baseline (first day) and 24 hours later. Intelligence and motor ability were assessed at 5-6 years.
RESULTS—Infants who died or sustained disability had significantly higher plasma noradrenaline levels on the second day of life. Noradrenaline levels above 9.0 nmol/l were most predictive of death (likelihood ratio 3.27; 95% confidence interval 1.48 to 7.23) and death plus disability (likelihood ratio 3.55; 95% confidence interval 1.77to 7.10). There was no correlation between neonatal catecholamine levels and cognitive or motor impairment at 5-6 years.
CONCLUSIONS—Elevated noradrenaline levels are associated with adverse outcome in preterm infants; however, the power to predict death or disability is limited and they are not predictive of later motor or cognitive impairment.

 PMID:11124926

  1. Immunotherapy in Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-01-01

    Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

  2. Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology.

    PubMed

    Selby, Mark J; Engelhardt, John J; Johnston, Robert J; Lu, Li-Sheng; Han, Minhua; Thudium, Kent; Yao, Dapeng; Quigley, Michael; Valle, Jose; Wang, Changyu; Chen, Bing; Cardarelli, Pina M; Blanset, Diann; Korman, Alan J

    2016-01-01

    The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical development strategy that predicted these clinical results. Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was observed with concurrent, but not sequential CTLA-4 and PD-1 blockade. Significant antitumor activity was maintained using a fixed dose of anti-CTLA-4 antibody with decreasing doses of anti-PD-1 antibody in the MC38 model. Immunohistochemical and flow cytometric analyses confirmed that CD3+ T cells accumulated at the tumor margin and infiltrated the tumor mass in response to the combination therapy, resulting in favorable effector and regulatory T-cell ratios, increased pro-inflammatory cytokine secretion, and activation of tumor-specific T cells. Similarly, in vitro studies with combined ipilimumab and nivolumab showed enhanced cytokine secretion in superantigen stimulation of human peripheral blood lymphocytes and in mixed lymphocyte response assays. In a cynomolgus macaque toxicology study, dose-dependent immune-related gastrointestinal inflammation was observed with the combination therapy; this response had not been observed in previous single agent cynomolgus studies. Together, these in vitro assays and in vivo models comprise a preclinical strategy for the identification and development of highly effective antitumor combination immunotherapies. PMID:27610613

  3. Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology

    PubMed Central

    Selby, Mark J.; Engelhardt, John J.; Johnston, Robert J.; Lu, Li-Sheng; Han, Minhua; Thudium, Kent; Yao, Dapeng; Quigley, Michael; Valle, Jose; Wang, Changyu; Chen, Bing; Cardarelli, Pina M.; Blanset, Diann; Korman, Alan J.

    2016-01-01

    The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical development strategy that predicted these clinical results. Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was observed with concurrent, but not sequential CTLA-4 and PD-1 blockade. Significant antitumor activity was maintained using a fixed dose of anti-CTLA-4 antibody with decreasing doses of anti-PD-1 antibody in the MC38 model. Immunohistochemical and flow cytometric analyses confirmed that CD3+ T cells accumulated at the tumor margin and infiltrated the tumor mass in response to the combination therapy, resulting in favorable effector and regulatory T-cell ratios, increased pro-inflammatory cytokine secretion, and activation of tumor-specific T cells. Similarly, in vitro studies with combined ipilimumab and nivolumab showed enhanced cytokine secretion in superantigen stimulation of human peripheral blood lymphocytes and in mixed lymphocyte response assays. In a cynomolgus macaque toxicology study, dose-dependent immune-related gastrointestinal inflammation was observed with the combination therapy; this response had not been observed in previous single agent cynomolgus studies. Together, these in vitro assays and in vivo models comprise a preclinical strategy for the identification and development of highly effective antitumor combination immunotherapies. PMID:27610613

  4. A randomized trial of immunotherapy for persistent genital warts

    PubMed Central

    Jardine, David; Lu, Jieqiang; Pang, James; Palmer, Cheryn; Tu, Quanmei; Chuah, John; Frazer, Ian H.

    2012-01-01

    Aim To determine whether immunotherapy with HPV6 L1 virus like particles (VLPs) without adjuvant (VLP immunotherapy) reduces recurrence of genital warts following destructive therapy. Trial design A randomized placebo controlled blinded study of treatment of recurrent genital warts amenable to destructive therapy, conducted independently in Australia and China. Methods Patients received conventional destructive therapy of all evident warts together with intramuscular administration of 1, 5 or 25 µg of VLP immunotherapy, or of placebo immunotherapy (0.9% NaCl), as immunotherapy at week 0 and week 4. Primary outcome, assessed at week 8, was recurrence of visible warts. Results Of 33 protocol compliant Brisbane recipients of placebo immunotherapy, 11 were disease free at two months, and a further 9 demonstrated reduction of > 50% in total wart area. Wart area reduction following destructive treatment correlated with prior duration of disease. Among 102 protocol compliant Brisbane recipients of VLP immunotherapy, disease reduction was significantly greater than among the placebo immunotherapy (50% ± s.e.m. 7%) recipients for subjects receiving 5 µg or 25 µg of VLP immunotherapy/dose (71% ± s.e.m.7%) but not for those receiving 1 µg VLP immunotherapy/dose (42% ± 7%). Of 52 protocol compliant placebo immunotherapy recipients in Wenzhou, 37 were disease free at two months, and a further 8 had > 50% disease reduction. Prior disease duration was much shorter in Wenzhou subject (8.1 ± 1.1 mo) than in Brisbane subjects (53.7 ± 5.5 mo). No significant reduction in mean wart area was observed for the 168 Wenzhou protocol compliant subjects who also received VLP immunotherapy. Conclusions This study confirms the findings in a previous open label trial that administration of VLP immunotherapy may assist in clearance of recurrent genital warts in patients for whom destructive therapy is unsuccessful and that unsuccessful destructive therapy is more common with increasing

  5. Allergen-specific immunotherapy in atopic eczema.

    PubMed

    Darsow, Ulf; Forer, Ingeborg; Ring, Johannes

    2011-08-01

    Aeroallergens are relevant eliciting factors of allergic rhinoconjunctivitis and bronchial asthma but also of atopic eczema. The use of allergen-specific immunotherapy as in respiratory atopic diseases is controversial in patients with atopic eczema, but refined diagnostic methods to characterize subgroups of patients with relevant allergies and the results of smaller controlled studies give rise to new approaches in this field. This article reviews the theoretical problems and practical results associated with allergen-specific immunotherapy in atopic eczema. PMID:21461718

  6. Efficacy of grass-maize pollen oral immunotherapy in patients with seasonal hay-fever: a double-blind study.

    PubMed

    Van Niekerk, C H; De Wet, J I

    1987-11-01

    Forty patients with a well-documented history of seasonal hay fever and a positive skin-prick test specific to grass pollen, including Bermuda grass and maize pollen (Zea maize), were allocated randomly on a double-blind basis to receive either an oral mixed grass-maize pollen extract or a matched placebo during the 1981/1982 grass pollen season. After 12 months the code was broken and patients on placebo were transferred to active therapy while patients on active therapy continued with maintenance therapy for another 12 months during the 1982/1983 grass pollen season. The assessment of the effect of the orally administered grass-maize pollen extract was on the clinical symptoms. During the first year the patients on active therapy had significantly fewer hay fever symptoms during the summer months compared with the placebo group. During the second study year, with all patients on active therapy, both groups had markedly milder symptoms compared with the placebo group. Side-effects were negligible. This study concludes that oral immunotherapy with grass-maize pollen extract in grass pollen-sensitive seasonal hay fever patients is safe and effective.

  7. Neonatal jaundice, aflatoxins and naphthols: report of a study in Ibadan, Nigeria.

    PubMed

    Sodeinde, O; Chan, M C; Maxwell, S M; Familusi, J B; Hendrickse, R G

    1995-06-01

    This study set out to investigate the prevalence of naphthols and aflatoxins in the sera of babies with neonatal jaundice and their mothers in order to determine whether they contribute to the occurrence of unexplained neonatal jaundice in Ibadan. Blood was obtained from 327 jaundiced neonates and 80 of their mothers, and 60 non-jaundiced controls and seven of their mothers admitted to hospital between April 1989 and April 1991. Blood group, bilirubin concentration, erythrocyte G6PD status, aflatoxin and naphthol concentrations in blood were measured. Altogether, 30.9% of the jaundiced neonates were G6PD-deficient, compared with 13.3% of controls (chi 2 = 6.88; p = 0.009). Aflatoxins were detected in 27.4% of jaundiced neonates, 17% of their mothers, 16.6% of controls and 14.4% of control mothers. Naphthols were detected in 7.2% of jaundiced babies, 6.3% of their mothers, 6.25% of control babies and 14.4% of their mothers. Analysis of the data revealed that either G6PD deficiency or the presence of any serum aflatoxin is a risk factor for neonatal jaundice; odds ratio were 2.97 (95%) confidence intervals (CI): 1.31-6.74) and 2.68 (CI: 1.18-6.10), respectively. This study demonstrates that G6PD deficiency and/or the presence of serum aflatoxins are risk factors for neonatal jaundice in Nigeria. Aflatoxins are an additional risk factor not previously reported.

  8. Quantity and Timing of Maternal Prenatal Smoking on Neonatal Body Composition: The Healthy Start Study

    PubMed Central

    Harrod, Curtis S; Reynolds, Regina M; Chasan-Taber, Lisa; Fingerlin, Tasha E; Glueck, Deborah H; Brinton, John T; Dabelea, Dana

    2014-01-01

    Objective To examine the dose-dependent and time-specific relationships of prenatal smoking with neonatal body mass, fat mass (FM), fat-free mass (FFM) and fat to fat-free mass ratio (F:FFM), as measured by air displacement plethysmography (PEA POD). Study design We analyzed 916 mother-neonate pairs participating in the longitudinal pre-birth cohort study, Healthy Start. Maternal prenatal smoking information was collected in early-, mid- and late-pregnancy by self-report. Neonatal body composition was measured by PEA POD following delivery. Multiple general linear regression models were adjusted for maternal and neonatal characteristics. Results For each additional pack smoked during pregnancy, neonatal body mass was significantly reduced (adjusted mean difference: −2.8 grams; 95% confidence interval [CI]: −3.9 to −1.8; P<0.001), FM (−0.7 g [−1.1 to −0.3]; P<0.001) and FFM (−2.1 g [−2.9 to −1.3]; P<0.001). Neonates exposed to prenatal smoking throughout pregnancy had significantly less body mass (P<0.001), FM (P<0.001) and FFM (P <0.001) compared with those unexposed. However, neonates of mothers who only smoked before late-pregnancy had no significant differences in body mass (P = 0.47), FM (P = 0.43) or FFM (P = 0.59) compared with unexposed offspring. Conclusions Exposure to prenatal smoking leads to systematic growth restriction. Smoking cessation before late-pregnancy may reduce the body composition consequences of exposure to prenatal smoking. Follow-up of this cohort is needed to determine the influence of catch-up growth on early-life body composition and the risk of childhood obesity. PMID:25063722

  9. Maternal Fuels and Metabolic Measures During Pregnancy and Neonatal Body Composition: The Healthy Start Study

    PubMed Central

    Shapiro, Allison L.; Brinton, John T.; Glueck, Deborah H.; Martinez, Mercedes; Kohn, Mary; Harrod, Curtis; Friedman, Jacob E.; Dabelea, Dana

    2015-01-01

    Context: The impact of specific maternal fuels and metabolic measures during early and late gestation on neonatal body composition is not well defined. Objective: To determine how circulating maternal glucose, lipids, and insulin resistance in the first and second halves of pregnancy influence neonatal body composition. Design: A prospective pre-birth cohort enrolling pregnant women, the Healthy Start Study, was conducted, in which fasting maternal serum samples were collected twice during pregnancy to measure glucose, insulin, hemoglobin A1c, triglyceride, total cholesterol, high-density lipoprotein, and free fatty acids. Neonatal body composition was measured with air displacement plethysmography. Setting: An observational epidemiology study of pregnant women attending obstetric clinics at the University of Colorado, Anschutz Medical Center. Participants: This analysis includes 804 maternal-neonate pairs. Results: A strong positive linear relationship between maternal estimated insulin resistance (homeostasis model of assessment for insulin resistance) in the first half of pregnancy and neonatal fat mass (FM) and FM percentage (FM%) was detected, independent of prepregnancy body mass index (BMI). In the second half of pregnancy, positive linear relationships between maternal glucose levels and offspring FM and FM% were observed, independent of prepregnancy BMI. An inverse relationship was detected between high-density lipoprotein in the first half of pregnancy and FM, independent of prepregnancy BMI. Free fatty acid levels in the second half of pregnancy were positively associated with higher birth weight, independent of prepregnancy BMI. Conclusion: Maternal insulin resistance in the first half of pregnancy is highly predictive of neonatal FM%, whereas maternal glycemia, even within the normal range, is an important driver of neonatal adiposity in later pregnancy, independent of prepregnancy BMI. Our data provide additional insights on potential maternal factors

  10. A practical view of immunotherapy for food allergy

    PubMed Central

    2016-01-01

    Food allergy is common and sometimes life threatening for Korean children. The current standard treatment of allergen avoidance and self-injectable epinephrine does not change the natural course of food allergy. Recently, oral, sublingual, and epicutaneous immunotherapies have been studied for their effectiveness against food allergy. While various rates of desensitization (36% to 100%) and tolerance (28% to 75%) have been induced by immunotherapies for food allergy, no single established protocol has been shown to be both effective and safe. In some studies, immunologic changes after immunotherapy for food allergy have been revealed. Adverse reactions to these immunotherapies have usually been localized, but severe systemic reactions have been observed in some cases. Although immunotherapy cannot be recommended for routine practice yet, results from recent studies demonstrate that immunotherapies are promising for the treatment of food allergy. PMID:26958062

  11. Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: Case study

    PubMed Central

    Heimberger, Amy B.; Sun, Wei; Hussain, S. Farzana; Dey, Mahua; Crutcher, Lamonne; Aldape, Ken; Gilbert, Mark; Hassenbusch, Samuel J.; Sawaya, Raymond; Schmittling, Bob; Archer, Gary E.; Mitchell, Duane A.; Bigner, Darell D.; Sampson, John H.

    2008-01-01

    Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemo-therapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell count, specifically the CD4 and CD8 counts, there was no cumulative decline in the patient described in this case report. Depriving patients of this agent, in order to treat with immunotherapy, is controversial. Despite conventional dogma, we demonstrated that chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide-induced lymphopenia may prove to be synergistic with a peptide vaccine secondary to inhibition of regulatory T cells or their delayed recovery. PMID:18079360

  12. Immunotherapy prolongs the serum CEA-TPA-CA15.3 lead time at the metastatic progression in endocrine-dependent breast cancer patients: a retrospective longitudinal study.

    PubMed

    Nicolini, A; Carpi, A; Ferrari, P; Rossi, G

    2008-05-01

    In metastatic breast cancer tumour markers' increase predicts, by a few months (lead time) disease progression. In breast cancer patients with endocrine dependent metastatic disease, we reported a prolonged clinical benefit and overall survival when first line conventional antiestrogen hormone therapy was started at the lead time and also when an immunotherapy schedule was added to the same conventional hormone treatment. Thirty-two of these last patients were considered (group a). In 27 (group b) of these 32 patients who progressed during first line salvage hormone plus immunotherapy the lead time at the progression of metastatic disease during therapy was compared with that at the onset of metastases when the same patients were without treatment and with that of a control group (group c) who did not receive immunotherapy. At disease progression, CEA-TPA-CA15.3 sensitivity was 92.5% in the group b (studied patients) and 88.5% in the group c (controls). At the progression in the group b, CEA-TPA-CA15.3 lead time (m+/-sd, months) was significantly longer than in group c (12.1+/-12.9 vs 2.4+/-4.0) (P=0.000). Besides, in group b the lead time was significantly longer at the progression than at the metastatic onset (P=0.003) while in the group c the difference was near to significance (P=0.05). The CEA-TPA-CA15.3 tumour marker panel accurately predicted metastatic disease progression and immunotherapy significantly prolonged the CEA-TPA-CA15.3 lead time. This can be used for anticipating salvage treatment in these patients.

  13. Defining the critical hurdles in cancer immunotherapy

    PubMed Central

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  14. Defining the critical hurdles in cancer immunotherapy.

    PubMed

    Fox, Bernard A; Schendel, Dolores J; Butterfield, Lisa H; Aamdal, Steinar; Allison, James P; Ascierto, Paolo Antonio; Atkins, Michael B; Bartunkova, Jirina; Bergmann, Lothar; Berinstein, Neil; Bonorino, Cristina C; Borden, Ernest; Bramson, Jonathan L; Britten, Cedrik M; Cao, Xuetao; Carson, William E; Chang, Alfred E; Characiejus, Dainius; Choudhury, A Raja; Coukos, George; de Gruijl, Tanja; Dillman, Robert O; Dolstra, Harry; Dranoff, Glenn; Durrant, Lindy G; Finke, James H; Galon, Jerome; Gollob, Jared A; Gouttefangeas, Cécile; Grizzi, Fabio; Guida, Michele; Håkansson, Leif; Hege, Kristen; Herberman, Ronald B; Hodi, F Stephen; Hoos, Axel; Huber, Christoph; Hwu, Patrick; Imai, Kohzoh; Jaffee, Elizabeth M; Janetzki, Sylvia; June, Carl H; Kalinski, Pawel; Kaufman, Howard L; Kawakami, Koji; Kawakami, Yutaka; Keilholtz, Ulrich; Khleif, Samir N; Kiessling, Rolf; Kotlan, Beatrix; Kroemer, Guido; Lapointe, Rejean; Levitsky, Hyam I; Lotze, Michael T; Maccalli, Cristina; Maio, Michele; Marschner, Jens-Peter; Mastrangelo, Michael J; Masucci, Giuseppe; Melero, Ignacio; Melief, Cornelius; Murphy, William J; Nelson, Brad; Nicolini, Andrea; Nishimura, Michael I; Odunsi, Kunle; Ohashi, Pamela S; O'Donnell-Tormey, Jill; Old, Lloyd J; Ottensmeier, Christian; Papamichail, Michael; Parmiani, Giorgio; Pawelec, Graham; Proietti, Enrico; Qin, Shukui; Rees, Robert; Ribas, Antoni; Ridolfi, Ruggero; Ritter, Gerd; Rivoltini, Licia; Romero, Pedro J; Salem, Mohamed L; Scheper, Rik J; Seliger, Barbara; Sharma, Padmanee; Shiku, Hiroshi; Singh-Jasuja, Harpreet; Song, Wenru; Straten, Per Thor; Tahara, Hideaki; Tian, Zhigang; van Der Burg, Sjoerd H; von Hoegen, Paul; Wang, Ena; Welters, Marij Jp; Winter, Hauke; Withington, Tara; Wolchok, Jedd D; Xiao, Weihua; Zitvogel, Laurence; Zwierzina, Heinz; Marincola, Francesco M; Gajewski, Thomas F; Wigginton, Jon M; Disis, Mary L

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  15. Defining the critical hurdles in cancer immunotherapy.

    PubMed

    Fox, Bernard A; Schendel, Dolores J; Butterfield, Lisa H; Aamdal, Steinar; Allison, James P; Ascierto, Paolo Antonio; Atkins, Michael B; Bartunkova, Jirina; Bergmann, Lothar; Berinstein, Neil; Bonorino, Cristina C; Borden, Ernest; Bramson, Jonathan L; Britten, Cedrik M; Cao, Xuetao; Carson, William E; Chang, Alfred E; Characiejus, Dainius; Choudhury, A Raja; Coukos, George; de Gruijl, Tanja; Dillman, Robert O; Dolstra, Harry; Dranoff, Glenn; Durrant, Lindy G; Finke, James H; Galon, Jerome; Gollob, Jared A; Gouttefangeas, Cécile; Grizzi, Fabio; Guida, Michele; Håkansson, Leif; Hege, Kristen; Herberman, Ronald B; Hodi, F Stephen; Hoos, Axel; Huber, Christoph; Hwu, Patrick; Imai, Kohzoh; Jaffee, Elizabeth M; Janetzki, Sylvia; June, Carl H; Kalinski, Pawel; Kaufman, Howard L; Kawakami, Koji; Kawakami, Yutaka; Keilholtz, Ulrich; Khleif, Samir N; Kiessling, Rolf; Kotlan, Beatrix; Kroemer, Guido; Lapointe, Rejean; Levitsky, Hyam I; Lotze, Michael T; Maccalli, Cristina; Maio, Michele; Marschner, Jens-Peter; Mastrangelo, Michael J; Masucci, Giuseppe; Melero, Ignacio; Melief, Cornelius; Murphy, William J; Nelson, Brad; Nicolini, Andrea; Nishimura, Michael I; Odunsi, Kunle; Ohashi, Pamela S; O'Donnell-Tormey, Jill; Old, Lloyd J; Ottensmeier, Christian; Papamichail, Michael; Parmiani, Giorgio; Pawelec, Graham; Proietti, Enrico; Qin, Shukui; Rees, Robert; Ribas, Antoni; Ridolfi, Ruggero; Ritter, Gerd; Rivoltini, Licia; Romero, Pedro J; Salem, Mohamed L; Scheper, Rik J; Seliger, Barbara; Sharma, Padmanee; Shiku, Hiroshi; Singh-Jasuja, Harpreet; Song, Wenru; Straten, Per Thor; Tahara, Hideaki; Tian, Zhigang; van Der Burg, Sjoerd H; von Hoegen, Paul; Wang, Ena; Welters, Marij Jp; Winter, Hauke; Withington, Tara; Wolchok, Jedd D; Xiao, Weihua; Zitvogel, Laurence; Zwierzina, Heinz; Marincola, Francesco M; Gajewski, Thomas F; Wigginton, Jon M; Disis, Mary L

    2011-12-14

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  16. A Pilot Metabolic Profiling Study of Patients With Neonatal Jaundice and Response to Phototherapy.

    PubMed

    Cai, A; Qi, S; Su, Z; Shen, H; Yang, Y; Cai, W; Dai, Y

    2016-08-01

    Phototherapy has been widely used in treating neonatal jaundice, but detailed metabonomic profiles of neonatal jaundice patients and response to phototherapy have not been characterized. Our aim was to depict the serum metabolic characteristics of neonatal jaundice patients relative to controls and changes in response to phototherapy. A (1) H nuclear magnetic resonance (NMR)-based metabonomic approach was employed to study the metabolic profiling of serum from healthy infants (n = 25) and from infants with neonatal jaundice (n = 30) pre- and postphototherapy. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA). The PLS-DA and OPLS-DA model identified nine metabolites capable of distinguishing patients from controls. In addition, 28 metabolites such as β-glucose, α-glucose, valine, and pyruvate changed in response to phototherapy. This study offers useful information on metabolic disorders in neonatal jaundice patients and the effects of phototherapy on lipids, amino acid, and energy metabolism. PMID:27306191

  17. Trends in Cancer Immunotherapy

    PubMed Central

    Murphy, Joseph F.

    2010-01-01

    Modulation of the immune system for therapeutic ends has a long history, stretching back to Edward Jenner’s use of cowpox to induce immunity to smallpox in 1796. Since then, immunotherapy, in the form of prophylactic and therapeutic vaccines, has enabled doctors to treat and prevent a variety of infectious diseases, including cholera, poliomyelitis, diphtheria, measles and mumps. Immunotherapy is now increasingly being applied to oncology. Cancer immunotherapy attempts to harness the power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is capable of recognizing and eliminating tumor cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for cancer immunotherapy is to apply advances in cellular and molecular immunology and develop strategies that effectively and safely augment antitumor responses. PMID:20703326

  18. Immunotherapy for Cervical Cancer

    Cancer.gov

    In an early phase NCI clinical trial, two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer.

  19. Cancer immunotherapy in children

    Cancer.gov

    More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient

  20. IMMUNOTHERAPY IN ACUTE LEUKEMIA

    PubMed Central

    Leung, Wing

    2010-01-01

    Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371

  1. A randomized controlled study of peanut oral immunotherapy (OIT): clinical desensitization and modulation of the allergic response

    PubMed Central

    Varshney, Pooja; Jones, Stacie M.; Scurlock, Amy M.; Perry, Tamara T.; Kemper, Alex; Steele, Pamela; Hiegel, Anne; Kamilaris, Janet; Carlisle, Suzanne; Yue, Xiaohong; Kulis, Mike; Pons, Laurent; Vickery, Brian; Burks, A. Wesley

    2011-01-01

    Background Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials. Objective To investigate the safety and effectiveness of OIT for peanut allergy in a double blind, placebo-controlled study. Methods In this multicenter study, peanut-allergic children ages 1-16 years received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge at approximately one year. Titrated skin prick tests (SPT) and laboratory studies were performed at regular intervals. Results Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study due to allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (N=16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), while placebo subjects (N=9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg) [p<0.001]. In contrast to the placebo group, the peanut OIT group showed reductions in SPT size (p<0.001), IL-5 (p=0.01), and IL-13 (p=0.02) and increases in peanut-specific IgG4 (p<0.001). Peanut OIT subjects had initial increases in peanut-specific IgE (p<0.01) but did not show significant change from baseline by the time of OFC. The ratio of FoxP3 hi: FoxP3 intermediate CD4+CD25+ T cells increased at the time of OFC (p=0.04) in peanut OIT subjects. Conclusion These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The present study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance. PMID:21377034

  2. Lentiviral vectors in cancer immunotherapy.

    PubMed

    Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

    2015-01-01

    Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

  3. The future of sublingual immunotherapy.

    PubMed

    Marcucci, F; Duse, M; Frati, F; Incorvaia, C; Marseglia, G L; La Rosa, M

    2009-01-01

    Sublingual immunotherapy (SLIT) is currently the most prescribed form of allergen immunotherapy in many European countries. Its use has been accepted in the international consensus publications, and recently also the scepticism of USA scientists is attenuated. Still, this treatment may be improved, and the possible developments consist of modification of the materials, use of adjuvants and use of recombinant allergens. Moreover, new applications of SLIT, such as food allergy, seem promising. Concerning materials, the future form of SLIT is likely to be represented by tablets, which were already tested for efficacy and safety with grass pollen extracts, and are likely to increase the convenience for the patient by the use of no-updosing schedule. Adjuvants fitting with the characteristics of SLIT seem to be CpG oligodeoxynucleotides (CpG), able to interact with the Toll-like receptor 9 (TLR9) whose activation induces a Th1-like pattern of cytokine release, combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3-Dex), and Lactobacillus plantarum. The approach with recombinant allergens, named component-resolved diagnosis, offers the possibility to tailor immunotherapy, which was found to be effective in two randomized trials of subcutaneous SIT (16-17), while studies with SLIT are not yet available. Regarding food allergy, an important controlled study demonstrated that SLIT with hazelnut is able to increase patients tolerance over possible reactions from inadvertent assumption of the culprit food, and warrants for further trials with other foods. PMID:19944008

  4. Prenatal, Perinatal, and Neonatal Risk Factors for Specific Language Impairment: A Prospective Pregnancy Cohort Study

    ERIC Educational Resources Information Center

    Whitehouse, Andrew J. O.; Shelton, W. M. R.; Ing, Caleb; Newnham, John P.

    2014-01-01

    Purpose: Although genetic factors are known to play a causal role in specific language impairment (SLI), environmental factors may also be important. This study examined whether there are prenatal, perinatal, and neonatal factors that are associated with childhood SLI. Method: Participants were members of the Raine Study, a prospective cohort…

  5. Using Infant Massage Following a Mother's Unfavorable Neonatal Intensive Care Unit Experiences: A Case Study

    ERIC Educational Resources Information Center

    Lappin, Grace

    2005-01-01

    The purpose of this case study was to explore the synchronous behaviors enacted by mother and infant with blindness. In the study, a mother's less than optimal experience with the neonatal intensive care unit (NICU) had a profound effect not only on her and her infant son, who was born 3 months prematurely and was visually impaired, but also on…

  6. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers

    PubMed Central

    Kim, Jung Hoon; Kim, Bum Jun; Kim, Hyeong Su; Kim, Jung Han

    2016-01-01

    Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers. However, the era of cancer immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we briefly review the current status and perspective of immunotherapeutic approaches in patients with gastrointestinal cancers. PMID:27698896

  7. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers

    PubMed Central

    Kim, Jung Hoon; Kim, Bum Jun; Kim, Hyeong Su; Kim, Jung Han

    2016-01-01

    Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers. However, the era of cancer immunotherapy in gastrointestinal cancers is still in an inchoate stage. Here we briefly review the current status and perspective of immunotherapeutic approaches in patients with gastrointestinal cancers.

  8. A prospective study of the effect of delivery type on neonatal weight gain pattern in exclusively breastfed neonates born in Shiraz, Iran

    PubMed Central

    2010-01-01

    Background In this exploratory study, the contribution of delivery type to the weight gain pattern for full-term infants with exclusive breastfeeding in the first month of infancy was determined. In addition, breastfeeding success among cesarean section (C-section) delivery mothers based on their neonate's weight gain at the end of the first month of infancy was evaluated. Methods A cohort of 92 neonates born in Shiraz, from July 10 to August 10, 2007 was followed longitudinally. The data were collected during the first month postpartum at three occasions: 3 to 7 days postpartum, 10-21 days postpartum and 24-31 days postpartum. Results Among 92 mothers in this study, 35 (38%) were delivered by C-section. Generalized estimating equation (GEE) showed that delivery type (p < 0.01), receipt of advice about breastfeeding (p = 0.03) and neonate's age (p < 0.01) significantly affected weight gain. GEE estimated the values of the parameters under study and the testing contribution of each factor to weight gain, leading to the conclusion that gender, parities and maternal education did not contribute to weight gain. The neonate's weight gain pattern for C-section deliveries lies below that of normal vaginal deliveries until 25 days postpartum, when weight gain for C-section deliveries became higher than that for normal vaginal deliveries. Conclusions Type of delivery contributes strongly to the weight gain pattern in the first month of infancy. In spite of greater weight loss among C-section birth neonates in the first days of life, at the end of the first month neonates showed a similar weight gain. Consequently, mothers with C-section delivery can successfully exclusively breastfeed. PMID:20181024

  9. New strategies for allergen immunotherapy.

    PubMed

    Carnés, Jerónimo; Robinson, Douglas S

    2008-06-01

    Specific allergen immunotherapy, consisting in the administration of increasing amounts of offending allergens into sensitive patients was first used nearly one hundred years ago and remains in use worldwide for treatment of allergic rhinitis and asthma. It has been recognised as the only effective treatment for type I allergic diseases when the appropriate quantities of allergens are used. The immunological mechanisms by which specific immunotherapy is effective include the modulation of T cells and the response of B-cells and is accompanied by significant decreases of specific IgE and increases in allergen specific IgG antibodies, mainly IgG4. While specific allergen injection immunotherapy is highly effective and the most common way of administration other routes such as oral or intranasal ways have been considered as and alternative to subcutaneous injections. During the last century, allergenic vaccines have been prepared using individual allergens adsorbed to different adjuvant substances. These vaccines have demonstrated efficacy and good results in different clinical trials. However, many novel approaches to allergen immunotherapy have been developed in the last years in order to increase the safety and efficacy of allergenic vaccines. In that way, different and modern vaccines have been prepared including more purified products such as depigmented allergen extracts; allergoids, consisting on big molecules of thousands of kDa, which contain all the individual allergens and show a significant decrease in severe adverse reactions; peptides or small aminoacid sequences; recombinant allergens; hypoallergenic vaccines where the IgE binding sites have been modified; or allergen-CpG fusion molecules. New presentations are under study and new treatments will be developed in the near future with the objective that the prevention of allergic disease may become a reality. The review article also discuss recent patent related to the field. PMID:19075996

  10. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

    PubMed Central

    Morse, Michael A; Garst, Jennifer; Osada, Takuya; Khan, Shubi; Hobeika, Amy; Clay, Timothy M; Valente, Nancy; Shreeniwas, Revati; Sutton, Mary Ann; Delcayre, Alain; Hsu, Di-Hwei; Le Pecq, Jean-Bernard; Lyerly, H Kim

    2005-01-01

    Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors PMID:15723705

  11. Socioeconomic inequalities in survival and provision of neonatal care: population based study of very preterm infants

    PubMed Central

    Draper, Elizabeth S; Manktelow, Bradley N; Field, David J

    2009-01-01

    Objectives To assess socioeconomic inequalities in survival and provision of neonatal care among very preterm infants. Design Prospective cohort study in a geographically defined population. Setting Former Trent health region of the United Kingdom (covering about a twelfth of UK births). Participants All infants born between 22+0 and 32+6 weeks’ gestation from 1 January 1998 to 31 December 2007 who were alive at the onset of labour and followed until discharge from neonatal care. Main outcome measures Survival to discharge from neonatal care per 1000 total births and per 1000 very preterm births. Neonatal care provision for very preterm infants surviving to discharge measured with length of stay, provision of ventilation, and respiratory support. Deprivation measured with the UK index of multiple deprivation 2004 score at super output area level. Results 7449 very preterm singleton infants were born in the 10 year period. The incidence of very preterm birth was nearly twice as high in the most deprived areas compared with the least deprived areas. Consequently rates of mortality due to very preterm birth per 1000 total births were almost twice as high in the most deprived areas compared with the least deprived (incidence rate ratio 1.94, 95% confidence interval 1.62 to 2.32). Mortality rates per 1000 very preterm births, however, showed little variation across all deprivation fifths (incidence rate ratio for most deprived fifth versus least deprived 1.02, 0.86 to 1.20). For infants surviving to discharge from neonatal care, measures of length of stay and provision of ventilation and respiratory support were similar across all deprivation fifths. Conclusions The burden of mortality and morbidity is greater among babies born to women from deprived areas because of increased rates of very preterm birth. After very preterm birth, however, survival rates and neonatal care provision is similar for infants from all areas. PMID:19952036

  12. Mucin 1-specific active cancer immunotherapy with tecemotide (L-BLP25) in patients with multiple myeloma: An exploratory study

    PubMed Central

    Rossmann, Eva; Österborg, Anders; Löfvenberg, Eva; Choudhury, Aniruddha; Forssmann, Ulf; von Heydebreck, Anja; Schröder, Andreas; Mellstedt, Håkan

    2014-01-01

    Patients (n = 34) with previously untreated, slowly progressive asymptomatic stage I/II multiple myeloma or with stage II/III multiple myeloma in stable response/plateau phase following conventional anti-tumor therapy were immunized repeatedly with the antigen-specific cancer immunotherapeutic agent tecemotide (L-BLP25). Additionally, patients were randomly allocated to either single or multiple low doses of cyclophosphamide to inhibit regulatory T cells (Treg). Immunization with tecemotide resulted in the induction/augmentation of a mucin 1-specific immune response in 47% of patients. The immune responses appeared to involve a Th1-like cellular immune response involving CD4 and CD8 T cells. The rate of immune responses was similar with single versus multiple dosing of cyclophosphamide and in patients with vs. without pre-existing mucin 1 immunity. On-treatment reductions in the slope of M-protein concentration over time (but not fulfilling clinical criteria for responses with conventional anti-tumor agents) were observed in 45% of evaluable patients, predominantly in those without versus with pre-existing mucin 1 immunity and in patients with early stage disease. No differences were seen in patients receiving single or multiple cyclophosphamide dosing. Treatment with tecemotide was generally well tolerated. Repeated vs. single dosing of cyclophosphamide had no impact on Treg numbers and was stopped after a case of fatal encephalitis that was assessed as possibly study-related. Tecemotide immunotherapy induces mucin 1-specific cellular immune responses in a substantial proportion of patients, with preliminary evidence of changes in the M-protein concentration time curve in a subset of patients. PMID:25483677

  13. Multicenter Study of Hand Carriage of Potential Pathogens by Neonatal ICU Healthcare Personnel

    PubMed Central

    Ferng, Yu-hui; Clock, Sarah A.; Wong-Mcloughlin, Jennifer; DeLaMora, Patricia A.; Perlman, Jeffrey M.; Gray, Kelly S.; Paul, David A.; Prasad, Priya A.; Zaoutis, Theoklis E.; Alba, Luis R.; Whittier, Susan; Larson, Elaine L.; Saiman, Lisa

    2015-01-01

    A multicenter surveillance study was performed to determine the rates of hand carriage of potential pathogens among healthcare personnel in four neonatal intensive care units. Staphylococcus aureus, enterococci, and gram-negative bacilli were recovered from 8%, 3%, and 2% of 1000 hand culture samples, respectively. PMID:26336605

  14. Parents' Experiences during Their Infant's Transition from Neonatal Intensive Care Unit to Home: A Qualitative Study

    ERIC Educational Resources Information Center

    Hutchinson, Sharon W.; Spillet, Marydee A.; Cronin, Mary

    2012-01-01

    Limited literature exists which examines how parents of infants hospitalized in the Neonatal Intensive Care Unit (NICU) transition from their infant's NICU hospital stay to home. This study examines the question, "What are the experiences of parents during their infant's transition from the NICU to home?" Grounded theory methods served as the…

  15. Alterations of Hippocampal Projections in Adult Macaques with Neonatal Hippocampal Lesions: A Diffusion Tensor Imaging Study

    PubMed Central

    Meng, Yuguang; Payne, Christa; Li, Longchuan; Hu, Xiaoping; Zhang, Xiaodong; Bachevalier, Jocelyne

    2014-01-01

    Neuropsychological and brain imaging studies have demonstrated persistent deficits in memory functions and structural changes after neonatal neurotoxic hippocampal lesion in monkeys. However, the relevant microstructural changes in the white matter of affected brain regions following this early insult remain unknown. This study assessed white matter integrity in the main hippocampal projections of adult macaque monkeys with neonatal hippocampal lesions, by diffusion tensor imaging (DTI). Data analysis was performed using tract-based spatial statistics (TBSS) and compared with volume of interest statistics. Alterations of fractional anisotropy (FA) and diffusivity indices were observed in fornix, temporal stem, ventromedial prefrontal cortex and optical radiations. To further validate the lesion effects on the prefrontal cortex, probabilistic diffusion tractography was used to examine the integrity of the fiber connections between hippocampus and ventromedial prefrontal cortex, and alterations were found in these connections. In addition, increased radial diffusivity in the left ventromedial prefrontal cortex correlated negatively with the severity of deficits in working memory in the same monkeys. The findings revealed microstructural changes due to neonatal hippocampal lesion, and confirmed that neonatal neurotoxic hippocampal lesions resulted in significant and enduring functional alterations in the hippocampal projection system. PMID:25204865

  16. [Cancer genetic immunotherapy].

    PubMed

    Paul, S; Regulier, E; Etienne, R

    2002-01-01

    The concept of cancer immunotherapy and the resulting technical advances have evolved considerably during the last decade. However, cancer treatment by recombinant IL-2 or IFN-alpha still represents today the best therapeutic way for the treatment of renal carcinoma, melanoma and in some cases lymphoma. The immunotherapy approaches such as vaccination, gene and cellular therapy, have not yet demonstrated a sufficient clinical efficacy for the treatment of solid tumors. The goal of this review is to summarize the different approaches to cancer immunotherapy developed today. Specific approaches such as antigenic vaccination will be first described, then non-specific approaches such as gene transfer on the tumor site of immuno-stimulating genes will be discussed. PMID:12507600

  17. Immunotherapy for colorectal cancer.

    PubMed

    Koido, Shigeo; Ohkusa, Toshifumi; Homma, Sadamu; Namiki, Yoshihisa; Takakura, Kazuki; Saito, Keisuke; Ito, Zensho; Kobayashi, Hiroko; Kajihara, Mikio; Uchiyama, Kan; Arihiro, Seiji; Arakawa, Hiroshi; Okamoto, Masato; Gong, Jianlin; Tajiri, Hisao

    2013-12-14

    The incidence of colorectal cancer (CRC) is on the rise, and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although chemotherapy and radiation therapy can improve survival rates, it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC. In this review, we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials, including peptide vaccines, dendritic cell-based cancer vaccines, whole tumor cell vaccines, viral vector-based cancer vaccines, adoptive cell transfer therapy, antibody-based cancer immunotherapy, and cytokine therapy. The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms. PMID:24379570

  18. Immunotherapy for Gastroesophageal Cancer

    PubMed Central

    Goode, Emily F.; Smyth, Elizabeth C.

    2016-01-01

    Survival for patients with advanced oesophageal and stomach cancer is poor; together these cancers are responsible for more than a million deaths per year globally. As chemotherapy and targeted therapies such as trastuzumab and ramucirumab result in modest improvements in survival but not long-term cure for such patients, development of alternative treatment approaches is warranted. Novel immunotherapy drugs such as checkpoint inhibitors have been paradigm changing in melanoma, non-small cell lung cancer and urothelial cancers. In this review, we assess the early evidence for efficacy of immunotherapy in patients with gastroesophageal cancer in addition to considering biomarkers associated with response to these treatments. Early results of Anti- Programmed Cell Death Protein-1 (anti-PD-1), anti-PD-L1 and anti-Cytotoxic T-lymphocyte assosciated protein-4 (anti-CTLA4) trials are examined, and we conclude with a discussion on the future direction for immunotherapy for gastroesophageal cancer patients. PMID:27669318

  19. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies

    PubMed Central

    Lervolino, Luciana Garcia; Baldin, Paulo Eduardo Almeida; Picado, Silvia Miguéis; Calil, Karina Barreto; Viel, Ana Amélia; Campos, Luiz Alexandre Freixo

    2011-01-01

    Sickle cell anemia is the best known hereditary blood disorder; there are serious complications associated with the condition. Diagnosis and early intervention reduce morbidity and mortality. These benefits have resulted in the widespread use of newborn screening education programs. In Brazil, the National Neonatal Screening Program established by decree 822/01 included sickle cell disease in the list of diseases tested in the so called "heel prick test". Since then, national studies of the results of this program have been periodically published. To review the literature in order to assess the prevalence of sickle cell trait and sickle cell anemia from data of national neonatal screening studies on hemoglobin S (Hb S). A bibliographic review was carried out using the key words: sickle cell anemia & hemoglobinopathies & neonatal screening & Brazil in the Bireme and SciELO databases. Original Brazilian studies presenting data on prevalence of the sickle cell trait (Hb AS) and sickle cell anemia (Hb SS) based on neonatal screening for Hb S were analysed. Twelve original national studies were identified with prevalences varying from 1.1% to 9.8% for the sickle cell trait and from 0.8 to 60 per 100,000 live births for sickle cell disease in different Brazilian regions. Conclusion: Neonatal screening for Hb S is a very useful method to assess the prevalence of sickle cell trait (Hb AS) and sickle cell anemia (Hb SS) in Brazil. There is a heterogeneous distribution of this disease with the highest prevalence in the northeastern region and the lowest prevalence in the south. PMID:23284244

  20. Estimation of gestational age, using neonatal anthropometry: a cross-sectional study in India.

    PubMed

    Thawani, Rajat; Dewan, Pooja; Faridi, M M A; Arora, Shilpa Khanna; Kumar, Rajeev

    2013-12-01

    Prematurity is a significant contributor to neonatal mortality in India. Conventionally, assessment of gestational age of newborns is based on New Ballard Technique, for which a paediatric specialist is needed. Anthropometry of the newborn, especially birthweight, has been used in the past to predict the gestational age of the neonate in peripheral health facilities where a trained paediatrician is often not available. We aimed to determine if neonatal anthropometric parameters, viz. birthweight, crown heel-length, head-circumference, mid-upper arm-circumference, lower segment-length, foot-length, umbilical nipple distance, calf-circumference, intermammary distance, and hand-length, can reliably predict the gestational age. The study also aimed to derive an equation for the same. We also assessed if these neonatal anthropometric parameters had a better prediction of gestational age when used in combination compared to individual parameters. We evaluated 1,000 newborns in a cross-sectional study conducted in Guru Teg Bahadur Hospital in Delhi. Detailed anthropometric estimation of the neonates was done within 48 hours after birth, using standard techniques. Gestational age was estimated using New Ballard Scoring. Out of 1,250 consecutive neonates, 1,000 were included in the study. Of them, 800 randomly-selected newborns were used in devising the model, and the remaining 200 newborns were used in validating the final model. Quadratic regression analysis using stepwise selection was used in building the predictive model. Birthweight (R=0.72), head-circumference (R = 0.60), and mid-upper arm-circumference (R = 0.67) were found highly correlated with gestation. The final equation to assess gestational age was as follows: Gestational age (weeks) = 5.437 x W-0.781 x W(2) + 2.815 x HC-0.041 x HC(2) + 0.285 x MUAC-22.745 where W=Weight, HC=Head-circumference and MUAC=Mid-upper arm-circumference; Adjusted R = 0.76. On validation, the predictability of this equation is 46

  1. Estimation of Gestational Age, Using Neonatal Anthropometry: A Cross-sectional Study in India

    PubMed Central

    Thawani, Rajat; Faridi, M.M.A.; Arora, Shilpa Khanna; Kumar, Rajeev

    2013-01-01

    Prematurity is a significant contributor to neonatal mortality in India. Conventionally, assessment of gestational age of newborns is based on New Ballard Technique, for which a paediatric specialist is needed. Anthropometry of the newborn, especially birthweight, has been used in the past to predict the gestational age of the neonate in peripheral health facilities where a trained paediatrician is often not available. We aimed to determine if neonatal anthropometric parameters, viz. birthweight, crown heel-length, head-circumference, mid-upper arm-circumference, lower segment-length, foot-length, umbilical nipple distance, calf-circumference, intermammary distance, and hand-length, can reliably predict the gestational age. The study also aimed to derive an equation for the same. We also assessed if these neonatal anthropometric parameters had a better prediction of gestational age when used in combination compared to individual parameters. We evaluated 1,000 newborns in a cross-sectional study conducted in Guru Teg Bahadur Hospital in Delhi. Detailed anthropometric estimation of the neonates was done within 48 hours after birth, using standard techniques. Gestational age was estimated using New Ballard Scoring. Out of 1,250 consecutive neonates, 1,000 were included in the study. Of them, 800 randomly-selected newborns were used in devising the model, and the remaining 200 newborns were used in validating the final model. Quadratic regression analysis using stepwise selection was used in building the predictive model. Birthweight (R=0.72), head-circumference (R=0.60), and mid-upper arm-circumference (R=0.67) were found highly correlated with gestation. The final equation to assess gestational age was as follows: Gestational age (weeks)=5.437×W–0.781×W2+2.815×HC–0.041×HC2+0.285×MUAC–22.745 where W=Weight, HC=Head-circumference and MUAC=Mid-upper arm-circumference; Adjusted R=0.76. On validation, the predictability of this equation is 46% (±1 week), 75

  2. Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig

    PubMed Central

    Dyson, Rebecca M.; Palliser, Hannah K.; Lakkundi, Anil; de Waal, Koert; Latter, Joanna L.; Clifton, Vicki L.; Wright, Ian M. R.

    2014-01-01

    Abstract Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion–reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29–36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68–71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion–reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period. PMID:25350751

  3. Study of the sensitivity of neonates to digoxin: contribution of erythrocyte /sup 86/Rb uptake test

    SciTech Connect

    Zannad, F.; Marchal, F.; Royer, R.J.; Vert, P.; Robert, J.

    1981-01-01

    In general, there is little agreement how digoxin should be used in newborn, and the results of studies in this field seem contradictory. This study attempts a quantitative assessment of the number and the sensitivity of cellular receptors for digoxin in the organism, by the in vitro measurement of erythrocyte /sup 86/Rb neonates compared with adults and old people. Red blood cells are first incubated with differing concentrations of digoxin, and then incubated with /sup 86/Rb. The initial level of /sup 86/Rb uptake (Rbi) is that observed in the absence of digoxin. The 50% index of captation (IC50) is the digoxin concentration in nanograms per ml at which /sup 86/Rb uptake is half Rbi. Three grups of patients were studied: Group I: 12 neonates, less that 5 days old; Group II: 11 adults (26 to 57 years old); Group III: 9 elderly people (71 to 82 years old). Rbi was significantly lower in neonates (Mean +/- SD: 25.8% +/- 3.5, P less than 0.001) and in the elderly (29.9% +/- 3.1) than in adults (36.8% +/- 4.6). IC50 was significantly lower in the elderly (12.1 mg/ml +/- 2.4) than in the adult patients (20.5 ng/ml +/- 5.5, P less than 0.001). In the newborns, values of IC50 were widely scattered (16.2 ng/ml +/- 7.2). The authors suggest that since Rbi reflects Na+, K+-ATPase activity, this activity is diminished in newborn and old people, and indicates that they have fewer cellular recaptors for digoxin than adults. In the elderly, the low IC50 would imply increased sensitivity to digoxin. In neonates, the wide range of values for IC50 suggests considerable individual variation in sensitivity to digoxin. The results aer consistent with the recently recomnended lower dosages of digoxin i neonates.

  4. Maternal Urinary Bisphenol A during Pregnancy and Maternal and Neonatal Thyroid Function in the CHAMACOS Study

    PubMed Central

    Gunier, Robert B.; Bradman, Asa; Holland, Nina T.; Calafat, Antonia M.; Eskenazi, Brenda; Harley, Kim G.

    2012-01-01

    Background: Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt thyroid function. Although thyroid hormones play a determinant role in human growth and brain development, no studies have investigated relations between BPA exposure and thyroid function in pregnant women or neonates. Objective: Our goal was to evaluate whether exposure to BPA during pregnancy is related to thyroid hormone levels in pregnant women and neonates. Methods: We measured BPA concentration in urine samples collected during the first and second half of pregnancy in 476 women participating in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We also measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in women during pregnancy, and TSH in neonates. Results: Associations between the average of the two BPA measurements and maternal thyroid hormone levels were not statistically significant. Of the two BPA measurements, only the one taken closest in time to the TH measurement was significantly associated with a reduction in total T4 (β = –0.13 µg/dL per log2 unit; 95% CI: –0.25, 0.00). The average of the maternal BPA concentrations was associated with reduced TSH in boys (–9.9% per log2 unit; 95% CI: –15.9%, –3.5%) but not in girls. Among boys, the relation was stronger when BPA was measured in the third trimester of pregnancy and decreased with time between BPA and TH measurements. Conclusion: Results suggest that exposure to BPA during pregnancy is related to reduced total T4 in pregnant women and decreased TSH in male neonates. Findings may have implications for fetal and neonatal development. PMID:23052180

  5. Stillbirth and neonatal death among female cancer survivors: A national cohort study.

    PubMed

    Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2016-09-01

    The number of cancer survivors continues to increase worldwide. Many of these survivors have had children of their own. It is less well-known whether radiation therapy or chemotherapy could affect the risk of stillbirth and neonatal death for these children. To explore this research questions, we identified all women diagnosed with cancer between 1958 and 2012 from the Swedish Cancer Register and they were further linked to the Swedish Medical Birth Register to identify their subsequent child birth between 1973 and 2012. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between stillbirth and neonatal death and maternal cancer diagnosis. As compared to the children without maternal cancer, the risk of stillbirth was significantly higher among children of female cancer survivors born within three years after cancer diagnosis with an OR of 1.92 (95% CI 1.03-3.57). The incidence of neonatal death did not show a significant change. For women with more than one pregnancy after cancer diagnosis, the risk of stillbirth and neonatal death was lower for the second child birth compared to the first child birth. Our study suggested that the risk of stillbirth was negatively associated with the time after cancer diagnosis, providing evidence that the adverse effect associated with cancer treatment may diminish with time. PMID:27101797

  6. Neonatal mortality in India's rural poor: Findings of a household survey and verbal autopsy study in Rajasthan, Bihar and Odisha.

    PubMed

    Dogra, Vishal; Khanna, Rajesh; Jain, Anuradha; Kumar, Ajay M V; Shewade, Hemant D; Majumdar, Suman S

    2015-06-01

    In 2011, Save the Children India launched a project for the disadvantaged population of Rajasthan, Bihar and Odisha. As a baseline activity, neonatal deaths during January-December 2012 were investigated using modified verbal autopsy tool in six sub-district-level administrative units (blocks) adopting 30-cluster sample survey approach. Our study reported a total of 189 neonatal deaths of which 50% occurred at home and 39% happened on Day 1. About half of the deaths occurred in blocks from Bihar. High number of neonatal deaths belonged to households that were below poverty line (64%) and other disadvantaged classes (46%); among mothers who were illiterate (65%), <20 years of age (54%) and during their first-order births (36%). Birth asphyxia was a major cause of neonatal deaths across all blocks. These findings indicate need for easy and early access to transport services, specialized neonatal care and advocacy targeted towards increasing community awareness. PMID:25825343

  7. Immunotherapy in urothelial carcinoma: fade or future standard?

    PubMed Central

    Breyer, Johannes; Burger, Maximilian

    2016-01-01

    Immunotherapy of non-muscle-invasive bladder carcinoma by Bacillus-Calmette-Guérin (BCG) instillation is a well-established treatment option since decades. Despite this fact, the immunocellular basis was first studied in recent years. New aspects of immunotherapy, also for progressed bladder carcinoma, might follow promising research on immunological targets. PMID:27785423

  8. Onset of oral allergic syndrome during birch sublingual immunotherapy.

    PubMed

    Ciprandi, G

    2012-08-01

    Pollen allergy may be frequently associated with oral allergy to fruits and/or vegetables (the so called oral allergic syndrome). Some studies reported a possible positive effect exerted by allergen-specific immunotherapy on OAS course, while others did not. A case of OAS case onset after starting sublingual immunotherapy is reported.

  9. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  10. Specific immunotherapy in ovarian cancer: a systematic review.

    PubMed

    Alipour, Soroush; Zoghi, Samaneh; Khalili, Nastaran; Hirbod-Mobarakeh, Armin; Emens, Leisha A; Rezaei, Nima

    2016-10-01

    Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several approaches of active and passive immunotherapy for EOC have been studied. The aim of this systematic review was to assess the clinical efficacy of specific immunotherapy in patients with EOC. We found 4524 references in seven databases and we included ten controlled clinical trials with 2285 patients with EOC reporting five active immunotherapeutic agents and three passive immunotherapies. Meta-analysis of six studies showed that overall there was not any significant difference in overall survival and recurrence-free survival between patients undergoing specific immunotherapy and those in control group. Most of the studies we evaluated reported a positive outcome from treatment with specific immunotherapy, although this was not significant. PMID:27605068

  11. Specific immunotherapy in ovarian cancer: a systematic review.

    PubMed

    Alipour, Soroush; Zoghi, Samaneh; Khalili, Nastaran; Hirbod-Mobarakeh, Armin; Emens, Leisha A; Rezaei, Nima

    2016-10-01

    Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several approaches of active and passive immunotherapy for EOC have been studied. The aim of this systematic review was to assess the clinical efficacy of specific immunotherapy in patients with EOC. We found 4524 references in seven databases and we included ten controlled clinical trials with 2285 patients with EOC reporting five active immunotherapeutic agents and three passive immunotherapies. Meta-analysis of six studies showed that overall there was not any significant difference in overall survival and recurrence-free survival between patients undergoing specific immunotherapy and those in control group. Most of the studies we evaluated reported a positive outcome from treatment with specific immunotherapy, although this was not significant.

  12. Immunotherapy for tuberculosis: what's the better choice?

    PubMed

    Guo, Shuliang; Zhao, Jinqiu

    2012-06-01

    A Th1/Th2 imbalance in tuberculosis (TB) patients caused by a decreased Th1 response and an increased Th2 response is a significant factor in the pathogenesis and development of TB. Protective immune responses to TB include bacteriostatic and bactericidal responses. Unfortunately, however, immunoprotection and immune pathology co-exist in TB patients. Immunotherapy for TB principally aims to restore the Th1/Th2 balance by enhancing the Th1 response and suppressing the excessive Th2 response. Immunotherapy for TB can be classified into three categories: immune-enhancing therapy using cytokines, immunosuppressive therapy, and immunomodulatory therapy. Immunomodulatory therapy targets the Th1/Th2 imbalance and includes cytokine regulation therapy, antibody regulation therapy, a multi-dose heat-inactivated Mycobacterium vaccae vaccine, thymosin hormones and a DNA vaccine. A new approach in supplementary TB immunotherapy is to simultaneously up-regulate the Th1 response and down-regulate the Th2 response. While immunotherapy can contribute to TB treatment, it may also cause immunopathological injury. Therefore, immunotherapy needs to be improved and further studied to maximize its potential.

  13. A Pilot Prospective Study of Fetomaternal Hemorrhage Identified by Anemia in Asymptomatic Neonates

    PubMed Central

    Stroustrup, Annemarie; Plafkin, Callie

    2016-01-01

    Background Fetomaternal hemorrhage (FMH) is a poorly understood condition in which fetal erythrocytes transfer to the maternal circulation via a faulty placental barrier. Little is known about the true incidence, epidemiology, or pathophysiology of FMH in the general pregnant population as existing studies are based on retrospective cohorts and manifest diagnosis and selection bias. Objective To evaluate the practicability of a prospective study of fetomaternal hemorrhage in the general population based on antepartum maternal blood testing and neonatal anemia. Study Design Prospective cohort study. Result Nineteen pregnant women were enrolled prior to the term delivery of twenty well infants. Five neonates were unexpectedly anemic on first postnatal testing. Antenatal maternal blood samples associated with 2 of 5 anemic newborns had positive Kleihauer-Betke testing while no newborn with a normal postnatal blood count had an associated abnormal Kleihauer-Betke test. Conclusion Clinically significant FMH may be more common than previously thought. Prospective epidemiological study of FMH is feasible. PMID:26765555

  14. Reliability of routine clinical measurements of neonatal circumferences and research measurements of neonatal skinfold thicknesses: findings from the Born in Bradford study.

    PubMed

    West, Jane; Manchester, Ben; Wright, John; Lawlor, Debbie A; Waiblinger, Dagmar

    2011-03-01

    Assessing neonatal size reliably is important for research and clinical practice. The aim of this study was to examine the reliability of routine clinical measurements of neonatal circumferences and of skinfold thicknesses assessed for research purposes. All measurements were undertaken on the same population of neonates born in a large maternity unit in Bradford, UK. Technical error of measurement (TEM), relative TEM and the coefficient of reliability are reported. Intra-observer TEMs for routine circumference measurements were all below 0.4 cm and were generally within ± 2-times the mean. Inter-observer TEM ranged from 0.20 to 0.36 cm for head circumference, 0.19 to 0.39 cm for mid upper arm circumference and from 0.39 to 0.77 cm for abdominal circumference. Intra and inter-observer TEM for triceps skinfold thickness ranged from 0.22 to 0.35 mm and 0.15 to 0.54 mm, respectively. Subscapular skinfold thickness TEM values were 0.14 to 0.25 mm for intra-observer measurements and 0.17 to 0.63 mm for inter-observer measurements. Relative TEM values for routine circumferences were all below 4.00% but varied between 2.88% and 14.23% for research skinfold measurements. Reliability was mostly between 80% and 99% for routine circumference measurements and ≥ 70% for most research skinfold measurements. Routine clinical measurements of neonatal circumferences are reliably assessed in Bradford. Assessing skinfolds in neonates has variable reliability, but on the whole is good. The greater intra-observer, compared with inter-observer, reliability for both sets of measurements highlights the importance of having a minimal number of assessors whenever possible.

  15. Active Immunotherapy of Cancer.

    PubMed

    Chodon, Thinle; Koya, Richard C; Odunsi, Kunle

    2015-01-01

    Clinical progress in the field of cancer immunotherapy has been slow for many years but within the last 5 years, breakthrough successes have brought immunotherapy to the forefront in cancer therapy. Promising results have been observed in a variety of cancers including solid tumors and hematological malignancies with adoptive cell therapy using natural host tumor infiltrating lymphocytes, host cells that have been genetically engineered with antitumor T-cell receptors or chimeric antigen receptors, immune checkpoint inhibitors like anti-CTLA-4, anti-PD-1 or PD-L1 monoclonal antibodies and oncolytic virus-based immunotherapy. However, most treatment modalities have shown limited efficacy with single therapy. The complex nature of cancer with intra- and inter-tumor antigen and genomic heterogeneity coupled with the immune suppressive microenvironment emphasizes the prospect of personalized targeted immunotherapy to manipulate the patient's own immune system against cancer. For successful, robust and long-lasting cure of cancer, a multi-modal approach is essential, combining anti-tumor cell therapy with manipulation of multiple pathways in the tumor microenvironment to ameliorate tumor-induced immunosuppression. PMID:26575466

  16. Immediate versus delayed umbilical cord clamping in premature neonates born < 35 weeks: a prospective, randomized, controlled study.

    PubMed

    Kugelman, Amir; Borenstein-Levin, Liron; Riskin, Arieh; Chistyakov, Irena; Ohel, Gonen; Gonen, Ron; Bader, David

    2007-05-01

    The purpose of this study was to test whether delayed versus immediate cord clamping would result in higher blood pressure (BP) and hematocrit (Hct), and to assess its clinical effects on the neonatal course in premature neonates (< 35 weeks). This was a prospective, masked, randomized, controlled study. Prior to delivery, 35 neonates were randomly assigned to immediate cord clamping (ICC) at 5 to 10 seconds, and a comparable group of 30 neonates were randomly assigned to delayed cord clamping (DCC) at 30 to 45 seconds. Intention-to-treat analyses revealed that the DCC group tended to have higher initial diastolic BP and higher Hct (especially in vaginally delivered neonates). Infants weighing < 1500 g with DCC tended to have higher mean BP, and needed less mechanical ventilation and surfactant compared with ICC neonates. Infants with DCC did not experience more polycythemia (Hct > 60%), but had a trend toward higher bilirubin levels with no differences in the phototherapy needs. DCC seems to be safe and may be beneficial when compared with ICC in premature neonates. However, the differences between the two methods were modest and the clinical relevance needs to be assessed further by larger studies and additional meta-analysis of randomized trials.

  17. Immunotherapy in asthma.

    PubMed

    Warrington, Richard

    2010-09-01

    Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, as well as variable airflow obstruction within the lung. With time, such airflow obstruction may become permanent due to remodeling. It has been treated for more than 100 years by subcutaneous immunotherapy with allergen extracts but in recent years, other forms and types of immunotherapy have been introduced. Perhaps the most successful of these to date, is sublingual immunotherapy, which has attained significant usage in European countries but has yet to make inroads into clinical practice in North America. Other mechanisms to modify the inflammatory responses of asthma have included immunotherapy with recombinant allergens, the use of allergen peptides targeting antigen-specific T cells and the administration of Toll-like receptor agonists coupled to allergen proteins. As the inflammatory responses in asthma frequently involve IgE, a modified monoclonal antibody to IgE and interfering with its binding to the IgE receptor have gained acceptance for treating severe allergic asthma. Other monoclonal antibodies or recombinant receptor antagonists are being assessed for their ability to block other contributors to the inflammatory response. Finally, attempts have been made to generate autoantibody responses to cytokines implicated in asthma. Most of these therapies aim to modify or inhibit the so-called Th 2 immune response, which is implicated in many forms of asthma, or to inhibit cytokines involved in these responses. However, an added benefit of classical immunotherapy seems to be the ability to prevent the allergic progression to new sensitivities and new forms of allergic disease.

  18. Use of resting state functional MRI to study brain development and injury in neonates

    PubMed Central

    Smyser, Christopher D.; Neil, Jeffrey J.

    2015-01-01

    Advances in methodology have led to expanded application of resting state functional MRI (rs-fMRI) to the study of term and prematurely-born infants during the first years of life, providing fresh insight into the earliest forms of functional cerebral development. In this review, we detail our evolving understanding of the use of rs-fMRI for studying neonates. We initially focus on the biological processes of cortical development related to resting state network development. We then review technical issues principally affecting neonatal investigations, including the effects of subject motion during acquisition and image distortions related to magnetic susceptibility effects. We next summarize the literature in which rs-fMRI is used to study normal brain development during the early postnatal period, the effects of prematurity and the effects of cerebral injury. Finally, we review potential future directions for the field, such as the use of complementary imaging modalities and advanced analysis techniques. PMID:25813667

  19. Comparative Study of Hearing Impairment among Healthy and Intensive Care unit Neonates in Mashhad, North East Iran

    PubMed Central

    Farhat, Ahmadshah; Ghasemi, Mohammad Mehdi; Akhondian, Javad; Mohammadzadeh, Ashraf; Esmaeili, Habibollah; Amiri, Rana; Raoof Saeb, Ali Asqar; Tale, Mohammad Reza; Madani Sani, Faezeh

    2015-01-01

    Introduction: According to World Health Organization (WHO) 2001 statistics, hearing disorders are the most common congenital disease, and the incidence rate among high-risk newborns is as much as ten times as high as that in healthy neonates. However, 78% of screening test failures are well-baby nursery babies. The Joint Committee on Infants’ Hearing (JCIH) has emphasized the importance of early diagnosis and treatment in neonates with hearing impairments in order to preserve their maximum linguistic skills. The aim of our study was to compare the prevalence of hearing loss among babies in the neonatal intensive care unit (NICU) and the rooming-in unit (RIU). Materials and Methods: Neonates born in three hospitals in Mashhad between 2008 to 2010 were studied prospectively and screened for auditory disorders using the oto acoustic emission (OAE) test at the time of discharge and 3 weeks later. To confirm hearing loss, the auditory steady state response (ASSR) test was used among those participants who failed both OAE tests. Results: Two-thousand and sixty-three neonates from the NICU were screened and compared with a control group consisting of 8,724 neonates from the RIU or the well-baby nursery. At the end of the study, hearing impairment as confirmed by failure in the ASSR test was diagnosed in 31 neonates (26 in the control group [0.30%] and five in the NICU group [1.94%]). Conclusion: In our study, the prevalence of hearing disorders among NICU neonates was 6.5-times greater than that among babies from the RIU or well-baby unit. This observation demonstrates the importance of universal screening programs particularly for high-risk population neonates. PMID:26788475

  20. Oral Immunotherapy for Food Allergy.

    PubMed

    Burbank, Allison J; Sood, Puja; Vickery, Brian P; Wood, Robert A

    2016-02-01

    Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut.

  1. Oral Immunotherapy for Food Allergy.

    PubMed

    Burbank, Allison J; Sood, Puja; Vickery, Brian P; Wood, Robert A

    2016-02-01

    Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cow's milk, hen's egg, and peanut. PMID:26617227

  2. Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study

    PubMed Central

    Carroli, Guillermo; Zavaleta, Nelly; Donner, Allan; Wojdyla, Daniel; Faundes, Anibal; Velazco, Alejandro; Bataglia, Vicente; Langer, Ana; Narváez, Alberto; Valladares, Eliette; Shah, Archana; Campodónico, Liana; Romero, Mariana; Reynoso, Sofia; de Pádua, Karla Simônia; Giordano, Daniel; Kublickas, Marius; Acosta, Arnaldo

    2007-01-01

    Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery. Design Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health. Setting 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data Participants 106 546 deliveries reported during the three month study period, with data available for 97 095 (91% coverage). Main outcome measures Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics. Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor

  3. Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study

    PubMed Central

    Signorello, Lisa B; Mulvihill, John J; Green, Daniel M; Munro, Heather M; Stovall, Marilyn; Weathers, Rita E; Mertens, Ann C; Whitton, John A; Robison, Leslie L; Boice, John D

    2010-01-01

    Summary Background The reproductive implications of mutagenic treatments given to children with cancer are not clear. By studying the risk of untoward pregnancy outcomes, we indirectly assessed the risk of transmission of germline damage to the offspring of survivors of childhood cancer who were given radiotherapy and chemotherapy. Methods We did a retrospective cohort analysis, within the Childhood Cancer Survivor Study (CCSS), of the risk of stillbirth and neonatal death among the offspring of men and women who had survived childhood cancer. Patients in CCSS were younger than 21 years at initial diagnosis of an eligible cancer, were treated at 25 US institutions and one Canadian institution, and had survived for at least 5 years after diagnosis. We quantified the chemotherapy given to patients, and the preconception radiation doses to the testes, ovaries, uterus, and pituitary gland, and related these to the risk of stillbirth or neonatal death using Poisson regression analysis. Findings Among 1148 men and 1657 women who had survived childhood cancer, there were 4946 pregnancies. Irradiation of the testes (16 [1%] of 1270; adjusted relative risk 0·8 [95% CI 0·4–1·6]; mean dose 0·53 Gy [SD 1·40]) and pituitary gland (17 [3%] of 510, 1·1 [0·5–2·4] for more than 20·00 Gy; mean dose 10·20 Gy [13·0] for women), and chemotherapy with alkylating drugs (26 [2%] of 1195 women, 0·9 [0·5–1·5]; ten [1%] of 732 men, 1·2 [0·5–2·5]) were not associated with an increased risk of stillbirth or neonatal death. Uterine and ovarian irradiation significantly increased risk of stillbirth and neonatal death at doses greater than 10·00 Gy (five [18%] of 28, 9·1 [3·4–24·6]). For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1·00–2·49 Gy significantly increased the risk of stillbirth or neonatal death (three [4%] of 69, 4·7 [1·2–19·0]). Interpretation Our findings do not support concern about heritable

  4. Immunotherapy of Childhood Sarcomas.

    PubMed

    Roberts, Stephen S; Chou, Alexander J; Cheung, Nai-Kong V

    2015-01-01

    Pediatric sarcomas are a heterogeneous group of malignant tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing's family of tumors, rhabdomyosarcoma and osteosarcoma. Most patients that present with localized stage are curable with surgery and/or chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New therapies for these patients are urgently needed. Immunotherapy is an established treatment modality for both liquid and solid tumors, and in pediatrics, most notably for neuroblastoma and osteosarcoma. In the past, immunomodulatory agents such as interferon, interleukin-2, and liposomal-muramyl tripeptide phosphatidyl-ethanolamine have been tried, with some activity seen in subsets of patients; additionally, various cancer vaccines have been studied with possible benefit. Monoclonal antibody therapies against tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA-4 and PD-1 are being actively explored in pediatric sarcomas. Building on the success of adoptive T cell therapy for EBV-related lymphoma, strategies to redirect T cells using chimeric antigen receptors and bispecific antibodies are rapidly evolving with potential for the treatment of sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and tumor vaccines. The future integration of antibody-based and cell-based therapies into an overall treatment strategy of sarcoma will be discussed.

  5. Neonatal tumours.

    PubMed

    Moore, S W

    2013-12-01

    Neonatal or perinatal tumours frequently relate to prenatal or developmental events and have a short exposure window which provides an opportunity to study tumours in a selective sensitive period of development. As a result, they display a number of host-specific features which include occasional spontaneous maturational changes with cells still responding to developmental influences. Neonatal tumours (NNT) are studied for a number of important reasons. Firstly, many of the benign tumours arising from soft tissue appear to result from disturbances in growth and development and some are associated with other congenital anomalies. Study of these aspects may open the door for investigation of genetic and epigenetic changes in genes controlling foetal development as well as environmental and drug effects during pregnancy. Secondly, the clinical behaviour of NNT differs from that of similar tumours occurring later in childhood. In addition, certain apparently malignant NNT can 'change course' in infancy leading to the maturation of apparently highly malignant tumours. Thirdly, NNT underline the genetic associations of most tumours but appear to differ in the effects of proto-oncogenes and other oncogenic factors. In this context, there are also connections between the foetal and neonatal period and some "adult" cancers. Fourthly, they appear to arise in a period in which minimal environmental interference has occurred, thus providing a unique potential window of opportunity to study the pathogenesis of tumour behaviour. This study will seek to review what is currently known in each of these areas of study as they apply to NNT. Further study of the provocative differences in tumour behaviour in neonates provides insights into the natural history of cancer in humans and promotes novel cancer therapies.

  6. Immunology and Immunotherapy of Neuroblastoma

    PubMed Central

    Seeger, Robert C.

    2012-01-01

    Purpose This review demonstrates the importance of immunobiology and immunotherapy research for understanding and treating neuroblastoma. Principal results The first suggestions of immune system-neuroblastoma interactions came from in vitro experiments showing that lymphocytes from patients were cytotoxic for their own tumor cells and from evaluations of tumors from patients that showed infiltrations of immune system cells. With the development of monoclonal antibody (mAb) technology, a number of mAbs were generated against neuroblastoma cells lines and were used to define tumor associated antigens. Disialoganglioside (GD2) is one such antigen that is highly expressed by virtually all neuroblastoma cells and so is a useful target for both identification and treatment of tumor cells with mAbs. Preclinical research using in vitro and transplantable tumor models of neuroblastoma has demonstrated that cytotoxic T lymphocytes (CTLs) can specifically recognize and kill tumor cells as a result of vaccination or of genetic engineering that endows them with chimeric antigen receptors. However, CTL based clinical trials have not progressed beyond pilot and phase I studies. In contrast, anti-GD2 mAbs have been extensively studied and modified in pre-clinical experiments and have progressed from phase I through phase III clinical trials. Thus, the one proven beneficial immunotherapy for patients with high-risk neuroblastoma uses a chimeric anti-GD2 mAb combined with IL-2 and GM-CSF to treat patients after they have received intensive cyto-reductive chemotherapy, irradiation, and surgery. Ongoing pre-clinical and clinical research emphasizes vaccine, adoptive cell therapy, and mAb strategies. Recently it was shown that the neuroblastoma microenvironment is immunosuppressive and tumor growth promoting, and strategies to overcome this are being developed to enhance anti-tumor immunotherapy. Conclusions Our understanding of the immunobiology of neuroblastoma has increased

  7. [Sublingual immunotherapy in children. Immunotherapy Committee of the Spanish Society for Clinical Immunology and Pediatric Allergology].

    PubMed

    Lleonart, R; Muñoz, F; Eseverri, J L; Martínez-Cañabate, A; Tabar, A I; Pedemonte, C

    2003-01-01

    Sublingual immunotherapy is currently attracting growing interest because of its ease of administration and, according to previous studies, its infrequent and mild adverse effects. However, at least in children, the efficacy of this therapy has not been completely demonstrated. In addition, the mechanisms of action remain to be elucidated since few studies have been published and the results have been contradictory and sometimes inconclusive. For this reason, we performed a literature review through the MEDLINE database, selecting double-blind studies carried out in children. Only 10 studies meeting these requirements were retrieved. All the studies were performed by European researchers and nine were published in European journals. Efficacy was evaluated by clinical parameters and by reduction in medication use. The results on efficacy are not homogeneous, although most support the utility of this route of administration. Moreover, reports of allergens other than those used in these studies dust mites and grass pollens are lacking. In conclusion, further studies evaluating the efficacy of this therapy in children are required. Among the general population, if the efficacy of sublingual immunotherapy in the treatment of sensitization to hymenoptera venoms were demonstrated, as has been the case with subcutaneous immunotherapy, the utility of this route of administration would be definitively confirmed. Finally, sublingual immunotherapy could be used in children who have shown systemic reactions to subcutaneous immunotherapy or who refuse to undergo injections.

  8. Neonatal sepsis of vertical transmission: an epidemiological study from the "Grupo de Hospitales Castrillo".

    PubMed

    López Sastre, J B; Coto Cotallo, G D; Fernández Colomer, B

    2000-01-01

    A prospective multicenter study was designed to assess the epidemiology of neonatal sepsis of vertical transmission in Spain. The study was carried out by the "Grupo de Hospitales Castrillo" that included the neonatal services of 19 tertiary care (reference) hospitals and 9 secondary care hospitals. Prospective data from infants with culture-proved neonatal sepsis, clinical sepsis and bacteremia were recorded for 1995 to 1997. In a total of 203,288 neonates, proven sepsis was diagnosed in 515 (rate of 2.5 per 1000 live births), clinical sepsis in 724 (rate of 3.6 per 1000 live births), and bacteremia of vertical transmission in 155 (rate of 0.76 per 1000 live births). Very low birth weight (VLBW) infants (< or = 1500 g) showed a significantly higher incidence of confirmed sepsis (26.5 per 1000 live births) and clinical sepsis (32.4 per 1000 live births) than infants weighing > 1500 g. Streptococcus agalactiae was the most frequent causative pathogen in cases of proven sepsis (51%) and bacteremia (33%), but Escherichia coli was the most frequently recovered organism in the VLBW group. The mortality rate of proven sepsis was significantly higher than that of clinical sepsis (8.7% versus 4.3%) (P < 0.01). In the VLBW cohort, there were no significant differences in the mortality rate between proven sepsis and clinical sepsis. In conclusion, clinical sepsis was the most frequent diagnosis, probably related to intrapartum chemoprophylaxis. Streptococcus agalactiae was the most frequent causative pathogen of culture-positive sepsis and bacteremia, whereas E. coli was the most significant in VLBW infants.

  9. Neonatal neurodevelopment and prenatal exposure to dichlorodiphenyldichloroethylene (DDE): a cohort study in Mexico.

    PubMed

    Bahena-Medina, Lilia Araceli; Torres-Sánchez, Luisa; Schnaas, Lourdes; Cebrián, Mariano E; Chávez, Carmen Hernández; Osorio-Valencia, Erika; Hernández, Rosa María García; López-Carrillo, Lizbeth

    2011-01-01

    Prenatal exposure to dichlorodiphenyldichloroethylene (DDE) is associated with decreased motor development during the first year of life, though the effects of DDE in the neonatal stage are not conclusive. The main aim of this study was to evaluate the association between prenatal DDE exposure and neonatal neurodevelopment in a cohort from four municipalities in the state of Morelos, Mexico. The children (265), born from pregnancies with no perinatal complications, were evaluated at 1 month of age (± 7 days) for the presence of abnormal reflexes with the Brazelton Scale (NBAS), neurological soft signs with the Graham-Rosenblith Scale, as well as mental and psychomotor development by the Bayley Scales of Infant Development. Maternal DDE concentrations during each trimester of the pregnancy were determined by gas chromatography. Multiple linear and ordinal logistic models assessed the association between DDE and the outcomes of interest. Prenatal exposure to DDE was associated with a non-significant increase in neurological soft signs (6-8%) and a decrease in psychomotor (β(1T) = -0.02) and mental (β(2T) = -0.03 and β(3T) = -0.19) development. Our results are consistent with previous studies and suggest that prenatal DDE exposure is not associated with neurological functions present in the neonatal stage.

  10. Declawing of neonatal rabbits destined for use in animal biosafety level 4 containment studies.

    PubMed

    Perdue, K A; Shaw, R E; Mage, R G

    2000-05-01

    To protect personnel and protective outerwear from damage by scratching, rabbits to be housed in an Animal Biosafety Level 4 (ABSL4) facility are declawed routinely. The objective of the study presented here was to establish a procedure for declawing all four feet of neonatal rabbits in preparation for use in ABSL4 studies. Combining procedures conducted in private veterinary practice to remove dewclaws of canine pups with those used to declaw cats, we declawed rabbit kits at 3 to 8 days of age. Declawing neonates was believed to be advantageous because they are non-ambulatory, have soft, cartilaginous digits, and do not have extensive hair growth. These features resulted in decreased surgical preparation and surgery time, minimal bleeding, and minimal aftercare. The optimal age for declawing a litter was 6 or 7 days. Declawing of neonatal rabbits is relatively simple and efficient to perform and offers advantages over declawing of older animals. By using the method described, rabbits can be introduced into ABSL4 facilities by 12 weeks of age with confidence that nail regrowth will not occur. PMID:11178319

  11. [Alpha fetoprotein and neonatal jaundice. Contribution to the study of a physiopathologic mechanism].

    PubMed

    Tourne, C E; Brettes, J P; Guez, G; Ritter, J; Gandar, R

    1977-01-01

    The increase in the maternal plasma A.F.P. level is due to an hypoxia of the foetus. The prospective study of 851 single pregnancies shows that there is a significant rise in the A.F.P. levels during the last days of the pregnancy if the babies are going to exhibit a so-called physiological jaundice at birth: the decrease of the A.F.P. levels in these cases is four times slower than in normal cases. The prospective study of another group of 404 pregnancies gave the same results for the A.F.P. level of the blood of the umbilical cord. Statistical analysis showed that the pathological conditions capable of increasing the A.F.P. levels are related to neo-natal jaundice. The neo-natal jaundice may be due to a factor of foetal hypoxia capable of inducing an over stimulation of the foetal erythropoiesis. The results of this mechanism would be a quantitative disequilibrium between an increased hemolysis and a reduced bilirubine fixation capacity during the neo-natal period.

  12. Comprehensive Longitudinal Study Challenges the Existence of Neonatal Imitation in Humans.

    PubMed

    Oostenbroek, Janine; Suddendorf, Thomas; Nielsen, Mark; Redshaw, Jonathan; Kennedy-Costantini, Siobhan; Davis, Jacqueline; Clark, Sally; Slaughter, Virginia

    2016-05-23

    Human children copy others' actions with high fidelity, supporting early cultural learning and assisting in the development and maintenance of behavioral traditions [1]. Imitation has long been assumed to occur from birth [2-4], with influential theories (e.g., [5-7]) placing an innate imitation module at the foundation of social cognition (potentially underpinned by a mirror neuron system [8, 9]). Yet, the very phenomenon of neonatal imitation has remained controversial. Empirical support is mixed and interpretations are varied [10-16], potentially because previous investigations have relied heavily on cross-sectional designs with relatively small samples and with limited controls [17, 18]. Here, we report surprising results from the most comprehensive longitudinal study of neonatal imitation to date. We presented infants (n = 106) with nine social and two non-social models and scored their responses at 1, 3, 6, and 9 weeks of age. Longitudinal analyses indicated that the infants did not imitate any of the models, as they were just as likely to produce the gestures in response to control models as they were to matching models. Previous positive findings were replicated in limited cross-sections of the data, but the overall analyses confirmed these findings to be mere artifacts of restricted comparison conditions. Our results undermine the idea of an innate imitation module and suggest that earlier studies reporting neonatal imitation were methodologically limited. PMID:27161497

  13. Accurate method to study static volume-pressure relationships in small fetal and neonatal animals.

    PubMed

    Suen, H C; Losty, P D; Donahoe, P K; Schnitzer, J J

    1994-08-01

    We designed an accurate method to study respiratory static volume-pressure relationships in small fetal and neonatal animals on the basis of Archimedes' principle. Our method eliminates the error caused by the compressibility of air (Boyle's law) and is sensitive to a volume change of as little as 1 microliters. Fetal and neonatal rats during the period of rapid lung development from day 19.5 of gestation (term = day 22) to day 3.5 postnatum were studied. The absolute lung volume at a transrespiratory pressure of 30-40 cmH2O increased 28-fold from 0.036 +/- 0.006 (SE) to 0.994 +/- 0.042 ml, the volume per gram of lung increased 14-fold from 0.39 +/- 0.07 to 5.59 +/- 0.66 ml/g, compliance increased 12-fold from 2.3 +/- 0.4 to 27.3 +/- 2.7 microliters/cmH2O, and specific compliance increased 6-fold from 24.9 +/- 4.5 to 152.3 +/- 22.8 microliters.cmH2O-1.g lung-1. This technique, which allowed us to compare changes during late gestation and the early neonatal period in small rodents, can be used to monitor and evaluate pulmonary functional changes after in utero pharmacological therapies in experimentally induced abnormalities such as pulmonary hypoplasia, surfactant deficiency, and congenital diaphragmatic hernia. PMID:8002489

  14. Immunotherapy in food allergy.

    PubMed

    Kamdar, Toral; Bryce, Paul J

    2010-05-01

    Food allergies are caused by immune responses to food proteins and represent a breakdown of oral tolerance. They can range from mild pruritus to life-threatening anaphylaxis. The only current consensus for treatment is food avoidance, which is fraught with compliance issues. For this reason, there has been recent interest in immunotherapy, which may induce desensitization and possibly even tolerance. Through these effects, immunotherapy may decrease the potential for adverse serious reactions with accidental ingestions while potentially leading to an overall health benefit. In this review, we discuss the mechanisms of food allergy and give an overview of the various immunotherapeutic options and current supporting evidence, as well as look towards the future of potential novel therapeutic modalities.

  15. Immunotherapy for tularemia.

    PubMed

    Skyberg, Jerod A

    2013-11-15

    Francisella tularensis is a gram-negative bacterium that causes the zoonotic disease tularemia. Francisella is highly infectious via the respiratory route (~10 CFUs) and pulmonary infections due to type A strains of F. tularensis are highly lethal in untreated patients (> 30%). In addition, no vaccines are licensed to prevent tularemia in humans. Due to the high infectivity and mortality of pulmonary tularemia, F. tularensis has been weaponized, including via the introduction of antibiotic resistance, by several countries. Because of the lack of efficacious vaccines, and concerns about F. tularensis acquiring resistance to antibiotics via natural or illicit means, augmentation of host immunity, and humoral immunotherapy have been investigated as countermeasures against tularemia. This manuscript will review advances made and challenges in the field of immunotherapy against tularemia.

  16. Maternal care receptivity and its relation to perinatal and neonatal mortality. A rural study.

    PubMed

    Bhardwaj, N; Hasan, S B; Zaheer, M

    1995-04-01

    A longitudinal study was conducted on 212 pregnant women from May 1987 to April 1988. Maternal Care Receptivity (MCR) "an innovative approach" was adopted for the assessment of maternal care services provided to pregnant mothers at their door steps. During follow-up, scores were allotted to each of the services rendered and antenatal status of pregnant women. Depending on the score--MCR was classified as high (11 to 8), moderate (7 to 4) or poor (3 to 0). Perinatal and neonatal deaths were recorded and an inverse relationship between MCR and perinatal and mortalities was observed (z = 5.46, p < 0.0001). Significantly, no perinatal or neonatal deaths occurred in women with high MCR. One of the most important cause of high PNMR and neonatal mortality rate in developing countries is poor MCR, i.e., under utilization of even the existing maternal health services. The main reasons for this under utilization appear to be poverty, illiteracy, ignorance and lack of faith in modern medicine.

  17. Maternal care receptivity and its relation to perinatal and neonatal mortality. A rural study.

    PubMed

    Bhardwaj, N; Hasan, S B; Zaheer, M

    1995-04-01

    A longitudinal study was conducted on 212 pregnant women from May 1987 to April 1988. Maternal Care Receptivity (MCR) "an innovative approach" was adopted for the assessment of maternal care services provided to pregnant mothers at their door steps. During follow-up, scores were allotted to each of the services rendered and antenatal status of pregnant women. Depending on the score--MCR was classified as high (11 to 8), moderate (7 to 4) or poor (3 to 0). Perinatal and neonatal deaths were recorded and an inverse relationship between MCR and perinatal and mortalities was observed (z = 5.46, p < 0.0001). Significantly, no perinatal or neonatal deaths occurred in women with high MCR. One of the most important cause of high PNMR and neonatal mortality rate in developing countries is poor MCR, i.e., under utilization of even the existing maternal health services. The main reasons for this under utilization appear to be poverty, illiteracy, ignorance and lack of faith in modern medicine. PMID:8635804

  18. Somatic stimulation causes frontoparietal cortical changes in neonates: a functional near-infrared spectroscopy study.

    PubMed

    Kashou, Nasser H; Dar, Irfaan A; Hasenstab, Kathryn A; Nahhas, Ramzi W; Jadcherla, Sudarshan R

    2017-01-01

    Palmar and plantar grasp are the foremost primitive neonatal reflexes and functions. Persistence of these reflexes in infancy is a sign of evolving cerebral palsy. Our aims were to establish measurement feasibility in a clinical setting and to characterize changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbD) concentration in the bilateral frontoparietal cortex in unsedated neonates at the crib-side using functional near-infrared spectroscopy (fNIRS). We hypothesized that bilateral concentration changes will occur upon somatic central and peripheral somatic stimulation. Thirteen preterm neonates (five males) underwent time 1, and six (two males) returned for time 2 (mean [Formula: see text] and 47.0 weeks, respectively). Signals from a total of 162 somatic stimuli responses were measured. Response amplitude, duration, and latency were log-transformed and compared between palmar, plantar, and oromotor stimuli using linear mixed models, adjusted for cap, electroencephalogram abnormality, time (1 versus 2), and Sarnat score, if necessary. The oromotor stimulus resulted in a 50% greater response than the palmar or plantar stimuli for HbO left and right hemisphere duration ([Formula: see text]). There were no other statistically significant differences between stimuli for any other outcome ([Formula: see text]). Utilizing fNIRS in conjunction with occupational and physical therapy maneuvers is efficacious to study modifiable and restorative neurophysiological mechanisms. PMID:27570791

  19. Immunotherapy of pancreatic carcinoma.

    PubMed

    Märten, Angela

    2008-05-01

    Patients with carcinoma of the exocrine pancreas have especially poor prognosis with a five-year survival rate of <1% and a median survival of 4-6 months. Pancreatic carcinoma is a systemic disease, insensitive to radiotherapy and mostly to chemotherapy. Accordingly, new treatment modalities are worth being investigated. One of the promising approaches is immunotherapy. Several phase I/II trials that have been published show interesting results, whereupon antibody-based strategies seem to fail and unspecific stimulation or vaccination with peptides look encouraging. Furthermore, phase II trials dealing with combination therapies are highly promising. One of them, a combination of chemoradiotherapy plus interferon-alpha is currently tested in a randomized phase III trial. As most of the trials had enrolled only limited numbers of patients and most of the trials were not conducted and/or reported according to the new standards it is difficult to draw final conclusions from the discussed trials. Immuno-monitoring was performed only in 40% of the discussed publications. In all cases immune responses were observed and correlation with the clinical outcome is discussed. Immunotherapy of pancreatic adenocarcinoma and especially combination therapies including immunotherapy is an up-and-coming approach and needs to be investigated in well conducted phase III randomized controlled trials accompanied by appropriate immuno-monitoring.

  20. Immunotherapy of Cancer in 2012

    PubMed Central

    Kirkwood, John M.; Butterfield, Lisa H.; Tarhini, Ahmad A.; Zarour, Hassane; Kalinski, Pawel; Ferrone, Soldano

    2012-01-01

    The immunotherapy of cancer has made significant strides in the past few years due to improved understanding of the underlying principles of tumor biology and immunology. These principles have been critical in the development of immunotherapy in the laboratory and in the implementation of immunotherapy in the clinic. This improved understanding of immunotherapy, enhanced by increased insights into the mechanism of tumor immune response and its evasion by tumors, now permits manipulation of this interaction and elucidates the therapeutic role of immunity in cancer. Also important, this improved understanding of immunotherapy and the mechanisms underlying immunity in cancer has fueled an expanding array of new therapeutic agents for a variety of cancers. Pegylated interferon-α2b as an adjuvant therapy and ipilimumab as therapy for advanced disease, both of which were approved by the United States Food and Drug Administration for melanoma in March 2011, are 2 prime examples of how an increased understanding of the principles of tumor biology and immunology have been translated successfully from the laboratory to the clinical setting. Principles that guide the development and application of immunotherapy include antibodies, cytokines, vaccines, and cellular therapies. The identification and further elucidation of the role of immunotherapy in different tumor types, and the development of strategies for combining immunotherapy with cytotoxic and molecularly targeted agents for future multimodal therapy for cancer will enable even greater progress and ultimately lead to improved outcomes for patients receiving cancer immunotherapy. PMID:22576456

  1. Customized versus population-based birth weight charts for the detection of neonatal growth and perinatal morbidity in a cross-sectional study of term neonates.

    PubMed

    Carberry, Angela E; Raynes-Greenow, Camille H; Turner, Robin M; Jeffery, Heather E

    2013-10-15

    Customized birth weight charts that incorporate maternal characteristics are now being adopted into clinical practice. However, there is controversy surrounding the value of these charts in the prediction of growth and perinatal outcomes. The objective of this study was to assess the use of customized charts in predicting growth, defined by body fat percentage, and perinatal morbidity. A total of 581 term (≥37 weeks' gestation) neonates born in Sydney, Australia, in 2010 were included. Body fat percentage measurements were taken by using air displacement plethysmography. Objective composite measurements of perinatal morbidity were used to identify neonates who had poor outcomes; these data were extracted from medical records. The value of customized charts was assessed by calculating positive predictive values, negative predictive values, and odds ratios with 95% confidence intervals. Customized versus population-based charts did not improve the prediction of either low body fat percentage (59% vs. 66% positive predictive value and 87% vs. 89% negative predictive value, respectively) or high body fat percentage (48% vs. 53% positive predictive value and 90% vs. 89% negative predictive value, respectively). Customized charts were not better than population-based charts at predicting perinatal morbidity (for customized charts, odds ratio = 1.02, 95% confidence interval: 1.01, 1.04; for population-based charts, odds ratio = 1.03, 95% confidence interval: 1.01, 1.05) per percentile decrease in birth weight. Customized birth weight charts do not provide significant improvements over population-based charts in predicting neonatal growth and morbidity.

  2. A European perspective on immunotherapy for food allergies.

    PubMed

    Beyer, Kirsten

    2012-05-01

    Food allergies are common, and frequently, the only treatment option is strict avoidance. Unfortunately, many patients accidentally ingest allergenic foods, which can result in severe anaphylactic reactions. Several immunotherapies are being developed for food allergies; these involve oral, sublingual, epicutaneous, or subcutaneous administration of small amounts of native or modified allergens to induce immune tolerance. Oral immunotherapy seems to be the most promising approach based on results from small uncontrolled and controlled studies. However, it is a challenge to compare results among immunotherapy trials because of differences in protocols. Studies conducted thus far have tested the most prevalent food allergens: it is not clear whether their results can be extended to other allergens. Sublingual administration of immunotherapy has shown some efficacy and fewer side effects than oral administration in some trials, yet neither approach can be recommended for routine practice. Controlled studies with larger numbers of subjects are needed to determine short- and long-term efficacy and side effects. In Europe immunotherapy trials for food allergies face many ethical and regulatory issues. Guidelines from the European Medicine Agency on the clinical development of products for specific immunotherapy of allergic diseases do not adequately address immunotherapy for food allergies, especially for therapies that orally administer native food or that include pediatric patients.

  3. Oral immunotherapy for allergic conjunctivitis.

    PubMed

    Ishida, Waka; Fukuda, Ken; Harada, Yosuke; Yagita, Hideo; Fukushima, Atsuki

    2014-11-01

    Antigen-specific immunotherapy is expected to be a desirable treatment for allergic diseases. Currently, antigen-specific immunotherapy is performed by administering disease-causing antigens subcutaneously or sublingually. These approaches induce long-term remission in patients with allergic rhinitis or asthma. The oral route is an alternative to subcutaneous and sublingual routes, and can also induce long-term remission, a phenomenon known as "oral tolerance." The effectiveness of oral tolerance has been reported in the context of autoimmune diseases, food allergies, asthma, atopic dermatitis, and allergic rhinitis in both human patients and animal models. However, few studies have examined its efficacy in animal models of allergic conjunctivitis. Previously, we showed that ovalbumin feeding suppressed ovalbumin-induced experimental allergic conjunctivitis, indicating the induction of oral tolerance is effective in treating experimental allergic conjunctivitis. In recent years, transgenic rice has been developed that can induce oral tolerance and reduce the severity of anaphylaxis. The major Japanese cedar pollen antigens in transgenic rice, Cryptomeria japonica 1 and C. japonica 2, were deconstructed by molecular shuffling, fragmentation, and changes in the oligomeric structure. Thus, transgenic rice may be an effective treatment for allergic conjunctivitis.

  4. Cancer immunotherapy and immunological memory.

    PubMed

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

      Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

  5. Sublingual immunotherapy: a comprehensive review.

    PubMed

    Cox, Linda S; Larenas Linnemann, Désirée; Nolte, Hendrik; Weldon, David; Finegold, Ira; Nelson, Harold S

    2006-05-01

    Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non-cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients. PMID:16675328

  6. Cancer immunotherapy and immunological memory.

    PubMed

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

      Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy. PMID:27181230

  7. A review of allergoid immunotherapy: is cat allergy a suitable target?

    PubMed

    Nguyen, Nhung T; Raskopf, Esther; Shah-Hosseini, Kija; Zadoyan, Gregor; Mösges, Ralph

    2016-01-01

    To modify the course of allergy, different types of specific allergen immunotherapy have been developed such as sublingual immunotherapy and subcutaneous immunotherapy with native allergens or subcutaneous immunotherapy with polymerized allergoids. However, the optimal specific immunotherapy, especially for cat allergy, remains undetermined. Few studies investigating immunotherapy in cat allergy have been published, and the risk of serious adverse reactions and systemic reactions has often been an important issue. Monomeric allergoids have lower allergenic potential while their immunogenicity remains constant, resulting in excellent safety with notable efficacy. Specific immunotherapy with monomeric allergoids could, therefore, be of high value, especially in cat allergy as well as other types of allergy, and bring relief to a great community of patients.

  8. A study on early-onset neonatal group B streptococcal infection, Bulgaria, 2007-2011.

    PubMed

    Todorova-Christova, M; Vacheva, R; Decheva, A; Nikolov, A; Slancheva, B; Stoichkova, D; Christova, E; Shopova, E; Hitrova, S; Masseva, A; Yarakova, N; Kraleva, I; Takova, T S; Dimitrova, N; Dobreva, A

    2014-09-01

    This study examines neonatal group B streptococcal (GBS) colonization and its relation to early-onset GBS disease (EOGBSD), based upon the experience of leading obstetrics and gynecology centers in Bulgaria. The objectives of the study were to update neonatal colonization rates and to assess relationships between clinically differentiated cases (culture-proven GBS newborns) and risk factors inherent to the infant and mother, using a computerized file. The neonatal GBS colonization rate ranged from 5.48 to 12.19 per 1000 live births. Maternal-fetal infection (MFI, a provisional clinical diagnosis in culture-proven colonized infants with initial signs of infection that is usually overcome with antibiotic treatment) and/or intrapartum asphyxia (IA) have been demonstrated as the most frequent clinical manifestations, with significant correlations for the primary diagnosis, but not affirmative for the final diagnosis at discharge, resulting from adequate treatment of neonates. MFI and IA were significantly related to prematurity, and reciprocally, prematurity was associated with the risk of MFI, indirectly suggesting that preterm birth or PPROM (preterm premature rupture of membranes, an obstetric indication associated with early labor and delivery, one of the major causes of preterm birth) is a substantial risk factor for EOGBSD. The regression analysis indicated that in the case of a newborn with MFI, a birth weight 593.58 g lower than the birth weight of an infant without this diagnosis might be expected. Testing the inverse relationship, i.e., the way birth weight influences a certain diagnosis (logistic regression) established the presence of a relationship between birth weight categories (degree of prematurity) and the diagnosis of MFI. The proportions and odds ratios, converted into probabilities that a baby would develop MFI, indicate the particularly high risk for newborns with extremely low and very low birth weight: extremely low birth weight (≤1000 g), the

  9. [Decisions on limiting treatment in critically-ill neonates: a multicenter study].

    PubMed

    2002-12-01

    Backgrounds Some patients with a poor prognosis cause serious doubts about the real benefit of life-sustaining treatment. In some cases the possibility of limiting those treatments is raised. Such end-of-life decisions provoke ethical dilemmas and questions about procedure.ObjectivesTwo determine the frequency of end-of-life decisions in neonates, patient characteristics, and the criteria used by those taking decisions.Patients and methodsWe performed a multicenter, descriptive, prospective study. Neonates from 15 neonatal intensive care units who died during their stay in the hospital between 1999 and 2000, as well as those in whom end-of-life decisions were taken, were included. End-of-life decisions were defined as clinical decisions to withhold or withdraw life-sustaining treatment.ResultsA total of 330 patients were included. End-of-life decisions were taken in 171 (52 %); of these, 169 (98.8 %) died. The remaining 159 patients (48.2 %) died without treatment limitation. The main disorders involving end-of-life decisions were congenital malformation (47 %), neurologic disorders secondary to perinatal asphyxia and intracranial hemorrhage-periventricular leukomalacia (37 %). Of the 171 neonates, treatment was withheld in 80 and vital support was withdrawn in 91. The most frequently withdrawn life-sustaining treatment was mechanical ventilation (68 %). The criteria most commonly used in end-of-life decisions were poor vital prognosis (79.5 %), and current and future quality of life (37 % and 48 % respectively). The patient's external factors such as unfavorable family environment or possible negative consequences for familial equilibrium were a factor in 5 % of decisions.ConclusionsThe present study, the first of this type performed in Spain, reveals little-known aspects about the clinical practice of withholding and/or withdrawing life-sustaining treatment in critically ill neonates. End-of-life decisions were frequent (52 %) and were followed by death in most

  10. [Experimental and clinical study of adoptive immunotherapy combined with preadministration of OK-432: a method to augment the therapeutic effect].

    PubMed

    Kan, N; Okino, T; Nakanishi, M; Sato, K; Mise, K; Teramura, Y; Yamasaki, S; Hori, T; Ohgaki, K; Tobe, T

    1989-04-01

    Our previous method of adoptive immunotherapy using IL2-cultured autologous lymphocytes consists of (1) in vitro sensitization by sonicated autologous tumor extract, (2) the induction and proliferation of active CTL by crude IL2, and (3) the preadministration of OK-432 for the augmentation of the therapeutic effect. Here we describe a new method to augment the therapeutic effect of OK432-combined AIT. In BALB/c mice with advanced malignant ascites (MOPC 104E), serial therapy with OK-432, cyclophosphamide and AIT significantly prolonged the survival compared with other therapeutic schedules through synergism between host's effector cells induced by immuno-chemotherapy and transferred killer cells. Many patients with advanced malignancies, for example, unresectable gastrointestinal cancer, locally advanced breast cancer or lung metastases of breast cancer, respond to such immuno-chemo-lymphocytotherapy, while previous OK432-combined AIT was effective only in malignant pleural effusion or metastatic liver tumor from breast cancer or peritoneal dissemination of gastric cancer.

  11. [Study of the quality of interhospital transport of sick neonates by selected ambulances in the Witwatersrand area].

    PubMed

    Roux, J C; Nolte, A G; Muller, M E

    1989-12-01

    The quality of the inter hospital transport of ill neonates, by selected ambulances in the Witwatersrand area, was investigated by means of the case study method. Of the fifteen case studies investigated, eleven neonates were transported by a private ambulance and four by provincial ambulances. Data regarding the maternal- and neonatal history, the optimal maintenance of the neonate's condition, the communication system, as well as aspects relating to the transport personnel, were collected by means of a structured instrument. Retrospective auditing of records, structured interviewing and direct observation/inspection were utilised as the research techniques. The quality of the inter hospital transport of ill neonates, especially by the private ambulance, is not up to standard. Deterioration of the neonate's body temperature, heart and respiration rates, as well as the serum glucose values after transport, were of the more important findings. The lack of equipment, especially in the private ambulance, increases the risk of transport. Staff development and formal control by a local committee, as well as a national control body, are recommended.

  12. Midwifery students receiving the newborn at birth: A pilot study of the impact of structured training in neonatal resuscitation.

    PubMed

    Bull, Angela; Sweet, Linda

    2015-09-01

    The experience of midwifery students in receiving the newborn at birth, before and after structured training in neonatal resuscitation: A pilot study. The practice of receiving the newborn, including neonatal resuscitation is an essential component of midwifery. Anecdotal evidence suggests preparation for the task is ad hoc within midwifery curricula, leading to student's anxiety. This paper reports impacts of neonatal resuscitation training upon levels of knowledge, preparedness, and anxiety for midwifery students receiving the newborn. Midwifery students participated in an online questionnaire before and after neonatal resuscitation training. The responses collected were subjected to descriptive analysis. Of 10 students invited, 6 completed the pre and post course questionnaires. Knowledge of the responsibility in receiving the newborn and instigation of resuscitation increased after attending the course. Steps to prepare to receive the newborn and clinical signs for initial assessment remained static. Students felt more prepared to receive the newborn after the course but did not improve in their preparation to initiate resuscitation. Anxiety levels remained static. Structured neonatal resuscitation training and strategies to ensure application of skills learnt should be embedded into midwifery curricula. Midwifery students' experience in receiving the newborn and neonatal resuscitation is worthy of further study.

  13. Maternal and Antenatal Risk Factors for Stillbirths and Neonatal Mortality in Rural Bangladesh: A Case-Control Study

    PubMed Central

    Owais, Aatekah; Faruque, Abu Syed Golam; Das, Sumon K.; Ahmed, Shahnawaz; Rahman, Shahed; Stein, Aryeh D.

    2013-01-01

    Objective To identify maternal and antenatal factors associated with stillbirths and neonatal deaths in rural Bangladesh. Study Design A prospective cohort study is being conducted to evaluate a maternal and child nutrition program in rural Bangladesh. Cases were all stillbirths and neonatal deaths that occurred in the cohort between March 7, 2011 and December 30, 2011. Verbal autopsies were used to determine cause of death. For each case, four controls were randomly selected from cohort members alive at age 3-months. Multivariable logistic regression was used to identify factors associated with these deaths. Results Overall, 112 adverse pregnancy outcomes (44 stillbirths, 19/1,000 births; 68 neonatal deaths, 29/1,000 live births) were reported. Of the stillbirths 25 (56.8%) were fresh. The main causes of neonatal death were birth asphyxia (35%), sepsis (28%) and preterm birth (19%). History of bleeding during pregnancy was the strongest risk factor for stillbirths (adjusted odds ratio 22.4 [95% confidence interval 2.5, 197.5]) and neonatal deaths (adjusted odds ratio 19.6 [95% confidence interval 2.1, 178.8]). Adequate maternal nutrition was associated with decreased risk of neonatal death (adjusted odds ratio 0.4 [95% confidence interval 0.2, 0.8]). Conclusions Identifying high-risk pregnancies during gestation and ensuring adequate antenatal and obstetric care needs to be a priority for any community-based maternal and child health program in similar settings. PMID:24244638

  14. Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin Diagnostic Accuracy Studies.

    PubMed

    Chiesa, Claudio; Pacifico, Lucia; Osborn, John F; Bonci, Enea; Hofer, Nora; Resch, Bernhard

    2015-07-01

    To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative.EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS.We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies.We found 18 articles (1998-2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing.Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS.

  15. Update on Allergy Immunotherapy

    PubMed Central

    2005-01-01

    This article summarizes and provides commentary regarding guidelines on the administration of immunotherapy (IT) for allergic airway disease. Recent investigations have provided important insights into the immunologic mechanism of IT and the prominent role of interleukin-10-producing regulatory T lymphocytes. The most important aspect of successful IT is the administration of an appropriate dose of an extract containing a sufficient concentration of the relevant allergen. This is largely possible now only with standardized extracts. When the major allergen content of successful IT extracts was quantified, efficacy was demonstrated across a surprisingly narrow concentration range (approximately 5-24 μg per injection), irrespective of the extract. This presumably reflects the concentration of an antigen that drives an immune response toward tolerance. It may be predicted that as major allergen content is quantified in currently nonstandardized extracts, effective IT will also be achieved by administering a dose in this range, in contrast to current practices involving fairly arbitrary dosing decisions. With the availability of nonsedating antihistamines, intranasal corticosteroids, and the leukotriene modifiers, inadequate pharmacologic response or intolerable side effects are less commonly the major indications for starting IT for allergic rhinitis (AR). However, with the recognition that a relatively short course (3-5 years) of IT can provide long-term immunomodulation and clinical benefit, a desire to avoid long-term pharmacotherapy and the associated high costs may be the primary indication for IT in AR cases. While evidence overwhelmingly supports the beneficial influences of IT in asthma cases, the positioning of IT for this disorder is not established. The observed prevention of asthma in children who have AR is intriguing, but further studies are required to assess the extent to which the prevalence and severity of chronic asthma will be reduced when these

  16. A longitudinal study of distortion product otoacoustic emission ipsilateral suppression and input/output characteristics in human neonates.

    PubMed

    Abdala, Carolina

    2003-12-01

    Past work has shown that distortion product otoacoustic emission (DPOAE) (2f1-f2) ipsilateral suppression and input/output (I/O) characteristics are not adult-like in prematurely born neonates [Abdala, J. Acoust. Soc. Am. 110, 1465-1476 (2001)]. These age differences are most pronounced at f2 = 6000 Hz and have been interpreted to indicate a subtle immaturity in human cochlear function prior to term birth. It is still not clear, however, whether term-born neonates are completely adult-like in cochlear function. To study this question, DPOAE suppression and I/O functions for f2 = 6000 Hz were measured in a group of prematurely born neonates at weekly intervals over a period of 7-8-weeks, a group of normal-hearing adults, and during a one-time test session in a group of term-born neonates. Results show that there was no significant change in suppression tuning, suppression growth, and various I/O characteristics across test session for premature neonates, but there was an age-group effect; even once prematurely born neonates reached the equivalence of term-like status (38-40-weeks postconceptional weeks), they continued to show narrower suppression tuning than adults, shallower suppression growth for low-frequency side suppressor tones, and an elevated amplitude saturation plateau on the I/O function. Term-born neonates showed DPOAE results that were comparable to those measured from premature neonates and unlike adult findings. These results suggest that a subtle immaturity in cochlear function persists into the postnatal period. PMID:14714805

  17. A longitudinal study of distortion product otoacoustic emission ipsilateral suppression and input/output characteristics in human neonates

    NASA Astrophysics Data System (ADS)

    Abdala, Carolina

    2003-12-01

    Past work has shown that distortion product otoacoustic emission (DPOAE) (2f1-f2) ipsilateral suppression and input/output (I/O) characteristics are not adult-like in prematurely born neonates [Abdala, J. Acoust. Soc. Am. 110, 1465-1476 (2001)]. These age differences are most pronounced at f2=6000 Hz and have been interpreted to indicate a subtle immaturity in human cochlear function prior to term birth. It is still not clear, however, whether term-born neonates are completely adult-like in cochlear function. To study this question, DPOAE suppression and I/O functions for f2=6000 Hz were measured in a group of prematurely born neonates at weekly intervals over a period of 7-8-weeks, a group of normal-hearing adults, and during a one-time test session in a group of term-born neonates. Results show that there was no significant change in suppression tuning, suppression growth, and various I/O characteristics across test session for premature neonates, but there was an age-group effect; even once prematurely born neonates reached the equivalence of term-like status (38-40-weeks postconceptional weeks), they continued to show narrower suppression tuning than adults, shallower suppression growth for low-frequency side suppressor tones, and an elevated amplitude saturation plateau on the I/O function. Term-born neonates showed DPOAE results that were comparable to those measured from premature neonates and unlike adult findings. These results suggest that a subtle immaturity in cochlear function persists into the postnatal period.

  18. A longitudinal study of distortion product otoacoustic emission ipsilateral suppression and input/output characteristics in human neonates.

    PubMed

    Abdala, Carolina

    2003-12-01

    Past work has shown that distortion product otoacoustic emission (DPOAE) (2f1-f2) ipsilateral suppression and input/output (I/O) characteristics are not adult-like in prematurely born neonates [Abdala, J. Acoust. Soc. Am. 110, 1465-1476 (2001)]. These age differences are most pronounced at f2 = 6000 Hz and have been interpreted to indicate a subtle immaturity in human cochlear function prior to term birth. It is still not clear, however, whether term-born neonates are completely adult-like in cochlear function. To study this question, DPOAE suppression and I/O functions for f2 = 6000 Hz were measured in a group of prematurely born neonates at weekly intervals over a period of 7-8-weeks, a group of normal-hearing adults, and during a one-time test session in a group of term-born neonates. Results show that there was no significant change in suppression tuning, suppression growth, and various I/O characteristics across test session for premature neonates, but there was an age-group effect; even once prematurely born neonates reached the equivalence of term-like status (38-40-weeks postconceptional weeks), they continued to show narrower suppression tuning than adults, shallower suppression growth for low-frequency side suppressor tones, and an elevated amplitude saturation plateau on the I/O function. Term-born neonates showed DPOAE results that were comparable to those measured from premature neonates and unlike adult findings. These results suggest that a subtle immaturity in cochlear function persists into the postnatal period.

  19. Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies.

    PubMed

    Carnielli, Virgilio P; Giorgetti, Chiara; Simonato, Manuela; Vedovelli, Luca; Cogo, Paola

    2016-01-01

    Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call 'endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named 'exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

  20. Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies.

    PubMed

    Carnielli, Virgilio P; Giorgetti, Chiara; Simonato, Manuela; Vedovelli, Luca; Cogo, Paola

    2016-01-01

    Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call 'endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named 'exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases. PMID:27251153

  1. A Randomized Controlled Study of Manikin Simulator Fidelity on Neonatal Resuscitation Program Learning Outcomes

    ERIC Educational Resources Information Center

    Curran, Vernon; Fleet, Lisa; White, Susan; Bessell, Clare; Deshpandey, Akhil; Drover, Anne; Hayward, Mark; Valcour, James

    2015-01-01

    The neonatal resuscitation program (NRP) has been developed to educate physicians and other health care providers about newborn resuscitation and has been shown to improve neonatal resuscitation skills. Simulation-based training is recommended as an effective modality for instructing neonatal resuscitation and both low and high-fidelity manikin…

  2. Targeting dendritic cells in allergen immunotherapy.

    PubMed

    Novak, Natalija

    2006-05-01

    Allergen immunotherapy is a well-established strategy for treating allergic diseases with the goal of inducing allergen-specific tolerance. Identified mechanisms contributing to the therapeutic effect of immunotherapy include a shift of T helper 2 (Th2)-type immune responses to a modified Th2 immune response, a change of the balance of IgE-producing B cells to the production of IgG subtypes, in addition to increased IL-10 and TGF-beta secretion and activation of the suppressive functions of regulatory T-cells. Dendritic cells (DCs), which as outposts of the immune system are capable of T-cell priming through efficient allergen uptake by IgE receptors expressed on their cell surface. Most of the hypotheses concerning the function of DCs as facilitators of allergen-specific tolerance in allergen immunotherapy remain speculative. Therefore, studies must focus on the functional changes of DCs under immunotherapy to close the gap of knowledge about their exact role. These experimental data should help confirm the hypothesis of DCs as efficient silencers and potential target cells and take advantage of the bivalent character and tolerogenic properties of DCs. PMID:16701146

  3. Role of IL-2 in cancer immunotherapy.

    PubMed

    Jiang, Tao; Zhou, Caicun; Ren, Shengxiang

    2016-06-01

    Interleukin-2 (IL-2) is one of the key cytokines with pleiotropic effects on immune system. It has been approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. Recent progress has been made in our understanding of IL-2 in regulating lymphocytes that has led to exciting new directions for cancer immunotherapy. While improved IL-2 formulations might be used as monotherapies, their combination with other anticancer immunotherapies, such as adoptive cell transfer regimens, antigen-specific vaccination, and blockade of immune checkpoint inhibitory molecules, for example cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) mono-antibodies, would held the promise of treating metastatic cancer. Despite the comprehensive studies of IL-2 on immune system have established the application of IL-2 for cancer immunotherapy, a number of poignant obstacles remain for future research. In the present review, we will focus on the key biological features of IL-2, current applications, limitations, and future directions of IL-2 in cancer immunotherapy.

  4. Current progress in immunotherapy for pancreatic cancer.

    PubMed

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  5. Bioinformatics for cancer immunology and immunotherapy.

    PubMed

    Charoentong, Pornpimol; Angelova, Mihaela; Efremova, Mirjana; Gallasch, Ralf; Hackl, Hubert; Galon, Jerome; Trajanoski, Zlatko

    2012-11-01

    Recent mechanistic insights obtained from preclinical studies and the approval of the first immunotherapies has motivated increasing number of academic investigators and pharmaceutical/biotech companies to further elucidate the role of immunity in tumor pathogenesis and to reconsider the role of immunotherapy. Additionally, technological advances (e.g., next-generation sequencing) are providing unprecedented opportunities to draw a comprehensive picture of the tumor genomics landscape and ultimately enable individualized treatment. However, the increasing complexity of the generated data and the plethora of bioinformatics methods and tools pose considerable challenges to both tumor immunologists and clinical oncologists. In this review, we describe current concepts and future challenges for the management and analysis of data for cancer immunology and immunotherapy. We first highlight publicly available databases with specific focus on cancer immunology including databases for somatic mutations and epitope databases. We then give an overview of the bioinformatics methods for the analysis of next-generation sequencing data (whole-genome and exome sequencing), epitope prediction tools as well as methods for integrative data analysis and network modeling. Mathematical models are powerful tools that can predict and explain important patterns in the genetic and clinical progression of cancer. Therefore, a survey of mathematical models for tumor evolution and tumor-immune cell interaction is included. Finally, we discuss future challenges for individualized immunotherapy and suggest how a combined computational/experimental approaches can lead to new insights into the molecular mechanisms of cancer, improved diagnosis, and prognosis of the disease and pinpoint novel therapeutic targets.

  6. Targeting neoantigens for cancer immunotherapy.

    PubMed

    Lu, Yong-Chen; Robbins, Paul F

    2016-07-01

    Studies first carried out in the 1980s have demonstrated murine T cells can recognize mutated gene products, known as neoantigens, and that these T cells are capable of mediating tumor rejection. The first human tumor antigens isolated in the early 1990s were the products of non-mutated genes expressed in a tissue-specific manner; subsequent studies have indicated that tumor-infiltrating lymphocytes that are cultured in vitro frequently recognize mutated gene products. In addition, correlative studies indicate that clinical responses to therapies involving the use of antibodies directed against checkpoint inhibitors such as CTLA-4 and PD-1 may be associated with mutational burden, providing indirect evidence that these responses may primarily be mediated by neoantigen-reactive T cells. The importance of neoantigen-reactive T cells may be elucidated by the results of ongoing and future studies aimed at leveraging information gained from mutational profiling to enhance the potency of immunotherapies.

  7. Neonatal sepsis

    MedlinePlus

    ... BE. Perinatal viral infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ... K. Postnatal bacterial infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ...

  8. Oral Immunotherapy for Food Allergies.

    PubMed

    Feuille, Elizabeth; Nowak-Węgrzyn, Anna

    2016-01-01

    Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice. PMID:27355816

  9. Amyloid beta peptide immunotherapy in Alzheimer disease.

    PubMed

    Delrieu, J; Ousset, P J; Voisin, T; Vellas, B

    2014-12-01

    Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation.

  10. Immunotherapy for Alzheimer's disease.

    PubMed

    Farlow, Martin R; Brosch, Jared R

    2013-08-01

    The immune system plays a significant role in Alzheimer disease (AD). β-Amyloid deposition in the cortex is thought to be an initiating event in AD and the widely believed amyloid hypothesis proposes removal of amyloid may delay disease progression. Human trials of active or passive immune agents have failed to show benefit and increased adverse events of vasogenic edema and microhemorrhages. Evidence suggests the illness may be too advanced by the time patients are symptomatic with dementia. Future directions include better understanding of how and where immunotherapies should be targeted and treating patients at earlier stages of the illness.

  11. [Immunotherapy for Alzheimer's disease].

    PubMed

    Falkentoft, Alexander Christian; Hasselbalch, Steen Gregers

    2016-01-18

    Passive anti-beta-amyloid (Aß) immunotherapy has been shown to clear brain Aß deposits. Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD. Solanezumab and new monoclonal antibodies are being tested in patients with prodromal and preclinical AD in search for a disease-modifying treatment. PMID:26815584

  12. [Phenomenologic study about experiences when living the death in the neonatal critical care unit].

    PubMed

    Silva, Laureana Cartaxo Salgado Pereira; Valença, Cecília Nogueira; Germano, Raimunda Medeiros

    2010-01-01

    This research aimed at describing the care experiences of neonatal critical care nurses when facing the death and to understand their feelings before the death of the newborn. Qualitative research with a phenomenological approach, with the guiding question: How do you feel about the death of the newborn ICU where you work? Attended the interview 12 nurses and ICU nursing. Emerging feelings such as guilt, failure and denial. Understanding the phenomenon being studied, we affirm that the death of the newborn within the ICU is an experience of conflicting feelings, sometimes painful for the nurses.

  13. A Novel Urinary Biomarker Profile to Identify Acute Kidney Injury (AKI) in Critically Ill Neonates - A Pilot Study

    PubMed Central

    Hoffman, Suma Bhat; Massaro, An N.; Soler-García, Ángel A.; Perazzo, Sofia; Ray, Patricio E.

    2014-01-01

    Background The goal of this study was to assess the value of a urinary biomarker profile comprised of Neutrophil Gelatinase-associated Lipocalin (NGAL), Fibroblast Growth Factor-2 (FGF-2), and Epidermal Growth Factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. Methods We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n=10). Urine was collected at baseline, 48 hours of illness, and > 24 hours post recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 hours and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50% post recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. Results Fifteen at risk newborns had AKI. In the first 48 hours of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74% and specificity of 84%. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery, identified critically ill neonates with AKI. Conclusions These findings require validation in larger prospective studies. PMID:23783654

  14. A comparative cohort study on transfusion practice and outcome in two Dutch tertiary neonatal centres.

    PubMed

    Khodabux, C M; Hack, K E A; von Lindern, J S; Brouwers, H; Walther, F J; Brand, A

    2009-08-01

    The objective of this study was to investigate how a red blood cell transfusion volume of 15 or 20 mL kg(-1) body weight affects the total number of administered transfusions and neonatal complications in premature infants born before 32 gestational weeks. In this observational study, we analysed clinical data from two cohorts of 218 and 241 premature infants admitted to two neonatal centres which used the same transfusion guideline and product, but different transfusion volumes. Outcome parameters were the number of administered transfusions and the composite outcome of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage and mortality. The proportion of transfused infants was significantly lower (59 vs. 77%) in the centre using a lower transfusion volume of 15 mL kg(-1). In infants born between a gestational age of 24 0/7 weeks and 27 6/7 weeks. a similar proportion received transfusions in both centres, with an equal number of transfusions per infant. In infants born between a gestational age of 28 0/7 weeks and 31 6/7 weeks, the proportion of transfused infants (49 vs. 74%) was significantly higher in the centre using a larger transfusion volume. In these infants, transfusion with 20 mL kg(-1) resulted, however, in a mean reduction of one transfusion episode per infant. The higher proportion of transfused infants was associated with a higher pre-transfusion haematocrit in less ill infants, suggesting the use of different triggers based on clinical grounds. Composite clinical complications were similar in both cohorts. Clinical neonatal outcome was similar disregard of a higher proportion of transfused patients and a higher total amount of RBC transfused in one of the centres. A larger transfusion volume of 20 mL kg(-1) prolonged the interval until next transfusion and can reduce donor exposure in infants born between a gestational age of 28 0/7 weeks and 31 6/7 weeks.

  15. The relationship of maternal iodine status and neonatal thyrotropin concentration: a study in Southern Thailand.

    PubMed

    Jaruratanasirikul, Somchit; Chukamnerd, Jaruwan; Koranantakul, Ounjai; Chanvitan, Prasin; Ruaengrairatanaroj, Prasit; Sriplung, Hutcha

    2006-05-01

    Iodine deficiency disorder (IDD) is a global health problem. Previous studies in Southern Thailand have shown that the prevalence of goiter in schoolchildren is 3-5%, indicating that Southern Thailand is an iodine sufficient area. We conducted a study in pregnant women to determine their iodine status and whether there was an association between maternal urinary iodine excretion (UIE) and the neonatal thyrotropin (TSH) concentration. We recruited 244 pregnant women attending the antenatal clinic at Songklanagarind Hospital. Their mean age was 28.5 +/- 5.3 years (range 15-42) with a mean gestation age of 9.4 +/- 2.7 weeks (range 6-15). Ten ml urine was collected for UIE measurement. All women were delivered at Songklanagarind Hospital. The mean gestational age at delivery was 38.2 +/- 2.1 weeks (range 28-41). The median maternal UIE was 139.5 microg/l with 78 (32%) women having UIE below 100 microg/l. The median TSH of the infants was 4.14 mIU/l (range 0.30-17.89) with 88 (36.1%) of infants having TSH concentration above 5 mIU/l. Logistic regression analysis revealed that the odds ratio of pregnant women with UIE below 100 microg/l giving birth to infants with neonatal TSH above 5 mIU/l was 2.04 (95% confidence interval 1.17-3.66, p = 0.012). In conclusion, our findings demonstrate that 32% of pregnant women have UIE below 100 microg/l, and that UIE below 100 microg/l in pregnant women is associated with neonatal TSH concentration above 5 mIU/l. These findings suggest that iodine deficiency is prevalent in pregnant women in Southern Thailand.

  16. Neonatal nurses' views on the barriers to parenting in the intensive care nursery--a national study.

    PubMed

    Walker, S B

    1998-09-01

    A descriptive research study was undertaken at a national level to identify neonatal nurses' views on the barriers to parenting in the intensive care nursery. The objective of the study was to determine nurses' responses to the barriers to parenting identified in the literature. Relevant literature was examined and a questionnaire developed and pilot tested. In all, 794 questionnaires were distributed with neonatal nursing newsletters and in intensive care nurseries throughout NSW, the ACT, South Australia, Western Australia, the Northern Territory and Queensland. The Neonatal Nurses Association of Victoria and Tasmania did not respond to the invitation for its members to participate, so no questionnaires were distributed in these states. Neonatal nurses were asked to indicate the extent of their agreement with the issues identified in the literature on a four-point scale, with 1 the lowest score and 4 the highest. Of the 794 questionnaires distributed 298 were returned, representing a 37.5 per cent response rate. The results of the questionnaire indicate nurses' understanding of the environmental and emotional barriers confronting parents; however, there was little acknowledgment of nurse-initiated practices which also prevent parents fulfilling their parenting role. Responses to several questions were evenly divided, indicating inconsistency in neonatal nurses' views on what constitute barriers to parenting. The results of the questionnaire provide a national snapshot of the views of neonatal nurses with respect to the barriers confronting parents as they attempt to fulfil their parenting role and bring nurse-initiated barriers, such as policies and procedures, to the attention of neonatal nurses.

  17. Immunotherapy for TB.

    PubMed

    Doherty, T Mark

    2012-06-01

    Mycobacterium tuberculosis was one of the first human pathogens to be identified as the cause of a specific disease--TB. TB was also one of the first specific diseases for which immunotherapy was attempted. In more than a century since, multiple different immunotherapies have been attempted, alongside vaccination and antibiotic treatment, with varying degrees of success. Despite this, TB remains a major worldwide health problem that causes nearly 2 million deaths annually and has infected an estimated 2 billion people. A major reason for this is that M. tuberculosis is an ancient human pathogen that has evolved complex strategies for persistence in the human host. It has thus been long understood that, to effectively control TB, we will need to address the ability of the pathogen to establish a persistent, latent infection in most infected individuals. This review discusses what is presently known about the interaction of M. tuberculosis with the immune system, and how this knowledge has been used to design immunotherapeutic strategies.

  18. Dendritic cell immunotherapy: clinical outcomes

    PubMed Central

    Apostolopoulos, Vasso; Pietersz, Geoffrey A; Tsibanis, Anastasios; Tsikkinis, Annivas; Stojanovska, Lily; McKenzie, Ian FC; Vassilaros, Stamatis

    2014-01-01

    The use of tumour-associated antigens for cancer immunotherapy studies is exacerbated by tolerance to these self-antigens. Tolerance may be broken by using ex vivo monocyte-derived dendritic cells (DCs) pulsed with self-antigens. Targeting tumour-associated antigens directly to DCs in vivo is an alternative and simpler strategy. The identification of cell surface receptors on DCs, and targeting antigens to DC receptors, has become a popular approach for inducing effective immune responses against cancer antigens. Many years ago, we demonstrated that targeting the mannose receptor on macrophages using the carbohydrate mannan to DCs led to appropriate immune responses and tumour protection in animal models. We conducted Phase I, I/II and II, clinical trials demonstrating the effectiveness of oxidised mannan-MUC1 in patients with adenocarcinomas. Here we summarise DC targeting approaches and their efficacy in human clinical trials. PMID:25505969

  19. Neonatal nurses' views on the barriers to parenting in the intensive care nursery--a pilot study.

    PubMed

    Walker, S B

    1997-03-01

    A descriptive study, using a self-reporting questionnaire, was undertaken to identify neonatal nurses' views on barriers to parenting in the intensive care nursery. The objective of the study was to determine nurses' responses to the barriers to parenting identified in the nursing literature. Relevant literature was examined and the questionnaire developed. To determine reliability and validity, the questionnaire was examined by both medical and nursing experts and a pilot study was undertaken, with relevant changes made, as many answers reflect current unit policy rather than opinion. Questionnaires were distributed in an intensive care nursery in Brisbane, Australia; the nurses were asked to rate the extent of their agreement with the points identified in the literature on a seven-point scale, with 1 being the lowest score and 7 the highest. Of the 80 questionnaires distributed, 40 were returned. The results of the questionnaire indicated an understanding of the environmental and emotional barriers confronting parents. However, there was little acknowledgement of the nurse-initiated practices which also prevent parents fulfilling their parenting role. Evenly divided responses were received to several questions, indicating inconsistency in neonatal nurses' views on what constitute barriers to parenting. The results of the questionnaire are of value in extending neonatal nursing knowledge. They provide a snapshot of neonatal nurses' views on the barriers confronting parents as they attempt to fulfill their parenting role, and bring nurse-initiated barriers, such as policy and procedures, to the attention of neonatal intensive care nurses.

  20. A pilot study of Bifidobacterium breve in neonates undergoing surgery for congenital heart disease

    PubMed Central

    2014-01-01

    Background Probiotics have currently been widely used in patients undergoing various types of surgeries and improved their clinical outcomes, while data in pediatric cardiac surgery have been lacking. We investigated the safety and effects on the intestinal microbiota of the probiotic Bifidobacterium breve in neonates undergoing surgery for congenital heart disease. Methods This pilot, randomized study was performed in a single-center, university hospital-based pediatric intensive care unit (PICU). Twenty-one neonates undergoing surgery for congenital heart disease at >7 days after birth were randomly allocated to two groups: group A received 3 × 109 colony-forming units (CFU)/day of enteral B. breve strain Yakult (BBG-01), which was started 1 week before and terminated 1 week after surgery (n = 10), and group B did not receive BBG-01 (n = 11). Results The characteristics of the patients were similar in both groups. The postoperative days until fulfillment of the criteria for discharge from the PICU tended to be fewer in group A (8 [7–8] days) than in group B (9 [8–14] days) (p = 0.10). Likewise, the postoperative days to enteral nutrition or achievement of caloric goal tended to be fewer in group A than in group B. The Bifidobacterium in fecal samples after initiating BBG-01 in group A were significantly higher in number than that in group B. Enterobacteriaceae were significantly fewer in group A than in group B immediately (7.0 [3.9–7.7] vs. 8.5 [8.0–9.1] log10 cells/g) and 1 week (7.7 [7.0–8.1] vs. 9.3 [8.6–9.5] log10 cells/g) after surgery (p < 0.05 for both comparisons). The number of Pseudomonas after 1 week was significantly lower in group A than in group B (p = 0.04). The concentrations of total organic and acetic acids were also significantly higher in group A than in group B. The postoperative course was uncomplicated and all neonates were discharged alive from the PICU. Conclusions The perioperative

  1. Modified immunotherapy for alopecia areata.

    PubMed

    Yoshimasu, Takashi; Furukawa, Fukumi

    2016-07-01

    Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently high recommended sensitization dose of 1%-2% SADBE, often decreasing patient compliance. We assessed a modified immunotherapy for AA using SADBE at a starting concentration of 0.01% without sensitization. After one or two weeks of initial 0.01% SADBE application, the concentration of SADBE was increased gradually to 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 1% and 2% until the patients felt itching or erythema at the AA lesion site. The modified immunotherapy showed a response rate of 69.4% (25/36), equivalent to conventional immunotherapy using SADBE starting at 1%-2% sensitization. Furthermore, we investigated the combination therapy of SADBE and multiple courses of steroid pulses for AA. The response rate for combination therapy was 73.7% (28/38); however, the group receiving combination therapy showed a significant prevalence of severe AA compared with the group receiving modified immunotherapy only. We reviewed the efficacy and safety of modified immunotherapy without initial sensitization and combination therapy with immunotherapy and multiple courses of pulses for AA.

  2. Mouse Models of Tumor Immunotherapy.

    PubMed

    Ngiow, Shin Foong; Loi, Sherene; Thomas, David; Smyth, Mark J

    2016-01-01

    Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials. In this review, we will discuss the major classes of experimental mouse models of cancer commonly used for immunotherapy assessment and provide examples to guide the selection of appropriate models. We present some new data concerning the utility of a carcinogen-induced tumor model for comparing immunotherapies and combining immunotherapy with chemotherapy. We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients.

  3. Regional Neonatal Associates for cooperative study of platelet-activating factor (PAF). Summary report

    SciTech Connect

    Snyder, F.

    1992-11-01

    Lipid inflammatory mediators are thought to play an important role in the pathogenesis of the respiratory distress syndrome, including neonatal lung injury and bronchopulmonary dysplasia (BPD). One such mediator is platelet-activating factor (PAF), a potent bioactive phospholipid that induces adverse airway, vascular, and microcirculatory responses. To study the role of PAF in neonatal lung disease, we used an {sup 125}I-radioimmunoassay to measure PAF in whole blood and tracheal lavage in very low birthweight infants at 1, 3, 5, 9, 21 and 28 days after birth. PAF was found in the pulmonary lavagate and blood of ventilated infants as early as one day after birth. Lavagate levels of PAF increased with acute injury (pneumothorax, pneumonia) but were not associated with BPD. Our results indicate PAF could be associated with the pathogenesis of BPD. We suggest that as a consequence of the pathophysiologic processes associated with BPD, PAF is released by pulmonary cells. Our preliminary data indicate that low birthweight infants also have lower PAF acetylhydrolase levels in cord blood and tracheal lavagate as compared to adults. Therefore, it is possible the increased levels of PAF in the blood of low birthweight infants might be due to persistent transient increases in PAF alveolar levels coupled with lower blood acetylhydrolase activities and could be important in the development of symptoms associated with BPD. Future plans for this project call for completing the enzymatic study of acetylhydrolase activity in pulmonary lavage of the BPD infants.

  4. Neonates in Ahmedabad, India, during the 2010 heat wave: a climate change adaptation study.

    PubMed

    Kakkad, Khyati; Barzaga, Michelle L; Wallenstein, Sylvan; Azhar, Gulrez Shah; Sheffield, Perry E

    2014-01-01

    Health effects from climate change are an international concern with urban areas at particular risk due to urban heat island effects. The burden of disease on vulnerable populations in non-climate-controlled settings has not been well studied. This study compared neonatal morbidity in a non-air-conditioned hospital during the 2010 heat wave in Ahmedabad to morbidity in the prior and subsequent years. The outcome of interest was neonatal intensive care unit (NICU) admissions for heat. During the months of April, May, and June of 2010, 24 NICU admissions were for heat versus 8 and 4 in 2009 and 2011, respectively. Both the effect of moving the maternity ward and the effect of high temperatures were statistically significant, controlling for each other. Above 42 degrees Celsius, each daily maximum temperature increase of a degree was associated with 43% increase in heat-related admissions (95% CI 9.2-88%). Lower floor location of the maternity ward within hospital which occurred after the 2010 heat wave showed a protective effect. These findings demonstrate the importance of simple surveillance measures in motivating a hospital policy change for climate change adaptation-here relocating one ward-and the potential increasing health burden of heat in non-climate-controlled institutions on vulnerable populations.

  5. Development of immunoglobulins to venoms during specific immunotherapy.

    PubMed

    Palma-Carlos, M L; Santos, M C; Pedro, E; Branco-Ferreira, M; Spínola, A; Palma-Carlos, A G

    1999-03-01

    Immunotherapy against venoms (itv) is an efficacious treatment for most subjects who are allergic to hymnenoptera venoms. The authors studied 8 patients: 7 who were allergic to honey been venom and 1 who was allergic to wasp venom, followed for two years during immunotherapy with an aqueous extract of pure venoms from ALBAY Dome Hollister Stier. Specific IgE and IgG4 were evaluated by the Elisa Cap Technique of Pharmacia at different times: T0 before immunotherapy, T1 (one year after) and T2 (2 years after). A significant fall of specific IgE (p < 0.02) and a significant increase in specific IgG4 (p < 0.008) were seen during the two years in all patients. Four of the patients were re-stung and none had systemic reactions. These results suggest that increase in specific IgG4 is correlated with the protective effect of immunotherapy. PMID:10226679

  6. Unsuspected invasive neonatal gastrointestinal mucormycosis: A clinicopathological study of six cases from a tertiary care hospital

    PubMed Central

    Patra, Sushma; Vij, Mukul; Chirla, Dinesh K.; Kumar, Narendar; Samal, Subash C.

    2012-01-01

    Aim: To analyse the clinicopathological features of neonatal mucormycosis Materials and Methods: Retrospective analysis of cases of neonatal gastrointestinal mucormycosis. Results: There were six neonates with male: female ratio of 1:1. Except one all were preterm babies. The clinical presentation was abdominal distension in the majority. All were clinically diagnosed as either NEC or toxic megacolon with perforation. Neonatal gastrointestinal mucormycosis was not suspected clinically in any. All the children were explored immediately. Biopsy revealed transmural hemorrhagic necrosis/infarction of the intestinal wall with fungal hyphae. Conclusions: The physicians should have a high index of suspicion for gastrointestinal tract mucormycosis in neonates with metabolic disturbances who present with abdominal distension and pneumoperitoneum. Early diagnosis and aggressive medical and surgical treatment may improve the outcome of neonates with this potentially lethal invasive disease. PMID:23243366

  7. Neonatal HIV seroprevalence studies. A critique of national and international practices.

    PubMed

    Isaacman, S H; Miller, L A

    1993-09-01

    State agencies in the US began covertly testing newborn infants for antibodies to HIV in 1986. In so doing, the HIV serostatus of childbearing mothers is being assessed without directly sampling maternal blood, for neonatal infants harbor maternal antibodies. Approved by the Centers for Disease Control (CDC) and funded by the federal government, serosurveillance programs test virtually all live newborns in the US for antibodies to HIV. Neither is consent for testing sought or obtained from mothers, nor are results on infant serostatus ultimately provided to subjects. The authors oppose ongoing national serosurveillance for HIV on medical, economic, legal, and moral grounds; studies have after all already described the epidemiology of HIV diseases. This ongoing research project has no direct benefit to those tested and treats human subjects like simple laboratory animals. The paper calls attention to the program's inherent sexism, racism, eugenics, invasion of privacy, and science without control. Medical principles; issues of concern; neonatal HIV serosurveillance; ethical issues; legal issues; an overview of HIV testing guidelines; and testing justifications of the World Health Organization, the CDC, and state health agencies are considered in separate sections. The World Medical Association, American Medical Association, epidemiological ethics, and other ethical guidelines are raised in the discussion on ethics, while common law, constitutions, federal statues, the Nuremburg Code, and international laws are reviewed under the rubric of legal concerns.

  8. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    PubMed

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase. PMID:27362436

  9. The Predictive Value of Early Behavioural Assessments in Pet Dogs – A Longitudinal Study from Neonates to Adults

    PubMed Central

    Riemer, Stefanie; Müller, Corsin; Virányi, Zsófia; Huber, Ludwig; Range, Friederike

    2014-01-01

    Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2–10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40–50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited. PMID:25003341

  10. Association of caesarean section and neonatal death: a population-based case-control study in Islamic Republic of Iran.

    PubMed

    Ghaedmohammadi, Z; Anaraki, A; Khajeian, A; Khajehian, M; Ostovar, A

    2015-06-09

    The high caesarean section rate in the Islamic Republic of Iran could be a risk for adverse neonatal outcomes. This population-based, case-control study investigated the association of caesarean section and neonatal death. A total of 146 mothers whose babies had died during 28 days after birth were compared with 549 mothers with live newborns, according to delivery route and reasons for undergoing caesarean section. The crude odds ratio (OR) for the association of caesarean section and neonatal death was 1.97 (1.35-2.87). The adjusted OR was 2.19 (1.48-3.24) controlled for mother's education, parity and age. Adjusted ORs for elective caesarean, previous caesarean and emergency caesarean were 0.65 (0.26-1.62), 2.77 (1.64-4.66) and 2.51 (1.56-4.03) respectively. The ORs for caesarean delivery and neonatal death varied by mother's education, parity and age. The association of caesarean section with neonatal death is complex and is modified by other influencing factors.

  11. The predictive value of early behavioural assessments in pet dogs--a longitudinal study from neonates to adults.

    PubMed

    Riemer, Stefanie; Müller, Corsin; Virányi, Zsófia; Huber, Ludwig; Range, Friederike

    2014-01-01

    Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2-10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40-50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited.

  12. Imaging Biomarkers in Immunotherapy

    PubMed Central

    Juergens, Rosalyn A.; Zukotynski, Katherine A.; Singnurkar, Amit; Snider, Denis P.; Valliant, John F.; Gulenchyn, Karen Y.

    2016-01-01

    Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer. PMID:26949344

  13. Tau immunotherapy and imaging.

    PubMed

    Sigurdsson, Einar M

    2014-01-01

    Disappointing findings from recent phase III trials on amyloid-β (Aβ) immunotherapy for Alzheimer's disease (AD) have shifted the focus of such treatments to the tau protein. As tau pathology correlates better with the degree of dementia than Aβ plaque burden, it is a more attractive target once cognitive impairments are evident, while Aβ therapies may be better suited for the presymptomatic phase of the disease. Over 12 years ago, we initiated a tau immunotherapy program, seeking to alleviate the functional impairments associated with tau lesions in tauopathies. We have reported that various active and passive tau immunizations diminish tau pathology and improve function, including cognition, in different mouse models. Both extra- and intracellular pathways are likely involved. The antibodies may block the spread of tau pathology via microglial phagocytosis of the antibody-tau complex and facilitate lysosomal tau clearance in neurons after endosomal uptake. We have observed such antibody internalization following intracarotid injection in mice and in various culture models. These include brain slices and primary neurons from tangle mice as well as human neuroblastoma cell lines. Antibody targeting of different intracellular protein aggregates, including α-synuclein, Aβ and superoxide dismutase has been reported by others. Now, several laboratories have confirmed and extended our findings using various active and passive tau immunizations in different models, thereby clearly establishing the feasibility of this approach for clinical trials. We are also working on imaging approaches to monitor tau pathology, its consequences and the efficacy of treatments. Dire need exists for such diagnostic methods for tauopathies. Overall, therapies and diagnostic tools targeting tau pathology have a great potential for AD and other tauopathies.

  14. Immunotherapy for gastric premalignant lesions and cancer.

    PubMed

    Zorzetto, Valerio; Maddalo, Gemma; Basso, Daniela; Farinati, Fabio

    2012-06-01

    Chronic atrophic gastritis, a precancerous change for gastric cancer, shows a loss of appropriate glands, Helicobacter pylori infection and autoimmune gastritis being the two main etiologic factors. While H. pylori eradication is the mandatory treatment for the former, no etiologic treatment is available for the latter, in which a Th1-type response, modulated by Tregs and Th17 cells, is involved. H. pylori-related atrophic gastritis is a risk factor for gastric adenocarcinoma, while autoimmune atrophic gastritis is also linked to a substantial risk of gastric type I carcinoid, related to the chronic stimulus exerted by hypergastrinemia on enterochromaffin-like cells. Several studies have been published on gastric cancer treatment through an active specific immunotherapy, aimed at improving the immunoregulatory response and increasing the circulating tumor-specific T cells. No study on immunotherapy of carcinoids is available but, in our experience, the administration of an antigastrin 17 vaccine induced carcinoid regression in two out of three patients treated.

  15. Genomic determinants of cancer immunotherapy.

    PubMed

    Miao, Diana; Van Allen, Eliezer M

    2016-08-01

    Cancer immunotherapies - including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade - yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict which patients are most likely to benefit from cancer immunotherapy. Continued work in harnessing genomic, transcriptomic, and immunological data from clinical cohorts of immunotherapy-treated patients will bring the promises of precision medicine to immuno-oncology.

  16. A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum Disorders, Including a Comparison with Other Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Atladóttir, H. Ó.; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.

    2015-01-01

    The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all…

  17. Treatment of peanut allergy with rush immunotherapy.

    PubMed

    Oppenheimer, J J; Nelson, H S; Bock, S A; Christensen, F; Leung, D Y

    1992-08-01

    Peanut and peanut products are a common food in the diet. Peanuts are also one of the most common foods responsible for food-induced anaphylaxis. Patients rarely lose sensitivity to peanuts. Although the ideal treatment is avoidance, this is often not possible because of hidden exposures; therefore, a more effective treatment is needed. Subjects with confirmed peanut allergy were treated in a double-blind, placebo-controlled study with peanut immunotherapy or placebo. Objective measures of efficacy included changes in symptom score during double-blind placebo-controlled peanut challenge (DBPCPC) and titrated end point prick skin tests (PST). Three subjects treated with peanut immunotherapy completed the study. These subjects displayed a 67% to 100% decrease in symptoms induced by DBPCPC. Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract. One placebo-treated subject completed the study. This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut. Two other placebo-treated subjects underwent a second PST session. These subjects had a 1- to 2-log increase in skin test sensitivity to peanut. All peanut-treated subjects were able to reach maintenance dose, and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy. The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease. It should be noted, however, that the rate of systemic reactions with rush immunotherapy was 13.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Maternal low glycaemic index diet, fat intake and postprandial glucose influences neonatal adiposity – secondary analysis from the ROLO study

    PubMed Central

    2014-01-01

    Background The in utero environment is known to affect fetal development however many of the mechanisms by which this occurs remain unknown. The aim of this study was to examine the association between maternal dietary macronutrient intake and lifestyle throughout pregnancy and neonatal weight and adiposity. Methods This was an analysis of 542 mother and infant pairs from the ROLO study (Randomised cOntrol trial of LOw glycaemic index diet versus no dietary intervention to prevent recurrence of fetal macrosomia). Food diaries as well as food frequency and lifestyle and physical activity questionnaires were completed during pregnancy. Maternal anthropometry was measured throughout pregnancy and neonatal anthropometry was measured at birth. Results Multiple linear regression analysis revealed the main maternal factor associated with increased birth weight was greater gestational weight gain R2adj23.3% (F = 11.547, p < 0.001). The main maternal factor associated with increased birth length was non-smoking status R2adj27.8% (F = 6.193, p < 0.001). Neonatal central adiposity (determined using waist:length ratio) was negatively associated with maternal age, and positively associated with the following parameters: smoking status, maternal pre-pregnancy arm circumference, percentage energy from saturated fat in late pregnancy, postprandial glucose at 28 weeks gestation and membership of the control group with a positive trend towards association with trimester 2 glycaemic load R2adj 38.1% (F = 8.000, p < 0.001). Conclusions Several maternal diet and lifestyle factors were associated with neonatal anthropometry . Low glycaemic index dietary intervention in pregnancy was found to have a beneficial effect on neonatal central adiposity. Additionally, central adiposity was positively associated with maternal dietary fat intake and postprandial glucose highlighting the important role of healthy diet in pregnancy in promoting normal neonatal adiposity

  19. An Examination of Clinical and Immunologic Outcomes in Food Allergen Immunotherapy by Route of Administration.

    PubMed

    Chiang, David; Berin, M Cecilia

    2015-06-01

    Allergen immunotherapy for the treatment of food allergy has been a subject of intensive study within the last 10 years. After an unsuccessful attempt with subcutaneous immunotherapy for peanut allergy, other routes with varying degrees of safety and efficacy have been tested for peanut, milk, and egg allergies. In this review, we summarize the results to date with oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy for the treatment of food allergy. While results of immunotherapy trials are promising, increases in efficacy are commonly associated with an increased side effect profile. There is a need for additional research beginning at the preclinical level to develop safe and effective treatments for food allergy. PMID:26141581

  20. Safety of allergen immunotherapy: a review of premedication and dose adjustment.

    PubMed

    Morris, A Erika; Marshall, Gailen D

    2012-03-01

    From the first allergen immunotherapy proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. The major risk, however small, with allergen immunotherapy is anaphylaxis. There has been considerable interest and debate regarding risk factors for immunotherapy reactions (local and systemic) and interventions to reduce the occurrence of these reactions. One of these interventions that is especially debated regards dose adjustment for various reasons, but in particular for local reactions. In this review, we discuss the safety of immunotherapy and provide a comprehensive review of the literature regarding immunotherapy schedules and doses.

  1. Porcine pilot study of MRI-guided HIFU treatment for neonatal intraventricular hemorrhage (IVH)

    NASA Astrophysics Data System (ADS)

    Looi, Thomas; Waspe, Adam; Mougenot, Charles; Amaral, Joao; Temple, Michael; Hynynen, Kullervo; Drake, James

    2012-11-01

    Intraventricular hemorrhage (IVH) occurs in 15% of premature babies and 50% of IVH cases progress to posthemorrhagic ventricular dilation due to large blood clots forming in the ventricles. Existing treatments such as tissue plasminogen activator (tPA) and surgical intervention have severe side effects in paediatric patients that include excessive bleeding and complications. This study investigates the feasibility of MR-HIFU for sonothrombolysis of blood clots from IVH using natural acoustic windows, known as fontanelles, in the skulls of newborns. The study involved 2 elements: a phantom study to examine beam limitations and acoustic properties, and an in-vivo porcine study. A phantom skull was created from sample patient data and was used to analyze reachability of the Philips Sonavelle system. Acoustic measurements of the phantom (attenuation of 5-14 dB and speed of sound of 1722-2965 m/s) indicated the phantom effectively mimics neonatal skull bone. For the ex-vivo studies, a porcine clot was created and sonicated for 5 mins at 500W with a 0.5% duty cycle. For the in-vivo experiment, a vertex craniotomy was performed and porcine blood was injected into the lateral ventricle under ultrasound guidance. Sonication using the prior parameters induced cavitation and post-sonication T1 and T2 images verified clot lysis. Further H&E analysis showed no presence of blood in the ventricles. These positive results show that MR-HIFU has potential as a noninvasive tool for sonothrombolysis of neonatal IVH clots.

  2. A neonatal pneumococcal conjugate vaccine trial in Papua New guinea: study population, methods and operational challenges.

    PubMed

    Phuanukoonnon, S; Reeder, J C; Pomat, W S; Van den Biggelaar, A H J; Holt, P G; Saleu, G; Opa, C; Michael, A; Aho, C; Yoannes, M; Francis, J; Orami, T; Namuigi, P; Siba, P M; Richmond, P C; Lehmann, D

    2010-01-01

    Infants in Papua New Guinea (PNG) are at a high risk of invasive pneumococcal disease, and a substantial burden of this falls on children less than six months old. PNG is planning to introduce a pneumococcal conjugate vaccine for infants in the near future, but to make the maximum impact neonatal immunization will have to be considered. To provide evidence on safety and immunogenicity for neonatal and early infant immunization, we undertook an open randomized controlled trial of 7-valent pneumococcal conjugate vaccine (7vPCV). 318 children received 7vPCV at ages 0, 1 and 2 months or at 1, 2 and 3 months or not at all. All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. This was a large and complex trial: village reporters visited participants weekly during the first year and fortnightly for a further 6 months and nurses monitored self-reported morbidity and collected many thousands of biological samples. The study team was remarkably successful in achieving the study aims, with 18-month follow-up completed on 77% of enrolled children and over 80% of scheduled samples collected. While the results of the trial will be reported elsewhere, this paper discusses the design of the study and dissects out some of the main reasons for its successful completion. Strong community engagement was an essential factor in success and the principles of equitable partnership and service provision led to a strong research partnership. A two-stage consent process, comprising primary assent followed by later informed consent, led to a high drop-out before initial enrolment, but an outstanding retention of those enrolled in the study. We conclude that factors such as strong community participation, reciprocity and a good relationship between the study team and participants are just as important as the technical elements of laboratory testing and data handling in ensuring the success of a vaccine trial in PNG. PMID:23163191

  3. Pregnancy planning, smoking behaviour during pregnancy, and neonatal outcome: UK millennium cohort study

    PubMed Central

    2013-01-01

    Background Pre-pregnancy health and care are important for the health of the future generations. Smoking during pregnancy has been well-researched and there is clear evidence of harm. But there has been little research on the health impact of planning for pregnancy. This study aims to investigate the independent effects of pregnancy planning and smoking during pregnancy on neonatal outcome. Methods This analysis made use of data from the UK Millennium Cohort Study. The study sample consisted of 18,178 singleton babies born in UK between 2000 and 2001. The neonatal outcomes of interest were low birthweight (<2.5 Kg) and pre-term birth (<37 completed weeks gestation). Logistic regression was used to estimate the association between pregnancy planning and/or smoking and neonatal outcome. Adjusted odds ratios were used to calculate population attributable risk fractions (PAFs). Results 43% of mothers did not plan their pregnancy and 34% were smoking just before and/or during pregnancy. Planners were half as likely to be smokers just before pregnancy, and more likely to give up or reduce the amount smoked if smokers. Unplanned pregnancies had 24% increased odds of low birth weight and prematurity compared to planned pregnancies (AORLBW1.24, 95% CI 1.04-1.48; AORPREM1.24, 95% CI 1.05-1.45), independent of smoking status. The odds of low birth weight for babies of mothers who were smoking just before pregnancy was 91% higher than that of mothers who were not (AORLBW1.91, 95% CI 1.56-2.34). Women who quit or reduced the amount smoked during pregnancy lowered the risk of a low birth weight baby by one third (AORLBW0.66, 95% CI 0.51-0.85) compared with women whose smoking level did not change. Smaller effects were found for prematurity. If all women planned their pregnancy and did not smoke before or during pregnancy, 30% of low birthweight and 14% of prematurity could, in theory, be avoided. Conclusions Planning a pregnancy and avoiding smoking during pregnancy has clear

  4. The sweet side of tumor immunotherapy.

    PubMed

    Freire, Teresa; Osinaga, Eduardo

    2012-07-01

    Carbohydrate signatures on tumor cells have functional implications in tumor growth and metastasis and constitute valuable tools in cancer diagnosis and immunotherapy. Increasing data regarding the mechanisms by which they are recognized by the immune system are facilitating the design of more efficient immunotherapeutic protocols based on cancer-associated glycan structures. Recent molecular and proteomic studies revealed that carbohydrates are recognized, not only by B cells and antibodies, but also by cells from the innate arm of immunity, as well as by T cells, and are able to induce specific T-cell immunity and cytotoxicity. In this review, we discuss and update the different strategies targeting tumor-associated carbohydrate antigens that are being evaluated for antitumor immunotherapy, an approach that will be highly relevant, especially when combined with other strategies, in the future fight against cancer.

  5. Dendritic cell-based immunotherapy in mesothelioma.

    PubMed

    Cornelissen, Robin; Lievense, Lysanne A; Heuvers, Marlies E; Maat, Alexander P; Hendriks, Rudi W; Hoogsteden, Henk C; Hegmans, Joost P; Aerts, Joachim G

    2012-10-01

    Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treatment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunotherapeutic strategies to improve the prognosis of patients with mesothelioma. In the last decade, progress in knowledge of the modulation of the immune system to attack the tumor has been remarkable, but the optimal strategy for immunotherapy has yet to be unraveled. Because of their potent antigen-presenting capacity, dendritic cells are acknowledged as a promising agent in immunotherapeutic approaches in a number of malignancies. This review gives an update and provides a future perspective in which immunotherapy may improve the outcome of mesothelioma therapy.

  6. Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens.

    PubMed

    Valenta, Rudolf; Linhart, B; Swoboda, I; Niederberger, V

    2011-06-01

    The broad applicability of allergen-specific immunotherapy for the treatment and eventually prevention of IgE-mediated allergy is limited by the poor quality and allergenic activity of natural allergen extracts that are used for the production of current allergy vaccines. Today, the genetic code of the most important allergens has been deciphered; recombinant allergens equalling their natural counterparts have been produced for diagnosis and immunotherapy, and a large panel of genetically modified allergens with reduced allergenic activity has been characterized to improve safety of immunotherapy and explore allergen-specific prevention strategies. Successful immunotherapy studies have been performed with recombinant allergens and hypoallergenic allergen derivatives and will lead to the registration of the first recombinant allergen-based vaccines in the near future. There is no doubt that recombinant allergen-based vaccination strategies will be generally applicable to most allergen sources, including respiratory, food and venom allergens and allow to produce safe allergy vaccines for the treatment of the most common forms of IgE-mediated allergies.

  7. An Experimental Study of the Potential Biological Effects Associated with 2-D Shear Wave Elastography on the Neonatal Brain.

    PubMed

    Li, Changtian; Zhang, Changsheng; Li, Junlai; Cao, Xiaolin; Song, Danfei

    2016-07-01

    2-D Shear wave elastography (SWE) imaging is widely used in clinical practice, and some researchers have applied this technique in the evaluation of neonatal brains. However, the immediate and long-term impacts of dynamic radiation force exposure on the neonatal central nervous system remain unknown. In this study, we exposed neonatal mice to 2-D SWE scanning for 10 min, 20 min and 30 min under diagnostic mode (mechanical index [MI]: 1.3; thermal index [TI]: 0.5), respectively. For the control group, the neonatal mice were sham irradiated for 30 min with the machine powered off. Their brains were collected and analyzed using histologic staining and western blot analysis at 24 h and 3 mo after the 2-D SWE scanning. The Morris water maze (MWM) test was used to assess learning and memory function of the mice at 3 mo of age. The results indicated that using 2-D SWE in evaluating brains of neonatal mice does not cause detectable histologic changes, nor does it have long-term effects on their learning and memory abilities. However, the PI3 K/AKT/mTOR pathway was disturbed when the 2-D SWE scanning lasted for more than 30 min, and the expression of p-PKCa was suppressed by 10 min or more in 2-D SWE scanning. Although these injuries may be self-repaired as the mice grow, more attention should be paid to the scanning duration when applying 2-D-SWE elastography in the assessment of neonatal brains.

  8. Oral immunotherapy in birch pollen hay fever.

    PubMed

    Taudorf, E; Laursen, L C; Lanner, A; Björksten, B; Dreborg, S; Søborg, M; Weeke, B

    1987-08-01

    Previous controlled trials with oral administration of allergen have not demonstrated any treatment effect in patients with allergic rhinoconjunctivitis or asthma. In the present double-blind, placebo-controlled trial, we have tested the effect of oral immunotherapy in adult patients with birch pollinosis. Thirty-nine patients completed this 18-month study comprising two birch pollen seasons. The patients received enterosoluble capsules daily, and the actively treated patients reached a cumulated dose of 280 times 10(6) biologic units of birch pollen extract, which is about 200 times higher than the dose used in conventional subcutaneous immunotherapy. We found a significant decrease in eye symptom scores and conjunctival sensitivity to birch pollen, as determined by conjunctival provocation test, as well as a numerical but nonsignificant decrease in nasal symptom scores, nasal sensitivity as determined by nasal provocation test, and antiallergic medication. The treatment was safe, and only a few slight side effects were observed. We thus conclude that our study demonstrates a clinical effect of oral immunotherapy in birch pollinosis.

  9. Congenitally Deaf Children's Care Trajectories in the Context of Universal Neonatal Hearing Screening: A Qualitative Study of the Parental Experiences

    ERIC Educational Resources Information Center

    Hardonk, Stefan; Desnerck, Greetje; Loots, Gerrit; Van Hove, Geert; Van Kerschaver, Erwin; Sigurjonsdottir, Hanna Bjorg; Vanroelen, Christophe; Louckx, Fred

    2011-01-01

    The objective of this study is to examine the early care trajectories of congenitally deaf children from a parental perspective, starting with universal neonatal hearing screenings. The analysis using a three-dimensional care trajectory concept is aimed at developing a basic typology of postscreening care trajectories. Children with…

  10. Risk factors for Enterobacter septicemia in a neonatal unit: case-control study.

    PubMed

    Fok, T F; Lee, C H; Wong, E M; Lyon, D J; Wong, W; Ng, P C; Cheung, K L; Cheng, A F

    1998-11-01

    Thirty cases of Enterobacter aerogenes or Enterobacter cloacae septicemia diagnosed over a 32-month period in a tertiary care neonatal unit were enrolled in a case-control study. Each case patient was matched with two controls (patients occupying the cots nearest the case patient when the latter developed septicemia). Of the 32 perinatal characteristics evaluated, 11 were identified by univariate analysis to be significantly associated with the infection. These included parents being residents of the Vietnamese refugee camps, respiratory distress syndrome, necrotizing enterocolitis, umbilical arterial catheterization, umbilical venous catheterization, bladder catheterization, mechanical ventilation, antibiotic treatment, peripheral venous catheterization, nasogastric intubation, and parenteral nutrition. Multivariate analysis, however, showed that preceding bladder catheterization and ongoing parenteral nutrition were the only independent risk factors for enterobacter septicemia. Strict aseptic technique in the preparation of parenteral nutrition fluid and avoidance of bladder catheterization are measures that may reduce the risk of enterobacter sepsis for newborns.

  11. [Neonatal bacterial meningitis: prospective study of the long-term outcome of 55 children].

    PubMed

    Jornada Krebs, V L; De Albuquerque Diniz, E M; Costa Vaz, F A; Marques Dias, M J; Takiguti, C; Araújo Ramos, J L

    1996-03-01

    Fifty-five infants who presented bacterial neonatal meningitis were prospectively studied to analyze the frequency and the type of sequelae. All the infants were full term newborns. There were 38 boys and 17 girls; the age of disease onset varied from 3 to 28 days. The causative organism was represented mainly by enterobacteriae. The median time of follow-up was 5 years. The frequency of neurologic sequelae was 63.7%, represented mainly by neuropsychomotor development delay (58.2%), hydrocephaly (45.5%) and convulsions (34.5%). Severe motor abnormalities ocurred in 23.6% of children (quadriplegia, diplegia, hemiparesia and ataxia). Convulsions in the acute phase of the disease and the positive cerebrospinal fluid culture were highly associated to sequelae. The school performance, obtained in 25 children, showed presence of disabilities in 48% of cases, which were significantly associated to mental retardation. PMID:8736149

  12. Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates

    PubMed Central

    Fuchs, Aline; Guidi, Monia; Giannoni, Eric; Werner, Dominique; Buclin, Thierry; Widmer, Nicolas; Csajka, Chantal

    2014-01-01

    Aim This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population. Methods All gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®). Results A total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h−1 (CV 28%), central volume of distribution (Vc) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h−1 and peripheral volume of distribution (Vp) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced Vc. Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg−1, at extended intervals to achieve adequate concentrations. Conclusions This observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring. PMID:24938850

  13. Immunotherapy for lung cancer: advances and prospects.

    PubMed

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  14. Immunotherapy for lung cancer: advances and prospects

    PubMed Central

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  15. Laser immunotherapy of canine and feline neoplasia

    NASA Astrophysics Data System (ADS)

    Woods, J. P.; Bartels, Kenneth E.; Davidson, Ellen B.; Ritchey, Jerry W.; Lehenbauer, Terry W.; Nordquist, Robert E.; Chen, Wei R.

    1998-07-01

    The major cause of treatment failure in human and veterinary cancer patients is tumor invasion and metastasis. The inability of local therapy (surgery, radiation, photodynamic therapy) to eradicate a metastatic cancer presents a challenge in the therapy of residual or micrometastatic disease. Because of its local therapy limitations, chromophore-enhanced selective photothermal laser treatment has been augmented with a superimposed laser-induced systemic photobiological reaction, laser immunotherapy. Laser immunotherapy is a novel cancer treatment consisting of: (1) a laser in the infrared wavelength range (i.e. 805 nm solid state laser); (2) a photosensitizer of the corresponding absorption peak [i.e. indocyanine green (ICG)]; and (3) an immunoadjuvant [i.e. glycated chitosan gel (GCG)]. The intratumor injection of the photosensitizer (ICG) and immunoadjuvant (GCG) solution is followed by noninvasive laser irradiation. The laser energy causes tumor cell destruction by photothermal interaction to reduce the tumor burden and at the same time exposes tumor antigens. The immunoadjuvant concomitantly stimulates the host to mount a systemic anti-tumor immune response against the remaining cells of the tumor and to induce a long-term, tumor-specific immunity. This study investigates the feasibility of utilizing laser immunotherapy as an adjunctive therapy for the control of feline fibrosarcoma in future.

  16. Neonatal teeth.

    PubMed

    Kovac, J; Kovac, D

    2011-01-01

    Teeth that are present at birth are called natal teeth, and teeth that emerge through the gingiva during the first 4 weeks of life are called neonatal teeth. The incidence of the appearance of natal and neonatal teeth has been reported to be between once every 800 and once every 6000 births. Natal and neonatal teeth may be uncomfortable for a nursing mother and present a risk of aspiration and swallowing by the infant if they are loose. Also, they may cause irritation and trauma to the infant's soft tissues. Under these circumstances, natal and neonatal teeth need to be extracted. In this article, a case report of two neonatal teeth in a five week old girl is presented. The teeth were present in the mandibular incisor region and were excessively mobile and caused discomfort for the nursing mother. They were extracted because of the fear of aspiration (Fig. 4, Ref. 10).

  17. Use of High Resolution 3D Diffusion Tensor Imaging to Study Brain White Matter Development in Live Neonatal Rats

    PubMed Central

    Cai, Yu; McMurray, Matthew S.; Oguz, Ipek; Yuan, Hong; Styner, Martin A.; Lin, Weili; Johns, Josephine M.; An, Hongyu

    2011-01-01

    High resolution diffusion tensor imaging (DTI) can provide important information on brain development, yet it is challenging in live neonatal rats due to the small size of neonatal brain and motion-sensitive nature of DTI. Imaging in live neonatal rats has clear advantages over fixed brain scans, as longitudinal and functional studies would be feasible to understand neuro-developmental abnormalities. In this study, we developed imaging strategies that can be used to obtain high resolution 3D DTI images in live neonatal rats at postnatal day 5 (PND5) and PND14, using only 3 h of imaging acquisition time. An optimized 3D DTI pulse sequence and appropriate animal setup to minimize physiological motion artifacts are the keys to successful high resolution 3D DTI imaging. Thus, a 3D rapid acquisition relaxation enhancement DTI sequence with twin navigator echoes was implemented to accelerate imaging acquisition time and minimize motion artifacts. It has been suggested that neonatal mammals possess a unique ability to tolerate mild-to-moderate hypothermia and hypoxia without long term impact. Thus, we additionally utilized this ability to minimize motion artifacts in magnetic resonance images by carefully suppressing the respiratory rate to around 15/min for PND5 and 30/min for PND14 using mild-to-moderate hypothermia. These imaging strategies have been successfully implemented to study how the effect of cocaine exposure in dams might affect brain development in their rat pups. Image quality resulting from this in vivo DTI study was comparable to ex vivo scans. fractional anisotropy values were also similar between the live and fixed brain scans. The capability of acquiring high quality in vivo DTI imaging offers a valuable opportunity to study many neurological disorders in brain development in an authentic living environment. PMID:22013426

  18. Safety of blood transfusions using 27 gauge neonatal PICC lines: an in vitro study on hemolysis.

    PubMed

    Repa, A; Mayerhofer, M; Cardona, F; Worel, N; Deindl, P; Pollak, A; Berger, A; Haiden, N

    2013-12-01

    Blood transfusions are required by the majority of extremely premature infants. Packed red blood cells (PRBCs) are usually applied via simple peripheral cannulas. In situations where no peripheral venous access is achievable, 27 Gauge (G) neonatal PICC lines - that are ideally exclusively dedicated to application of parenteral nutrition - may represent a useful alternative access for PRBC transfusions. However, transfusion via small scaled catheters may damage PRBCs and lead to hemolysis. We here evaluate whether transfusion of irradiated PRBCs via 27 G PICC lines leads to hemolysis in vitro.Experimental transfusions of gamma-irradiated PRBCs were performed at increasing velocities (2.5, 3.7, 5 ml/h; full force manual push approximating 30 ml/h) via 27 G PICC lines of 20 and 30 cm length. Parameters of hemolysis (lactate dehydrogenase, potassium and free hemoglobin) were measured from the supernatants of transfused PRBCs and the percentage of hemolysis was calculated.Potassium and lactate dehydrogenase after transfusion at increasing velocities did not differ significantly from negative controls. Free hemoglobin levels showed a small but significant increase at the slowest transfusion speed (2.5 ml/h) using the 30 cm 27 G PICC line, with a relative hemolysis of only 0.13%. A manual push (approximating 30 ml/h) showed no significant changes of parameters from baseline.We conclude that transfusion of gamma-irradiated PRBCs using a 27 G neonatal PICC line does not cause clinically relevant hemolysis in vitro. Clinical studies are needed to confirm the feasibility and safety of the approach in vivo.

  19. [Study of body proportionality using Rohrer s Ponderal Index and degree of intrauterine growth retardation in full-term neonates].

    PubMed

    Leão Filho, José Carneiro; de Lira, Pedro Israel Cabral

    2003-01-01

    An observational, cross-sectional study was used to describe the anthropometric characteristics of 549 full-term neonates with respect to body proportionality. The anthropometric measures used were: weight (W), length (L), head circumference (HC), Rohrer s Ponderal Index (PI), W/HC ratio, and L/HC ratio. Severity of intrauterine growth retardation (IUGR) was studied through z-score distribution. Small-for-gestational-age (SGA) was defined as a z-score value < -2, and the cutoff for PI, W/HC, and L/HC was determined as the mean minus one standard deviation for the local reference population. Based on PI, 72.8% of SGA neonates and 12.8% of appropriate-for-gestational-age (AGA) neonates were disproportionate. Based on the L/HC ratio the results were 25.6% and 11.6%, respectively, while with the W/HC ratio, all SGA and 16.3% of AGA neonates were disproportionate. According to all criteria there was an observed significant linear tendency to increase the disproportionality as IUGR increased. PMID:14999327

  20. Immunotherapy for lung cancer.

    PubMed

    Bradbury, Penelope A; Shepherd, Frances A

    2008-06-01

    Reports of tumor regression after infection date back as far as 1550 bc. In the twentieth century, Dr. William Coley, witnessing regression of a malignant tumor in one of his patients after a bacterial infection, developed the first cancer treatment vaccine derived from killed bacteria, with some reported success. However, despite decades of research, no specific, active tumor vaccine has been approved for the treatment of cancer. In lung cancer, initial attempts to modulate the immune system with nonspecific therapies were unsuccessful. However, more sophisticated specific vaccines have now been developed, and an increasing number are being evaluated in randomized phase 3 trials, raising hopes that vaccines may be an additional novel therapy for patients with lung cancer. This article reviews the following seven vaccines, which have entered randomized trials: L-BLP25 (Stimuvax), BEC-2, 1E10, PF-3512676 (Promune), melanoma-associated antigen A3 immunotherapeutic, granulocyte-macrophage colony-stimulating factor-transduced allogeneic cancer cellular immunotherapy, and belagenpumatucel-L (Lucanix).

  1. Immunotherapy for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Kosten, Thomas R.

    2013-01-01

    Substance use disorders continue to be major medical and social problems worldwide. Current medications for substance use disorders have many limitations such as cost, availability, medication compliance, dependence, diversion of some to illicit use and relapse to addiction after discontinuing their use. Immunotherapies using either passive monoclonal antibodies or active vaccines have distinctly different mechanisms and therapeutic utility from small molecule approaches to treatment. They have great potential to help the patient achieve and sustain abstinence and have fewer of the above limitations. This review covers the cocaine vaccine development in detail and provides an overview of directions for developing anti-addiction vaccines against the abuse of other substances. The notable success of the first placebo-controlled clinical trial of a cocaine vaccine, TA-CD, has led to an ongoing multi-site, Phase IIb clinical trial in 300 subjects. The results from these trials are encouarging further development of the cocaine vacine as one of the first anti-addiction vaccines to go forward to the U.S. Food and Drug Administration for review and approval for human use. PMID:22229313

  2. Immunotherapy of Brain Cancer.

    PubMed

    Roth, Patrick; Preusser, Matthias; Weller, Michael

    2016-01-01

    The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti-cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors. PMID:27260656

  3. Immunotherapy of Colorectal Cancer.

    PubMed

    Jäger, Dirk; Halama, Niels; Zörnig, Inka; Klug, Paula; Krauss, Jürgen; Haag, Georg-Martin

    2016-01-01

    It is known that the immune response, reflected by high T cell infiltrates in primary tumors and metastases, influences the clinical course of colorectal cancer (CRC). Therefore, immunotherapy concepts have been adapted from other tumor entities, which typically rely on the activation of T cells in the tumor microenvironment (e.g. blockade of the immune checkpoint molecules PD-1 and CTLA-4). However, most of the strategies using the approved checkpoint inhibitors and/or combination strategies have more or less failed to produce impressive results in early phase trials in CRC. Therefore, a number of novel targets for checkpoint inhibition are currently in early phase clinical testing (TIM-3, Lag-3, OX40, GITR, 4-1BB, CD40, CD70). A simple activation of infiltrating T cells will not, however, lead to a meaningful anti-tumor response without modulating the environmental factors in CRC. Thus, it is absolutely necessary to improve our understanding of the complex regulation of the tumor microenvironment in CRC to design individual combination treatments leading to effective immune control. PMID:27259331

  4. Immunotherapy for malignant glioma.

    PubMed

    Suryadevara, Carter M; Verla, Terence; Sanchez-Perez, Luis; Reap, Elizabeth A; Choi, Bryan D; Fecci, Peter E; Sampson, John H

    2015-01-01

    Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  5. Lymphoma Immunotherapy: Current Status

    PubMed Central

    Zappasodi, Roberta; de Braud, Filippo; Di Nicola, Massimo

    2015-01-01

    The rationale to treat lymphomas with immunotherapy comes from long-standing evidence on their distinctive immune responsiveness. Indolent B-cell non-Hodgkin lymphomas, in particular, establish key interactions with the immune microenvironment to ensure prosurvival signals and prevent antitumor immune activation. However, reports of spontaneous regressions indicate that, under certain circumstances, patients develop therapeutic antitumor immunity. Several immunotherapeutic approaches have been thus developed to boost these effects in all patients. To date, targeting CD20 on malignant B cells with the antibody rituximab has been the most clinically effective strategy. However, relapse and resistance prevent to cure approximately half of B-NHL patients, underscoring the need of more effective therapies. The recognition of B-cell receptor variable regions as B-NHL unique antigens promoted the development of specific vaccines to immunize patients against their own tumor. Despite initial promising results, this strategy has not yet demonstrated a sufficient clinical benefit to reach the regulatory approval. Several novel agents are now available to stimulate immune effector functions or counteract immunosuppressive mechanisms, such as engineered antitumor T cells, co-stimulatory receptor agonist, and immune checkpoint-blocking antibodies. Thus, multiple elements can now be exploited in more effective combinations to break the barriers for the induction of anti-lymphoma immunity. PMID:26388871

  6. Verbal/social autopsy study helps explain the lack of decrease in neonatal mortality in Niger, 2007–2010

    PubMed Central

    Kalter, Henry D; Yaroh, Asma Gali; Maina, Abdou; Koffi, Alain K; Bensaïd, Khaled; Amouzou, Agbessi; Black, Robert E

    2016-01-01

    Background This study was one of a set of verbal/social autopsy (VASA) investigations undertaken by the WHO/UNICEF–supported Child Health Epidemiology Reference Group to estimate the causes and determinants of neonatal and child deaths in high priority countries. The study objective was to help explain the lack of decrease in neonatal mortality in Niger from 2007 to 2010, a period during which child mortality was decreasing. Methods VASA interviews were conducted of a random sample of 453 neonatal deaths identified by the 2010 Niger National Mortality Survey (NNMS). Causes of death were determined by expert algorithm analysis, and the prevalence of household, community and health system determinants were examined along the continuum of maternal and newborn care, the Pathway to Survival for newborn illnesses, and an extended pathway for maternal complications. The social autopsy findings were compared to available data for survivors from the same cohort collected by the NNMS and the 2012 Niger Demographic and Health Survey. Findings Severe neonatal infection and birth asphyxia were the leading causes of early neonatal death in the community and facilities. Death in the community after delayed careseeking for severe infection predominated during the late neonatal period. The levels of nearly all demographic, antenatal and delivery care factors were in the direction of risk for the VASA study decedents. They more often resided rurally (P < 0.001) and their mothers were less educated (P = 0.03) and gave birth when younger (P = 0.03) than survivors’ mothers. Their mothers also were less likely to receive quality antenatal care (P < 0.001), skilled attendance at birth (P = 0.03) or to deliver in an institution (P < 0.001). Nearly half suffered an obstetric complication, with more maternal infection (17.9% vs 0.2%), antepartum hemorrhage (12.5% vs 0.5%) and eclampsia/preeclampsia (9.5% vs 1.6%) than for all births in Niger. Their mothers also

  7. Labour and Neonatal Outcome in Small for Gestational Age Babies Delivered Beyond 36+0 Weeks: A Retrospective Cohort Study

    PubMed Central

    Boers, K. E.; van der Post, J. A. M.; Mol, Ben W. J.; van Lith, J. M. M.; Scherjon, S. A.

    2011-01-01

    Objective. Small for gestational age (SGA) is associated with increased neonatal morbidity and mortality. At present, evidence on whether these pregnancies should be managed expectantly or by induction is lacking. To get insight in current policy we analysed data of the National Dutch Perinatal Registry (PRN). Methods. We used data of all nulliparae between 2000 and 2005 with a singleton in cephalic presentation beyond 36+0 weeks, with a birth weight below the 10th percentile. We analysed two groups of pregnancies: (I) with isolated SGA and (II) with both SGA and hypertensive disorders. Onset of labour was related to route of delivery and neonatal outcome. Results. Induction was associated with a higher risk of emergency caesarean section (CS), without improvement in neonatal outcome. For women with isolated SGA the relative risk of emergency CS after induction was 2.3 (95% Confidence Interval [CI] 2.1 to 2.5) and for women with both SGA and hypertensive disorders the relative risk was 2.7 (95% CI 2.3 to 3.1). Conclusion. Induction in pregnancies complicated by SGA at term is associated with a higher risk of instrumental deliveries without improvement of neonatal outcome. Prospective studies are needed to determine the best strategy in suspected IUGR at term. PMID:21490789

  8. Discrimination of fearful and angry emotional voices in sleeping human neonates: a study of the mismatch brain responses

    PubMed Central

    Zhang, Dandan; Liu, Yunzhe; Hou, Xinlin; Sun, Guoyu; Cheng, Yawei; Luo, Yuejia

    2014-01-01

    Appropriate processing of human voices with different threat-related emotions is of evolutionarily adaptive value for the survival of individuals. Nevertheless, it is still not clear whether the sensitivity to threat-related information is present at birth. Using an odd-ball paradigm, the current study investigated the neural correlates underlying automatic processing of emotional voices of fear and anger in sleeping neonates. Event-related potential data showed that the fronto-central scalp distribution of the neonatal brain could discriminate fearful voices from angry voices; the mismatch response (MMR) was larger in response to the deviant stimuli of anger, compared with the standard stimuli of fear. Furthermore, this fear–anger MMR discrimination was observed only when neonates were in active sleep state. Although the neonates' sensitivity to threat-related voices is not likely associated with a conceptual understanding of fearful and angry emotions, this special discrimination in early life may provide a foundation for later emotion and social cognition development. PMID:25538587

  9. Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.

    PubMed

    Jha, Shaili C; Meltzer-Brody, Samantha; Steiner, Rachel J; Cornea, Emil; Woolson, Sandra; Ahn, Mihye; Verde, Audrey R; Hamer, Robert M; Zhu, Hongtu; Styner, Martin; Gilmore, John H; Knickmeyer, Rebecca C

    2016-07-30

    The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy. PMID:27254086

  10. Serratia marcescens in a neonatal intensive care unit: two long-term multiclone outbreaks in a 10-year observational study.

    PubMed

    Casolari, Chiara; Pecorari, Monica; Della Casa, Elisa; Cattani, Silvia; Venturelli, Claudia; Fabio, Giuliana; Tagliazucchi, Sara; Serpini, Giulia Fregni; Migaldi, Mario; Marchegiano, Patrizia; Rumpianesi, Fabio; Ferrari, Fabrizio

    2013-10-01

    We investigated two consecutive Serratia marcescens (S. marcescens) outbreaks which occurred in a neonatal intensive care unit (NICU) of a tertiary level hospital in North Italy in a period of 10 years (January 2003-December 2012). Risk factors associated with S. marcescens acquisition were evaluated by a retrospective case-control study. A total of 21,011 clinical samples was examined: S. marcescens occurred in 127 neonates: 43 developed infection and 3 died. Seven clusters were recorded due to 12 unrelated clones which persisted for years in the ward, although no environmental source was found. The main epidemic clone A sustaining the first cluster in 2003 reappeared in 2010 as an extended spectrum ?-lactamase (ESBL)-producing strain and supporting the second epidemic. Birth weight, gestational age, use of invasive devices and length of stay in the ward were significantly related to S. marcescens acquisition. The opening of a new ward for non-intensive care-requiring neonates, strict adherence to alcoholic hand disinfection, the timely identification and isolation of infected and colonized neonates assisted in containing the epidemics. Genotyping was effective in tracing the evolution and dynamics of the clones demonstrating their long-term persistence in the ward.

  11. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study

    PubMed Central

    De Franco, Elisa; Flanagan, Sarah E; Houghton, Jayne AL; Allen, Hana Lango; Mackay, Deborah JG; Temple, I Karen; Ellard, Sian; Hattersley, Andrew T

    2015-01-01

    Summary Background Traditional genetic testing focusses on analysis of one or a few genes according to clinical features; this approach is changing as improved sequencing methods enable simultaneous analysis of several genes. Neonatal diabetes is the presenting feature of many discrete clinical phenotypes defined by different genetic causes. Genetic subtype defines treatment, with improved glycaemic control on sulfonylurea treatment for most patients with potassium channel mutations. We investigated the effect of early, comprehensive testing of all known genetic causes of neonatal diabetes. Methods In this large, international, cohort study, we studied patients with neonatal diabetes diagnosed with diabetes before 6 months of age who were referred from 79 countries. We identified mutations by comprehensive genetic testing including Sanger sequencing, 6q24 methylation analysis, and targeted next-generation sequencing of all known neonatal diabetes genes. Findings Between January, 2000, and August, 2013, genetic testing was done in 1020 patients (571 boys, 449 girls). Mutations in the potassium channel genes were the most common cause (n=390) of neonatal diabetes, but were identified less frequently in consanguineous families (12% in consanguineous families vs 46% in non-consanguineous families; p<0·0001). Median duration of diabetes at the time of genetic testing decreased from more than 4 years before 2005 to less than 3 months after 2012. Earlier referral for genetic testing affected the clinical phenotype. In patients with genetically diagnosed Wolcott-Rallison syndrome, 23 (88%) of 26 patients tested within 3 months from diagnosis had isolated diabetes, compared with three (17%) of 18 patients referred later (>4 years; p<0·0001), in whom skeletal and liver involvement was common. Similarly, for patients with genetically diagnosed transient neonatal diabetes, the diabetes had remitted in only ten (10%) of 101 patients tested early (<3 months) compared with 60

  12. Does allergen-specific immunotherapy induce contact allergy to aluminium?

    PubMed

    Netterlid, Eva; Hindsén, Monica; Siemund, Ingrid; Björk, Jonas; Werner, Sonja; Jacobsson, Helene; Güner, Nuray; Bruze, Magnus

    2013-01-01

    Persistent, itching nodules have been reported to appear at the injection site after allergen-specific immuno-therapy with aluminium-precipitated antigen extract, occasionally in conjunction with contact allergy to aluminium. This study aimed to quantify the development of contact allergy to aluminium during allergen-specific immunotherapy. A randomized, controlled, single-blind multicentre study of children and adults entering allergen-specific immunotherapy was performed using questionnaires and patch-testing. A total of 205 individuals completed the study. In the 3 study groups all subjects tested negative to aluminium before allergen-specific immunotherapy and 4 tested positive after therapy. In the control group 4 participants tested positive to aluminium. Six out of 8 who tested positive also had atopic dermatitis. Positive test results were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was not shown to be a risk factor for contact allergy to aluminium. Among those who did develop aluminium allergy, children and those with atopic dermatitis were more highly represented.

  13. Use of extensively hydrolysed formula for refeeding neonates postnecrotising enterocolitis: a nationwide survey-based, cross-sectional study

    PubMed Central

    Lapillonne, Alexandre; Matar, Maroun; Adleff, Ariane; Chbihi, Marwa; Kermorvant-Duchemin, Elsa; Campeotto, Florence

    2016-01-01

    Objective To evaluate the prevalence of and reasons for using extensively hydrolysed formulas (EHFs) of cow's milk proteins in the French neonatal units as well as the modality of their prescription for refeeding infants recovering from necrotising enterocolitis (NEC). Methods A multicentre nationwide cross-sectional study using a questionnaire to address the prevalence of use and the reasons for prescribing EHF in hospitalised neonates and to examine the protocols and the actual reasons for their use for refeeding infants in recovery from NEC. The questionnaire was sent to only 1 senior neonatologist in each neonatal unit included in the study. Results More than half of the French neonatal units participated in the survey. 91% of the surveyed units used EHF. Of 1969 infants hospitalised on the day the survey was run, 12% were fed on an EHF. 11% of the EHF prescriptions were due to previous NEC. The main reasons for using an EHF to feed infants post-NEC were the absence of human milk (75%) and surgical management of NEC (17%). When given, EHF was mainly prescribed for a period varying between 15 days and 3 months. None of the involved units continued using the EHF after 6 months of age. More than half of the surveyed units acknowledged hospitalising infants for the initiation of weaning EHF but only 21% of them tested these infants for cow's milk allergy. Conclusions The prevalence of EHF use in the French neonatal units is high. Refeeding infants post-NEC is one of the main reasons for such a high prevalence. The main incentive for using an EHF is the absence of human breast milk, either maternal or donor. PMID:27388344

  14. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    PubMed Central

    2014-01-01

    We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  15. Impact of managed clinical networks on NHS specialist neonatal services in England: population based study

    PubMed Central

    Gale, C; Santhakumaran, S; Nagarajan, S; Statnikov, Y

    2012-01-01

    Objective To assess the impact of reorganisation of neonatal specialist care services in England after a UK Department of Health report in 2003. Design A population-wide observational comparison of outcomes over two epochs, before and after the establishment of managed clinical neonatal networks. Setting Epoch one: 294 maternity and neonatal units in England, Wales, and Northern Ireland, 1 September 1998 to 31 August 2000, as reported by the Confidential Enquiry into Stillbirths and Sudden Deaths in Infancy Project 27/28. Epoch two: 146 neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit, 1 January 2009 to 31 December 2010. Participants Babies born at a gestational age of 27+0-28+6 (weeks+days): 3522 live births in epoch one; 2919 babies admitted to a neonatal unit within 28 days of birth in epoch two. Intervention The national reorganisation of neonatal services into managed clinical networks. Main outcome measures The proportion of babies born at hospitals providing the highest volume of neonatal specialist care (≥2000 neonatal intensive care days annually), having an acute transfer (within the first 24 hours after birth) and/or a late transfer (between 24 hours and 28 days after birth) to another hospital, assessed by change in distribution of transfer category (“none,” “acute,” “late”), and babies from multiple births separated by transfer. For acute transfers in epoch two, the level of specialist neonatal care provided at the destination hospital (British Association of Perinatal Medicine criteria). Results After reorganisation, there were increases in the proportions of babies born at 27-28 weeks’ gestation in hospitals providing the highest volume of neonatal specialist care (18% (631/3495) v 49% (1325/2724); odds ratio 4.30, 95% confidence interval 3.83 to 4.82; P<0.001) and in acute and late postnatal transfers (7% (235) v 12% (360) and 18% (579) v 22% (640), respectively

  16. Monoclonal antibodies in cancer immunotherapy.

    PubMed

    Reisfeld, R A

    1992-06-01

    The preceding article focused on some novel approaches for the adjuvant treatment of human melanoma and neuroblastoma with mAbs against antigens preferentially expressed on these tumors. It should be emphasized that the major goal of the immunotherapy modalities described here is to apply them in an adjuvant setting for the treatment of micrometastases. The major aim is to decrease the rate of development of metastases in a setting of very low tumor burden and ultimately achieve a prolongation in life span. The combination of powerful modern technologies achieving genetic engineering of mAbs, resulting in more human-like molecules, will lead to a reevaluation of these reagents alone or in combination with molecularly defined cytokines and growth factors for the immunotherapy of cancer. The initial, albeit anectodal, findings, of phase I clinical trials mentioned in this article lead to cautious optimism that immunotherapy may find a place and will eventually contribute to the adjuvant treatment of cancer.

  17. Emerging nanotechnologies for cancer immunotherapy.

    PubMed

    Shukla, Sourabh; Steinmetz, Nicole F

    2016-05-01

    Founded on the growing insight into the complex cancer-immune system interactions, adjuvant immunotherapies are rapidly emerging and being adapted for the treatment of various human malignancies. Immune checkpoint inhibitors, for example, have already shown clinical success. Nevertheless, many approaches are not optimized, require frequent administration, are associated with systemic toxicities and only show modest efficacy as monotherapies. Nanotechnology can potentially enhance the efficacy of such immunotherapies by improving the delivery, retention and release of immunostimulatory agents and biologicals in targeted cell populations and tissues. This review presents the current status and emerging trends in such nanotechnology-based cancer immunotherapies including the role of nanoparticles as carriers of immunomodulators, nanoparticles-based cancer vaccines, and depots for sustained immunostimulation. Also highlighted are key translational challenges and opportunities in this rapidly growing field.

  18. Neonatal renal vein thrombosis.

    PubMed

    Brandão, Leonardo R; Simpson, Ewurabena A; Lau, Keith K

    2011-12-01

    Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.

  19. Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy

    PubMed Central

    Li, Lisha

    2016-01-01

    Background Although many patients with allergic rhinitis have symptoms due to sensitization to more than one kind of allergens, and mixed allergen extracts are widely used for immunotherapy, there are few published trials. Objective Our study aimed to evaluate the effect of multiple-allergen immunotherapy on improving the symptoms and quality of life of allergic rhinitis patients. Methods We performed a 1-year single-center observation study of subcutaneous immunotherapy using house dust mite extract (n = 12), weed pollen extract (n = 21), or mixed house dust mite/weed pollen extract (n = 11) in 44 allergic rhinitis patients. All the allergens responsible for the symptom of each patient were included in his immunotherapy. Symptom score, medication score, and quality of life of the patients were evaluated before and after 1-year immunotherapy. Quality of life was evaluated with the Rhinoconjunctivitis Quality of Life Questionnaire. Results In all 3 groups receiving subcutaneous immunotherapy, significant improvement of symptom score, medication score, and quality of life was found vs. baseline at 1 year, irrespective of the allergen used. In the weed pollen season, the changes of quality of life questionnaire score after 1-year treatment were not significantly different between the weed pollen group (1.55 ± 1.24) and the mixed house dust mite/weed pollen group (1.14 ± 1.01). The same happened in the nonpollen seasons, during which dust mite immunotherapy (1.23 ± 1.63) and mixed immunotherapy (0.60 ± 0.47) did not show significantly different effect on the quality of life. Conclusion The multiple-allergen immunotherapy might be effective in polysensitized allergic rhinitis patients, and could improve their quality of life. Our result did not show significant difference between the effects of multiple-allergen immunotherapy and mono-allergen immunotherapy. PMID:27489789

  20. Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study.

    PubMed

    Doniņa, Simona; Strēle, Ieva; Proboka, Guna; Auziņš, Jurgis; Alberts, Pēteris; Jonsson, Björn; Venskus, Dite; Muceniece, Aina

    2015-10-01

    An oncolytic, nonpathogenic ECHO-7 virus adapted for melanoma that has not been genetically modified (Rigvir) is approved and registered for virotherapy, an active and specific immunotherapy, in Latvia since 2004. The present retrospective study was carried out to determine the effectiveness of Rigvir in substage IB, IIA, IIB and IIC melanoma patients on time to progression and overall survival. White patients (N=79) who had undergone surgical excision of the primary melanoma tumour were included in this study. All patients were free from disease after surgery and classified into substages IB, IIA, IIB and IIC. Circulating levels of clinical chemistry parameters were recorded. Survival was analysed by Cox regression. Rigvir significantly (P<0.05) prolonged survival in substage IB-IIC melanoma patients following surgery compared with patients who were under observation (according to current guidelines). The hazard ratio for patients under observation versus treated with Rigvir was statistically significantly different: hazard ratio 6.27 for all, 4.39 for substage IIA-IIB-IIC and 6.57 for substage IIB-IIC patients. The follow-up period was not statistically different between both treatment groups. These results indicate that the patients treated with Rigvir had a 4.39-6.57-fold lower mortality than those under observation. In this study, there was no untoward side effect or discontinuation of Rigvir treatment. Safety assessment of adverse events graded according to NCI CTCAE did not show any value above grade 2 in Rigvir-treated patients. In conclusion, Rigvir significantly prolongs survival in early-stage melanoma patients without any side effect.

  1. Risk estimates for neonatal myotonic dystrophy.

    PubMed Central

    Glånz, A; Fråser, F C

    1984-01-01

    Children who inherit the autosomal dominant gene for myotonic dystrophy from their mother rather than their father may develop the severe neonatal type rather than the late onset type. The families of 22 neonatal type probands and 59 late onset type probands were studied to determine the risk of occurrence and recurrence of the neonatal type. The frequency of the neonatal type in sibs of neonatal type probands was 29%, or 37% if cases of neonatal deaths are counted as affected. This is significantly higher than the 6% of the neonatal type found in the offspring of affected women not ascertained through a child with the neonatal type. These data suggest that certain women carrying the gene for myotonic dystrophy are predisposed to have children affected with the neonatal type rather than the late onset type. The female near relatives of these women do not seem to share this predisposition. The data should be useful for genetic counseling. PMID:6748014

  2. Cancer immunotherapy using tumor cryoablation.

    PubMed

    Sidana, Abhinav

    2014-01-01

    Cryoablation is increasingly being used as a primary treatment for localized cancers and as a salvage therapy for metastatic cancers. Anecdotal clinical reports and animal experiments have confirmed an induction of systemic antitumor immune response by tumor cryoablation. To capitalize on the stimulatory effects of cryoablation for cancer immunotherapy, this response must be intensified using other immunomodulatory agents. This article reviews the preclinical and clinical evidence and discusses the mechanism of the antitumor immune response generated by cryoablation. The rationale and evidence behind several immunotherapy approaches that can be combined with cryoablation to devise a cryoimmunotherapeutic strategy with a potential to impact the progression of metastatic disease are described.

  3. Recent advances and future of immunotherapy for glioblastoma

    PubMed Central

    Kamran, Neha; Calinescu, Alexandra; Candolfi, Marianela; Chandran, Mayuri; Mineharu, Yohei; Assad, Antonela S; Koschmann, Carl; Nunez, Felipe; Lowenstein, Pedro; Castro, Maria

    2016-01-01

    Introduction Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival benefit observed with immunotherapies in cancers such as melanoma and prostate cancer has fuelled research into evaluating immunotherapies for GBM. Areas covered Preclinical studies have brought a wealth of information for improving the prognosis of GBM and multiple clinical studies are evaluating a wide array of immunotherapies for GBM patients. This review highlights advances in the development of immunotherapeutic approaches. We discuss the strategies and outcomes of active and passive immunotherapies for GBM including vaccination strategies, gene therapy, check point blockade and adoptive T cell therapies. We also focus on immunoediting and tumor neoantigens that can impact the efficacy of immunotherapies. Expert opinion Encouraging results have been observed with immunotherapeutic strategies; some clinical trials are reaching phase III. Significant progress has been made in unraveling the molecular and genetic heterogeneity of GBM and its implications to disease prognosis. There is now consensus related to the critical need to incorporate tumor heterogeneity into the design of therapeutic approaches. Recent data also indicates that an efficacious treatment strategy will need to be combinatorial and personalized to the tumor genetic signature. PMID:27411023

  4. Neonatal conjunctivitis

    MedlinePlus

    Newborn conjunctivitis; Conjunctivitis of the newborn; Ophthalmia neonatorum; Eye infection - neonatal conjunctivitis ... diseases spread through sexual contact to prevent newborn conjunctivitis caused by these infections. Putting eye drops into ...

  5. Neonatal Death

    MedlinePlus

    ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Neonatal death ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Complications & Loss ...

  6. Oral immunotherapy for food allergy: mechanisms and role in management.

    PubMed

    Nowak-Węgrzyn, A; Albin, S

    2015-02-01

    With the emergence of food allergy as an important public health problem, it has become clear that there is an unmet need in regard to treatment. In particular, IgE-mediated food allergy that is associated with risk of fatal anaphylaxis has been the subject of multiple studies in the past decade. The growing body of evidence derived from multiple centres and various study designs indicates that for IgE-mediated food allergy, immunomodulation through food immunotherapy is possible; however, the extent of protection afforded by such treatment is highly variable. At this time, the capacity for food immunotherapy to restore permanent tolerance to food has not been demonstrated conclusively. This review will discuss these topics as they apply to the most important studies of food oral immunotherapy.

  7. Neonatal mortality in Meerut district.

    PubMed

    Garg, S K; Mishra, V N; Singh, J V; Bhatnagar, M; Chopra, H; Singh, R B

    1993-09-01

    A study of neonatal mortality in Meerut district revealed an infant mortality rate of 50.1 per 1000 live births. Neonatal mortality accounted for 37.8% of infant mortality with a neonatal mortality rate of 19.0 per 1000 live births. 90.5% of these neonates were delivered at home largely by untrained personnel (57.2%). Only 28.6% of these neonates were treated by qualified doctors and only 30.9% of their mothers were fully immunized against tetanus. At least 2/3rd of neonatal mortality was due to exogenous factors with tetanus neonatorum and septicaemia being the principal causes of mortality each accounting for a mortality rate of 4.7 per 1000 live births. PMID:8112786

  8. Neonatal sepsis of nosocomial origin: an epidemiological study from the "Grupo de Hospitales Castrillo".

    PubMed

    López Sastre, J B; Coto Cotallo, D; Fernández Colomer, B

    2002-01-01

    A prospective multicenter study was designed to assess the frequency, etiology, and mortality of nosocomial neonatal sepsis diagnosed between 1996 and 1997 in the neonatology services of 27 acute-care hospitals in Spain ("Grupo de Hospitales Castrillo"). Nosocomial sepsis is defined in the literature using chronological criteria (> 3-7 days of life at the onset of symptoms); accordingly, there is the possibility of including late-onset maternally acquired sepsis or of excluding early-onset nosocomial sepsis (< 3-7 days of life). For these reasons, in this study, cases of nosocomial sepsis that developed at < or = 3-7 days after birth (early onset) were also recorded and maternally acquired sepsis diagnosed beyond 3-7 days of life were excluded. Using these criteria in a total of 30,993 admissions to the neonatal units of the participating hospitals, the nosocomial sepsis rate was 2.1% with an incidence density of 0.89 per 1000 patient days. Sepsis rate was significantly more frequent among very low birth weight (VLBW) infants (15.6%) than among those weighing > or = 1500 g (1.16%) (P < 0.001). Fifty-eight percent of all isolates were Gram-positive organisms, mainly Staphylococcus epidermidis (42%). Gram-negative organisms were isolated in 29.5% of cases (Escherichia coli and Klebsiella spp. were the most commonly isolated pathogens) and fungal infections in 12%, with absolute predominance of Candida spp. The overall mortality rate was 11.8% and the following subgroups had significantly higher (P < 0.001) mortality rates: sepsis caused by Gram-negative organisms (19% vs. 5.1% in Gram-positive pathogens) and sepsis caused by Pseudomonas aeruginosa (33.3% vs. 9.4% for the total number of sepsis caused by the remaining causative pathogens). Sepsis caused by S. epidermidis showed a significantly lower mortality rate (5.5%) compared with overall sepsis for the remaining etiologies (14.2%) (P < 0.001). In VLBW infants, the mortality rate was significantly higher than in

  9. [A study on early-onset group "B" streptococcal neonatal infection].

    PubMed

    Vacheva, R; Todorova, M; Decheva, A; Yarakova, N; Kraleva, I; Takova, Ts; Dimitrova, N; Dobreva, A

    2012-01-01

    The results achieved with 80% reduction in the incidence of early-onset neonatal group B streptococcal (GBS) sepsis following the implementation of the preliminary (1996, 2002) and subsequently the revised (2010) guidelines for intrapartum antibiotic prophylaxis imposed the discussion on a large scale of the updated:--algorithms for GBS screening (35-37 weeks of gestation) with the recommended dosage of penicillin-G for intrapartum antibiotic prophylaxis for women having normal labor and delivery;--algorithms for GBS screening and intrapartum antibiotic prophylaxis for women with preterm labor (PPROM) or premature rupture of membranes (PROM);--intrapartum antibiotic prophylaxis regimens for women with penicillin allergy;--algorithm for management of newborns with respect to risk of early-onset GBS disease. The present study is aimed at studying the distribution of the early-onset GBS disease in our country based on the data of leading obstetrics & gynecology clinics and wards. The aim is to diferrentiate clinically the cases and investigate the influence of the known risk factors on the part of the mother. A special accent is put over the microbiological diagnostics of cases in view of CDC expanded recommendations on the laboratory methods for identification of GBS. As a final conclusion the necessity for introduction of an official registration of the early- and late-onset GBS disease in the country is emphasized.

  10. Parents’ Perspectives on Safety in Neonatal Intensive Care: A Mixed-Methods Study

    PubMed Central

    Lyndon, Audrey; Jacobson, Carrie H.; Fagan, Kelly M.; Wisner, Kirsten; Franck, Linda S.

    2014-01-01

    Background & Objectives Little is known about how parents think about neonatal intensive care unit (NICU) safety. Due to their physiologic immaturity and small size, infants in NICUs are especially vulnerable to injury from their medical care. Campaigns are underway to integrate patients and family members into patient safety. This study aimed to describe how parents of infants in the NICU conceptualize patient safety and what kinds of concerns they have about safety. Methods This mixed-methods study employed questionnaires, interviews, and observation with parents of infant patients in an academic medical centre NICU. Measures included parent stress, family-centredness, and types of safety concerns. Results 46 parents completed questionnaires and 14 of these parents also participated in 10 interviews (including 4 couple interviews). Infants had a range of medical and surgical problems, including prematurity, congenital diaphragmatic hernia, and congenital cardiac disease. Parents were positive about their infants’ care and had low levels of concern about the safety of procedures. Parents reporting more stress had more concerns. We identified three overlapping domains in parent’s conceptualizations of safety in the NICU, including physical, developmental, and emotional safety. Parents demonstrated sophisticated understanding of how environmental, treatment, and personnel factors could potentially influence their infants’ developmental and emotional health. Conclusions Parents have safety concerns that cannot be addressed solely by reducing errors in the NICU. Parent engagement strategies that respect parents as partners in safety and address how clinical treatment articulates with physical, developmental, and emotional safety domains may result in safety improvements. PMID:24970266

  11. Disialoganglioside directed immunotherapy of neuroblastoma.

    PubMed

    Modak, Shakeel; Cheung, Nai-Kong V

    2007-02-01

    Achieving a cure for metastatic neuroblastoma remains a challenge despite sensitivity to chemotherapy and radiotherapy. Most patients achieve remission, but a failure to eliminate minimal residual disease (MRD) often leads to relapse. Immunotherapy is potentially useful for chemotherapy-resistant disease and may be particularly effective for low levels of MRD that are below the threshold for detection by routine radiological and histological methods. Disialoganglioside (GD2), a surface glycolipid antigen that is ubiquitous and abundant on neuroblastoma cells is an ideal target for immunotherapy. Anti-GD2 monoclonal antibodies currently form the mainstay of neuroblastoma immunotherapy and their safety profile has been well-established. Although responses in patients with gross disease have been observed infrequently, histologic responses of bone marrow disease are consistently achieved in >75 percent of patients with primary refractory neuroblastoma. The advent of highly sensitive and specific molecular assays to measure MRD has confirmed the efficacy anti-GD2 antibody immunotherapy in patients with subclinical disease. Such markers will allow further optimization of other anti-MRD therapies. We review the current status of anti-GD2 clinical trials for neuroblastoma and novel preclinical GD2-targeted strategies for this rare but often lethal childhood cancer.

  12. Technological advances in adoptive immunotherapy.

    PubMed

    Oelke, Mathias; Krueger, Christine; Schneck, Jonathan P

    2005-01-01

    Adoptive immunotherapy is an attractive and elegant strategy for treating a variety of life-threatening diseases. Several approaches have been developed to generate antigen-specific CD4+ and CD8+ T cells for adoptive T-cell therapy in cancer and infectious diseases. Currently, many approaches are based on either the use of autologous peptide pulsed dendritic cells as antigen-presenting cells or nonspecific expansion of T cells. Unfortunately, current approaches lack the ability to serve as reproducible and economically viable methods. Several groups are developing new artificial approaches to overcome problems associated with dendritic cells and the nonspecific expansion of T-cell clones in order to make adoptive immunotherapy more feasible and effective. Thus, by increasing the availability of adoptive immunotherapy, we will be able to better determine the efficacy of the approaches in the treatment of a variety of diseases. In this review, we focus on technological advances that will facilitate adoptive immunotherapy. Specifically, we summarize current strategies which are either based on artificial antigen-presenting cells or on T-cell receptor gene transfer. PMID:15753966

  13. Immunotherapy toxic in obese mice.

    PubMed

    2015-01-01

    New research shows immunotherapy can cause lethal inflammation in both young and aged mice that are obese. Restricting calories in aged mice protected them from toxicity, and giving young obese mice a drug for autoimmune disease prevented the fatal reactions. PMID:25583780

  14. Future perspectives in cancer immunotherapy

    PubMed Central

    Mountzios, Giannis; Curigliano, Giuseppe

    2016-01-01

    The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors. In particular, immune check-point inhibition in melanoma, non-small-cell lung cancer and renal cancer, peptide vaccination in prostate cancer and glioblastoma, and oncolytic immunotherapy in melanoma are well-established therapeutic modalities that have obtained approval by regulatory authorities and are already in clinical use. A large number of ongoing clinical trials involving thousands of patients are currently seeking to define the appropriate tumor type, therapeutic setting, treatment combination and patient populations in order to maximize clinical benefit from immunotherapeutic agents. In this context, identification of the patients whose tumors are most likely to respond to immunotherapy by the use of appropriate biomarkers will be crucial for the optimal implementation of immunotherapy into the therapeutic armamentarium. PMID:27563660

  15. Engineering opportunities in cancer immunotherapy.

    PubMed

    Jeanbart, Laura; Swartz, Melody A

    2015-11-24

    Immunotherapy has great potential to treat cancer and prevent future relapse by activating the immune system to recognize and kill cancer cells. A variety of strategies are continuing to evolve in the laboratory and in the clinic, including therapeutic noncellular (vector-based or subunit) cancer vaccines, dendritic cell vaccines, engineered T cells, and immune checkpoint blockade. Despite their promise, much more research is needed to understand how and why certain cancers fail to respond to immunotherapy and to predict which therapeutic strategies, or combinations thereof, are most appropriate for each patient. Underlying these challenges are technological needs, including methods to rapidly and thoroughly characterize the immune microenvironment of tumors, predictive tools to screen potential therapies in patient-specific ways, and sensitive, information-rich assays that allow patient monitoring of immune responses, tumor regression, and tumor dissemination during and after therapy. The newly emerging field of immunoengineering is addressing some of these challenges, and there is ample opportunity for engineers to contribute their approaches and tools to further facilitate the clinical translation of immunotherapy. Here we highlight recent technological advances in the diagnosis, therapy, and monitoring of cancer in the context of immunotherapy, as well as ongoing challenges.

  16. Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants

    PubMed Central

    Lam, Phung Khanh; Trieu, Huynh T.; Lubis, Inke Nadia D.; Loan, Huynh T.; Thuy, Tran Thi Diem; Wills, Bridget; Parry, Christopher M.; Day, Nicholas P.J.; Qui, Phan T.; Yen, Lam Minh; Thwaites, C. Louise

    2015-01-01

    Summary Objectives Most data regarding the prognosis in neonatal tetanus originate from regions where limited resources have historically impeded management. It is not known whether recent improvements in critical care facilities in many low- and middle-income countries have affected indicators of a poor prognosis in neonatal tetanus. We aimed to determine the factors associated with worse outcomes in a Vietnamese hospital with neonatal intensive care facilities. Methods Data were collected from 107 cases of neonatal tetanus. Clinical features on admission were analyzed against mortality and a combined endpoint of ‘death or prolonged hospital stay’. Results Multivariable analysis showed that only younger age (odds ratio (OR) for mortality 0.69, 95% confidence interval (CI) 0.48–0.98) and lower weight (OR for mortality 0.06, 95% CI 0.01–0.54) were significantly associated with both the combined endpoint and death. A shorter period of onset (OR 0.94, 95% CI 0.88–0.99), raised white cell count (OR 1.17, 95% CI 1.02–1.35), and time between first symptom and admission (OR 3.77, 95% CI 1.14–12.51) were also indicators of mortality. Conclusions Risk factors for a poor outcome in neonatal tetanus in a setting with critical care facilities include younger age, lower weight, delay in admission, and leukocytosis. PMID:25499039

  17. Challenges and Frugal Remedies for Lowering Facility Based Neonatal Mortality and Morbidity: A Comparative Study

    PubMed Central

    Amadi, Hippolite O.; Osibogun, Akin O.; Eyinade, Olateju; Kawuwa, Mohammed B.; Uwakwem, Angela C.; Ibekwe, Maryann U.; Alabi, Peter; Ezeaka, Chinyere; Eleshin, Dada G.; Ibadin, Mike O.

    2014-01-01

    Millennium development goal target on infant mortality (MDG4) by 2015 would not be realised in some low-resource countries. This was in part due to unsustainable high-tech ideas that have been poorly executed. Prudent but high impact techniques could have been synthesised in these countries. A collaborative outreach was initiated to devise frugal measures that could reduce neonatal deaths in Nigeria. Prevailing issues of concern that could militate against neonatal survival within care centres were identified and remedies were proffered. These included application of (i) recycled incubator technology (RIT) as a measure of providing affordable incubator sufficiency, (ii) facility-based research groups, (iii) elective training courses for clinicians/nurses, (iv) independent local artisans on spare parts production, (v) power-banking and apnoea-monitoring schemes, and (v) 1/2 yearly failure-preventive maintenance and auditing system. Through a retrospective data analyses 4 outreach centres and one “control” were assessed. Average neonatal mortality of centres reduced from 254/1000 to 114/1000 whilst control remained at 250/1000. There was higher relative influx of incubator-dependent-neonates at outreach centres. It was found that 43% of mortality occurred within 48 hours of presentation (d48) and up to 92% of d48 were of very-low birth parameters. The RIT and associated concerns remedies have demonstrated the vital signs of efficiency that would have guaranteed MDG4 neonatal component in Nigeria. PMID:25140183

  18. Neonatal Immune Tolerance Induction to Allow Long-Term Studies With an Immunogenic Therapeutic Monoclonal Antibody in Mice.

    PubMed

    Piccand, Matthieu; Bessa, Juliana; Schick, Eginhard; Senn, Claudia; Bourquin, Carole; Richter, Wolfgang F

    2016-03-01

    The purpose of this study is to test the feasibility of neonatal immune tolerance induction in mice to enable long-term pharmacokinetic studies with immunogenic therapeutic monoclonal antibodies (mAb). Neonatal immune tolerance was induced by transfer of a mAb to neonatal mice via colostrum from nursing mother mice treated with two subcutaneous doses of a tolerogen starting within the first 24 h after delivery. Adalimumab and efalizumab were administered as tolerogens at various dose levels. Tolerance induction was evaluated in the offspring after reaching adulthood at 8 weeks of age. After a single intravenous injection of the same mAb as used for tolerance induction, the pharmacokinetics of the mAb and formation of anti-drug antibodies (ADA) in plasma were assessed using ELISA. Tolerance induction to adalimumab was achieved in a maternal dose-dependent manner. Adalimumab immune-tolerant offspring showed a slower adalimumab clearance (4.24 ± 0.32 mL/day/kg) as compared to the control group (12.09 ± 3.81 mL/day/kg). In the control group, accelerated clearance started 7 days after adalimumab dosing, whereas immune-tolerant offspring showed a log-linear terminal concentration-time course. In the offspring, the absence of predose ADA levels was indicative of successful tolerance induction. The second test compound efalizumab was not immunogenic in mice under our experimental conditions. Overall, the present study demonstrated the suitability of neonatal immune tolerance induction for a 4-week single dose study in adult mice with a human therapeutic mAb that is otherwise immunogenic in laboratory animals. PMID:26603888

  19. Neonatal Immune Tolerance Induction to Allow Long-Term Studies With an Immunogenic Therapeutic Monoclonal Antibody in Mice.

    PubMed

    Piccand, Matthieu; Bessa, Juliana; Schick, Eginhard; Senn, Claudia; Bourquin, Carole; Richter, Wolfgang F

    2016-03-01

    The purpose of this study is to test the feasibility of neonatal immune tolerance induction in mice to enable long-term pharmacokinetic studies with immunogenic therapeutic monoclonal antibodies (mAb). Neonatal immune tolerance was induced by transfer of a mAb to neonatal mice via colostrum from nursing mother mice treated with two subcutaneous doses of a tolerogen starting within the first 24 h after delivery. Adalimumab and efalizumab were administered as tolerogens at various dose levels. Tolerance induction was evaluated in the offspring after reaching adulthood at 8 weeks of age. After a single intravenous injection of the same mAb as used for tolerance induction, the pharmacokinetics of the mAb and formation of anti-drug antibodies (ADA) in plasma were assessed using ELISA. Tolerance induction to adalimumab was achieved in a maternal dose-dependent manner. Adalimumab immune-tolerant offspring showed a slower adalimumab clearance (4.24 ± 0.32 mL/day/kg) as compared to the control group (12.09 ± 3.81 mL/day/kg). In the control group, accelerated clearance started 7 days after adalimumab dosing, whereas immune-tolerant offspring showed a log-linear terminal concentration-time course. In the offspring, the absence of predose ADA levels was indicative of successful tolerance induction. The second test compound efalizumab was not immunogenic in mice under our experimental conditions. Overall, the present study demonstrated the suitability of neonatal immune tolerance induction for a 4-week single dose study in adult mice with a human therapeutic mAb that is otherwise immunogenic in laboratory animals.

  20. Doctors and the health industry: a case study of transcutaneous oxygen monitoring in neonatal intensive care.

    PubMed

    Miké, V; Krauss, A N; Ross, G S

    1996-05-01

    This case study presents an industry perspective on medical innovation. Introduced as a scientific breakthrough in the late 1970s, transcutaneous oxygen monitoring was rapidly adopted for routine use in neonatal intensive care. But plagued by technical problems, it was within a decade being replaced by pulse oximetry, a still more recent technology. Its use in efforts to prevent retinopathy of prematurity, an eye disease of preterm newborns often leading to blindness, proved disappointing. The project included interviews with executives and design engineers of companies marketing the device, with investigators who had pioneered the technology, and with senior practicing neonatologists. The findings, reflecting complexity and uncertainty, are relevant to issues concerning health care in the United States and other developed nations. They centre on the key role and ultimate responsibility of the medical profession, with a need for greater attention to the scientific training of health care workers, as perceived by members of the medical device industry. The views of senior investigators are integrated into the picture, with discussion of major challenges faced by the medical community.

  1. Exploiting the Immunomodulatory Properties of Chemotherapeutic Drugs to Improve the Success of Cancer Immunotherapy.

    PubMed

    Kersten, Kelly; Salvagno, Camilla; de Visser, Karin E

    2015-01-01

    Cancer immunotherapy is gaining momentum in the clinic. The current challenge is to understand why a proportion of cancer patients do not respond to cancer immunotherapy, and how this can be translated into the rational design of combinatorial cancer immunotherapy strategies aimed at maximizing success of immunotherapy. Here, we discuss how tumors orchestrate an immunosuppressive microenvironment, which contributes to their escape from immune attack. Relieving the immunosuppressive networks in cancer patients is an attractive strategy to extend the clinical success of cancer immunotherapy. Since the clinical availability of drugs specifically targeting immunosuppressive cells or mediators is still limited, an alternative strategy is to use conventional chemotherapy drugs with immunomodulatory properties to improve cancer immunotherapy. We summarize the preclinical and clinical studies that illustrate how the anti-tumor T cell response can be enhanced by chemotherapy-induced relief of immunosuppressive networks. Treatment strategies aimed at combining chemotherapy-induced relief of immunosuppression and T cell-boosting checkpoint inhibitors provide an attractive and clinically feasible approach to overcome intrinsic and acquired resistance to cancer immunotherapy, and to extend the clinical success of cancer immunotherapy.

  2. Prostate cancer as a model for tumour immunotherapy.

    PubMed

    Drake, Charles G

    2010-08-01

    Advances in basic immunology have led to an improved understanding of the interactions between the immune system and tumours, generating renewed interest in approaches that aim to treat cancer immunologically. As clinical and preclinical studies of tumour immunotherapy illustrate several immunological principles, a review of these data is broadly instructive and is particularly timely now that several agents are beginning to show evidence of efficacy. This is especially relevant in the case of prostate cancer, as recent approval of sipuleucel-T by the US Food and Drug Administration marks the first antigen-specific immunotherapy approved for cancer treatment. Although this Review focuses on immunotherapy for prostate cancer, the principles discussed are applicable to many tumour types, and the approaches discussed are highlighted in that context.

  3. Antigen-based immunotherapy for autoimmune disease: current status

    PubMed Central

    Hirsch, Darren Lowell; Ponda, Punita

    2015-01-01

    Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease. PMID:27471707

  4. Past, present and future targets for immunotherapy in ovarian cancer.

    PubMed

    Schwab, Carlton L; English, Diana P; Roque, Dana M; Pasternak, Monica; Santin, Alessandro D

    2014-01-01

    Ovarian cancer is the leading cause of death from gynecologic malignancy in the US. Treatments have improved with conventional cytotoxic chemotherapy and advanced surgical techniques but disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. Ovarian cancer immunotherapy is targeting tumors through active, passive and adoptive approaches. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the different immunotherapies available for ovarian cancer as well as current ongoing studies and potential future directions.

  5. Past, present and future targets for immunotherapy in ovarian cancer

    PubMed Central

    Schwab, Carlton L; English, Diana P; Roque, Dana M; Pasternak, Monica; Santin, Alessandro D

    2015-01-01

    Ovarian cancer is the leading cause of death from gynecologic malignancy in the US. Treatments have improved with conventional cytotoxic chemotherapy and advanced surgical techniques but disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. Ovarian cancer immunotherapy is targeting tumors through active, passive and adoptive approaches. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the different immunotherapies available for ovarian cancer as well as current ongoing studies and potential future directions. PMID:25524384

  6. Distribution study of Chlamydia trachomatis genotypes in symptomatic patients in Buenos Aires, Argentina: association between genotype E and neonatal conjunctivitis

    PubMed Central

    2010-01-01

    Background Chlamydia trachomatis infections are the most prevalent sexually transmitted bacterial infections in the world. There is scarce data available referring to the distribution of C. trachomatis genotypes in Argentina. The aim of this study was to identify the genotypes of C. trachomatis circulating in the metropolitan area of Buenos Aires (Argentina) associated with ophthalmia neonatorum and genital infections. Findings From 2001 to 2006, 199 positive samples for C. trachomatis infection from symptomatic adult patients and neonates with ophthalmia neonatorum from two public hospitals were studied. C. trachomatis genotypes were determined by PCR-RFLP of an ompA fragment. Genotype E was the most prevalent regardless of the sample origin (46.3% 57/123 in adults and 72.4% 55/76 in neonates), followed by genotype D (19.5% 24/123) and F (14.6% 18/123) in adults, and G (9.2% 7/76) and D (7.9% 6/76) in neonates. We detected a significantly higher frequency of genotype E (p < 0.001, OR = 3.03 (1.57neonatal conjunctivitis, which may indicate an epidemiological association between this genotype and the newborn population. The present study also contributed to increase the knowledge on genotype distribution of Chlamydia trachomatis in symptomatic adult patients in Buenos Aires, Argentina, in which genotypes E, D and F were the predominant ones. PMID:20181127

  7. Solving the Problem of Nonadherence to Immunotherapy.

    PubMed

    Bender, Bruce G; Lockey, Richard F

    2016-02-01

    Allergen immunotherapy (AIT) can improve allergic response by modifying the underlying disease. Many patients are nonadherent, and do not achieve full benefit. Numerous studies reveal that fewer than 10% of patients complete a full course and that most abandon treatment in the first year. The development and testing of interventions to improve AIT are emerging. Data from adherence interventions in other chronic conditions provide guidance to allergists/immunologists. Evidence-based communication strategies-patient-centered care, motivational interviewing, and shared-decision making-underscore the importance of taking time to establish trust, understand patient concerns and priorities, and involve the patient in decisions regarding AIT.

  8. Prediction of Severe Neonatal Hyperbilirubinemia Using Cord Blood Hydrogen Peroxide: A Prospective Study

    PubMed Central

    Chou, Hung-Chieh; Chien, Chiang-Ting; Tsao, Po-Nien; Hsieh, Wu-Shiun; Chen, Chien-Yi; Chang, Mei-Hwei

    2014-01-01

    Background We hypothesized that cord blood hydrogen peroxide (H2O2) could be utilized to predict the severity of neonatal hyperbilirubinemia. Methods We prospectively enrolled term or near-term healthy neonates. Cord blood and capillary blood at three days of age were measured for hydrogen peroxide and bilirubin concentrations. For newborns with hyperbilirubinemia, further blood samples were obtained at five and seven days of age. Newborns were divided into severe or less severe hyperbilirubinemic groups (peak bilirubin ≥17 mg/dL or not). The sensitivity, specificity, and negative predictive values were determined. Results There were 158 neonates enrolled. The incidence of neonatal hyperbilirubinemia was 30.5% for a concentration ≥15 mg/dl. The rising patterns were similar among bilirubin concentrations and hydrogen peroxide levels during the first few days of life. There was a strong positive correlation between bilirubin concentrations and hydrogen peroxide levels after correlation analysis. The rate of severe hyperbilirubinemia was 13.3%. It revealed that a cord blood hydrogen peroxide signal level of 2500 counts/10 seconds was an appropriate cut-off for predicting severe hyperbilirubinemia. Sensitivity and the negative predictive value were 76.2% and 93.3%, respectively. Conclusions Our findings confirm that hydrogen peroxide levels and bilirubin concentrations in cord and neonatal blood are closely related. A cord blood hydrogen peroxide level above 2500 counts/10 seconds associated with a high predictive value for severe hyperbilirubinemia. This method provides information about which neonate should be closely followed after discharge from the nursery. PMID:24466244

  9. Evaluation of a Comprehensive Delivery Room Neonatal Resuscitation and Adaptation Score (NRAS) Compared to the Apgar Score: A Pilot Study.

    PubMed

    Jurdi, Shadi R; Jayaram, Archana; Sima, Adam P; Hendricks Muñoz, Karen D

    2015-01-01

    This study evaluated the interrater reliability and perceived importance of components of a developed neonatal adaption score, Neonatal Resuscitation Adaptation Score (NRAS), for evaluation of resuscitation need in the delivery room for extremely premature to term infants. Similar to the Apgar, the NRAS highest score was 10, but greater weight was given to respiratory and cardiovascular parameters. Evaluation of provider (N = 17) perception and scoring pattern was recorded for 5 clinical scenarios of gestational ages 23 to 40 weeks at 1 and 5 minutes and documenting NRAS and Apgar score. Providers assessed the tool twice within a 1-month interval. NRAS showed superior interrater reliability (P < .001) and respiratory component reliability (P < .001) for all gestational ages compared to the Apgar score. These findings identify an objective tool in resuscitation assessment of infants, especially those of smaller gestation age, allowing for greater discrimination of postbirth transition in the delivery room.

  10. Postoperative immunotherapy of murine C1300-neuroblastoma.

    PubMed

    Fowler, C L; Brooks, S P; Rossman, J E; Cooney, D R

    1990-02-01

    Low-dose cyclophosphamide (CY) is an immunomodulating agent that down-regulates T suppressor cell function. This study investigates postoperative immunotherapy with CY as an alternate treatment for advanced immunogenic tumors such as neuroblastoma that typically respond poorly to traditional high-dose chemotherapy. A/J mice with 1.5-cm subcutaneous C1300-neuroblastoma (C1300-NB) tumors were divided into the following treatment groups: I, untreated (n = 14); II, 85% tumor resection (n = 18); III, sham-operated (n = 18); IV, multiple-dose CY (n = 6); V, 85% resection and single-dose CY (n = 14); VI, 85% resection and multiple-dose CY (n = 14). CY (100 mg/kg, intraperitoneally) was given initially 24 hours post-operatively to groups IV, V, and VI. Groups IV and VI also received weekly maintenance doses of 25 mg/kg CY. Results showed significantly increased survival (log-rank test) in CY-treated groups (IV, V, VI) compared with control groups (I,II,III). Cures were observed only in groups receiving partial resection plus CY (V, 7%; VI, 29%). Although surgical debulking of tumor alone (II) did not enhance survival, the procedure normalized depressed total lymphocyte counts and the subpopulation of Lyt 2,3+ (T suppressor/cytolytic cells) in the immediate postoperative period during which immunotherapy with CY was instigated. This may have contributed to the success of CY immunotherapy. To characterize the tumor-host immune interaction, additional studies were performed. Results showed the following. (1) Mice cured by debulking plus CY (from groups V and VI) could not be successfully reimplanted with C1300-NB, demonstrating immunologic mediation by CY.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Porcine sensitized lymph node cells (immunotherapy) and attenuated irradiation for infiltrative transitional cells carcinoma of bladder.

    PubMed

    Cockett, A T; de Sant'agnese, P A; Hamlin, D J; Keys, H M

    1982-06-01

    Thirty-four patients wih infiltrative bladder carcinoma, Stage B2C or higher were treated with immunotherapy and irradiation. Seventeen patients are alive, and 17 have succumbed to their disease. Eight patients underwent cystectomy after immunotherapy and irradiation; 6 of 8 are alive and well at the present time. The technique of immunotherapy is outlined. New methodology for sequential CT scans and scheduled bladder biopsies is mentioned. The 17 patients have survived twelve to sixty-nine months after immunotherapy and irradiation. Downstaging is demonstrated based on sequential CT scans of the bony pelvis and histologic biopsy. The biopsies reveal eosinophilia and multinucleated giant cells, a specific response to immunotherapy. A prospective randomized study will be initiated.

  12. Neonatal pain.

    PubMed

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback.

  13. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease

    PubMed Central

    Sibley, Cailin H; Chioato, Andrea; Felix, Sandra; Colin, Laurence; Chakraborty, Abhijit; Plass, Nikki; Rodriguez-Smith, Jackeline; Brewer, Carmen; King, Kelly; Zalewski, Christopher; Kim, H Jeffrey; Bishop, Rachel; Abrams, Ken; Stone, Deborah; Chapelle, Dawn; Kost, Bahar; Snyder, Christopher; Butman, John A; Wesley, Robert; Goldbach-Mansky, Raphaela

    2014-01-01

    Objective To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin-associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID). Methods 6 patients were enrolled in this 24-month, open-label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patientreported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at month 6. Results All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staphylococcus aureus infection) occurred. Conclusions Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although low-grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed. ClinicalTrials.gov identifier NCT00770601. PMID:24906637

  14. Tumor microenvironment: hypoxia and buffer capacity for immunotherapy.

    PubMed

    Liu, Chenghu; Gao, Shangxian; Qu, Zhonghua; Zhang, Lining

    2007-01-01

    In recent years, significant progress has been made in the study of tumor biology and anti-tumor immunotherapy. However, the cellular and molecular mechanisms of tumor progression still remain obscure. As we know, tumor microenvironment that can directly influence tumor development and prognosis has attracted much attention of large number of immunologists. Accumulated evidence has suggested that tumor microenvironment is in a hypoxic condition, under which immune cells may exhibit distinct functions compared to those under normal oxygen tension. The article we propose here will offer a novel point of view for understanding tumor microenvironment in order to instruct clinical immunotherapy. Just like the pH buffer system in human body, interactions of immune cells in tumor microenvironment may also constitute a buffer system, the balance of which is of great importance during immunotherapy for tumors. However, many protocols for tumor immunotherapy in clinic at present have not taken it into account, so the therapeutic outcome is often disappointing. In the present study, we have demonstrated the effect of Corynebacterium parvum, a well known immune stimulator, on malignant melanoma. Cell ingredients in tumor-infiltrating lymphocytes (TIL) and their anti-tumor effect have been altered when dosage of Corynebacterium parvum is changed. So, to obtain better therapeutic purposes, what we should do first is to detect an index to evaluate immune buffer capacity for the patient during tumor immunotherapy, then to choose appropriate drug doses to augment buffer capacity for their immune buffer system. Taken together, the hypothesis proposed here may help understand the pathogenesis of tumor progression and design more effective strategy for clinical immunotherapy for tumors. PMID:17360127

  15. Radiation risk assessment in neonatal radiographic examinations of the chest and abdomen: a clinical and Monte Carlo dosimetry study

    NASA Astrophysics Data System (ADS)

    Makri, T.; Yakoumakis, E.; Papadopoulou, D.; Gialousis, G.; Theodoropoulos, V.; Sandilos, P.; Georgiou, E.

    2006-10-01

    Seeking to assess the radiation risk associated with radiological examinations in neonatal intensive care units, thermo-luminescence dosimetry was used for the measurement of entrance surface dose (ESD) in 44 AP chest and 28 AP combined chest-abdominal exposures of a sample of 60 neonates. The mean values of ESD were found to be equal to 44 ± 16 µGy and 43 ± 19 µGy, respectively. The MCNP-4C2 code with a mathematical phantom simulating a neonate and appropriate x-ray energy spectra were employed for the simulation of the AP chest and AP combined chest-abdominal exposures. Equivalent organ dose per unit ESD and energy imparted per unit ESD calculations are presented in tabular form. Combined with ESD measurements, these calculations yield an effective dose of 10.2 ± 3.7 µSv, regardless of sex, and an imparted energy of 18.5 ± 6.7 µJ for the chest radiograph. The corresponding results for the combined chest-abdominal examination are 14.7 ± 7.6 µSv (males)/17.2 ± 7.6 µSv (females) and 29.7 ± 13.2 µJ. The calculated total risk per radiograph was low, ranging between 1.7 and 2.9 per million neonates, per film, and being slightly higher for females. Results of this study are in good agreement with previous studies, especially in view of the diversity met in the calculation methods.

  16. Amyloid-ß-directed immunotherapy for Alzheimer's disease

    PubMed Central

    Lannfelt, L; Relkin, N R; Siemers, E R

    2014-01-01

    Lannfelt L, Relkin NR, Siemers ER (Uppsala University, Uppsala, Sweden; Weill Cornell Medical College, New York, NY; and Eli Lilly and Co., Indianapolis, IN, USA). Amyloid-ß-directed immunotherapy for Alzheimer’s disease. (Key Symposium). J Intern Med 2014; 275: 284–295. Current treatment options for Alzheimer's disease (AD) are limited to medications that reduce dementia symptoms. Given the rapidly ageing populations in most areas of the world, new therapeutic interventions for AD are urgently needed. In recent years, a number of drug candidates targeting the amyloid-ß (Aß) peptide have advanced into clinical trials; however, most have failed because of safety issues or lack of efficacy. The Aß peptide is central to the pathogenesis, and immunotherapy against Aß has attracted considerable interest. It offers the possibility to reach the target with highly specific drugs. Active immunization and passive immunization have been the most widely studied approaches to immunotherapy of AD. A favourable aspect of active immunization is the capacity for a small number of vaccinations to generate a prolonged antibody response. A potential disadvantage is the variability in the antibody response across patients. The potential advantages of passive immunotherapy include the reproducible delivery of a known amount of therapeutic antibodies to the patient and rapid clearance of those antibodies if side effects develop. A disadvantage is the requirement for repeated infusions of antibodies over time. After more than a decade of research, anti-amyloid immunotherapy remains one of the most promising emerging strategies for developing disease-modifying treatments for AD. In this review, we examine the presently ongoing Aß-directed immunotherapies that have passed clinical development Phase IIa. PMID:24605809

  17. Stagnant Neonatal Mortality and Persistent Health Inequality in Middle-Income Countries: A Case Study of the Philippines

    PubMed Central

    Kraft, Aleli D.; Nguyen, Kim-Huong; Jimenez-Soto, Eliana; Hodge, Andrew

    2013-01-01

    Background The probability of survival through childhood continues to be unequal in middle-income countries. This study uses data from the Philippines to assess trends in the prevalence and distribution of child mortality and to evaluate the country’s socioeconomic-related child health inequality. Methodology Using data from four Demographic and Health Surveys we estimated levels and trends of neonatal, infant, and under-five mortality from 1990 to 2007. Mortality estimates at national and subnational levels were produced using both direct and indirect methods. Concentration indices were computed to measure child health inequality by wealth status. Multivariate regression analyses were used to assess the contribution of interventions and socioeconomic factors to wealth-related inequality. Findings Despite substantial reductions in national under-five and infant mortality rates in the early 1990s, the rates of declines have slowed in recent years and neonatal mortality rates remain stubbornly high. Substantial variations across urban-rural, regional, and wealth equity-markers are evident, and suggest that the gaps between the best and worst performing sub-populations will either be maintained or widen in the future. Of the variables tested, recent wealth-related inequalities are found to be strongly associated with social factors (e.g. maternal education), regional location, and access to health services, such as facility-based delivery. Conclusion The Philippines has achieved substantial progress towards Millennium Development Goal 4, but this success masks substantial inequalities and stagnating neonatal mortality trends. This analysis supports a focus on health interventions of high quality – that is, not just facility-based delivery, but delivery by trained staff at well-functioning facilities and supported by a strong referral system – to re-start the long term decline in neonatal mortality and to reduce persistent within-country inequalities in child

  18. Proportion of neonatal readmission attributed to length of stay for childbirth: a population-based cohort study

    PubMed Central

    Metcalfe, Amy; Mathai, Matthews; Liu, Shiliang; Leon, Juan Andres; Joseph, K S

    2016-01-01

    Objective Most literature on length of stay (LOS) for childbirth focuses on ‘early’ discharge as opposed to ‘optimal’ time of discharge and has conflicting results due to heterogeneous definitions of ‘early’ discharge and differing eligibility criteria for these programmes. We aimed to determine the LOS associated with the lowest neonatal readmission rate following childbirth by examining the incidence pattern of neonatal readmission for different LOS using the Kitagawa decomposition. Design Retrospective cohort study using administrative hospitalisation data. Setting Canada (excluding Quebec) from 2003 to 2010. Patients Term, singleton live births without congenital anomalies. Interventions LOS for childbirth. Main outcome measure Neonatal readmissions within 30 days of birth. Results 1 875 322 live births were included. Neonatal LOS peaked at day 1 (47.3%) after vaginal birth and day 3 (49.3%) following caesarean section; 4.2% of infants were readmitted following vaginal birth and 2.2% after caesarean section. In 2008–2010, most readmissions occurred among infants discharged in the first 2 days (83.8%) following a vaginal birth and among infants discharged in the first 3 days (81.7%) following a caesarean birth. Readmissions increased from 4.1% in 2003–2005 to 4.6% in 2008–2010 among vaginal births and from 2.0% to 2.4% among caesarean births and occurred mostly due to changes in the day-specific readmission rates and not due to reductions in LOS. Conclusions Patterns of readmission suggest that readmission rates are lowest following a 1–2-day stay following a vaginal birth and a 2–4-day stay following a caesarean birth given the outpatient support in the community. PMID:27630070

  19. Preclinical development and first-in-human study of ATX-MS-1467 for immunotherapy of MS

    PubMed Central

    Streeter, Heather B.; Rigden, Rachel; Martin, Keith F.; Scolding, Neil J.

    2015-01-01

    Objective: The study was designed to test the efficacy of ATX-MS-1467 in a relevant preclinical model and to assess its safety for the treatment of patients with secondary progressive multiple sclerosis (SPMS). Methods: ATX-MS-1467 was tested for its ability to suppress experimental autoimmune encephalomyelitis (EAE) in the (Ob x DR2)F1 mouse both before and after disease onset. Safety was assessed by clinical assessment, MRI analysis, and the measurement of immune responses to self- and nonself-antigens in patients with SPMS. Results: ATX-MS-1467 displayed a dose-dependent inhibition of EAE and was more effective than glatiramer acetate in the treatment of ongoing disease in humanized mice. A phase 1 open-label dose-escalating study demonstrated that ATX-MS-1467 was safe and well-tolerated in a group of 6 patients with SPMS, up to a dose of 800 µg. Conclusions: The results of this study support further development of ATX-MS-1467 in a clinical trial powered to investigate the immunologic and clinical benefits of treatment in relapsing-remitting MS. Classification of evidence: This study provides Class IV evidence that ATX-MS-1467 is safe and tolerated in a group of 6 patients with SPMS. PMID:25798453

  20. Further studies on the absorption of actinide elements from the gastrointestinal tract of neonatal animals.

    PubMed

    Sullivan, M F; Gorham, L S

    1982-10-01

    Plutonium retention was measured after intragastric administration to neonatal rats, dogs and swine. At 1 week after administration, substantially more of the actinide remained in swine and dogs than in rats. The quantity of 238Pu absorbed by piglets was markedly influenced by such factors as compound solubility, mass of plutonium administered, oxidation state of the actinide, and age of the animal at gavage. Cortisone treatment reduced absorption, but was less effective in piglets than in neonatal rats. Measurements of 238Pu transport from ligated segments of the neonatal swine intestine indicated highest absorption from the duodenum, where the actinide was shown, autoradiographically, to be deposited in the epithelial region; in the ileum, deposition was predominantly in the lacteal region. Absorption of actinides by neonatal swine decreased in the order of 233U greater than 238Pu greater than 237Np greater than 244Cm greater than 241Am. Measurements at 1 yr after gavage showed a much higher retention by swine than by rats.

  1. Immunotherapy strategies for spinal cord injury.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Chen, Kai-Ting; Shu, Ya-Hai; Qiu, Chun-Hong

    2015-01-01

    Regeneration in the central nervous system (CNS) of adult mammalian after traumatic injury is limited, which often causes permanent functional motor and sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation has also been proved to play a crucial role in secondary degeneration following SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however, only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently, the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have made good progresses in treating many CNS degenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs through vaccinating with

  2. Heliotherapy for Neonatal Hyperbilirubinemia in Southwest, Nigeria: A Baseline Pre-Intervention Study

    PubMed Central

    Emokpae, Abieyuwa A.; Mabogunje, Cecilia A.; Imam, Zainab O.; Olusanya, Bolajoko O.

    2016-01-01

    Background A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital. Methods We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children’s Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression. Results Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%–19.3%) and 31.5% (95% CI: 28.8%–34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%–6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy. Conclusions Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings. PMID:27003893

  3. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

    PubMed

    Gastaldi, Matteo; Thouin, Anaïs; Vincent, Angela

    2016-01-01

    Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies. PMID:26692392

  4. [Cancer immunotherapy by immuno-checkpoint blockade].

    PubMed

    Kawakami, Yutaka

    2015-10-01

    As cancer immunotherapies utilizing anti-tumor T-cell responses, immuno-checkpoint blockade and adoptive T-cell immunotherapy have recently achieved durable responses even in advanced cancer patients with metastases. Administration of antibodies on the T-cell surface, CTLA-4 and PD-1 (or PD-1 ligand PD-L1), resulted in tumor regression of not only melanoma and renal cell cancer which were known to be relatively sensitive to immunotherapy, but also various malignancies including lung, bladder, ovarian, gastric, and head and neck cancers, as well as hematological malignancies such as Hodgkin and B-cell malignant lymphomas. These findings have changed the status of immunotherapy in the development of cancer treatments. Currently, development of combinations employing cancer immunotherapy with immuno-checkpoint blockade, as well as personalized cancer immunotherapy based on the evaluation of pretreatment immune status, are in progress.

  5. Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study

    PubMed Central

    Kiblawi, Zeina N.; Smith, Lynne M.; Diaz, Sabrina D.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry

    2013-01-01

    Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How MA use during pregnancy affects neonatal and infant neurobehavior is unknown. Methods The Infant Development, Environment, and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. 17,961 were eligible and 3,705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or GC/MS confirmation of amphetamine and metabolites in meconium. Comparison subjects were matched (race, birth weight, maternal education, insurance), denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, or phencyclidine. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life and again at one month to 380 enrollees (185 exposed, 195 comparison). ANOVA tested exposure effects on NNNS summary scores at birth and one month. GLM repeated measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates. Results By one month of age, both groups demonstrated higher quality of movement (P=.029), less lethargy (P=.001), and fewer asymmetric reflexes (P=.012), with no significant differences in NNNS scores between the exposed and comparison groups. Over the first month of life, arousal increased in exposed infants but decreased in comparison infants (p=.031) and total stress was decreased in exposed infants with no change in comparison infants (p=.026). Conclusions Improvement in total stress and arousal were observed in MA-exposed newborns by one month of age relative to the newborn period. PMID:24588296

  6. An observational study of associations among maternal fluids during parturition, neonatal output, and breastfed newborn weight loss

    PubMed Central

    2011-01-01

    Background Newborn weight measurements are used as a key indicator of breastfeeding adequacy. The purpose of this study was to explore non-feeding factors that might be related to newborn weight loss. The relationship between the intravenous fluids women receive during parturition (the act of giving birth, including time in labour or prior to a caesarean section) and their newborn's weight loss during the first 72 hours postpartum was the primary interest. Methods In this observational cohort study, we collected data about maternal oral and IV fluids during labour or before a caesarean section. Participants (n = 109) weighed their newborns every 12 hours for the first three days then daily to Day 14, and they weighed neonatal output (voids and stools) for three days. Results At 60 hours (nadir), mean newborn weight loss was 6.57% (SD 2.51; n = 96, range 1.83-13.06%). When groups, based on maternal fluids, were compared (≤1200 mls [n = 21] versus > 1200 [n = 53]), newborns lost 5.51% versus 6.93% (p = 0.03), respectively. For the first 24 hours, bivariate analyses show positive relationships between a) neonatal output and percentage of newborn weight lost (r(96) = 0.493, p < 0.001); and b) maternal IV fluids (final 2 hours) and neonatal output (r(42) = 0.383, p = 0.012). At 72 hours, there was a positive correlation between grams of weight lost and all maternal fluids (r(75) = 0.309, p = 0.007). Conclusions Timing and amounts of maternal IV fluids appear correlated to neonatal output and newborn weight loss. Neonates appear to experience diuresis and correct their fluid status in the first 24 hours. We recommend a measurement at 24 hours, instead of birth weight, for baseline when assessing weight change. Because practices can differ between maternity settings, we further suggest that clinicians should collect and analyze data from dyads in their care to determine an optimal baseline measurement. PMID:21843338

  7. Targeted cytokines for cancer immunotherapy.

    PubMed

    Lode, H N; Reisfeld, R A

    2000-01-01

    Targeting of cytokines into the tumor microenvironment using antibody-cytokine fusion proteins, called immunocytokines, represents a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and immune mechanisms involved in targeting interleukin-2 (IL-2) to neuroectodermal tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14.18-IL-2). Treatment of established melanoma metastases with ch14.18-IL-2 resulted in eradication of disease followed by a vaccination effect protecting mice from lethal challenges with wild-type tumor calls. In a syngeneic neuroblastoma model, targeted IL-2 was effective in the amplification of a weak memory immune response previously induced by IL-12 gene therapy using an engineered linear version of this heterodimeric cytokine. These findings show that targeted IL-2 may provide an effective tool in cancer immunotherapy and establish the missing link between T cell-mediated vaccination and objective clinical responses.

  8. RESEARCH ADVANCES IN NEUROBLASTOMA IMMUNOTHERAPY.

    PubMed

    Booker, Latania Y; Ishola, Titilope A; Bowen, Kanika A; Chung, Dai H

    2009-05-01

    Neuroblastoma is the third most common pediatric cancer in the United States and is responsible for 15% of pediatric cancer-related deaths. Despite major advances in multimodal therapy, the clinical outcome for several patients remains poor. Due to the desperate need for innovativation and improved success in the treatment and management of neuroblastoma, research interests in immunotherapy have been on the rise in recent years. Current immunotherapeutic approaches under investigation include antibodies targeting the neuroblastoma antigen GD2, cytokine stimulation of immune cells, use of immunocytokine conjugates, radioimmunotherapy, and tumor-primed dendritic cells. Immunotherapy could serve as a safe alternative or adjunct to current therapeutic protocols and would presumptively have fewer deleterious effects making it more favorable to patients.

  9. Tecemotide: An antigen-specific cancer immunotherapy

    PubMed Central

    Wurz, Gregory T; Kao, Chiao-Jung; Wolf, Michael; DeGregorio, Michael W

    2015-01-01

    The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients. PMID:25483673

  10. Tecemotide: an antigen-specific cancer immunotherapy.

    PubMed

    Wurz, Gregory T; Kao, Chiao-Jung; Wolf, Michael; DeGregorio, Michael W

    2014-01-01

    The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients. PMID:25483673

  11. Effect of lactational exposure of olanzapine on body weight of mice: a comparative study on neonates of both the sexes during post-natal development.

    PubMed

    Mishra, A C; Mohanty, B

    2010-07-01

    Adverse impact of atypical antipsychotic drugs on body weight of adult and juvenile groups has been well-documented both at clinical and preclinical investigations. However, studies on impact of drug on body weight during fetal or neonatal development received little attention. The present study is the first-ever preclinical investigation demonstrating the effect of lactational exposure of olanzapine (4, 8, and 10 mg/kg) and risperidone (1 and 2 mg/kg), two widely prescribed antipsychotics, on body weight of mice neonates. Body weight gain was observed with both the drugs, although a sex-related differential response was noted. In olanzapine-exposed female neonates, the weight gain was more with the highest dose. Male neonates showed a reverse trend, i.e. the highest gain with the lowest dose. Female neonates exposed to risperidone also showed significant, but less gain as compared to their olanzapine-exposed counterparts. Risperidone-exposed male neonates showed little body weight gain. Waist-to-hip ratio and plasma prolactin level were measured to explain the reason behind the body weight gain, but there were deviations with respect to drug and sex. The body weight gain may be the overall manifestations of drug-induced endocrine and metabolic dysregulations. PMID:19164496

  12. Novel immunotherapies in lymphoid malignancies

    PubMed Central

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J.; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted ‘breakthrough’ designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  13. House dust allergy and immunotherapy

    PubMed Central

    Thomas, Wayne R.

    2012-01-01

    HDM allergy is associated with asthma, allergic rhinitis and atopic dermatitis. In many countries childhood asthma is predominantly found in HDM-allergic children with their probability of developing disease being proportional to their IgE antibody titers and the early development of Th2 responses. While the pathogenesis is complex and increasingly linked to infection the immunologically-based allergen immunotherapy and anti-IgE antibody therapy are highly beneficial. Immunotherapy could be a short-term treatment providing lifelong relief but the current regimens depend on repeated administration of allergen over years. Immunological investigations point to a contribution of responses outside the Th2 pathway and multiple potential but unproven control mechanisms. Over half of the IgE antibodies are directed to the group 1 and 2 allergens with most of remainder to the group 4, 5, 7 and 21 allergens. This hierarchy found in high and low responders provides a platform for introducing defined allergens into immunotherapy and defined reagents for investigation. PMID:22894952

  14. [Current Approaches in Cancer Immunotherapy].

    PubMed

    Otáhal, P; Trněný, M

    2015-01-01

    Methods of cancer immunotherapy have finally entered clinical medicine after years of preclinical research. Currently, there are several methods, which have proven to be very effective even in cases of incurable cancer. Antitumor monoclonal antibodies are among major therapeutic anti-cancer drugs and have been successfully used for many ears. Novel group of antibodies are immunomodulatory antibodies which can break tumor -specific immune tolerance and induce regression of tumors by nonspecific activation of immune system. Bispecific antibodies represent a novel class of anticancer agents which can induce expansion of T cells in vivo, blinatumomab is an example of such agents and is currently available for the treatment of acute B -cell leukemia. Cellular immunotherapy is also very effective, especially the use of Chimeric receptor modified T-cells for the therapy of B- cell lymphoproliferative diseases. Although it is a very complicated and expensive method, it is highly effective approach which can induce remission even in previously hopeless conditions. The goal of this article is to explain the basic principles of cancer immunotherapy and summarize the newest findings in this field.

  15. Translating Neurodevelopmental Care Policies Into Practice: The Experience of Neonatal ICUs in France—The EPIPAGE-2 Cohort Study

    PubMed Central

    Coquelin, Anaëlle; Cuttini, Marina; Khoshnood, Babak; Glorieux, Isabelle; Claris, Olivier; Durox, Mélanie; Kaminski, Monique; Ancel, Pierre-Yves; Arnaud, Catherine

    2016-01-01

    Objectives: To describe the implementation of neurodevelopmental care for newborn preterm infants in neonatal ICUs in France in 2011, analyze changes since 2004, and investigate factors associated with practice. Design: Prospective national cohort study of all births before 32 weeks of gestation. Setting: Twenty-five French regions. Participants: All neonatal ICUs (n = 66); neonates surviving at discharge (n = 3,005). Interventions: None. Measurements and Main Results: Neurodevelopmental care policies and practices were assessed by structured questionnaires. Proportions of neonates initiating kangaroo care during the first week of life and those whose mothers expressed breast milk were measured as neurodevelopmental care practices. Multilevel logistic regression analyses were used to investigate relationships between kangaroo care or breast-feeding practices and unit policies, taking into account potential confounders. Free visiting policies, bed availability for parents, and kangaroo care encouragement significantly improved between 2004 and 2011 but with large variabilities between units. Kangaroo care initiation varied from 39% for neonates in the most restrictive units to 68% in less restrictive ones (p < 0.001). Individual factors associated with kangaroo care initiation were gestational age (odds ratio, 5.79; 95% CI, 4.49–7.48 for babies born at 27–31 wk compared with babies born at 23–26 wk) and, to a lesser extent, single pregnancy, birthweight above the 10th centile, and mother’s employment before pregnancy. At unit level, policies and training in neurodevelopmental care significantly influenced kangaroo care initiation (odds ratio, 3.5; 95% CI, 1.8–7.0 for Newborn Individualized Developmental Care and Assessment Program implementation compared with no training). Breast milk expression by mothers was greater in units with full-time availability professionals trained for breast-feeding support (60% vs 73%; p < 0.0001). Conclusions

  16. Dropouts in sublingual allergen immunotherapy trials - a systematic review.

    PubMed

    Makatsori, M; Scadding, G W; Lombardo, C; Bisoffi, G; Ridolo, E; Durham, S R; Senna, G

    2014-05-01

    Participant dropouts can reduce the power of allergen immunotherapy clinical trials. Evaluation of the dropout rate and reasons for dropout are important not only in the planning of clinical studies but are also relevant for adherence to immunotherapy in daily clinical practice. A systematic review was carried out in order to establish the overall dropout rate among published double-blind, placebo-controlled randomized clinical trials of sublingual immunotherapy for respiratory allergic diseases. Dropouts were analysed in regards to allergen, formulation, treatment schedule, participant age, study size, number of centres and type of allergic disease. Relative dropout rates in placebo and active groups as well as reasons for dropout were also assessed. A total of 81 studies, comprising 9998 patients, were included. Dropout rates in sublingual immunotherapy controlled studies do not appear to be a major problem with a composite dropout percentage of 14% (95% CI:11.9-16). Furthermore, they are not different for active compared to placebo-treated participants. This lends support to the positive clinical outcomes seen in meta-analyses of these trials. PMID:24673502

  17. Major Placenta Previa: Rate, Maternal and Neonatal Outcomes Experience at a Tertiary Maternity Hospital, Sohag, Egypt: A Prospective Study

    PubMed Central

    Ahmed, Salah Roshdy; Aitallah, Abdusaeed; Abdelghafar, Hazem M.

    2015-01-01

    Introduction Major degree placenta is a serious health issue and is associated with high fetal-maternal morbidity and mortality. Literature from developing countries is scant. Aim To determine the prevalence and maternal and neonatal outcomes among women with major placenta previa (PP). Materials and Methods A prospective descriptive study of 52 singleton pregnancies with PP was evaluated in this study. The study was conducted at Sohag University Hospital, Egypt from January through June 2014. Outcome measures, including the prevalence of PP, maternal and neonatal outcomes, and case-fatality rate. Results The total number of deliveries performed during the study period was 3841, of them, 52 cases were placenta previa. Thus, the prevalence of PP was 1.3%. The mean of previous cesarean scars was 2.2±1.4. Of women with PP, 26.4% (n=14) had placenta accreta. In total, 15.1% (n=8) of women underwent an obstetric hysterectomy. From the total no. of babies, 13.2% (n=7) were delivered fresh stillborn babies. Of the surviving babies (n=45), 20% (n=9) required admission to NICU. The frequencies of bowel and bladder injuries were 3.8% (n=2) and 13.2% (n=7) respectively. There was no maternal death in this study. Conclusion The rate of PP is comparable to previous studies, however, the rate of placenta accreta is high. Also, there are high rates of neonatal mortality and intraoperative complications which can be explained by accreta. The study highlights the need to revise maternity and child health services. PMID:26674539

  18. Neonatal infectious diseases: evaluation of neonatal sepsis.

    PubMed

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal, and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation, and early initiation of therapy are required to prevent adverse outcomes. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis.

  19. Personalized cancer immunotherapy using Systems Medicine approaches.

    PubMed

    Gupta, Shailendra K; Jaitly, Tanushree; Schmitz, Ulf; Schuler, Gerold; Wolkenhauer, Olaf; Vera, Julio

    2016-05-01

    The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected by the tumor microenvironment. Altogether, the tumor-immunity interaction is a complex multi-scale biological system whose analysis requires a systemic view to succeed in developing efficient immunotherapies for cancer and immune-related diseases. In this review we discuss the necessity and the structure of a systems medicine approach for the design of anticancer immunotherapies. We support the idea that the approach must be a combination of algorithms and methods from bioinformatics and patient-data-driven mathematical models conceived to investigate the role of clinical interventions in the tumor-immunity interaction. For each step of the integrative approach proposed, we review the advancement with respect to the computational tools and methods available, but also successful case studies. We particularized our idea for the case of identifying novel tumor-associated antigens and therapeutic targets by integration of patient's immune and tumor profiling in case of aggressive melanoma.

  20. Personalized cancer immunotherapy using Systems Medicine approaches.

    PubMed

    Gupta, Shailendra K; Jaitly, Tanushree; Schmitz, Ulf; Schuler, Gerold; Wolkenhauer, Olaf; Vera, Julio

    2016-05-01

    The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected by the tumor microenvironment. Altogether, the tumor-immunity interaction is a complex multi-scale biological system whose analysis requires a systemic view to succeed in developing efficient immunotherapies for cancer and immune-related diseases. In this review we discuss the necessity and the structure of a systems medicine approach for the design of anticancer immunotherapies. We support the idea that the approach must be a combination of algorithms and methods from bioinformatics and patient-data-driven mathematical models conceived to investigate the role of clinical interventions in the tumor-immunity interaction. For each step of the integrative approach proposed, we review the advancement with respect to the computational tools and methods available, but also successful case studies. We particularized our idea for the case of identifying novel tumor-associated antigens and therapeutic targets by integration of patient's immune and tumor profiling in case of aggressive melanoma. PMID:26174229

  1. Combination immunotherapies for type 1 diabetes mellitus.

    PubMed

    Pozzilli, Paolo; Maddaloni, Ernesto; Buzzetti, Raffaella

    2015-05-01

    Immunotherapies for type 1 diabetes mellitus (T1DM) have been the focus of intense basic and clinical research over the past few decades. Restoring β-cell function is the ultimate goal of intervention trials that target the immune system in T1DM. In an attempt to achieve this aim, different combination therapies have been proposed over the past few years that are based on treatments tackling the various mechanisms involved in the destruction of β cells. The results of clinical trials have not matched expectations based on the positive results from preclinical studies. The heterogeneity of T1DM might explain the negative results obtained, but previous trials have not addressed this issue. However, novel promising combination therapies are being developed, including those that couple immunomodulators with drugs that stimulate β-cell regeneration in order to restore normoglycaemia. This strategy is an encouraging one to pursue the goal of finding a cure for T1DM. This Review summarizes the available data about combination immunotherapies in T1DM, particularly addressing their clinical importance. The available data supporting the use of registered drugs, such as proton pump inhibitors and incretin-based agents, that have been shown to induce β-cell regeneration will also be discussed.

  2. An update on immunotherapy for food allergy

    PubMed Central

    Scurlock, Amy M.; Jones, Stacie M.

    2013-01-01

    Purpose of the review Recent investigation has resulted in significant advances toward definitive therapeutic options for food allergy. In this review, we will explore novel immunotherapeutic interventions for the active treatment of food allergy. Recent findings Because the injection route for allergen immunotherapy to foods has been associated with an unacceptable risk of severe anaphylactic reactions, use of mucosally targeted therapeutic strategies is of significant interest for food allergy. Allergen-specific immunotherapeutic approaches such as oral, sublingual, epicutaneous, and peptide immunotherapy have demonstrated efficacy in increasing threshold dose and inducing immunologic changes associated with both desensitization and oral tolerance in animal and human trials. More global immunomodulatory strategies, such as Traditional Chinese Medicine and anti-IgE therapy have been shown to effectively target the allergic response, and clinical trials are ongoing to determine the efficacy and safety in human food allergy. Summary The advent of therapies that target the mucosal immune response to promote oral tolerance have shown great promise in the treatment of food hypersensitivity. However, there is still significant risk of adverse reactions associated with these therapeutic strategies and further study is needed to carefully advance these therapeutic modalities toward general clinical implementation. PMID:20856110

  3. [Differences between neonatal mortality and stillbirth rates in Brazil: a study based on the Unified Health System (SIH/SUS) Hospital Information System].

    PubMed

    de Andrade Schramm, J M; Szwarcwald, C L

    2000-01-01

    The main objective of this article is to estimate stillbirth and neonatal mortality rates in Brazilian States based upon the country's Hospital Information System. Analysis of 1995 data reveals contrasting rates between the various regions of the country. In order to elucidate the States' different rates, we focused on the association between indicators of coverage, utilization, and access to the Unified Health System (SUS). The results for the neonatal period mostly showed higher early neonatal mortality rates when compared to late neonatal mortality rates, higher neonatal mortality rates in the States comprising the South and Southeast regions, less variable rates between those States, and extremely low rates in some States of the North, Central-West, and Northeast regions. The limited supply of SUS services and low access to same are relevant constraints on health care for the population in the North and Northeast. Aspects related to quality of childbirth and neonatal care are also reflected in the rates studied. The findings suggest that spatial and temporal monitoring of these rates could provide analytical support for organizing the Maternal and Child Health Program. PMID:11175526

  4. The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths

    PubMed Central

    Becher, J; Bell, J; Keeling, J; McIntosh, N; Wyatt, B

    2004-01-01

    Background: A proportion of neonatal deaths from asphyxia have been shown to be associated with pre-existing brain injury. Objectives: (a) To compare the epidemiology of infants displaying signs of birth asphyxia with those not showing signs; (b) to examine the neuropathology and determine if possible the timing of brain insult comparing asphyxiated with non-asphyxiated infants; (c) to compare the clinical features of those born with birth asphyxia with and without pre-labour damage. Methods: Over a two year period, all 22 Scottish delivery units collected clinical details on early neonatal deaths. Requests for post mortem included separate requests for detailed neuropathological examination of the brain. Infants were classified into two groups: birth asphyxia and non-birth asphyxia. Clinicopathological correlation was used to attempt to define the time of brain insult. Results: Detailed clinical data were available on 137 of 174 early neonatal deaths that met the inclusion criteria. Seventy of 88 parents who had agreed to post mortem examination consented to a detailed examination of additional samples from the brain; in 53 of these cases the infant was born in an asphyxiated condition. All asphyxiated and encephalopathic infants, 38% of mature and 52% of preterm infants with features of birth asphyxia but without encephalopathy, and only one of 12 infants without any signs of birth asphyxia showed damage consistent with onset before the start of labour. Conclusions: In a large proportion of neonatal deaths, brain injury predates the onset of labour. This is more common in infants born in an asphyxiated condition. PMID:15321957

  5. Excessive carbohydrate intake in pregnancy and neonatal obesity: study in Cap Bon, Tunisia.

    PubMed Central

    de Schampheleire, I; Parent, M A; Chatteur, C

    1980-01-01

    A high incidence (over 20%) of obesity was found in 250 neonates living in a rural area of Tunisia, by using weight and ponderal index per gestational age as the nutritional index. Maternal diabetes was probably excluded. Two surveys on nutritional habits--one on the general population and the other on pregnant women--showed a tendency to consume a high carbohydrate and low protein diet. The effect of a badly balanced maternal diet on the fetus is discussed. PMID:7436503

  6. Systemic and local reactions of bee venom immunotherapy in Iran.

    PubMed

    Bemanian, Mohammad Hassan; Farhoudi, Abolhassan; Pourpak, Zahra; Gharagozlou, Mohammad; Movahedi, Masoud; Nabavi, Mohammad; Mozafari, Habibeh; Mohammadzadeh, Iraj; Chavoshzadeh, Zahra; Shirkhoda, Zahra

    2007-12-01

    Severe allergic reactions during specific immunotherapy may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during specific immunotherapy in patients with allergy towards hymenoptera venom in the Iranian population. A prospective study was performed using the clinical reports of 27 patients with anaphylaxis to bee venom (Apis melifera, Geupes vespula and Geupes Polites). Ten patients treated with Cluster protocol during 2002 and 2006 After diagnosis of hymenoptera sting allergy according to history and intradermal tests, the patient were treated with Cluster protocol immunotherapy. The protocol lasted 6 weeks with an increase in the concentration of venom from 0.01 microg/ml to 100 microg/ml. None of the patient received premedication. All patients with hymenoptera venom allergy received 120 injections. Anaphylactic reactions were classified according to the Mueller-classification. The frequencies of systemic reactions during Cluster protocol were 8.33% and 5% for yellow jacket and honey bee venom respectively. No patient experienced severe systemic reaction. Cluster protocol for hymenoptera immunotherapy is a reliable method for the treatment of anaphylactic reactions to bee venom. It is safe with low cost and do not need hospitalization.

  7. Seasonal versus perennial immunotherapy: evaluation after three years of treatment.

    PubMed

    Muñoz Lejarazu, D; Bernaola, G; Fernández, E; Audícana, M; Ventas, P; Martín, S; Fernández de Corres, L

    1993-01-01

    We have performed a comparative study to evaluate seasonal and perennial schedules after 3 years of immunotherapy. Sixty patients suffering from rhinitis and/or asthma due to grass pollen sensitization were randomly allocated to receive a semi-depot extract of Phleum pratense according to a perennial or seasonal schedule. The last year of the study, 14 patients were recruited as a control group without immunotherapy. The cumulative dose was 602 BU in the perennial group and 372 BU in the seasonal group. The frequency and severity of side-effects were similar and very low in both treated groups. The IgE level was significantly lower after perennial immunotherapy at the end of the first 2 years. A seasonal decrease in specific IgG levels was observed in patients who interrupted immunotherapy, while this was not observed in patients under the perennial schedule. Symptoms and medication scores did not show differences between groups. Nevertheless, we found a significant difference between treated patients and the control group. PMID:8281355

  8. Pathophysiology of Citrobacter diversus neonatal meningitis: comparative studies in an infant mouse model.

    PubMed Central

    Soriano, A L; Russell, R G; Johnson, D; Lagos, R; Sechter, I; Morris, J G

    1991-01-01

    Citrobacter diversus is a cause of devastating neonatal meningitis, with illness characterized by formation of multiple brain abscesses. We developed an infant mouse intracranial inoculation model to evaluate the pathophysiology of C. diversus neonatal infections. Eighteen of 26 strains inoculated intracranially at a dose of ca. 3.3 x 10(3) CFU caused greater than 50% mortality in 2-day-old mice. No correlation was seen between the epidemiologic characteristics of a strain and its rate of mortality. When seven C. diversus isolates (four isolates from patients with meningitis, three from non-central nervous system [CNS] sites) were further evaluated, mortality was significantly correlated with bacteremia. The initial lesion in the CNS was a suppurative ventriculitis beginning 1 to 2 days postinoculation. Subsequent ventriculomegaly was associated with ventriculitis and periventricular abscessation. Brain lesions were seen with all strains, although strains of low virulence (as measured by having no bacteremia and low mortality) caused less-severe damage. An age-related susceptibility to C. diversus brain lesions was demonstrated, with 5-day-old mice showing a significant reduction in, and 8-day-old mice being apparently resistant to, infection and CNS damage. Our data indicate that C. diversus has a propensity to cause abscess formation in the neonatal mouse brain, with characteristic pathologic findings; however, the factors that determine whether a strain will cause meningitis in a human infant remain to be identified. Images PMID:2004815

  9. Pulmonary sequelae of neonatal respiratory distress in very low birthweight infants: a clinical and physiological study.

    PubMed Central

    Wong, Y C; Beardsmore, C S; Silverman, M

    1982-01-01

    Twenty infants, mechanically ventilated in the neonatal period for respiratory distress syndrome, were compared with 15 healthy controls, matched for birthweight(less than 1501 g) but greater in mean gestational age. Clinical features and lung mechanics (by whole body plethysmography) were recorded at 6-monthly intervals until about one year. THe neonatal course of the mechanically ventilated infants was commonly complicated by tracheobronchial hypersecretion and the later course by a fairly high incidence of lower respiratory tract illness. In this group, thoracic gas volume, dynamic compliance, pulmonary and airways conductance were all abnormal during the middle 4 months of the first year and reverted towards normal towards the end of the first year. The control group had normal lung mechanics. Early lung function tests were of limited value in predicting later lower respiratory tract illness, which was more common in boys, after neonatal mechanical ventilation for longer than 24 hours or raised ambient oxygen for longer than 5 days. There were few predictive physical signs. In this group of very low birthweight infants, respiratory distress syndrome of sufficient severity to require mechanical ventilation led to significant physiological and clinical disturbances of lung function which lasted into the second 6 months of life and which were particularly severe in those who had recurrent lower respiratory tract illness. PMID:7092305

  10. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol

    PubMed Central

    2012-01-01

    Background Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births. Methods We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color

  11. Novel optical system for neonatal brain imaging

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Zhou, Shuoming; Nioka, Shoko; Chance, Britton; Anday, Endla; Ravishankar, Sudha; Delivoria-Papadopoulos, Maria

    1999-03-01

    A highly portable, fast, safe and affordable imaging system that provides interpretable images of brain function in full- and pre-term neonates within a few seconds has been applied to neonates with normal and pathological states. We have used a uniquely sensitive optical tomography system, termed phased array, which has revealed significant functional responses, particularly to parietal stimulation in neonate brain. This system can indicate the blood concentration and oxygenation change during the parietal brain activation in full- and pre-term neonates. The preliminary clinical results, especially a longitudinal study of a cardiac arrest neonate, suggest a variety of future applications.

  12. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group.

    PubMed

    Okada, Hideho; Weller, Michael; Huang, Raymond; Finocchiaro, Gaetano; Gilbert, Mark R; Wick, Wolfgang; Ellingson, Benjamin M; Hashimoto, Naoya; Pollack, Ian F; Brandes, Alba A; Franceschi, Enrico; Herold-Mende, Christel; Nayak, Lakshmi; Panigrahy, Ashok; Pope, Whitney B; Prins, Robert; Sampson, John H; Wen, Patrick Y; Reardon, David A

    2015-11-01

    Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.

  13. Neonatal Hemochromatosis

    PubMed Central

    Feldman, Amy G.; Whitington, Peter F.

    2013-01-01

    Neonatal hemochromatosis is a clinical condition in which severe liver disease in the newborn is accompanied by extrahepatic siderosis. Gestational alloimmune liver disease (GALD) has been established as the cause of fetal liver injury resulting in nearly all cases of NH. In GALD, a women is exposed to a fetal antigen that she does not recognize as “self” and subsequently begins to produce IgG antibodies that are directed against fetal hepatocytes. These antibodies bind to fetal liver antigen and activate the terminal complement cascade resulting in hepatocyte injury and death. GALD can cause congenital cirrhosis or acute liver failure with and without iron overload and siderosis. Practitioners should consider GALD in cases of fetal demise, stillbirth, and neonatal acute liver failure. Identification of infants with GALD is important as treatment is available and effective for subsequent pregnancies. PMID:25755519

  14. A multivariate study of the effects of high-risk factors on performance on the Brazelton Neonatal Assessment Scale.

    PubMed

    Lester, B M; Emory, E K; Hoffman, S L

    1976-06-01

    The Brazelton Neonatal Assessment Scale was administered to 52 newborn infants. A factor analysis revealed 2 main factors, 1 along an attention-orientation dimension, the other relating to temperament arousal. A stepwise multiple linear regression analysis showed that the attention-orientation factor was related to birth weight, age of the mother, and sex and race of the baby. The only variable related to the temperament-arousal factor was 5-min Apgar scor. The study, although exploratory, demonstrates the use of multivariate techniques in the assessment of influences on newborn behavior.

  15. THE IMPACT OF MATERNAL OBESITY ON MOTHER AND NEONATAL HEALTH: STUDY IN A TERTIARY HOSPITAL OF ASTANA, KAZAKHSTAN

    PubMed Central

    AIMUKHAMETOVA, GULZHAN; UKYBASOVA, TALSHYN; HAMIDULLINA, ZAITUNA; ZHUBANYSHEVA, KARLYGASH; HARUN-OR-RASHID, MD.; YOSHIDA, YOSHITOKU; KASUYA, HIDEKI; SAKAMOTO, JUNICHI

    2012-01-01

    ABSTRACT This study was aimed to investigate the impact of maternal obesity on mothers and their neonatal health. Our study population consisted of 157 women with completed singleton pregnancies, which included both obese (Body mass index, BMI≥30) and non-obese women (BMI<30). Data were collected from case histories, and ante- and postnatal records at the tertiary hospital in Astana, Kazakhstan between January and February of 2008. Associations between pregnancy and delivery-related complications, outcomes, and maternal obesity were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model. Women aged 30 years or more were at higher risk of obesity (OR=3.1, 95% CI=0.8–11.6) than women less than 30 years old. Multiparous women were also at higher risk of obesity (OR=4.1, 95% CI=0.9–19.6) than primiparous ones. Obese women were also more likely to have longer hospital stays of more than 10 days (OR=2.2, 95% CI=0.8–6.2), and were more prone to eclampsia/pre-eclampsia (OR=24.7, 95% CI=2.2–44.8), cesarean sections (OR=2.1, 95% CI=0.7–6.2), and abnormal labor (OR=8.1, 95% CI=1.0–63.8) compared to non-obese women. Neonatal complications such as pneumonia (OR=3.4, 95% CI=0.6–20.2) and fetal macrosomia (OR=2.2, 95% CI=0.6–8.0) were also more common among babies born to obese mothers. Congenital baby birth defects were strongly associated with maternal obesity (P=0.016). We concluded that maternal obesity is associated with increased risks of both maternal and neonatal complications, and that such risks increase with advanced age and parity of the mother. Hence, medical practices must take these complications into account by ensuring an adaptable and early management in order to improve mothers and their neonatal health. PMID:22515114

  16. Neoantigen-based cancer immunotherapy.

    PubMed

    Bobisse, Sara; Foukas, Periklis G; Coukos, George; Harari, Alexandre

    2016-07-01

    Emerging clinical evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy in all cancer types. Recent clinical data clearly demonstrated that human tumor cells express antigenic peptides (epitopes) that can be recognized by autologous tumor-specific T cells and that enhancement of such immune reactivity can potentially lead to cancer control and cancer regression in patients with advanced disease. However, in most cases, it is unclear which tumor antigens (Ags) mediated cancer regression. Mounting evidence indicates that numerous endogenous mutated cancer proteins, a hallmark of tumor cells, can be processed into peptides and presented on the surface of tumor cells, leading to their immune recognition in vivo as "non-self" or foreign. Massively parallel sequencing has now overcome the challenge of rapidly identifying the comprehensive mutational spectrum of individual tumors (i.e., the "mutanome") and current technologies, as well as computational tools, have emerged that allow the identification of private epitopes derived from their mutanome and called neoantigens (neoAgs). On this basis, both CD4(+) and CD8(+) neoantigen-specific T cells have been identified in multiple human cancers and shown to be associated with a favorable clinical outcome. Notably, emerging data also indicate that neoantigen recognition represents a major factor in the activity of clinical immunotherapies. In the post-genome era, the mutanome holds promise as a long-awaited 'gold mine' for the discovery of unique cancer cell targets, which are exclusively tumor-specific and unlikely to drive immune tolerance, hence offering the chance for highly promising clinical programs of cancer immunotherapy. PMID:27563649

  17. Neoantigen-based cancer immunotherapy

    PubMed Central

    Bobisse, Sara; Coukos, George; Harari, Alexandre

    2016-01-01

    Emerging clinical evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy in all cancer types. Recent clinical data clearly demonstrated that human tumor cells express antigenic peptides (epitopes) that can be recognized by autologous tumor-specific T cells and that enhancement of such immune reactivity can potentially lead to cancer control and cancer regression in patients with advanced disease. However, in most cases, it is unclear which tumor antigens (Ags) mediated cancer regression. Mounting evidence indicates that numerous endogenous mutated cancer proteins, a hallmark of tumor cells, can be processed into peptides and presented on the surface of tumor cells, leading to their immune recognition in vivo as “non-self” or foreign. Massively parallel sequencing has now overcome the challenge of rapidly identifying the comprehensive mutational spectrum of individual tumors (i.e., the “mutanome”) and current technologies, as well as computational tools, have emerged that allow the identification of private epitopes derived from their mutanome and called neoantigens (neoAgs). On this basis, both CD4+ and CD8+ neoantigen-specific T cells have been identified in multiple human cancers and shown to be associated with a favorable clinical outcome. Notably, emerging data also indicate that neoantigen recognition represents a major factor in the activity of clinical immunotherapies. In the post-genome era, the mutanome holds promise as a long-awaited ‘gold mine’ for the discovery of unique cancer cell targets, which are exclusively tumor-specific and unlikely to drive immune tolerance, hence offering the chance for highly promising clinical programs of cancer immunotherapy. PMID:27563649

  18. Oral Immunotherapy for Treatment of Egg Allergy in Children

    PubMed Central

    Burks, A. Wesley; Jones, Stacie M.; Wood, Robert A.; Fleischer, David M.; Sicherer, Scott H.; Lindblad, Robert W.; Stablein, Donald; Henning, Alice K.; Vickery, Brian P.; Liu, Andrew H.; Scurlock, Amy M.; Shreffler, Wayne G.; Plaut, Marshall; Sampson, Hugh A.

    2012-01-01

    BACKGROUND For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy. METHODS In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months. RESULTS After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months. CONCLUSIONS These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; Clinical

  19. Neonatal circumcision.

    PubMed

    Lerman, S E; Liao, J C

    2001-12-01

    The merits of neonatal circumcision continue to be debated hotly. Some argue that circumcision is a "uniquely American medical enigma." Most of the world's male population remains uncircumcised; however, most boys born in the United States continue to undergo neonatal circumcision. Review of existing literature supports that most children who are uncircumcised do well from a medical standpoint and, thus, the question of whether US health care practitioners are subjecting neonates to an unnecessary surgical procedure remains. The medical benefits of circumcision are multiple, but most are small. The clearest medical benefit of circumcision is the relative reduction in the risk for a UTI, especially in early infancy. Although this risk [figure: see text] is real, the absolute numbers are small (risk ranges from 1 in 100 to 1 in 1000), and one investigator has estimated that it may take approximately 80 neonatal circumcisions to prevent one UTI. In the case of a patient with known urologic abnormalities that predispose to UTI, neonatal circumcision has a clearer role in terms of medical benefit to the patient. Most of the other medical benefits of circumcision probably can be realized without circumcision as long as access to clean water and proper penile hygiene are achieved. Proper penile hygiene should all but eliminate the risk for foreskin-related medical problems that will require circumcision. Moreover, proper hygiene and access to clean water has been shown to reduce the rate of development of squamous cell carcinoma of the penis in the uncircumcised population. Proper techniques on the care of the foreskin are illustrated in the American Academy of Pediatrics pamphlet titled "How to care for the uncircumcised penis." Regarding the relationship between STDs and circumcision, patient education and the practice of low-risk sexual behavior make a far greater impact than does routine circumcision in hopes of reducing the spread of HIV and other STDs. Nevertheless

  20. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  1. Immunotherapy: It Takes a Village

    PubMed Central

    Pardoll, Drew

    2016-01-01

    We in the cancer immunology and immunotherapy community are thrilled that Science named “Cancer immunotherapy” as 2013’s Breakthrough of the Year (J. Couzin-Frankel, 20 December 2013, p. 1432). The rapid succession of clinical successes by blocking antibodies to two immune checkpoints, CTLA-4 and PD-1, and by chimeric antigen-receptor-transduced T cells, shows the power of basic immunology when translated to therapy. As such, I write to acknowledge some of the key scientists whose basic discoveries paved the way for the clinical successes outlined in the Breakthrough issue. PMID:24723594

  2. Is prenatal childbirth preparation effective in decreasing adverse maternal and neonatal response to labor? A nested case-control study.

    PubMed

    Kim, Hyun Hee; Nava-Ocampo, Alejandro A; Kim, Sun Kyung; Kim, Seo Hui; Kim, Yun Ju; Han, Jung Yeol; Ahn, Hyun Kyong; Ryu, Hyun Mee; Yang, Jae Hyug; Kim, Moon Young

    2008-04-01

    Sophrology, based on a combination of Western relaxation therapy and Eastern yoga and meditation might decrease maternal stress during labor. This study aimed to evaluate whether prenatal sophrologic childbirth preparation may decrease maternal and neonatal adverse response associated with delivery. In a nested case-control study, 69 nulliparous, singleton pregnant women who underwent an educational course of sophrologic childbirth preparation were compared to 69 nulliparous, singleton, age- and gestational age-matched pregnant women who did not receive any childbirth preparation. All babies were vaginally delivered. Groups were not different (P > 0.05) in the number of neonates born with meconium-stained amniotic fluid as well as in the number of babies with Apgar score < or = 7 at 1 and 5 minutes after birth. Duration of labor was not different between groups. The number of women requiring oxytocin and delivering babies with low pH blood levels tended to be lower in the group undergoing sophrologic childbirth preparation, i.e. 58.0% vs 72.5% (P = 0.07) and 1.4% vs 10.9% (P = 0.06), respectively. In conclusion, we were unable to confirm that prenatal sophrologic childbirth preparation has a definitive role in decreasing adverse maternal and fetal response to pain or in shortening labor. Prospective cohort studies with a larger sample size or randomized trials may help to clarify this gap.

  3. Systems biology applied to vaccine and immunotherapy development

    PubMed Central

    2011-01-01

    Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs) plays in determining the nature and duration (immune memory) of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy) on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment. PMID:21933421

  4. [Fetal and neonatal immune thrombocytopenias. Study group "Mother-child immune thrombopenias"].

    PubMed

    Kaplan, C; Morel-Kopp, M C; Verdy, E; Pron, B; Tchernia, G

    1992-10-31

    Neonatal thrombocytopenia has benefited from the advances achieved during the last few years in platelet immunology and foetal therapy. The major risk of the disease is cerebral haemorrhage resulting in death or neurological sequelae. Establishing the aetiological diagnosis of immune thrombocytopenia makes it possible nowadays to apply the appropriate treatment and eventually to take care of future pregnancies. Treatments in utero of foeto-maternal alloimmunization have radically altered the natural course of foetal thrombocytopenia, thereby permitting the management of pregnancies at risk. On the other hand, so far no prenatal treatment has proved to be effective against thrombocytopenia due to maternal autoimmunity. PMID:1480577

  5. Neonatal antiphospholipid syndrome.

    PubMed

    Soares Rolim, A M; Castro, M; Santiago, M B

    2006-01-01

    Antiphospholipid syndrome (APS) is a clinical entity characterized by arterial and venous thrombosis, adverse obstetric outcome and the presence of antibodies against phospholipids in serum or plasma. The objective of the present study is to describe a rare case of APS that occurred in a neonate born from a patient previously diagnosed as primary APS. A male, preterm born twin infant, whose mother had been diagnosed as primary APS, developed thrombocytopenia, livedo reticularis, pericardial effusion and thrombosis of the left subclavian and external jugular veins concomitantly with severe respiratory tract infection soon after his delivery, that culminated with his death two months after the birth, in spite of the large spectrum antibiotic therapy and all supportive measures. Laboratory findings included high titers of IgM anticardiolipin antibodies and moderate titers of IgG isotype and negative antinuclear antibody, configuring a case of neonatal APS. Neonatal APS is a rare clinical condition, with only a few cases described in the literature. Its occurrence may depend on the passage of antibodies through the placenta or, as it seems to have occurred in the present case, by the production of de novo antibodies by the fetus. The present case illustrates the necessity of a higher surveillance of the neonates born from mothers with primary APS or systemic lupus erythematosus (SLE) for the eventual development of such complication. PMID:16761506

  6. Effect of birth order on neonatal morbidity and mortality among very low birthweight twins: a population based study

    PubMed Central

    Shinwell, E; Blickstein, I; Lusky, A; Reichman, B

    2004-01-01

    Objective: To study the effect of birth order on the risk for respiratory distress syndrome (RDS), chronic lung disease (CLD), adverse neurological findings, and death in very low birthweight (VLBW; < 1500 g) twins. Methods: A population based study of VLBW infants from the Israel National VLBW Infant Database. The sample included all complete sets of VLBW twin pairs admitted to all 28 neonatal intensive care units between 1995 and 1999. Outcome variables were compared by birth order and stratified by mode of delivery and gestational age, using General Estimating Equation models, with results expressed as odds ratio (OR) with 95% confidence interval (CI). Results: Second twins were at increased risk for RDS (OR 1.51, 95% CI 1.29 to 1.76), CLD (OR 1.36, 95% CI 1.11 to 1.66), and death (OR 1.24, 95% CI 1.02 to 1.51) but not for adverse neurological findings (OR 1.20, 95% CI 0.91 to 1.60). Mode of delivery did not significantly influence outcome. The odds ratio for RDS in the second twin was inversely related to gestational age, and the increased risk for RDS and CLD was found in both vaginal and caesarean deliveries. Conclusions: VLBW second twins are at increased risk for acute and chronic lung disease and neonatal mortality, irrespective of mode of delivery. PMID:14977899

  7. Dichotomy between T Cell and B Cell Tolerance to Neonatal Retroviral Infection Permits T Cell Therapy

    PubMed Central

    Mavrommatis, Bettina; Baudino, Lucie; Levy, Prisca; Merkenschlager, Julia; Eksmond, Urszula; Donnarumma, Tiziano; Young, George; Stoye, Jonathan

    2016-01-01

    Elucidation of the immune requirements for control or elimination of retroviral infection remains an important aim. We studied the induction of adaptive immunity to neonatal infection with a murine retrovirus, under conditions leading to immunological tolerance. We found that the absence of either maternal or offspring adaptive immunity permitted efficient vertical transmission of the retrovirus. Maternal immunodeficiency allowed the retrovirus to induce central Th cell tolerance in the infected offspring. In turn, this compromised the offspring’s ability to mount a protective Th cell–dependent B cell response. However, in contrast to T cells, offspring B cells were not centrally tolerized and retained their ability to respond to the infection when provided with T cell help. Thus, escape of retrovirus-specific B cells from deletional tolerance offers the opportunity to induce protective retroviral immunity by restoration of retrovirus-specific T cell help, suggesting similar T cell immunotherapies for persistent viral infections. PMID:27647833

  8. [Dendritic cells in cancer immunotherapy].

    PubMed

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities. PMID:26486534

  9. Novel immunotherapies for hematological malignancies

    PubMed Central

    Nelson, Michelle H.; Paulos, Chrystal M.

    2014-01-01

    Summary The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise the state of the art in immunotherapy with a focus on strategies that exploit the patient’s immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematological malignancies, including (i) conventional monoclonal therapies like rituximab, (ii) engineered monoclonal antibodies called bispecific T cell engagers (BiTEs), (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4 and IDO), and (iv) adoptive cell transfer (ACT) therapy with T cells engineered to express chimeric antigen receptors (CARs) or T-cell receptors (TCRs). We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

  10. Biological Response Modifier in Cancer Immunotherapy.

    PubMed

    Liu, Ronghua; Luo, Feifei; Liu, Xiaoming; Wang, Luman; Yang, Jiao; Deng, Yuting; Huang, Enyu; Qian, Jiawen; Lu, Zhou; Jiang, Xuechao; Zhang, Dan; Chu, Yiwei

    2016-01-01

    Biological response modifiers (BRMs) emerge as a lay of new compounds or approaches used in improving cancer immunotherapy. Evidences highlight that cytokines, Toll-like receptor (TLR) signaling, and noncoding RNAs are of crucial roles in modulating antitumor immune response and cancer-related chronic inflammation, and BRMs based on them have been explored. In particular, besides some cytokines like IFN-α and IL-2, several Toll-like receptor (TLR) agonists like BCG, MPL, and imiquimod are also licensed to be used in patients with several malignancies nowadays, and the first artificial small noncoding RNA (microRNA) mimic, MXR34, has entered phase I clinical study against liver cancer, implying their potential application in cancer therapy. According to amounts of original data, this chapter will review the regulatory roles of TLR signaling, some noncoding RNAs, and several key cytokines in cancer and cancer-related immune response, as well as the clinical cases in cancer therapy based on them.

  11. Development of Passive Immunotherapies for Synucleinopathies.

    PubMed

    Bergström, Ann-Louise; Kallunki, Pekka; Fog, Karina

    2016-02-01

    Immunotherapy using antibodies targeting alpha-synuclein has proven to be an effective strategy for ameliorating pathological and behavioral deficits induced by excess pathogenic alpha-synuclein in various animal and/or cellular models. However, the process of selecting the anti-alpha-synuclein antibody with the best potential to treat synucleinopathies in humans is not trivial. Critical to this process is a better understanding of the pathological processes involved in the synucleinopathies and how antibodies are able to influence these. We will give an overview of the first proof-of-concept studies in rodent disease models and discuss challenges associated with developing antibodies against alpha-synuclein resulting from the distribution and structural characteristics of the protein. We will also provide a status on the passive immunization approaches targeting alpha-synuclein that have entered, or are expected to enter, clinical evaluation.

  12. Honeybee venom immunotherapy: certainties and pitfalls.

    PubMed

    Bilò, M Beatrice; Antonicelli, Leonardo; Bonifazi, Floriano

    2012-11-01

    The honeybee is an interesting insect because of the fundamental agricultural role it plays, together with the composition of its venom, which presents new diagnostic and immunotherapeutic challenges. This article examines various aspects of honeybee venom allergy from epidemiology to diagnosis and treatment, with special emphasis on venom immunotherapy (VIT). Honeybee venom allergy represents a risk factor for severe systemic reaction in challenged allergic patients, for the diminished effectiveness of VIT, for more frequent side effects during VIT and relapse after cessation of treatment. Some strategies are available for reducing the risk of honeybee VIT-induced side effects; however, there is considerable room for further improvement in these all-important areas. At the same time, sensitized and allergic beekeepers represent unique populations for epidemiological, venom allergy immunopathogenesis and VIT mechanism studies.

  13. A longitudinal study on the effects of maternal smoking and secondhand smoke exposure during pregnancy on neonatal neurobehavior.

    PubMed

    Hernández-Martínez, Carmen; Arija Val, Victoria; Escribano Subías, Joaquín; Canals Sans, Josefa

    2012-06-01

    Maternal smoking during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant women and their fetuses. The long-term effects of prenatal exposure to smoke on child behavior and development have been the subject of more extensive research than have the short-term effects. Therefore, the aim of this work is to examine the effects of smoke exposure during pregnancy on neonatal behavior, including in our study a group of mothers exposed to secondhand smoke. The behavior of 282 healthy full-term newborns was assessed using the Neonatal Behavior Assessment Scale (NBAS) at 48-72 h of life. Sixty-two mothers smoked during pregnancy (no mother smoked more than 15 cig/day) and 17 were exposed to secondhand smoke. After adjusting for socio-demographic and obstetric factors, both newborns whose mothers smoked and those whose mothers were exposed to secondhand smoke showed significantly lower scores in the habituation cluster than non-smoking mothers. Exposure to secondhand smoke was also related to lower motor system cluster scores as well as some supplementary items and the newborns of smoking mothers showed significantly lower scores in the state regulation cluster and in some items of the state organization cluster than the newborns of non-smoking mothers. We conclude that active and passive smoking during pregnancy affects several aspects of neurobehavioral development, regardless of socio-demographic, obstetric and pediatric factors.

  14. Conditions for parents' participation in the care of their child in neonatal intensive care – a field study

    PubMed Central

    Wigert, Helena; Hellström, Anna-Lena; Berg, Marie

    2008-01-01

    Background To promote participation by parents in the care of their child in neonatal intensive care units (NICU), health professionals need better understanding of what facilitates and what obstructs participation. The aim was to elucidate conditions for parents' participation in the care of their child in NICUs. Methods A field study with a hermeneutic lifeworld approach was used and data were collected at two NICUs through participative observations and interviews with representatives of management, staff and parents. Results The results point to a number of contradictions in the way parents were offered the opportunity to participate in neonatal intensive care. Management and staff both had good ambitions to develop ideal care that promoted parent participation. However, the care including the conditions for parental participation was driven by the terms of the staff, routines focusing on the medical-technical care and environment, and budgetary constraints. Conclusion The result shows that tangible strategies need to be developed in NICUs aimed at optimising conditions for parents to be present and involved in the care of their child. PMID:18215259

  15. Congenitally deaf children's care trajectories in the context of universal neonatal hearing screening: a qualitative study of the parental experiences.

    PubMed

    Hardonk, Stefan; Desnerck, Greetje; Loots, Gerrit; Van Hove, Geert; Van Kerschaver, Erwin; Sigurjónsdóttir, Hanna Björg; Vanroelen, Christophe; Louckx, Fred

    2011-01-01

    The objective of this study is to examine the early care trajectories of congenitally deaf children from a parental perspective, starting with universal neonatal hearing screenings. The analysis using a three-dimensional care trajectory concept is aimed at developing a basic typology of postscreening care trajectories. Children with severe/profound hearing loss, registered in the Flanders' (Belgium) universal neonatal hearing screening program, born between 1999 and 2001. Thematic content analysis of qualitative data collected retrospectively from participant's parents. Two basic types of care trajectories emerged; based on differences in care-use in the phase of further diagnosis and related parental experiences. Subtypes resulted from events related to cochlear implantation. Five trajectory phases were identified: screening, further diagnosis, care and technology, cochlear implantation, and reduction of care and were characterized by specific parental experiences such as confusion, disbelief, disappointment, and uncertainty. Those experiences relate to care professionals' acts and communication and the child's functional evolution. Early care interventions could benefit from coordinated transition between phases, parent support throughout the care trajectory, and a broad approach to deafness in professionals' communication.

  16. Nationwide surveillance study of Clostridium difficile in Australian neonatal pigs shows high prevalence and heterogeneity of PCR ribotypes.

    PubMed

    Knight, Daniel R; Squire, Michele M; Riley, Thomas V

    2015-01-01

    Clostridium difficile is an important enteric pathogen of humans and the cause of diarrhea and enteritis in neonatal pigs. Outside Australia, prevalence in piglets can be up to 73%, with a single PCR ribotype (RT), 078, predominating. We investigated the prevalence and genotype of C. difficile in Australian pig herds. Rectal swabs (n = 229) were collected from piglets aged <7 days from 21 farms across Australia. Selective culture for C. difficile was performed and isolates characterized by PCR for toxin genes and PCR ribotyping. C. difficile was isolated from 52% of samples by direct culture on chromogenic agar and 67% by enrichment culture (P = 0.001). No association between C. difficile recovery or genotype and diarrheic status of either farm or piglets was found. The majority (87%; 130/154) of isolates were toxigenic. Typing revealed 23 different RTs, several of which are known to cause disease in humans, including RT014, which was isolated most commonly (23%; 36/154). RT078 was not detected. This study shows that colonization of Australian neonatal piglets with C. difficile is widespread in the herds sampled.

  17. The prenatal, perinatal and neonatal risk factors for children's developmental coordination disorder: a population study in mainland China.

    PubMed

    Hua, Jing; Gu, Guixiong; Jiang, Peiqi; Zhang, Lijun; Zhu, Liping; Meng, Wei

    2014-03-01

    We initially conducted a population-based study on developmental coordination disorder (DCD) in mainland China to explore the prenatal, perinatal and neonatal risk factors on DCD. A total of 4001 children were selected from 160 classes in 15 public nursery schools. The Movement Assessment Battery for Children-Second Edition (MABC-2) was used to assess the children's motor function. Crude and adjusted odds ratios were estimated to determine the strength of association using a multilevel logistic regression model with a random intercept. Three hundred and thirty children out of 4001 subjects met the DSM-IV criteria for DCD, and 3671 children were non-DCD. Maternal age, threatened abortion, fetal distress during labor, preterm birth, chronic lung disease and newborn pathological jaundice were related with DCD (OR=1.72, 2.72, 9.14, 5.17, 1.43, and 2.54, respectively, each p<0.05). Considered collectively, these risk factors may provide clues to an etiology of DCD. Additionally, the practitioners of maternity and child health care should improve the assessment and monitoring of the prenatal, perinatal and neonatal risk factors for DCD. PMID:24480608

  18. Lymphoma Microenvironment and Immunotherapy.

    PubMed

    Xu, Mina L; Fedoriw, Yuri

    2016-03-01

    Understanding of the lymphoma tumor microenvironment is poised to expand in the era of next-generation sequencing studies of the tumor cells themselves. Successful therapies of the future will rely on deeper appreciation of the interactions between elements of the microenvironment. Although the phenotypic, cytogenetic, and molecular characterization of tumor cells in lymphomas has progressed faster than most other solid organ tumors, concrete advancements in understanding the lymphoma microenvironment have been fewer. This article explores the composition of the lymphoma tumor microenvironment; its role in immune surveillance, evasion, and drug resistance; and its potential role in the development of targeted therapies.

  19. Ebstein's anomaly in neonates.

    PubMed

    Moura, C; Guimarães, H; Areias, J C; Moreira, J

    2001-09-01

    Ebstein's anomaly is a rare congenital heart disease abnormality in which the tricuspid valve leaflets do not attach normally to the tricuspid valve annulus. The effective tricuspid valve orifice is displaced apically into the right ventricle (RV), near the junction of the inlet and the trabecular parts of the RV. The authors present a retrospective study of the patients with Ebstein's anomaly admitted to a neonatal intensive care unit, in the period between January 1993 and March 2000. There were ten patients, representing 0.24% of total neonates and 1.99% of total congenital heart disease admitted to the institution in the same period. Fifty per cent were male and only one case had prenatal diagnosis. Holosystolic murmur (100%) from tricuspid regurgitation and cyanosis (80%) were the most frequent clinical findings. Chest X-ray was abnormal in 90% of the neonates, with a "balloon-shaped" enlarged heart. The main electrocardiographic findings were right atrial enlargement (70%) and arrhythmias (40%). Apical displacement of the septal leaflet of the tricuspid valve, to a maximum of 20 mm, and leaflets tethering to underlying RV myocardium were found in all patients. Tricuspid valve regurgitation was found in 90% (severe form in four cases). An atrial intracardiac shunt, mostly right-to-left, was also found in 50%. Digoxin was used (40%) to restore sinus rhythm. Fifty per cent of the neonates received intravenous prostaglandins. Two patients required a surgical procedure. Two patients died in the neonatal period. During the follow-up period (range 0.3-74.6 months), only one episode of supraventricular tachycardia was recorded. At present seven patients are clinically stable, three of them on medication.

  20. Improved Endpoints for Cancer Immunotherapy Trials

    PubMed Central

    Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

    2010-01-01

    Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

  1. Numerical simulation of a mathematical model of combination of immunotherapy and chemotherapy of cancer

    NASA Astrophysics Data System (ADS)

    Wei, Hsiu-Chuan; Hwang, Shin-Feng; Chen, Yuh-Yih; Chen, Tze-Jang

    2013-10-01

    In this study, a mathematical model of tumor growth with a combination of immunotherapy and chemotherapy is considered. A numerical simulation using human data in clinical literature is conducted. A numerical method based on the continuation technique is employed to locate the unstable fixed-point curve as the dosage varies. A combination of chemotherapy and immunotherapy can employ low dosages of drugs. The effect of the combined dosages is also investigated in this work.

  2. Rapid Eye Movement Sleep Behavior Disorder in Paraneoplastic Cerebellar Degeneration: Improvement with Immunotherapy

    PubMed Central

    Vale, Thiago Cardoso; Fernandes do Prado, Lucila Bizari; do Prado, Gilmar Fernandes; Povoas Barsottini, Orlando Graziani; Pedroso, José Luiz

    2016-01-01

    Study Objectives: To report two female patients with paraneoplastic cerebellar degeneration (PCD) related to breast cancer that presented with rapid eye movement-sleep behavior disorder (RBD) and improved sleep symptoms with immunotherapy. Methods: The two patients were evaluated through clinical scale and polysomnography before and after therapy with intravenous immunoglobulin. Results: RBD was successfully treated with immunotherapy in both patients. Score on the RBD screening questionnaire dropped from 10 to 1 or 0, allied with the normalization of polysomnographic findings. Conclusions: A marked improvement in RBD after immunotherapy in PCD raises the hypothesis that secondary RBD may be an immune-mediated sleep disorder. Citation: Vale TC, do Prado LB, do Prado GF, Barsottini OG, Pedroso JL. Rapid eye movement sleep behavior disorder in paraneoplastic cerebellar degeneration: improvement with immunotherapy. SLEEP 2016;39(1):117–120. PMID:26414894

  3. Co-stimulation with TNF receptor superfamily 4/25 antibodies enhances in-vivo expansion of CD4+CD25+Foxp3+ T cells (Tregs) in a mouse study for active DNA Aβ42 immunotherapy.

    PubMed

    Lambracht-Washington, Doris; Rosenberg, Roger N

    2015-01-15

    The study was designed to test DNA Aβ42 immunization in mice as alternative approach for possible active immunotherapy in Alzheimer patients. As results, we found polarized Th2 immune responses, efficient Aβ42 antibody levels, and disappearance of antigen specific T cells. In-vivo TNFRSF4/25 antibody co-stimulation enhanced Aβ42 specific T cell responses with initial Th2 expansion and subsequent development of Aβ42 specific CD4+CD25+Foxp3+ cells. It showed that Th2 biased responses due to gene gun immunizations propagate the development of regulatory T cells. In conclusion, full-length DNA Aβ42 immunization into skin results in a regulatory response with minimal risk of inflammation and autoimmunity. PMID:25595257

  4. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    SciTech Connect

    Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin

    2010-10-22

    Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed

  5. Case study of a high-risk neonate failing to thrive post-extracorporeal membrane oxygenation and post-necrotizing enterocolitis.

    PubMed

    Bishop, G C; Lobo, M L

    1994-06-01

    Infants discharged from neonatal intensive care units (NICUs) often face a long journey of chronic illness, family stresses, and financial burdens. Health care professionals involved in acute care need to be aware of the far-reaching repercussions of neonatal illness. This report presents a case study of a low-income, single mother from a rural community and her son, a neonatal intensive care unit (NICU) graduate post-extracorporeal membrane oxygenation (ECMO) and post-necrotizing enterocolitis (NEC) discharged with a gastronomy tube (g-tube) and failure to thrive (FTT), from his birth to 10 months of age. Family-focused interventions aimed at improving growth and developmental delays and providing family support will be discussed.

  6. Nanochemistry-based immunotherapy for HIV-1.

    PubMed

    Lori, F; Calarota, S A; Lisziewicz, J

    2007-01-01

    Highly active antiretroviral treatment (HAART), i.e. the combination of three or more drugs against human immunodeficiency virus type 1 (HIV-1), has greatly improved the clinical outcome of HIV-1-infected individuals. However, HAART is unable to reconstitute HIV-specific immunity and eradicate the virus. Several observations in primate models and in humans support the notion that cell-mediated immunity can control viral replication and slow disease progression. Thus, besides drugs, an immunotherapy that induces long-lasting HIV-specific T-cell responses could play a role in the treatment of HIV/AIDS. To induce such immune responses, DermaVir Patch has been developed. DermaVir consists of an HIV-1 antigen-encoding plasmid DNA that is chemically formulated in a nanoparticle. DermaVir is administered under a patch after a skin preparation that supports the delivery of the nanoparticle to Langerhans cells (LC). Epidermal LC trap and transport the nanomedicine to draining lymph nodes. While in transit, LC mature into dendritic cells (DC), which can efficiently present the DNA-encoded antigens to naïve T-cells for the induction of cellular immunity. Pre-clinical studies and Phase I clinical testing of DermaVir in HIV-1-infected individuals have demonstrated the safety and tolerability of DermaVir Patch. To further modulate cellular immunity, molecular adjuvants might be added into the nanoparticle. DermaVir Patch represents a new nanomedicine platform for immunotherapy of HIV/AIDS. In this review, the antiviral activity of DermaVir-induced cellular immunity is discussed. Furthermore, the action of some cytokines currently being tested as adjuvants are highlighted and the adjuvant effect of cytokine plasmid DNA included in the DermaVir nanoparticle is reviewed.

  7. Immunotherapy and chemotherapy in children with neuroblastoma.

    PubMed

    Nesbit, M E; Kersey, J; Finklestein, J; Weiner, J; Simmons, R

    1976-09-01

    Recent advances with immunotherapy in animal tumors suggested that trials with a combination of chemotherapy and immunotherapy in human malignant tumors might be worthwhile. A pilot program with Vibrio cholera neuraminidase-treated tumor cells plus BCG was tested in 3 patients who had had chemotherapy for disseminated neuroblastoma. Two of these children were in "complete remission" after radiation therapy and chemotherapy before the administration of immunotherapy. Relapse occurred in 5-6 months in all 3 patients. These disappointing results are discussed in relation to problems of current chemotherapy in disseminated neuroblastoma including results obtained at second-look operations in patients obtaining "complete remission."

  8. Rationale for combining immunotherapy with chemotherapy.

    PubMed

    Dalgleish, Angus G

    2015-01-01

    Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.

  9. Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms.

    PubMed

    Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F

    2016-04-14

    Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy. PMID:26888257

  10. Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms.

    PubMed

    Lykken, Jacquelyn M; Horikawa, Mayuka; Minard-Colin, Veronique; Kamata, Masahiro; Miyagaki, Tomomitsu; Poe, Jonathan C; Tedder, Thomas F

    2016-04-14

    Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal-1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy.

  11. A bacteriological study of the environment of pediatric ward and neonatal nursery.

    PubMed

    Shekhawat, P S; Singh, R N; Shekhawat, R; Joshi, K R

    1992-03-01

    The hospital environment is full of pathogens which may cause nosocomial infections. A bacteriological survey of hospital air, floor, water, milk and fomites was done. The air survey showed large number of bacteria carrying particles in air. A direct relation between floor area per person and bacterial contamination of air was established. The floor survey showed that there is abundance of bacteria on the hospital floors, much more than the accepted fair standards of house keeping. The hospital water had a high coliform and total bacterial count and stored tank water was more dirty. Neonatal nursery milk also had high total bacterial and coliform counts. Regular surveillance of hospital environment may help to reduce the incidence of cross infection.

  12. Prescribing of psychiatric medication to bereaved parents following perinatal/neonatal death: an observational study.

    PubMed

    Lacasse, Jeffrey R; Cacciatore, Joanne

    2014-01-01

    To examine psychiatric prescribing in response to perinatal/neonatal death, we analyzed data from a cross-sectional survey of 235 bereaved parents participating in an online support community. Of the 88 respondents prescribed medication, antidepressants were most common (n = 70, 79.5%) followed by benzodiazepines/sleep aids (n = 18, 20.5%). Many prescriptions were written shortly after the death (32.2% within 48 hr, 43.7% within a week, and 74.7% within a month). Obstetrician/gynecologists wrote most prescriptions given shortly after loss. Most respondents prescribed antidepressants took them long-term. This sample is select, but these data raise disturbing questions about prescribing practices for grieving parents. PMID:24588074

  13. An enzyme histochemical study of large muscle fibres in the neonatal mouse.

    PubMed Central

    Christie, K N; Stewart, R J; Bacciocchi, G

    1990-01-01

    Small clusters of extra large muscle fibres were identified in hindlimb muscles of neonatal mice (strain C57BL/10ScSn). At two days of age they had a significantly greater cross-sectional area than their normal counterparts (P less than 0.01). Fibre typing methods (NADH-tetrazolium reductase, ATPase and phosphorylase) classified them as 2A fast oxidative glycolytic (FOG fibres). The activity of NADH-tetrazolium reductase and the lysosomal enzymes beta-glucuronidase, acid phosphatase and dipeptidyl peptidase II were all elevated in the large fibres. Microsomal aminopeptidase (mAPP), a membrane-bound enzyme, also showed increased activity. The fibres are probably the mouse equivalent of the Wohlfart B fibres of the human fetus, with which comparison is made. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Figs. 9-10 PMID:2254160

  14. Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

    PubMed Central

    Tiller, Heidi; Kamphuis, Marije M; Flodmark, Olof; Papadogiannakis, Nikos; David, Anna L; Sainio, Susanna; Koskinen, Sinikka; Javela, Kaija; Wikman, Agneta Taune; Kekomaki, Riitta; Kanhai, Humphrey H H; Oepkes, Dick; Husebekk, Anne; Westgren, Magnus

    2013-01-01

    Objective To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. Design Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010. Setting 13 tertiary referral centres from nine countries across the world. Participants 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. Primary and secondary outcome measures Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. Results From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. Conclusions ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester. PMID:23524102

  15. Effects of surgery, immunization, and laser immunotherapy on a non-immunogenic metastic tumor model

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Huang, Zheng; Andrienko, Kirill; Stefanov, Stefan; Wolf, Roman F.; Liu, Hong

    2006-08-01

    Traditional local cancer treatment modalities include surgery and radiation, which has the immediate tumor response due to tumor removal or radiation induced cell death. However, such therapeutic approaches usually do not result in eradiation of tumors, particularly when treating metastatic tumors. In fact, local treatment of primary tumors may stimulate the growth and spread of remote metastasis. Commonly used systemic therapies include chemotherapy and immunotherapy, which target the dividing cells or the immune systems. However, in addition to the severe side effects, chemotherapy often suppresses the immune systems, hence lessening the host's ability to fight the disease. Immunotherapy, on the other hand, aims at educating and stimulating immune systems using either general immune enhancements or antigen-oriented specific immune stimulation. However, so far, the traditional immunotherapy has yielded only limited success in treating cancer patients. A different approach is needed. To combine the advantages of both local therapies for acute and targeted treatment responses and the systemic therapies for stimulation of the immune systems, laser immunotherapy was proposed to use selective photothermal therapy as the local treatment modality and the adjuvant-assisted immunotherapy for systemic control. Laser immunotherapy has show positive results in treating metastatic tumors. In this study, we conducted a comparative study using surgery, freeze-thaw immunization and laser immunotherapy in the treatment of metastatic rat mammary tumors. Our results showed that removal of the primary tumors was unsuccessful at changing the course of tumor progression. The tumor cell lysate immunization delayed the emergence of metastases but did not provide immunity against the tumor challenge. Laser immunotherapy, on the other hand, resulted in regression and eradication.

  16. Immunotherapy

    MedlinePlus

    ... Information Specialist Financial Support Online Chats Support Groups Peer-to-Peer Support LLS Community Blogs Caregiver Support Other Helpful ... Information Specialist Financial Support Online Chats Support Groups Peer-to-Peer Support LLS Community Blogs Caregiver Support ...

  17. Immunotherapy. Neuroblastoma as a model.

    PubMed

    Cheung, N K

    1991-04-01

    Combinations of aggressive therapy and radiotherapy directed at the primary tumor site as well as dose intensive chemotherapy against metastases can effectively induce complete remissions in patients with stage IV neuroblastomas. By virtue of its tumor specificity, the use of immunotherapy at the time when microscopic residual disease is present holds great promise in eradicating the tumors permanently. Monoclonal antibodies can accumulate selectively and at high concentrations in neuroblastomas. They have the potential of initiating complement activation and inflammation at the tumor site. Hematopoietic factors and cytokines can reinforce the body with tumoricidal leukocytes. Ex vivo activation of autologous white cells as well as arming by genetic manipulation can also produce tumor-seeking vehicles that may be therapeutically useful. As the knowledge of tumor and host immunobiology accumulates, the optimal combination of these approaches will become apparent.

  18. New treatments for allergen immunotherapy.

    PubMed

    Akdis, Mübeccel

    2014-01-01

    Allergen-specific immunotherapy (SIT) represents the only curative and specific way for the treatment of allergic diseases, which have reached a pandemic dimension in industrial countries affecting up to 20-30% of the population. Although applied for 100 years to cure allergy, SIT still faces several problems related to side effects and limited efficacy. Currently, allergen-SIT is performed with vaccines based on allergen extracts that can cause severe, often life threatening, anaphylactic reactions as well as new IgE sensitization to other allergens present in the extract. Low patient adherence and high costs due to long duration (3 to 5 years) of treatment have been commonly reported. Several strategies have been developed to tackle these issues and it became possible to produce recombinant allergen-SIT vaccines with reduced allergenic activity.

  19. New treatments for allergen immunotherapy

    PubMed Central

    2014-01-01

    Allergen-specific immunotherapy (SIT) represents the only curative and specific way for the treatment of allergic diseases, which have reached a pandemic dimension in industrial countries affecting up to 20-30% of the population. Although applied for 100 years to cure allergy, SIT still faces several problems related to side effects and limited efficacy. Currently, allergen-SIT is performed with vaccines based on allergen extracts that can cause severe, often life threatening, anaphylactic reactions as well as new IgE sensitization to other allergens present in the extract. Low patient adherence and high costs due to long duration (3 to 5 years) of treatment have been commonly reported. Several strategies have been developed to tackle these issues and it became possible to produce recombinant allergen-SIT vaccines with reduced allergenic activity. PMID:25258656

  20. Topical Immunotherapy in Alopecia Areata

    PubMed Central

    Singh, Gurcharan; Lavanya, MS

    2010-01-01

    Alopecia Areata (AA) is a common non-scarring alopecia directed against the anagenic hair follicle. Various treatment modalities have been used for the treatment of severe AA. Topical immunotherapy is the best documented treatment so far for severe and refractory AA. Dinitrochlorobenzene (DNCB), squaric acid dibutylester (SADBE), and diphencyprone (DPCP) are the contact allergens used for this purpose. DNCB has been found to be mutagenic by the Ames test and is largely replaced by DPCP and SADBE. DPCP and SADBE are both known to be non-mutagenic compounds and have comparable efficacy results and relapse rates. SADBE requires special solvents and additives to maintain its potency and is more expensive than the rest. DPCP has a response rate varying from 60% in severe Alopecia Areata to 17% in patients with alopecia totalis or universalis, and shows about 88 to 100% high response rate in patients with patchy Alopecia Areata. PMID:21188022

  1. [Current immunotherapy of multiple sclerosis].

    PubMed

    Paul, F; Ruprecht, K

    2015-08-01

    Following the introduction of interferon beta 1b as the first immunomodulatory therapy for multiple sclerosis (MS) in 1993, there are currently nine substances or substance classes approved for the treatment of MS (i.e. alemtuzumab, azathioprine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab and teriflunomide). Major developments during the last 5 years include the approval of orally administered medications (i.e. fingolimod, teriflunomide and dimethyl fumarate), a monoclonal antibody (alemtuzumab), as well as glatiramer acetate with an administration frequency three times a week and a pegylated formulation of interferon beta 1a. The broadened therapeutic options enable a more differentiated and individualized therapy of MS; however, evidence-based data for therapeutic decision-making relevant in clinical practice are not always available. Rare but potentially severe and even life-threatening side effects of immunotherapies for MS require continuous pharmacovigilance and adherence to risk management plans. PMID:26253589

  2. Trends in Prevalence and Characteristics of Post-Neonatal Cerebral Palsy Cases: A European Registry-Based Study

    ERIC Educational Resources Information Center

    Germany, Laurence; Ehlinger, Virginie; Klapouszczak, Dana; Delobel, Malika; Hollody, Katalin; Sellier, Elodie; De La Cruz, Javier; Alberge, Corine; Genolini, Christophe; Arnaud, Catherine

    2013-01-01

    The present paper aims to analyze trends over time in prevalence of cerebral palsy of post-neonatal origin, to investigate whether changes are similar according to severity and to describe the disability profile by etiology. Post-neonatal cases, birth years 1976 to 1998, were identified from the Surveillance of Cerebral Palsy in Europe…

  3. Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges.

    PubMed

    Cynis, Holger; Frost, Jeffrey L; Crehan, Helen; Lemere, Cynthia A

    2016-01-01

    Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer's disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer's patients is challenging. In recent years, a number of promising Aβ immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of Aβ peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 Aβ peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches. PMID:27363697

  4. Neonatal lupus.

    PubMed

    Robles, David T; Jaramillo, Lorena; Hornung, Robin L

    2006-12-10

    An otherwise healthy 5-week-old infant with erythematous plaques predominantly on the face and scalp presented to our dermatology clinic. The mother had been diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent. Neonatal lupus is a rare condition associated with transplacental transfer of IgG anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus. Active connective tissue disease in the mother does not have to be present and in fact is often absent. Although the cutaneous, hematologic and hepatic manifestations are transient, the potential for permanent heart block makes it necessary for this to be carefully ruled out. As in this case, the dermatologist may be the one to make the diagnosis and should be aware of the clinical presentation, work-up, and management of this important disease.

  5. Who Will Benefit from Cancer Immunotherapy?

    Cancer.gov

    Researchers have identified a “genetic signature” in the tumors of patients with advanced melanoma who responded to a form of immunotherapy called checkpoint blockade. The results could be the basis for a test that identifies likely responders.

  6. Immunotherapy: Disrupting the Cancer Treatment World

    MedlinePlus

    ... ACS » + - Text Size Immunotherapy: Disrupting the Cancer Treatment World By Elizabeth Mendes June 16, 2014 This story ... of cancer research in depth. The cancer research world is dedicating increasing energy to a rapidly evolving ...

  7. New types of immunotherapy in children.

    PubMed

    Rodríguez-Pérez, Noel; Penagos, Martin; Portnoy, Jay M

    2008-11-01

    Injection immunotherapy has been shown to be particularly beneficial in treating allergic rhinitis, mild to moderate asthma, and anaphylaxis caused by bee and wasp venom. It also produces a long-term, antigen-specific, protective immune effect and is the only treatment that offers the possibility of reducing the risk of asthma development in children with allergic rhinitis. Nonetheless, the potentially severe side effects associated with this form of immunotherapy limit its widespread use. Diverse preparations are being developed to increase its safety and improve its efficacy. These include alternative routes of administration, particularly the sublingual route; use of novel adjuvants, such as CpG oligonucleotides and mycobacterial vaccines; and other approaches, such as peptide immunotherapy, recombinant allergens, DNA vaccination, and combined therapy. Some of these immunotherapy forms have been evaluated in children.

  8. PROSTVAC® targeted immunotherapy candidate for prostate cancer.

    PubMed

    Shore, Neal D

    2014-01-01

    Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

  9. Perceptions, practices, and traditional beliefs related to neonatal jaundice among Egyptian mothers: A cross-sectional descriptive study.

    PubMed

    Moawad, Eman Mohamed Ibraheim; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim

    2016-09-01

    Neonatal jaundice (NNJ) is one of the most common neonatal disorders worldwide. It is still a main cause of avoidable brain damage, physical and mental impairment, and probable death in newborns.We aimed to assess perceptions, practices, and traditional beliefs among Egyptian mothers toward NNJ that may contribute to delayed presentation and inappropriate management of hyperbilirubinemia.This descriptive, cross-sectional study was conducted from January to May 2015. We interviewed 400 Egyptian mothers who gave birth in <1 month before the study using a structured questionnaire. Participants were recruited from outpatients of Cairo University Teaching Hospital.This study revealed unexpected moderate knowledge and attitude scores of Egyptian mothers in most domains with a mean of 6.6 and 20.6, respectively, although the majority of them were illiterate or had low educational attainment. In terms of knowledge, 52.3% of participants had adequate knowledge about NNJ in the aspects of awareness, risk factors, management, and complications. Almost all participants exhibited moderate (89.8%) and high levels (10%) of positive attitudes toward NNJ. Maternal sociodemographic factors influenced knowledge level, attitudes, and behaviors related to NNJ in Egypt. Working mothers and those residing in urban areas were significantly more knowledgeable (P = 0.023 and 0.021, respectively), and attained higher attitude scores (P < 0.001 and P < 0.001, respectively) than housewives and rural ones. Moreover, significantly higher attitude scores (P < 0.001) were attained by those who had completed their university [22.3 (SD = 3.1)] or postgraduate education [22.2 (SD = 3.6)].The majority of Egyptian mothers have a satisfactory level of knowledge and attitudes related to NNJ. However, cultural beliefs and traditional infant care practices still have an impact on mothers regardless of their educational level. PMID:27603393

  10. Allergen-specific immunotherapy induces Th1 shift in dogs with atopic dermatitis.

    PubMed

    Shida, Masayuki; Kadoya, Michiyo; Park, Seong-Jun; Nishifuji, Koji; Momoi, Yasuyuki; Iwasaki, Toshiroh

    2004-11-01

    Allergen-specific immunotherapy has been applied to canine atopic dermatitis. Despite the accumulated clinical evidence of its effect for atopic dogs, the basic immunologic mechanisms were not fully understood. In this study, the cytokine profile ex vivo in canine atopic dermatitis before and after allergen-specific immunotherapy was characterized using competitive reverse transcription-polymerase chain reaction (RT-PCR). Blood samples were collected from 10 dogs with atopic dermatitis and peripheral blood mononuclear cells were stimulated with house dust mite antigen. The levels of IFN-gamma and IL-4 mRNA were lower in atopic dogs compared with non-atopic controls. The ratio of IFN-gamma/IL-4 was low in atopic dogs indicating a cytokine profile polarized to Th2. The level of IFN-gamma after immunotherapy was significantly higher than that before (P < 0.05) whereas that of IL-4 mRNA was not changed. Consequently, the ratio of IFN-gamma/IL-4 after immunotherapy was significantly higher than that before immunotherapy (P < 0.05). These results indicate a Th2 cytokine bias is the dominant state in atopic dogs and allergen-specific immunotherapy causes a shift to wards a Th1 bias by enhancing IFN-gamma expression.

  11. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy.

    PubMed

    Sharabi, Andrew B; Lim, Michael; DeWeese, Theodore L; Drake, Charles G

    2015-10-01

    Checkpoint blockade immunotherapy has received mainstream attention as a result of striking and durable clinical responses in some patients with metastatic disease and a reasonable response rate in many tumour types. The activity of checkpoint blockade immunotherapy is not restricted to melanoma or lung cancer, and additional indications are expected in the future, with responses already reported in renal cancer, bladder cancer, and Hodgkin's lymphoma among many others. Additionally, the interactions between radiation and the immune system have been investigated, with several studies describing the synergistic effects on local and distant tumour control when radiation therapy is combined with immunotherapy. Clinical enthusiasm for this approach is strengthened by the many ongoing trials combining immunotherapy with definitive and palliative radiation. Herein, we discuss the biological and mechanistic rationale behind combining radiation with checkpoint blockade immunotherapy, with a focus on the preclinical data supporting this potentially synergistic combination. We explore potential hypotheses and important considerations for clinical trial designs. Finally, we reintroduce the notion of radiosensitising immunotherapy, akin to radiosensitising chemotherapy, as a potential definitive therapeutic modality.

  12. Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research.

    PubMed

    Fitchett, Elizabeth J A; Seale, Anna C; Vergnano, Stefania; Sharland, Michael; Heath, Paul T; Saha, Samir K; Agarwal, Ramesh; Ayede, Adejumoke I; Bhutta, Zulfiqar A; Black, Robert; Bojang, Kalifa; Campbell, Harry; Cousens, Simon; Darmstadt, Gary L; Madhi, Shabir A; Meulen, Ajoke Sobanjo-Ter; Modi, Neena; Patterson, Janna; Qazi, Shamim; Schrag, Stephanie J; Stoll, Barbara J; Wall, Stephen N; Wammanda, Robinson D; Lawn, Joy E

    2016-10-01

    Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.

  13. The value of in vitro studies in a case of neonatal diabetes with a novel Kir6.2-W68G mutation

    PubMed Central

    O'Connell, Susan M; Proks, Peter; Kramer, Holger; Mattis, Katia K; Sachse, Gregor; Joyce, Caroline; Houghton, Jayne A L; Ellard, Sian; Hattersley, Andrew T; Ashcroft, Frances M; O'Riordan, Stephen M P

    2015-01-01

    Key Clinical Message In infants, especially with novel previously undescribed mutations of the KATP channel causing neonatal diabetes, in vitro studies can be used to both predict the response to sulphonylurea treatment and support a second trial of glibenclamide at higher than standard doses if the expected response is not observed. PMID:26509030

  14. Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research.

    PubMed

    Fitchett, Elizabeth J A; Seale, Anna C; Vergnano, Stefania; Sharland, Michael; Heath, Paul T; Saha, Samir K; Agarwal, Ramesh; Ayede, Adejumoke I; Bhutta, Zulfiqar A; Black, Robert; Bojang, Kalifa; Campbell, Harry; Cousens, Simon; Darmstadt, Gary L; Madhi, Shabir A; Meulen, Ajoke Sobanjo-Ter; Modi, Neena; Patterson, Janna; Qazi, Shamim; Schrag, Stephanie J; Stoll, Barbara J; Wall, Stephen N; Wammanda, Robinson D; Lawn, Joy E

    2016-10-01

    Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines. PMID:27633910

  15. Cancer Immunotherapy: A Treatment for the Masses

    NASA Astrophysics Data System (ADS)

    Blattman, Joseph N.; Greenberg, Philip D.

    2004-07-01

    Cancer immunotherapy attempts to harness the exquisite power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is clearly capable of recognizing and eliminating tumor cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for immunotherapy is to use advances in cellular and molecular immunology to develop strategies that effectively and safely augment antitumor responses.

  16. Is immunotherapy an opportunity for effective treatment of drug addiction?

    PubMed

    Zalewska-Kaszubska, Jadwiga

    2015-11-27

    Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. PMID:26432911

  17. Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study

    PubMed Central

    Lee, Shoo K.; Shah, Prakesh S.; Singhal, Nalini; Aziz, Khalid; Synnes, Anne; McMillan, Douglas; Seshia, Mary M.

    2014-01-01

    Background: We previously demonstrated improvement in bronchopulmonary dysplasia and nosocomial infection among preterm infants at 12 neonatal units using the Evidence-based Practice for Improving Quality (EPIQ). In the current study, we assessed the association of Canada-wide implementation of EPIQ with mortality and morbidity among preterm infants less than 29 weeks gestational age. Methods: This prospective cohort study included 6026 infants admitted to 25 Canadian units between 2008 and 2012 (baseline year, n = 1422; year 1, n = 1611; year 2, n = 1508; year 3, n = 1485). Following a 1-year baseline period and 6 months of training and planning, EPIQ was implemented over 3 years. Our primary outcome was a composite of neonatal mortality and any of bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity, necrotizing enterocolitis and nosocomial infection. We compared outcomes for baseline and year 3 using multivariable analyses. Results: In adjusted analyses comparing baseline with year 3, the composite outcome (70% v. 65%; adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51 to 0.79), severe retinopathy (17% v. 13%; OR 0.60, 95% CI 0.45 to 0.79), necrotizing enterocolitis (10% v. 8%; OR 0.73, 95% CI 0.52 to 0.98) and nosocomial infections (32% v. 24%; OR 0.63, 95% CI 0.48 to 0.82) were significantly reduced. The composite outcome was lower among infants born at 26 to 28 weeks gestation (62% v. 52%; OR 0.62, 95% CI 0.49 to 0.78) but not among infants born at less than 26 weeks gestational age (90% v. 88%; OR 0.73, 95% CI 0.44 to 1.20). Interpretation: EPIQ methodology was generalizable within Canada and was associated with significantly lower likelihood of the composite outcome, severe retinopathy, necrotizing enterocolitis and nosocomial infections. Infants born at 26 to 28 weeks gestational age benefited the most. PMID:25135927

  18. Developments in immunotherapy for gastrointestinal cancer.

    PubMed

    Diaz, J L; Wanta, S M; Fishbein, T M; Kroemer, A

    2015-08-01

    Gastrointestinal (GI) cancers are the most commonly occurring cancer worldwide. Colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. Despite the advent of screening and the declining incidence of CRC overall, most patients are not diagnosed at an early, localized stage. Due to resistance to chemotherapy, recurrence, and metastatic disease, those diagnosed with advanced disease have only a 12% 5-year survival rate. Given the overwhelming global impact of CRC, the need for advanced therapy is crucial. Targeted immunotherapy in addition to surgical resection, traditional chemotherapy, and radiation therapy is on the rise. For the purpose of this review, we focused on the advances of immunotherapy, particularly in CRC, with mention of research pertaining to particular advances in immunotherapy for other aspects of the GI system. We review basic immunology and the microenvironment surrounding colorectal tumors that lead to immune system evasion and poor responses to chemotherapy. We also examined the way these obstacles are proving to be the targets of tumor specific immunotherapy. We will present current FDA approved immunotherapies such as monoclonal antibodies (mAb) targeting tumor specific antigens, as well as vaccines, adoptive cell therapy, cytokines, and check-point inhibitors. A summation of prior research, current clinical trials, and prospective therapies in murine models help delineate our current status and future strategies on CRC immunotherapy.

  19. Oncolytic Immunotherapy for Treatment of Cancer.

    PubMed

    Tsun, A; Miao, X N; Wang, C M; Yu, D C

    2016-01-01

    Immunotherapy entails the treatment of disease by modulation of the immune system. As detailed in the previous chapters, the different modes of achieving immune modulation are many, including the use of small/large molecules, cellular therapy, and radiation. Oncolytic viruses that can specifically attack, replicate within, and destroy tumors represent one of the most promising classes of agents for cancer immunotherapy (recently termed as oncolytic immunotherapy). The notion of oncolytic immunotherapy is considered as the way in which virus-induced tumor cell death (known as immunogenic cancer cell death (ICD)) allows the immune system to recognize tumor cells and provide long-lasting antitumor immunity. Both immune responses toward the virus and ICD together contribute toward successful antitumor efficacy. What is now becoming increasingly clear is that monotherapies, through any of the modalities detailed in this book, are neither sufficient in eradicating tumors nor in providing long-lasting antitumor immune responses and that combination therapies may deliver enhanced efficacy. After the rise of the genetic engineering era, it has been possible to engineer viruses to harbor combination-like characteristics to enhance their potency in cancer immunotherapy. This chapter provides a historical background on oncolytic virotherapy and its future application in cancer immunotherapy, especially as a combination therapy with other treatment modalities.

  20. Cancer-associated fibroblasts as targets for immunotherapy.

    PubMed

    Kakarla, Sunitha; Song, Xiao-Tong; Gottschalk, Stephen

    2012-11-01

    Immunotherapy for solid tumors has shown promise in preclinical as well as early clinical studies. However, its efficacy remains limited. The hindrance to achieving objective, long-lasting therapeutic responses in solid tumors is, in part, mediated by the dynamic nature of the tumor and its complex microenvironment. Tumor-directed therapies fail to eliminate components of the microenvironment, which can reinstate a tumorigenic milieu and contribute to recurrence. Cancer-associated fibroblasts (CAFs) form the most preponderant cell type in the solid tumor microenvironment. Given their pervasive role in facilitating tumor growth and metastatic dissemination, CAFs have emerged as attractive therapeutic targets in the tumor microenvironment. In this article, we highlight the cross-talk between CAFs and cancer cells, and discuss how targeting CAFs has the potential to improve current immunotherapy approaches for cancer.

  1. 24-h Langendorff-perfused neonatal rat heart used to study the impact of adenoviral gene transfer.

    PubMed

    Wiechert, S; El-Armouche, A; Rau, T; Zimmermann, W-H; Eschenhagen, T

    2003-08-01

    The human genome project has increased the demand for simple experimental systems that allow the impact of gene manipulations to be studied under controlled ex vivo conditions. We hypothesized that, in contrast to adult hearts, neonatal hearts allow long-term perfusion and efficient gene transfer ex vivo. A Langendorff perfusion system was modified to allow perfusion for >24 h with particular emphasis on uncompromised contractile activity, sterility, online measurement of force of contraction, inotropic response to beta-adrenergic stimulation, and efficient gene transfer. The hearts were perfused with serum-free medium (DMEM + medium 199, 4 + 1) supplemented with hydrocortisone, triiodothyronine, ascorbic acid, insulin, pyruvate, l-carnitine, creatine, taurine, l-glutamine, mannitol, and antibiotics recirculating (500 ml/2 hearts) at 1 ml/min. Hearts from 2 day-old rats beat constantly at 135-155 beats/min and developed active force of 1-2 mN. During 24 h of perfusion, twitch tension increased to approximately 165% of initial values (P < 0.05), whereas the inotropic response to isoprenaline remained constant. A decrease in total protein content of 10% and histological examination indicated moderate edema, but actin and calsequestrin concentration remained unchanged and perfusion pressure remained constant at 7-11 mmHg. Perfusion with a LacZ-encoding adenovirus at 3 x 108 active virus particles yielded homogeneous transfection of approximately 80% throughout the heart and did not affect heart rate, force of contraction, or response to isoprenaline compared with uninfected controls (n = 7 each). Taken together, the 24-h Langendorff-perfused neonatal rat heart is a relatively simple, inexpensive, and robust new heart model that appears feasible as a test bed for functional genomics.

  2. Neonate human remains: a window of opportunity to the molecular study of ancient syphilis.

    PubMed

    Montiel, Rafael; Solórzano, Eduvigis; Díaz, Nancy; Álvarez-Sandoval, Brenda A; González-Ruiz, Mercedes; Cañadas, Mari Pau; Simões, Nelson; Isidro, Albert; Malgosa, Assumpció

    2012-01-01

    Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of "La Ermita de la Soledad" (XVI-XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals. PMID:22567153

  3. Neonate Human Remains: A Window of Opportunity to the Molecular Study of Ancient Syphilis

    PubMed Central

    Montiel, Rafael; Solórzano, Eduvigis; Díaz, Nancy; Álvarez-Sandoval, Brenda A.; González-Ruiz, Mercedes; Cañadas, Mari Pau; Simões, Nelson; Isidro, Albert; Malgosa, Assumpció

    2012-01-01

    Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of “La Ermita de la Soledad” (XVI–XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals. PMID:22567153

  4. Neonatal hemodynamic response to visual cortex activity: high-density near-infrared spectroscopy study

    NASA Astrophysics Data System (ADS)

    Liao, Steve M.; Gregg, Nick M.; White, Brian R.; Zeff, Benjamin W.; Bjerkaas, Katelin A.; Inder, Terrie E.; Culver, Joseph P.

    2010-03-01

    The neurodevelopmental outcome of neonatal intensive care unit (NICU) infants is a major clinical concern with many infants displaying neurobehavioral deficits in childhood. Functional neuroimaging may provide early recognition of neural deficits in high-risk infants. Near-infrared spectroscopy (NIRS) has the advantage of providing functional neuroimaging in infants at the bedside. However, limitations in traditional NIRS have included contamination from superficial vascular dynamics in the scalp. Furthermore, controversy exists over the nature of normal vascular, responses in infants. To address these issues, we extend the use of novel high-density NIRS arrays with multiple source-detector distances and a superficial signal regression technique to infants. Evaluations of healthy term-born infants within the first three days of life are performed without sedation using a visual stimulus. We find that the regression technique significantly improves brain activation signal quality. Furthermore, in six out of eight infants, both oxy- and total hemoglobin increases while deoxyhemoglobin decreases, suggesting that, at term, the neurovascular coupling in the visual cortex is similar to that found in healthy adults. These results demonstrate the feasibility of using high-density NIRS arrays in infants to improve signal quality through superficial signal regression, and provide a foundation for further development of high-density NIRS as a clinical tool.

  5. Recent advances in immunotherapy and vaccine development for peanut allergy

    PubMed Central

    2015-01-01

    Peanut allergy is a common problem and can be the cause of severe, life-threatening allergic reactions. It rarely resolves, with the majority of patients carrying the disease onto adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion, but is also due to dietary and social restrictions. Current standard management involves avoidance, patient education and provision of emergency medication, for use in allergic reactions, when they occur. Efforts have been made to develop a vaccine for peanut allergy. Recent developments have also highlighted the use of immunotherapy, which has shown promise as an active form of treatment and may present a disease-modifying therapy for peanut allergy. So far, results, especially from oral immunotherapy studies, have shown good efficacy in achieving desensitization to peanut with a good safety profile. However, the capacity to induce long-term tolerance has not been demonstrated conclusively yet and larger, phase III studies are required to further investigate safety and efficacy of this intervention. Peanut immunotherapy is not currently recommended for routine clinical use or outside specialist allergy units. PMID:26288733

  6. Can Alzheimer disease be prevented by amyloid-β immunotherapy?

    PubMed Central

    Lemere, Cynthia A.; Masliah, Eliezer

    2010-01-01

    Alzheimer disease (AD) is the most common form of dementia. The amyloid-β (Aβ) peptide has become a major therapeutic target in AD on the basis of pathological, biochemical and genetic evidence that supports a role for this molecule in the disease process. Active and passive Aβ immunotherapies have been shown to lower cerebral Aβ levels and improve cognition in animal models of AD. In humans, dosing in the phase II clinical trial of the AN1792 Aβ vaccine was stopped when ~6% of the immunized patients developed meningoencephalitis. However, some plaque clearance and modest clinical improvements were observed in patients following immunization. As a result of this study, at least seven passive Aβ immunotherapies are now in clinical trials in patients with mild to moderate AD. Several second-generation active Aβ vaccines are also in early clinical trials. On the basis of preclinical studies and the limited data from clinical trials, Aβ immunotherapy might be most effective in preventing or slowing the progression of AD when patients are immunized before or in the very earliest stages of disease onset. Biomarkers for AD and imaging technology have improved greatly over the past 10 years and, in the future, might be used to identify presymptomatic, at-risk individuals who might benefit from Aβ immunization. PMID:20140000

  7. Recent advances in immunotherapy and vaccine development for peanut allergy.

    PubMed

    Anagnostou, Katherine

    2015-05-01

    Peanut allergy is a common problem and can be the cause of severe, life-threatening allergic reactions. It rarely resolves, with the majority of patients carrying the disease onto adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion, but is also due to dietary and social restrictions. Current standard management involves avoidance, patient education and provision of emergency medication, for use in allergic reactions, when they occur. Efforts have been made to develop a vaccine for peanut allergy. Recent developments have also highlighted the use of immunotherapy, which has shown promise as an active form of treatment and may present a disease-modifying therapy for peanut allergy. So far, results, especially from oral immunotherapy studies, have shown good efficacy in achieving desensitization to peanut with a good safety profile. However, the capacity to induce long-term tolerance has not been demonstrated conclusively yet and larger, phase III studies are required to further investigate safety and efficacy of this intervention. Peanut immunotherapy is not currently recommended for routine clinical use or outside specialist allergy units. PMID:26288733

  8. Cancer immunotherapy out of the gate: the 22nd annual Cancer Research Institute International Immunotherapy Symposium.

    PubMed

    Tontonoz, Matthew; Gee, Connie E

    2015-05-01

    The 22nd annual Cancer Research Institute (CRI) International Immunotherapy Symposium was held from October 5-8, 2014, in New York City. Titled "Cancer Immunotherapy: Out of the Gate," the symposium began with a Cancer Immunotherapy Consortium satellite meeting focused on issues in immunotherapy drug development, followed by five speaker sessions and a poster session devoted to basic and clinical cancer immunology research. The second annual William B. Coley lecture was delivered by Lieping Chen, one of the four recipients of the 2014 William B. Coley Award for Distinguished Research in Tumor Immunology; the other three recipients were Gordon Freeman, Tasuku Honjo, and Arlene Sharpe. Prominent themes of the conference were the use of genomic technologies to identify neoantigens and the emergence of new immune modulatory molecules, beyond CTLA-4 and PD-1/PD-L1, as new therapeutic targets for immunotherapy.

  9. Cancer immunotherapy out of the gate: the 22nd annual Cancer Research Institute International Immunotherapy Symposium.

    PubMed

    Tontonoz, Matthew; Gee, Connie E

    2015-05-01

    The 22nd annual Cancer Research Institute (CRI) International Immunotherapy Symposium was held from October 5-8, 2014, in New York City. Titled "Cancer Immunotherapy: Out of the Gate," the symposium began with a Cancer Immunotherapy Consortium satellite meeting focused on issues in immunotherapy drug development, followed by five speaker sessions and a poster session devoted to basic and clinical cancer immunology research. The second annual William B. Coley lecture was delivered by Lieping Chen, one of the four recipients of the 2014 William B. Coley Award for Distinguished Research in Tumor Immunology; the other three recipients were Gordon Freeman, Tasuku Honjo, and Arlene Sharpe. Prominent themes of the conference were the use of genomic technologies to identify neoantigens and the emergence of new immune modulatory molecules, beyond CTLA-4 and PD-1/PD-L1, as new therapeutic targets for immunotherapy. PMID:25941356

  10. Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study.

    PubMed

    Klingebiel, T; Bader, P; Bares, R; Beck, J; Hero, B; Jürgens, H; Lang, P; Niethammer, D; Rath, B; Handgretinger, R

    1998-08-01

    Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.

  11. Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy.

    PubMed

    Pilon-Thomas, Shari; Kodumudi, Krithika N; El-Kenawi, Asmaa E; Russell, Shonagh; Weber, Amy M; Luddy, Kimberly; Damaghi, Mehdi; Wojtkowiak, Jonathan W; Mulé, James J; Ibrahim-Hashim, Arig; Gillies, Robert J

    2016-03-15

    Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation. PMID:26719539

  12. Targeting NK Cells for Anticancer Immunotherapy: Clinical and Preclinical Approaches

    PubMed Central

    Carotta, Sebastian

    2016-01-01

    The recent success of checkpoint blockade has highlighted the potential of immunotherapy approaches for cancer treatment. Although the majority of approved immunotherapy drugs target T cell subsets, it is appreciated that other components of the immune system have important roles in tumor immune surveillance as well and thus represent promising additional targets for immunotherapy. Natural killer (NK) cells are the body’s first line of defense against infected or transformed cells, as they kill target cells in an antigen-independent manner. Although several studies have clearly demonstrated the active role of NK cells in cancer immune surveillance, only few clinically approved therapies currently exist that harness their potential. Our increased understanding of NK cell biology over the past few years has renewed the interest in NK cell-based anticancer therapies, which has lead to a steady increase of NK cell-based clinical and preclinical trials. Here, the role of NK cells in cancer immune surveillance is summarized, and several novel approaches to enhance NK cell cytotoxicity against cancer are discussed. PMID:27148271

  13. A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

    PubMed Central

    2010-01-01

    Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales. PMID:20843320

  14. Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy.

    PubMed

    Pilon-Thomas, Shari; Kodumudi, Krithika N; El-Kenawi, Asmaa E; Russell, Shonagh; Weber, Amy M; Luddy, Kimberly; Damaghi, Mehdi; Wojtkowiak, Jonathan W; Mulé, James J; Ibrahim-Hashim, Arig; Gillies, Robert J

    2016-03-15

    Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation.

  15. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    SciTech Connect

    Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  16. De-Risking Immunotherapy: Report of a Consensus Workshop of the Cancer Immunotherapy Consortium of the Cancer Research Institute.

    PubMed

    Mellman, Ira; Hubbard-Lucey, Vanessa M; Tontonoz, Matthew J; Kalos, Michael D; Chen, Daniel S; Allison, James P; Drake, Charles G; Levitsky, Hy; Lonberg, Nils; van der Burg, Sjoerd H; Fearon, Douglas T; Wherry, E John; Lowy, Israel; Vonderheide, Robert H; Hwu, Patrick

    2016-04-01

    With the recent FDA approvals of pembrolizumab and nivolumab, and a host of additional immunomodulatory agents entering clinical development each year, the field of cancer immunotherapy is changing rapidly. Strategies that can assist researchers in choosing the most promising drugs and drug combinations to move forward through clinical development are badly needed in order to reduce the likelihood of late-stage clinical trial failures. On October 5, 2014, the Cancer Immunotherapy Consortium of the Cancer Research Institute, a collaborative think tank composed of stakeholders from academia, industry, regulatory agencies, and patient interest groups, met to discuss strategies for de-risking immunotherapy development, with a focus on integrating preclinical and clinical studies, and conducting smarter early-phase trials, particularly for combination therapies. Several recommendations were made, including making better use of clinical data to inform preclinical research, obtaining adequate tissues for biomarker studies, and choosing appropriate clinical trial endpoints to identify promising drug candidates and combinations in nonrandomized early-phase trials.

  17. Efficacy of early neonatal vitamin A supplementation in reducing mortality during infancy in Ghana, India and Tanzania: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo. Methods/Design The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrolment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation. Discussion The three ongoing studies are the largest studies evaluating the

  18. The safety of self-administered allergen immunotherapy during the buildup and maintenance phases

    PubMed Central

    Schaffer, Frederick M.; Naples, Andrew R.; Ebeling, Myla; Hulsey, Thomas C.; Garner, Larry M.

    2015-01-01

    Background Self-administered allergen immunotherapy is considered controversial. We believe the implementation of a self-administration protocol characterized by patient preselection and a slow buildup phase is safe. Methods We analyzed 23,614 patient records and associated immunotherapy injections for systemic reactions (SR) during a 1-year period (2011 to 2012). SRs were graded in accordance with the World Allergy Organization (WAO) criteria. Results Thirty-seven SRs were reported for 23,614 patients who self-administered 2,021,600 injections yielding an annual SR rate of 0.16% (per patient) or 0.002% (per injection). Only 9 of 4643 pediatric (0.19%) and 28 of 18,971 adult patients (0.15%) experienced 1 or more SRs. No deaths (grade V SR) occurred. From 2009 through early 2014, over 90,000 patients received more than 10 million injections in accordance with the United Allergy Services (UAS) protocol without fatalities. Conclusion We believe this safety profile is due to a preselection of patients to exclude those with a high risk for adverse reactions and a slow immunotherapy buildup phase. In contrast, previous studies documented office-based SRs ranging from approximately 3% to greater than 14%. Thus, the UAS home-immunotherapy SR rate is significantly lower than office-based immunotherapy SR rates (p < 0.0001). The enhanced safety of this protocol results in a decreased frequency and severity of SRs. This safety report, derived from analyses of one of the largest patient cohorts studied, corroborates and expands the observations of previous studies of self-administered subcutaneous immunotherapy in a low-risk patient population by assessing self-administered allergen immunotherapy during the buildup and maintenance phases. PMID:25476041

  19. New routes for allergen immunotherapy

    PubMed Central

    Johansen, Pål; von Moos, Seraina; Mohanan, Deepa; Kündig, Thomas M.; Senti, Gabriela

    2012-01-01

    IgE-mediated allergy is a highly prevalent disease in the industrialized world. Allergen-specific immunotherapy (SIT) should be the preferred treatment, as it has long lasting protective effects and can stop the progression of the disease. However, few allergic patients choose to undergo SIT, due to the long treatment time and potential allergic adverse events. Since the beneficial effects of SIT are mediated by antigen presenting cells inducing Th1, Treg and antibody responses, whereas the adverse events are caused by mast cells and basophils, the therapeutic window of SIT may be widened by targeting tissues rich in antigen presenting cells. Lymph nodes and the epidermis contain high density of dendritic cells and low numbers of mast cells and basophils. The epidermis has the added benefit of not being vascularised thereby reducing the chances of anaphylactic shock due to leakage of allergen. Hence, both these tissues represent highly promising routes for SIT and are the focus of discussion in this review. PMID:23095873

  20. International consensus on allergy immunotherapy.

    PubMed

    Jutel, Marek; Agache, Ioana; Bonini, Sergio; Burks, A Wesley; Calderon, Moises; Canonica, Walter; Cox, Linda; Demoly, Pascal; Frew, Antony J; O'Hehir, Robin; Kleine-Tebbe, Jörg; Muraro, Antonella; Lack, Gideon; Larenas, Désirée; Levin, Michael; Nelson, Harald; Pawankar, Ruby; Pfaar, Oliver; van Ree, Ronald; Sampson, Hugh; Santos, Alexandra F; Du Toit, George; Werfel, Thomas; Gerth van Wijk, Roy; Zhang, Luo; Akdis, Cezmi A

    2015-09-01

    Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the World Allergy Organization, has decided to issue an international consensus on AIT.

  1. Melanoma immunotherapy dominates the field.

    PubMed

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  2. Melanoma immunotherapy dominates the field

    PubMed Central

    Diamantopoulos, Panagiotis

    2016-01-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  3. Immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G

    2005-09-01

    Immunotherapeutic strategies have become part of standard cancer treatment. Chimeric and humanized antibodies have demonstrated activity against a variety of tumors. Although the humanized anti-CD33 antibody HuM195 has only modest activity against overt acute myeloid leukemia (AML), it can eliminate minimal residual disease in acute promyelocytic leukemia. High-dose radioimmunotherapy with b-particle-emitting isotopes targeting CD33, CD45, and CD66 can potentially allow intensification of antileukemic therapy before hematopoietic stem cell transplantation. Conversely, a-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumor cell kill while sparing surrounding normal tissues. Targeted chemotherapy with the anti-CD33- calicheamicin construct gemtuzumab ozogamicin has produced remissions in relapsed AML and appears promising when used in combination with standard chemotherapy for newly diagnosed AML. T-cell recognition of peptide antigens presented on the cell surface in combination with major histocompatibility complex antigen provides another potentially promising approach for the treatment of AML. PMID:16091194

  4. A burden of knowledge: A qualitative study of experiences of neonatal intensive care nurses' concerns when keeping information from parents.

    PubMed

    Green, Janet; Darbyshire, Philip; Adams, Anne; Jackson, Debra

    2015-12-01

    Improved life-sustaining technology in the neonatal intensive care has resulted in an increased probability of survival for extremely premature babies. In the neonatal intensive care, the condition of a baby can deteriorate rapidly. Nurses and parents are together for long periods at the bedside and so form close and trusting relationships. Neonatal nurses as the constant caregivers may be presented with contradictory demands in attempting to meet the baby's needs and being a patient and family advocate. This article aims to explore the issues arising for neonatal nurses when holding information about changes to a condition of a baby that they are unable to share with parents. Data were collected via interviews with 24 neonatal nurses in New South Wales, Australia. A qualitative approach was used to analyse the data. The theme 'keeping secrets' was identified and comprised of three sub-themes 'coping with potentially catastrophic news', 'fear of inadvertent disclosure' and 'a burden that could damage trust'. Keeping secrets and withholding information creates internal conflict in the nurses as they balance the principle of confidentiality with the parent's right to know information. The neonatal nurses experienced guilt and shame when they were felt forced by circumstances to keep secrets or withhold information from the parents of extremely premature babies.

  5. Neonatal clinical screening of the hip in the diagnosis of developmental dysplasia of the hip: a 15-year prospective longitudinal observational study.

    PubMed

    Mace, J; Paton, R W

    2015-02-01

    Over a 15-year prospective period, 201 infants with a clinically unstable hip at neonatal screening were subsequently reviewed in a 'one stop' clinic where they were assessed clinically and sonographically. Their mean age was 1.62 weeks (95% confidence interval (CI) 1.35 to 1.89). Clinical neonatal hip screening revealed a sensitivity of 62% (mean, 62.6 95%CI 50.9 to 74.3), specificity of 99.8% (mean, 99.8, 95% CI 99.7 to 99.8) and positive predictive value (PPV) of 24% (mean, 26.2, 95% CI 19.3 to 33.0). Static and dynamic sonography for Graf type IV dysplastic hips had a 15-year sensitivity of 77% (mean, 75.8 95% CI 66.9 to 84.6), specificity of 99.8% (mean, 99.8, 95% CI 99.8 to 99.8) and a PPV of 49% (mean, 55.1, 95% CI 41.6 to 68.5). There were 36 infants with an irreducible dislocation of the hip (0.57 per 1000 live births), including six that failed to resolve with neonatal splintage. Most clinically unstable hips referred to a specialist clinic are female and stabilise spontaneously. Most irreducible dislocations are not identified from this neonatal instability group. There may be a small subgroup of females with instability of the hip which may be at risk of progression to irreducibility despite early treatment in a Pavlik harness. A controlled study is required to assess the value of neonatal clinical screening programmes. PMID:25628293

  6. Influence of sublingual immunotherapy on the expression of Mac-1 integrin in neutrophils from asthmatic children.

    PubMed

    Ciepiela, Olga; Zawadzka-Krajewska, Anna; Kotula, Iwona; Pyrzak, Beata; Demkow, Urszula

    2013-01-01

    Asthma can be effectively treated with sublingual immunotherapy. The influence of -sublingual immunotherapy on the function of granulocytes in asthmatic patients is largely unknown. Mac-1 integrin is a transmembrane protein containing α (CD11b) and β (CD18) chains. High expression of the complex is found on the surface of neutrophils, NK cells, and macrophages. CD11b/CD18 may bind to CD23, ICAM-1, ICAM-2, and ICAM-4. It plays a crucial role in diapedesis of neutrophils. The aim of the present study was to assess Mac-1 expression on neutrophils from asthmatic children before and after sublingual immunotherapy. Twenty five children aged of 8.1 ± 3.1 suffering from atopic asthma and allergic rhinitis, shortlisted for specific immunotherapy, served as the study group. Fifteen healthy individuals, aged 9.8 ± 3.4, served as a control group. The assessment of CD11b and CD18 expression on cells from peripheral blood was performed with a flow cytometer. The tests were performed before and after 12 months of sublingual immunotherapy. In the asthmatic children, 98.08 (90.79-99.12)% of Mac-1 positive neutrophils were detected. The group was divided into two subgroups: of more than 98% and less than 95% of neutrophils with CD11b/CD18 expression in the sample. After immunotherapy, the percentage of Mac-1 positive granulocytes increased to 99.60 (99.29-99.68)%, p = 0.01. In the control group, 90.56 (87.08-88.86)% granulocytes were Mac-1 positive, p = 0.002. We conclude that sublingual immunotherapy strongly influences the function of the immunological system, including Mac-1 expression on neutrophils.

  7. Advances in the understanding of cancer immunotherapy.

    PubMed

    Shore, Neal D

    2015-09-01

    The principal role of the immune system is to prevent and eradicate pathogens and infections. The key characteristics or features of an effective immune response include specificity, trafficking, antigen spread and durability (memory). The immune system is recognised to have a critical role in controlling cancer through a dynamic relationship with tumour cells. Normally, at the early stages of tumour development, the immune system is capable of eliminating tumour cells or keeping tumour growth abated; however, tumour cells may evolve multiple pathways over time to evade immune control. Immunotherapy may be viewed as a treatment designed to boost or restore the ability of the immune system to fight cancer, infections and other diseases. Immunotherapy manifests differently from traditional cancer treatments, eliciting delayed response kinetics and thus may be more effective in patients with lower tumour burden, in whom disease progression may be less rapid, thereby allowing ample time for the immunotherapy to evolve. Because immunotherapies may have a different mechanism of action from traditional cytotoxic or targeted biological agents, immunotherapy techniques have the potential to combine synergistically with traditional therapies.

  8. Immunotherapy for Alzheimer’s Disease

    PubMed Central

    Morgan, Dave

    2010-01-01

    Summary In 1999 a vaccine approach was found to reduce amyloid deposits in transgenic mice overproducing the amyloid precursor protein. This was followed closely by demonstrations that vaccines or passive immunotherapy could rescue memory deficits in these mice. Initial human clinical trials revealed apparent autoimmune reactions in a subset of patients, but also some cases of cognitive benefit and amyloid clearance. Further work with passive immunotherapy in mouse models confirmed exceptional clearing abilities of anti-amyloid antibodies even in older mice. However, in parallel with parenchymal amyloid clearance was the appearance of microhemorrhages and increased vascular amyloid deposition. Additional clinical trials with passive immunotherapy confirmed occasional appearance of microhemorrhage and occurrence of vasogenic edema in some patients, particularly those with the apolipoprotein E4 genotype. Recent data with positron emission tomography demonstrates trial participants passively immunized with anti-Aβ antibodies have reduced signals with amyloid binding ligands after 18 mo of therapy. Several anti-Aβ immunotherapies have reached phase 3 testing and immunotherapy is likely to be the first test of the amyloid hypothesis of Alzheimer’s disease. Identifying antibody variants that retain amyloid clearance with fewer adverse reactions remains a major focus of translational research in this area. PMID:21158978

  9. Neonatal lupus.

    PubMed

    Brucato, Antonio; Cimaz, Rolando; Stramba-Badiale, Marco

    2002-12-01

    Congenital heart block (CHB), defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0-27 d after birth), is a rare disorder closely linked to transplacental transport of maternal antibodies anti-Ro/SSA and anti-La/SSB. These antibodies may induce a myocarditis, or interact directly with calcium channel proteins with disturbance of transmembrane signaling at the level of the conduction tissue, or interfere with apoptosis. Depending on the severity of the process, the fetus may die in utero or a few days after birth or survive to the perinatal period and have a near-normal life; in most survivors a pace-maker must be implanted. Skin lesions, haematological disorders, and hepatic cholestasis are other transient clinical features of the syndrome. Sinus bradycardia and QT interval prolongation may be observed as well in babies born from anti-Ro/SSA positive mothers. The risk of recurrence of complete block ranges from 10-17%. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Their long-term outcome generally is more reassuring than previously assumed and arthralgias and dry eyes are the most common symptoms. A standard therapy for blocks detected in utero still does not exist. The prevalence of complete CHB in newborns of anti-Ro/SSA positive women and with known connective-tissue disease was 2%. Serial echocardiograms and obstetric sonograms, performed at least every 2 wk starting from the 16 wk gestation, are recommended in anti-Ro/SSA positive pregnant women.

  10. To explore the neonatal nurses' beliefs and attitudes towards caring for dying neonates in Taiwan.

    PubMed

    Chen, Chao-Huei; Huang, Li-Chi; Liu, Hsin-Li; Lee, Ho-Yu; Wu, Shu-Ya; Chang, Yue-Cune; Peng, Niang-Huei

    2013-12-01

    (1) To explore attitudes and beliefs of neonatal nurses toward nursing care for dying neonates; (2) to estimate the influence of neonatal nurses' personal and professional characteristics on their attitudes towards end-of life care for dying infants. A cross-sectional design was used. A questionnaire was used to collect data from 80 neonatal nurses. Research setting was four level III NICUs at four medical centers around the central region of Taiwan. Research participants were neonatal nurses who had worked for at least 1 year in one of level III NICUs and had been directly involved with the care of dying infants. Research participants were 80 neonatal nurses (response rate 100 %). Research findings identified eight barriers hindering neonatal palliative care practice. These barriers were insufficient communication due to the lack of an in-service educational program; the lack of available counseling help for neonatal clinicians; inability to express personal opinions, values and beliefs towards neonatal palliative care; insufficient staffing; the lack of unit policies/guidelines for supporting palliative care; the technological imperative; parental demands and personal beliefs about death and previous experience caring for dying infants. Further studies are needed to explore each barrier and to provide in-service neonatal palliative care educational programs that are needed to decrease these barriers.

  11. Driving an improved CAR for cancer immunotherapy.

    PubMed

    Huang, Xiaopei; Yang, Yiping

    2016-08-01

    The recent clinical success of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies represents a paradigm shift in cancer immunotherapy. Unfortunately, application of CAR T cell-mediated therapy for solid tumors has so far been disappointing, and the reasons for this poor response in solid tumors remain unknown. In this issue of the JCI, Cherkassky and colleagues report on their use of a murine model of human pleural mesothelioma to explore potential factors that limit CAR T cell efficacy. Their studies have uncovered the importance of the tumor microenvironment in the inhibition of CAR T cell functions, revealed a critical role for the programmed death-1 (PD-1) pathway in CAR T cell exhaustion within the tumor microenvironment, and demonstrated improved antitumor effects with a CAR T cell-intrinsic PD-1 blockade strategy using a dominant negative form of PD-1. Together, the results of this study lay the groundwork for further evaluation of mechanisms underlying CAR T cell immune evasion within the tumor microenvironment for the improvement of CAR T cell-mediated therapy for solid tumors.

  12. Driving an improved CAR for cancer immunotherapy.

    PubMed

    Huang, Xiaopei; Yang, Yiping

    2016-08-01

    The recent clinical success of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies represents a paradigm shift in cancer immunotherapy. Unfortunately, application of CAR T cell-mediated therapy for solid tumors has so far been disappointing, and the reasons for this poor response in solid tumors remain unknown. In this issue of the JCI, Cherkassky and colleagues report on their use of a murine model of human pleural mesothelioma to explore potential factors that limit CAR T cell efficacy. Their studies have uncovered the importance of the tumor microenvironment in the inhibition of CAR T cell functions, revealed a critical role for the programmed death-1 (PD-1) pathway in CAR T cell exhaustion within the tumor microenvironment, and demonstrated improved antitumor effects with a CAR T cell-intrinsic PD-1 blockade strategy using a dominant negative form of PD-1. Together, the results of this study lay the groundwork for further evaluation of mechanisms underlying CAR T cell immune evasion within the tumor microenvironment for the improvement of CAR T cell-mediated therapy for solid tumors. PMID:27454296

  13. Individual Differences and Auditory Conditioning in Neonates.

    ERIC Educational Resources Information Center

    Franz, W. K.; And Others

    The purposes of this study are (1) to analyze learning ability in newborns using heart rate responses to auditory temporal conditioning and (2) to correlate these with measures on the Brazelton Neonatal Behavioral Assessment Scale. Twenty normal neonates were tested using the Brazelton Scale on the third day of life. They were also given a…

  14. The Application of Natural Killer Cell Immunotherapy for the Treatment of Cancer

    PubMed Central

    Rezvani, Katayoun; Rouce, Rayne H.

    2015-01-01

    Natural killer (NK) cells are essential components of the innate immune system and play a critical role in host immunity against cancer. Recent progress in our understanding of NK cell immunobiology has paved the way for novel NK cell-based therapeutic strategies for the treatment of cancer. In this review, we will focus on recent advances in the field of NK cell immunotherapy, including augmentation of antibody-dependent cellular cytotoxicity, manipulation of receptor-mediated activation, and adoptive immunotherapy with ex vivo-expanded, chimeric antigen receptor (CAR)-engineered, or engager-modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack non-hematopoietic tissues, suggesting that an NK-mediated antitumor effect can be achieved in the absence of graft-vs.-host disease. Despite reports of clinical efficacy, a number of factors limit the application of NK cell immunotherapy for the treatment of cancer, such as the failure of infused NK cells to expand and persist in vivo. Therefore, efforts to enhance the therapeutic benefit of NK cell-based immunotherapy by developing strategies to manipulate the NK cell product, host factors, and tumor targets are the subject of intense research. In the preclinical setting, genetic engineering of NK cells to express CARs to redirect their antitumor specificity has shown significant promise. Given the short lifespan and potent cytolytic function of mature NK cells, they are attractive candidate effector cells to express CARs for adoptive immunotherapies. Another innovative approach to redirect NK cytotoxicity towards tumor cells is to create either bispecific or trispecific antibodies, thus augmenting cytotoxicity against tumor-associated antigens. These are exciting times for the study of NK cells; with recent advances in the field of NK cell biology and translational research, it is likely that NK cell immunotherapy will move to the forefront of cancer immunotherapy over the next few years. PMID

  15. Immunotherapy decreases seasonal rise in serum-soluble CD23 in seasonal allergic rhinitis.

    PubMed

    Ohashi, Y; Nakai, Y; Tanaka, A; Kakinoki, Y; Ohno, Y; Masamoto, T; Sakamoto, H; Kato, A; Washio, Y; Hayashi, M

    1998-05-01

    There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating IgE synthesis, but the in vivo physiologic significance remains to be established. This study investigated the seasonal changes in sCD23 in patients with seasonal allergic rhinitis. It included 112 adult patients with seasonal allergic rhinitis due to Japanese cedar pollens and 20 nonatopic healthy volunteers. The 64 patients of the pharmacotherapy group were treated with nonsedating antihistamine tablets alone throughout the pollen season and the remaining 48 patients of the immunotherapy group continued to be treated with immunotherapy. Serum concentrations of sCD23 were measured in each patient, before and during the pollen season of 1996, by a sandwich enzyme-linked immunosorbent assay. The serum levels of sCD23 in the pharmacotherapy group before the pollen season were significantly higher than those in the nonatopic group (P = .0130) and those in the immunotherapy group (P = .0316). Seasonal increase in sCD23 was significant in the pharmacotherapy group, irrespective of the clinical response (P < .0001). By contrast, sCD23 was not significantly increased in the good responders to immunotherapy (P = .1826), but was significantly increased in the poor responders to immunotherapy (P = .0052). A significant correlation between seasonal increase in rate in specific IgE and seasonal increase in rate in sCD23 was confirmed in both the pharmacotherapy group (rs = 0.321, P = .0107) and the immunotherapy group (rs = 0.474, P = .0012). In conclusion, seasonal rise in sCD23 is associated with and is probably involved in seasonal rise in specific IgE in patients with seasonal allergic rhinitis, and successful immunotherapy is capable of blunting seasonal increase in sCD23, thus resulting in attenuation of seasonal increase in specific IgE and clinical benefits during the pollen season. PMID:9591550

  16. The Obstacles against Nurse-Family Communication in Family-Centered Care in Neonatal Intensive Care Unit: a Qualitative Study

    PubMed Central

    Hadian Shirazi, Zahra; Sharif, Farkhondeh; Rakhshan, Mahnaz; Pishva, Narjes; Jahanpour, Faezeh

    2015-01-01

    Introduction: Communication is one of the key principles in Family-Centered Care (FCC). Studies have shown some drawbacks in communication between families and nurses. Therefore, the present study aimed to recognize the obstacles against nurse-family communication in FCC in Neonatal Intensive Care Unit (NICU). Methods: This qualitative study was conducted on 8 staff nurses in 2 NICUs affiliated to Shiraz University of Medical Sciences selected through purposive sampling. The data were collected using 8 deep semi-structured interviews and 3 observations. Then, they were analyzed through inductive content analysis. Results: Data analysis resulted in identification of 3 main categories and 7 subcategories. The first category was organizational factors with 2 subcategories of educational domain (inadequate education, lack of a system for nursing student selection, and poor professionalization) and clinical domain (difficult working conditions, lack of an efficient system for ongoing education and evaluation, and authoritarian management). The second category was familial factors with socio-cultural, psychological, and economic subcategories. The last category was the factors related to nurses with socio-cultural and psycho-physical subcategories. Conclusion: Identification of the obstacles against nurse-family communication helps managers of healthcare systems to plan and eliminate the challenges of effective communication. Besides, elimination of these factors leads to appropriate strategies in NICUs for effective application of FCC. PMID:26464837

  17. Cancer Immunotherapy for Gliomas: Overview and Future Directions.

    PubMed

    Hashimoto, Naoya

    2016-07-15

    Immunotherapy has been highlighted because we have obtained much evidence, which includes theoretical backborn as well as favorable results from clinical trials. As immunotherapy gives an apparently different cytotoxic mechanism and a little adverse event, the promising results are getting a lot of attention. In this article, cancer immunotherapy for gliomas is reviewed thoroughly from the literature, focusing on the clinical trial results.

  18. Review: Assessment of completeness of reporting in intervention studies using livestock: an example from pain mitigation interventions in neonatal piglets.

    PubMed

    O'Connor, A; Anthony, R; Bergamasco, L; Coetzee, J F; Dzikamunhenga, R S; Johnson, A K; Karriker, L A; Marchant-Forde, J N; Martineau, G P; Millman, S T; Pajor, E A; Rutherford, K; Sprague, M; Sutherland, M A; von Borell, E; Webb, S R

    2016-04-01

    Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.

  19. Status of Neonatal Pain Assessment and Management in Jordan.

    PubMed

    Abdel Razeq, Nadin M; Akuma, Akuma O; Jordan, Sue

    2016-08-01

    Current pain assessment and management in neonates need to be fully described before neonatal pain care can be optimized. This study's purpose was to report neonatal nurses' knowledge, existing pain assessment practice, and pharmacological pain management of neonates in Jordan. A cross-sectional descriptive study was conducted. Eighteen neonatal intensive care units in Jordan were included in the study. One hundred eighty-four neonatal nurses participated. Questionnaires were distributed by and returned to the neonatal intensive care units' managers between June and August 2014. Descriptive and inferential statistics were used to present study results. Of 240 questionnaires distributed, 184 useable responses were returned. Nurses' knowledge regarding neonates' neurological development, nociception, and need for neonatal pain management was suboptimal. The analgesics most commonly used to treat neonatal pain were acetaminophen (52%) and lidocaine (45%). Benzodiazepines, phenobarbitone, and muscles relaxants were also used. Most nurses (54%-97%) reported that pain emanating from most painful procedures was never or rarely treated. Circumcision, lumbar punctures, and chest tube insertion were assigned the highest pain scores (≥9), but were rarely accompanied by analgesia. Pain assessment scales were more likely to be used, and procedural pain was more likely to be treated, in private hospitals than public hospitals. Neonates who require special care still suffer unnecessary pain that could be avoided and managed by following best practice recommendations. Disparities between developed and developing countries in quality of neonatal pain care appear to exist. Resources for education and routine care are needed to address these discrepancies.

  20. Status of Neonatal Pain Assessment and Management in Jordan.

    PubMed

    Abdel Razeq, Nadin M; Akuma, Akuma O; Jordan, Sue

    2016-08-01

    Current pain assessment and management in neonates need to be fully described before neonatal pain care can be optimized. This study's purpose was to report neonatal nurses' knowledge, existing pain assessment practice, and pharmacological pain management of neonates in Jordan. A cross-sectional descriptive study was conducted. Eighteen neonatal intensive care units in Jordan were included in the study. One hundred eighty-four neonatal nurses participated. Questionnaires were distributed by and returned to the neonatal intensive care units' managers between June and August 2014. Descriptive and inferential statistics were used to present study results. Of 240 questionnaires distributed, 184 useable responses were returned. Nurses' knowledge regarding neonates' neurological development, nociception, and need for neonatal pain management was suboptimal. The analgesics most commonly used to treat neonatal pain were acetaminophen (52%) and lidocaine (45%). Benzodiazepines, phenobarbitone, and muscles relaxants were also used. Most nurses (54%-97%) reported that pain emanating from most painful procedures was never or rarely treated. Circumcision, lumbar punctures, and chest tube insertion were assigned the highest pain scores (≥9), but were rarely accompanied by analgesia. Pain assessment scales were more likely to be used, and procedural pain was more likely to be treated, in private hospitals than public hospitals. Neonates who require special care still suffer unnecessary pain that could be avoided and managed by following best practice recommendations. Disparities between developed and developing countries in quality of neonatal pain care appear to exist. Resources for education and routine care are needed to address these discrepancies. PMID:27108085

  1. The effects of severe iron-deficiency anaemia on maternal and neonatal outcomes: A case-control study in an inner-city London hospital.

    PubMed

    Luis, J; Fadel, M G; Lau, G Y; Houssein, S; Ravikumar, N; Yoong, W

    2016-05-01

    This case-control study investigates the effects of severe iron-deficiency anaemia in pregnancy on maternal and neonatal outcomes in a relatively deprived inner-city population in a North London hospital. The study group comprised of 106 women with haemoglobin (Hb) < 8 g/dl at any point during pregnancy, while controls were 106 women with Hb > 11 g/dl throughout pregnancy. The study group lost an average of 80 ml more blood at delivery (p = 0.032) and had higher rates of postpartum haemorrhage than the control group (27 vs 12 patients, p = 0.012). However, anaemia did not appear to influence other maternal or neonatal outcomes; these may have been confounded by antenatal intervention with oral haematinics or blood transfusion.

  2. Development of Novel Immunotherapies for Multiple Myeloma

    PubMed Central

    Al-Hujaily, Ensaf M.; Oldham, Robyn A. A.; Hari, Parameswaran; Medin, Jeffrey A.

    2016-01-01

    Multiple myeloma (MM) is a disorder of terminally differentiated plasma cells characterized by clonal expansion in the bone marrow (BM). It is the second-most common hematologic malignancy. Despite significant advances in therapeutic strategies, MM remains a predominantly incurable disease emphasizing the need for the development of new treatment regimens. Immunotherapy is a promising treatment modality to circumvent challenges in the management of MM. Many novel immunotherapy strategies, such as adoptive cell therapy and monoclonal antibodies, are currently under investigation in clinical trials, with some already demonstrating a positive impact on patient survival. In this review, we will summarize the current standards of care and discuss major new approaches in immunotherapy for MM. PMID:27618026

  3. Immunotherapy advances in uro-genital malignancies.

    PubMed

    Ratta, Raffaele; Zappasodi, Roberta; Raggi, Daniele; Grassi, Paolo; Verzoni, Elena; Necchi, Andrea; Di Nicola, Massimo; Salvioni, Roberto; de Braud, Filippo; Procopio, Giuseppe

    2016-09-01

    Immunotherapy for the treatment of cancer has made significant progresses over the last 20 years. Multiple efforts have been attempted to restore immune-mediated tumor elimination, leading to the development of several targeted immunotherapies. Data from recent clinical trials suggest that these agents might improve the prognosis of patients with advanced genito-urinary (GU) malignancies. Nivolumab has been the first immune checkpoint-inhibitor approved for pre-treated patients with metastatic renal cell carcinoma. Pembrolizumab and atezolizumab have shown promising results in both phase I and II trials in urothelial carcinoma. Brentuximab vedotin has demonstrated early signals of clinical activity and immunomodulatory effects in highly pre-treated patients with testicular germ cell tumors. In this review, we have summarized the major clinical achievements of immunotherapy in GU cancers, focusing on immune checkpoint blockade as well as the new immunomodulatory monoclonal antibodies (mAbs) under clinical evaluation for these malignancies.

  4. Development of Novel Immunotherapies for Multiple Myeloma.

    PubMed

    Al-Hujaily, Ensaf M; Oldham, Robyn A A; Hari, Parameswaran; Medin, Jeffrey A

    2016-01-01

    Multiple myeloma (MM) is a disorder of terminally differentiated plasma cells characterized by clonal expansion in the bone marrow (BM). It is the second-most common hematologic malignancy. Despite significant advances in therapeutic strategies, MM remains a predominantly incurable disease emphasizing the need for the development of new treatment regimens. Immunotherapy is a promising treatment modality to circumvent challenges in the management of MM. Many novel immunotherapy strategies, such as adoptive cell therapy and monoclonal antibodies, are currently under investigation in clinical trials, with some already demonstrating a positive impact on patient survival. In this review, we will summarize the current standards of care and discuss major new approaches in immunotherapy for MM. PMID:27618026

  5. Immunotherapy in prostate cancer: challenges and opportunities.

    PubMed

    Noguchi, Masanori; Koga, Noriko; Moriya, Fukuko; Itoh, Kyogo

    2016-01-01

    Although treatment options for castration-resistant prostate cancer (CRPC) have increased over the last decade, there remains a need for strategies that can provide durable disease control and long-term benefit. Recently, immunotherapy has emerged as a viable and attractive strategy for the treatment of CRPC. To date, there are multiple strategies to target the immune system, and several approaches including therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in clinical trials. With regard to this, we report the results of the most recent clinical trials investigating immunotherapy in CRPC and discuss the future development of immunotherapy for CRPC, as well as the potential importance of biomarkers in the future progress of this field.

  6. Clinical and Immunological Changes of Immunotherapy in Patients with Atopic Dermatitis: Randomized Controlled Trial

    PubMed Central

    Sánchez Caraballo, Jorge Mario; Cardona Villa, Ricardo

    2012-01-01

    Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients. PMID:23724240

  7. Immunotherapy in acute arsenic poisoning.

    PubMed

    Leikin, J B; Goldman-Leikin, R E; Evans, M A; Wiener, S; Hryhorczuk, D O

    1991-01-01

    We investigated the use of immunotherapy on the treatment of sodium arsenite toxicity. Female balb/c mice injected with arsanilic acid conjugated to a carrier protein (ovalbumin) were shown to produce antibodies (arsenic reactive serum, ARS) reactive with arsanilic acid and sodium arsenite. Serum was tested for anti-ARS antibodies using a solid phase radioimmunoassay. The antisera bound to ARS conjugated to the synthetic copolymer glutamic acid60 tyrosine30 when diluted as high as 1:4096. Following multiple injections of 100 micrograms of arsanilic acid--ovalbumin compound, mortality on injection with sodium arsenite 0.87 mg/kg i.p. one week later decreased to 0 deaths in 22 pretreated mice vs 9 deaths in 29 untreated mice (31% mortality; p less than .005). No decrease in mortality was noted at higher challenges (1.15 mg/kg) of sodium arsenite. Antisera from pretreated mice was injected 0.1 cc i.p. into 12 week old female balb/c mice followed by an injection of sodium arsenite 0.87 mg/kg i.p. at 10 minutes. Again a protective effect was observed with 0 deaths in 18 mice vs eight deaths in 21 mice (38%; p less than .005). Seventeen additional mice were given an injection of 0.87 mg/kg i.p. of sodium arsenite. After 30 minutes, all mice became symptomatic whereupon antisera 0.1 cc i.p. was given. The one day mortality (2/17, 12%) was possibly lower than the combined control mortality (17/50, 34%; p less than 0.07). There was no change in mortality noted when antisera was administered to mice acutely exposed to 5 mg/kg HgCl2.

  8. Neonatal Hemophilia: A Rare Presentation

    PubMed Central

    Proença, Elisa; Godinho, Cristina; Oliveira, Dulce; Guedes, Ana; Morais, Sara; Carvalho, Carmen

    2015-01-01

    Hemophilia A is a X-linked hereditary condition that lead to decreased factor VIII activity, occurs mainly in males. Decreased factor VIII activity leads to increased risk of bleeding events. During neonatal period, diagnosis is made after post-partum bleeding complication or unexpected bleeding after medical procedures. Subgaleal hemorrhage during neonatal period is a rare, severe extracranial bleeding with high mortality and usually related to traumatic labor or coagulation disorders. Subgaleal hemorrhage complications result from massive bleeding. We present a neonate with unremarkable family history and uneventful pregnancy with a vaginal delivery with no instrumentation, presenting with severe subgaleal bleeding at 52 hours of life. Aggressive support measures were implemented and bleeding managed. The unexpected bleeding lead to a coagulation study and the diagnosis of severe hemophilia A. There were no known sequelae. This case shows a rare hemophilia presentation reflecting the importance of coagulation studies when faced with unexplained severe bleeding. PMID:26734126

  9. Combining radiotherapy and immunotherapy: A revived partnership

    SciTech Connect

    Demaria, Sandra; Bhardwaj, Nina; McBride, William H.; Formenti, Silvia C. . E-mail: silvia.formenti@med.nyu.edu

    2005-11-01

    Ionizing radiation therapy (RT) is an important local modality for the treatment of cancer. The current rationale for its use is based largely on the ability of RT to kill the cancer cells by a direct cytotoxic effect. Nevertheless, considerable evidence indicates that RT effects extend beyond the mere elimination of the more radiosensitive fraction of cancer cells present within a tumor at the time of radiation exposure. For instance, a large body of evidence is accumulating on the ability of RT to modify the tumor microenvironment and generate inflammation. This might have far-reaching consequences regarding the response of a patient to treatment, especially if radiation-induced tumor cell kill were to translate into the generation of effective antitumor immunity. Although much remains to be learned about how radiation can impact tumor immunogenicity, data from preclinical studies provide the proof of principle that different immunotherapeutic strategies can be combined with RT to enhance antitumor effects. Conversely, RT could be a useful tool to combine with immunotherapy. This article will briefly summarize what is known about the impact of RT on tumor immunity, including tumor-associated antigens, antigen-presenting cells, and effector mechanisms. In addition, the experimental evidence supporting the contention that RT can be used as a tool to induce antitumor immunity is discussed, and a new approach to radioimmunotherapy of cancer is proposed.

  10. Father’s role in supporting breastfeeding of preterm infants in the neonatal intensive care unit: a qualitative study

    PubMed Central

    Denoual, H; Dargentas, M; Roudaut, S; Balez, R; Sizun, J

    2016-01-01

    Objective To analyse the social beliefs, representations and experiences of fathers of preterm newborns (NBs) regarding breastfeeding. Design A qualitative interview study with analysis of transcripts using the Alceste software. Setting A tertiary university hospital neonatal intensive care unit (NICU) in France. Participants 20 fathers of preterm NBs hospitalised in an NICU. Results The software classified 72% of the corpus into six lexical classes. Two main networks of classes emerged from the analysis: one for lactation, consisted of ‘breastfeeding’ and ‘expression of milk’ classes, and one for ‘care’. The analysis demonstrated that fathers were sensitive to arguments related to the health benefits of human milk. Fathers mentioned that breastfeeding preterm NBs was constraining and tiring for their partners (multiple daily sessions of milk expression with breast pumps, time constraints and need for supplements to tube-feeding…). They also mentioned how they could genuinely help their partners during breastfeeding. Conclusions The results of this qualitative study provide insight into how fathers can be supportive of breastfeeding when experiencing a preterm birth. Targeted information and practical advice provided by caregivers on the first days of life can help fathers to get involved in the breastfeeding process. PMID:27338878

  11. Assessment of Intraocular Measurements in Neonatal Foals and Association with Gender, Laterality, and Body Weight: A Clinical Study

    PubMed Central

    Valentini, Simona; Castagnetti, Carolina; Musella, Vincenzo; Spinella, Giuseppe

    2014-01-01

    Objective of this study was to describe intraocular measurements in newly born foals (1–7 days of age) and assess the association between globe measurements and gender, laterality, and body weight. B-scan ultrasonographic biometry was performed on both eyes of 22 healthy foals (44 eyes) ages 1–7 days using a 10-MHz transducer. Intraocular measurements (anterior chamber depth, central lens thickness, vitreous chamber depth, axial globe length, longitudinal globe length, lens poles distance) were carried out using the ultrasound internal calipers. The influence of gender (male or female), laterality (right or left eye), and body weight (“light” <48 kg; “heavy” ≥48 kg) on ocular measurements was analysed by the Student t test. Values of P<0.05 were accepted as significant for all analyses. Mean anterior chamber depth was 2.2±0.5 mm (Standard Deviation); central lens thickness was 9.9±0.8 mm; vitreous chamber depth was 15.5±1.1 mm; axial globe length was 27.6±1.6 mm; longitudinal globe length was 35.8±1.2 mm, and lens poles distance was 16.4±1.0 mm. Intraocular measurements were not influenced by gender, laterality nor body weight. This study provides reference values for intraocular measurements in neonatal foals and may be useful in the diagnosis and treatment of congenital and acquired pathologies involving the globe. PMID:25296286

  12. Neonatal thyroid-stimulating hormone level is influenced by neonatal, maternal, and pregnancy factors.

    PubMed

    Trumpff, Caroline; Vandevijvere, Stefanie; Moreno-Reyes, Rodrigo; Vanderpas, Jean; Tafforeau, Jean; Van Oyen, Herman; De Schepper, Jean

    2015-11-01

    The percentage of newborns with a neonatal whole blood thyroid-stimulating hormone (TSH) greater than 5 mIU/L has been used as an indicator of iodine deficiency at the population level. However, TSH levels in newborns may be influenced by many factors other than iodine status. The objective of this study was to identify neonatal, maternal, and pregnancy-related determinants of neonatal TSH levels in a retrospective cohort study. The study sample included 313 Belgian mothers and their 4- to 5-year-old children. The children had a neonatal TSH concentration between 0 and 15 mIU/L at neonatal screening, and blood samples were collected 3 to 5 days after birth. Children with suspected congenital hypothyroidism (neonatal TSH level >15 mIU/L), prematurely born (i.e., <37 weeks), or with a low birth weight (i.e., <2500 g) were excluded. Information about maternal and birth-related determinants was collected from the neonatal screening center via a self-administered questionnaire filled in by the mother together with the child's health booklet. Higher TSH levels were found in spring and winter compared to summer and autumn (P = .011). Higher TSH levels were associated with lifetime smoking behavior (up to child birth) in the mother (P = .005), lower weight gain during pregnancy (P = .014), and longer pregnancies (P = .003). This study showed that several neonatal, maternal, and pregnancy-related determinants are influencing neonatal TSH level. PMID:26428622

  13. Immunotherapies: The Blockade of Inhibitory Signals

    PubMed Central

    Wu, Yan-Ling; Liang, Jing; Zhang, Wen; Tanaka, Yoshimasa; Sugiyama, Hiroshi

    2012-01-01

    T lymphocytes require signaling by the T cell receptor and by nonclonotypic cosignaling receptors. The costimulatory and inhibitory signals profoundly influence the course of immune responses by amplifying or reducing the transcriptional effects of T cell receptor triggering. The inhibitory receptors such as CTLA-4, PD-1, and BTLA have recently drawn much attention as potential targets for immunotherapies. This review focuses on the progress that has been made with the mentioned receptors in the field of immunotherapies for autoimmune diseases, malignancies, infectious diseases, and transplantation. PMID:23197939

  14. Immunotherapy for advanced melanoma: future directions.

    PubMed

    Valpione, Sara; Campana, Luca G

    2016-02-01

    As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty.

  15. The effect of multiple allergen immunotherapy on exhaled nitric oxide in adults with allergic rhinitis

    PubMed Central

    2013-01-01

    Background There is a lack of objective measures of the clinical efficacy of allergen immunotherapy which relies on patients’ perception about the effect of this treatment. We studied whether the fraction of exhaled nitric oxide is affected by multiple allergen immunotherapy in polysensitized adult subjects with allergic rhinitis. We also looked for associations between exhaled nitric oxide and subjects’ demographics, symptom scores, and pulmonary function tests. Methods Twenty adult, polysensitized subjects with seasonal and perennial allergic rhinitis who chose to undergo allergen immunotherapy were enrolled. They were evaluated at baseline, and 4, 8, 12, 24, and 52 weeks later. Exhaled nitric oxide was reported as the mean of triplicate determinations. Findings Our results indicate that multiple allergen immunotherapy did not affect exhaled nitric oxide levels and such levels did not correlate with subjects’ demographics and pulmonary function tests. However, exhaled nitric oxide was associated with rhinoconjuctivitis and asthma symptom scores at the end of the study. Conclusions In polysensitized adult subjects with allergic rhinitis, exhaled nitric oxide levels are unaffected by multiple allergen immunotherapy. PMID:23958488

  16. Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors.

    PubMed

    Lechner, Melissa G; Russell, Sarah M; Bass, Rikki S; Epstein, Alan L

    2011-11-01

    In this article, the role of chemokines and costimulatory molecules in the immunotherapy of experimental murine solid tumors and immunotherapy used in ongoing clinical trials are presented. Chemokine networks regulate physiologic cell migration that may be disrupted to inhibit antitumor immune responses or co-opted to promote tumor growth and metastasis in cancer. Recent studies highlight the potential use of chemokines in cancer immunotherapy to improve innate and adaptive cell interactions and to recruit immune effector cells into the tumor microenvironment. Another critical component of antitumor immune responses is antigen priming and activation of effector cells. Reciprocal expression and binding of costimulatory molecules and their ligands by antigen-presenting cells and naive lymphocytes ensures robust expansion, activity and survival of tumor-specific effector cells in vivo. Immunotherapy approaches using agonist antibodies or fusion proteins of immunomodulatory molecules significantly inhibit tumor growth and boost cell-mediated immunity. To localize immune stimulation to the tumor site, a series of fusion proteins consisting of a tumor-targeting monoclonal antibody directed against tumor necrosis and chemokines or costimulatory molecules were generated and tested in tumor-bearing mice. While several of these reagents were initially shown to have therapeutic value, combination therapies with methods to delete suppressor cells had the greatest effect on tumor growth. In conclusion, a key conclusion that has emerged from these studies is that successful immunotherapy will require both advanced methods of immunostimulation and the removal of immunosuppression in the host.

  17. Role of miR-146a in Enforcing Effect of Specific Immunotherapy on Allergic Rhinitis.

    PubMed

    Liu, Hong-Jun; Zhang, Ai-Fen; Zhao, Na; Li, Xue-Zhong

    2016-01-01

    Allergic rhinitis (AR) is one of the common disorders in airway allergic inflammation. The pathogenesis of AR is unclear. It is accepted that immune deregulation is associated with the pathogenesis of AR. Recent reports suggest that a large number of micro RNAs (miR) can regulate immune functions. This study aims to investigate the role of miR-146a in an enforcing immunotherapy of AR. In this study, a mouse AR model was created. The levels of miR-146a in the mouse nasal mucosa were assessed by real time RT-PCR. A specific immunotherapy was performed in AR mice. The results showed that the AR mice had an AR-like inflammation in the nasal mucosa. Compared with naïve mice, markedly lower levels of miR-146a were detected in AR mice. The co-administration with miR-146a significantly enforced the effect of ovalbumin (OVA)-specific immunotherapy on inhibition of AR inflammation in the nasal mucosa. Further analysis showed that miR-146a induced transforming growth factor-β in dendritic cells; the latter induced naïve CD4(+) T cells to differentiate into regulatory T cells. In conclusion, miR-146a can enforce OVA-specific immunotherapy via inducing antigen-specific regulatory T cells. miR-146a may have therapeutic potential to be used in the immunotherapy of allergic diseases.

  18. Pregnant Women's Intentions and Subsequent Behaviors Regarding Maternal and Neonatal Service Utilization: Results from a Cohort Study in Nyanza Province, Kenya.

    PubMed

    Creanga, Andreea A; Odhiambo, George Awino; Odera, Benjamin; Odhiambo, Frank O; Desai, Meghna; Goodwin, Mary; Laserson, Kayla; Goldberg, Howard

    2016-01-01

    Higher use of maternal and neonatal health (MNH) services may reduce maternal and neonatal mortality in Kenya. This study aims to: 1) prospectively explore women's intentions to use MNH services (antenatal care, delivery in a facility, postnatal care, neonatal care) at <20 and 30-35 weeks' gestation and their actual use of these services; 2) identify predictors of intention-behavior discordance among women with positive service use intentions; 3) examine associations between place of delivery, women's reasons for choosing it, and birthing experiences. We used data from a 2012-2013 population-based cohort of pregnant women in the Demographic Surveillance Site in Nyanza province, Kenya. Of 1,056 women completing the study (89.1% response rate), 948 had live-births and 22 stillbirths, and they represent our analytic sample. Logistic regression analysis identified predictors of intention-behavior discordance regarding delivery in a facility and use of postnatal and neonatal care. At <20 and 30-35 weeks' gestation, most women intended to seek MNH services (≥93.9% and ≥87.5%, respectively, for all services assessed). Actual service use was high for antenatal (98.1%) and neonatal (88.5%) care, but lower for delivery in a facility (76.9%) and postnatal care (51.8%). Woman's age >35 and high-school education were significant predictors of intention-behavior discordance regarding delivery in a facility; several delivery-related factors were significantly associated with intention-behavior discordance regarding use of postnatal and neonatal care. Delivery facilities were chosen based on proximity to women's residence, affordability, and service quality; among women who delivered outside a health facility, 16.3% could not afford going to a facility. Good/very good birth experiences were reported by 93.6% of women who delivered in a facility and 32.6% of women who did not. We found higher MNH service utilization than previously documented in Nyanza province. Further

  19. Pregnant Women’s Intentions and Subsequent Behaviors Regarding Maternal and Neonatal Service Utilization: Results from a Cohort Study in Nyanza Province, Kenya

    PubMed Central

    Creanga, Andreea A.; Odhiambo, George Awino; Odera, Benjamin; Odhiambo, Frank O.; Desai, Meghna; Goodwin, Mary; Laserson, Kayla; Goldberg, Howard

    2016-01-01

    Higher use of maternal and neonatal health (MNH) services may reduce maternal and neonatal mortality in Kenya. This study aims to: 1) prospectively explore women’s intentions to use MNH services (antenatal care, delivery in a facility, postnatal care, neonatal care) at <20 and 30–35 weeks’ gestation and their actual use of these services; 2) identify predictors of intention-behavior discordance among women with positive service use intentions; 3) examine associations between place of delivery, women’s reasons for choosing it, and birthing experiences. We used data from a 2012–2013 population-based cohort of pregnant women in the Demographic Surveillance Site in Nyanza province, Kenya. Of 1,056 women completing the study (89.1% response rate), 948 had live-births and 22 stillbirths, and they represent our analytic sample. Logistic regression analysis identified predictors of intention-behavior discordance regarding delivery in a facility and use of postnatal and neonatal care. At <20 and 30–35 weeks’ gestation, most women intended to seek MNH services (≥93.9% and ≥87.5%, respectively, for all services assessed). Actual service use was high for antenatal (98.1%) and neonatal (88.5%) care, but lower for delivery in a facility (76.9%) and postnatal care (51.8%). Woman’s age >35 and high-school education were significant predictors of intention-behavior discordance regarding delivery in a facility; several delivery-related factors were significantly associated with intention-behavior discordance regarding use of postnatal and neonatal care. Delivery facilities were chosen based on proximity to women’s residence, affordability, and service quality; among women who delivered outside a health facility, 16.3% could not afford going to a facility. Good/very good birth experiences were reported by 93.6% of women who delivered in a facility and 32.6% of women who did not. We found higher MNH service utilization than previously documented in Nyanza

  20. Transient neonatal tyrosinaemia.

    PubMed

    Rice, D N; Houston, I B; Lyon, I C; Macarthur, B A; Mullins, P R; Veale, A M; Guthrie, R

    1989-01-01

    Children who had presented with transient neonatal tyrosinaemia (TNT) were compared with a group of unaffected controls at 7-9 years of age. A comprehensive psychometric assessment revealed significant differences between the groups in adaptive behaviour, psycholinguistic abilities, and speed of learning. In nearly all components of the tests used, higher levels of TNT were associated with lower levels of performance. This study demonstrates that TNT, a condition commonly regarded as benign in the short term, has long-term effects which may be detrimental to the child in school.

  1. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: Influence of Gestation Length and Timing of Neonatal Examinations on Litter Data in Controls

    EPA Science Inventory

    Laboratories conducting developmental and reproductive toxicity studies with rodents use varied protocols for determining the timing of neonatal litter examinations and subsequent measurements. Most laboratories determine timing based on the day of birth (DOB); l.e., gestation le...

  2. [STUDY OF THE INFLUENCE OF MINERAL FERTILIZERS ON THE NEONATAL MORBIDITY RATE IN INFANTS WITH CONGENITAL MALFORMATIONS (CM) IN THE BELGOROD REGION].

    PubMed

    Verzilina, I N; Chumosov, M I; Evdokimov, V I

    2015-01-01

    Results of the performed study showed that the use of mineral fertilizers for crops increases the risk of morbidity in neonates with congenital malformations (CM). P-elevated levels of relative environmental risk is established for: anomalies of the musculoskeletal system, multiple congenital malformations, the CM as a whole. Maximum environmental risk in the conditions of high load offertilizers on farmland is established for congenital abnormalities of the development of reproductive system in newborn infants (RR = 2,76).

  3. The Implementation of an Evidence-Based Bundle for Bloodstream Infections in Neonatal Intensive Care Units in Germany: A Controlled Intervention Study to Improve Patient Safety.

    PubMed

    Salm, Florian; Schwab, Frank; Geffers, Christine; Gastmeier, Petra; Piening, Brar

    2016-07-01

    OBJECTIVE To improve the patient safety of very-low-birthweight infants in neonatal departments in Germany. DESIGN Multicenter cohort study with a baseline (24 months), an intervention (12 months), and a postinterventional follow-up period (12 months) and time series analysis. STUDY POPULATION Very-low-birthweight patients from 32 neonatal departments in Germany. METHODS Neonatal departments showing a standardized infection ratio of bloodstream infection 10% higher than the expected number (standardized infection ratio ≥1.1) were invited to participate in the study. To reduce the occurrence of primary bloodstream infections, evidence-based bundles to improve catheter maintenance routines, insertion practice, and hand-hygiene compliance were implemented in the participating infirmaries. RESULTS Thirty-four departments participated in the study and 32 reported data. In total, 6,222 very-low-birthweight infants with 231,868 patient-days and 1,405 cases of bloodstream infections were analyzed. In the baseline period the pooled mean bloodstream infection rate was 6.63 (95% CI, 6.17-7.12) per 1,000 patient-days. The bloodstream infection rate decreased in the intervention period to 5.68 (relative risk, 0.86 [95% CI, 0.76-0.97]) and in the 1-year follow-up period to 5.31 per 1,000 patient-days (relative risk, 0.80 [95% CI, 0.70-0.92]). The multivariable time series analysis of monthly aggregated data showed a significant change in the slope for the frequency of bloodstream infections from the start to the end of the intervention (change in slope incidence rate ratio, 0.97; P=.001). CONCLUSION The implementation of an intervention bundle is feasible and can reduce bloodstream infections in neonatal departments. Infect Control Hosp Epidemiol 2016;37:798-804.

  4. [Allergen-specific immunotherapy for food allergies in childhood. Current options and future perspectives].

    PubMed

    Trendelenburg, Valérie; Blümchen, Katharina

    2016-07-01

    During recent years increasing research has been conducted on casual treatment options for food allergy, with focus on oral immunotherapy (OIT) for hen's egg, cow's milk and peanut allergy. Several studies could show that OIT leads to desensitization or an increase of threshold. However, severe adverse events during this treatment are not uncommon. Whether OIT leads to a sustained, 'robust' development of tolerance in patients has not yet been thoroughly investigated. Besides OIT, some studies on sublingual (SLIT) and epicutaneous immunotherapy (EPIT) were performed, aiming to improve the safety profile. Furthermore, there are some pilot studies investigating a combined treatment of SLIT and OIT or a combined use of anti-IgE treatment or probiotic supplementation with OIT. Further placebo-controlled trials with larger sample size are needed in order to develop standardized protocols before immunotherapy may be used as a therapeutic option for food allergy outside of clinical trials. PMID:27324376

  5. Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis

    PubMed Central

    Lourenço, Edmir Américo; Caldeira, Eduardo José; Carvalho, César Alexandre Fabrega; Cunha, Marcelo Rodriques; Carvalho, Marcus Vinícius Henriques; Passos, Saulo Duarte

    2015-01-01

    Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions. PMID:26722338

  6. Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis.

    PubMed

    Lourenço, Edmir Américo; Caldeira, Eduardo José; Carvalho, César Alexandre Fabrega; Cunha, Marcelo Rodriques; Carvalho, Marcus Vinícius Henriques; Passos, Saulo Duarte

    2016-01-01

    Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions. PMID:26722338

  7. Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice.

    PubMed

    Gregory, James A; Shepley-McTaggart, Ariel; Umpierrez, Michelle; Hurlburt, Barry K; Maleki, Soheila J; Sampson, Hugh A; Mayfield, Stephen P; Berin, M Cecilia

    2016-07-01

    Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen-specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut-allergic patients. We further found that immunotherapy using algal-produced Ara h 1 core domain confers protection from peanut-induced anaphylaxis in a murine model of peanut allergy.

  8. Immunotherapy using algal-produced Ara h 1 core domain suppresses peanut allergy in mice.

    PubMed

    Gregory, James A; Shepley-McTaggart, Ariel; Umpierrez, Michelle; Hurlburt, Barry K; Maleki, Soheila J; Sampson, Hugh A; Mayfield, Stephen P; Berin, M Cecilia

    2016-07-01

    Peanut allergy is an IgE-mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen-specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal-produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut-allergic patients. We further found that immunotherapy using algal-produced Ara h 1 core domain confers protection from peanut-induced anaphylaxis in a murine model of peanut allergy. PMID:26801740

  9. Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

    PubMed

    Qian, Haili; Wang, Haijuan; Guan, Xiuwen; Yi, Zongbi; Ma, Fei

    2016-06-01

    The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta-analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, P<0.001], but not 2-year progression-free survival (OR=1.81, 95% CI: 0.61-5.36, P=0.284). Specifically, early (OR=3.32, 95% CI: 1.38-7.95, P<0.01) but not advanced (OR=3.75, 95% CI: 0.96-14.68, P=0.057) NSCLC patients were likely to gain a large benefit from the adoptive immunotherapy. Most of the adoptive immunotherapy-induced adverse effects were self-limited, mainly including fever, shiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC. PMID:26872311

  10. Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors

    SciTech Connect

    Chang, A.E.; Shu, S.Y.; Chou, T.; Lafreniere, R.; Rosenberg, S.A.

    1986-07-01

    A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver.

  11. Neonatal networks: clinical research and quality improvement.

    PubMed

    Profit, Jochen; Soll, Roger F

    2015-12-01

    Worldwide, neonatal networks have been formed to address both the research and quality improvement agenda of neonatal-perinatal medicine. Neonatal research networks have led the way in conducting many of the most important clinical trials of the last 25 years, including studies of cooling for hypoxic-ischemic encephalopathy, delivery room management with less invasive support, and oxygen saturation targeting. As we move into the future, increasing numbers of these networks are tackling quality improvement initiatives as a priority of their collaboration. Neonatal quality improvement networks have been in the forefront of the quality movement in medicine and, in the 21st century, have contributed to many of the reported improvements in care. In the coming years, building and maintaining this community of care is critical to the success of neonatal-perinatal medicine.

  12. Systemic chemotherapy combined with local adoptive immunotherapy cures rats bearing 9L gliosarcoma.

    PubMed

    Kruse, C A; Mitchell, D H; Kleinschmidt-DeMasters, B K; Bellgrau, D; Eule, J M; Parra, J R; Kong, Q; Lillehei, K O

    1993-02-01

    Survival of Fischer rats bearing 9L gliosarcoma in the brain was measured to determine the efficacy of 1) systemically administered chemotherapy with local adoptive immunotherapy (chemo-adoptive immunotherapy) or 2) systemically administered chemo-immunotherapy. Winn assays, where tumor instillation coincided with the start of treatment, and one-week established tumor assays were conducted. Survival of chemo-adoptive immunotherapy treated groups given intraperitoneal cyclophosphamide and intracranial lymphokine activated killer cells and recombinant Interleukin-2 was significantly extended when compared to sham treated control groups, to groups given chemotherapy with intraperitoneal cyclophosphamide, and to groups treated by local adoptive immunotherapy with intracranial lymphokine activated killer cells and Interleukin-2. The killer cells were generated from spleens of donor rats that either had or had not been given cyclophosphamide 24 h earlier. Long-term survivors (9/39), sacrificed at day 70, were obtained only in the chemo-adoptive immunotherapy treated groups; 7/39 had no histologic evidence of tumor and had focal sterile abscesses at the site of killer cell instillation. Average group weight plotted over time showed that there was acceptable toxicity with chemo-adoptive immunotherapy; the toxicity was identical to that obtained with systemic cyclophosphamide treatment. In contrast, survival of chemo-immunotherapy treated groups given systemic cyclophosphamide and Interleukin-2 was not significantly extended from groups which were sham treated or treated only with systemic Interleukin-2. Rapid decline of average group weight plotted over time and early deaths following chemo-immunotherapy treatment indicated that the regimen was toxic. The effect of cyclophosphamide administration on the splenocytes of donor rats and the LAK cells generated from them was determined by in vitro studies analyzing cell number, viability, phenotypic expression and cytotoxicity

  13. Customized nutritional enhancement for pregnant women appears to lower incidence of certain common maternal and neonatal complications: an observational study.

    PubMed

    Stone, Leslie P; Stone, P Michael; Rydbom, Emily A; Stone, Lucas A; Stone, T Elliot; Wilkens, Lindsey E; Reynolds, Kathryn

    2014-11-01

    A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention. Intervention consisted of trimesterby-trimester nutrition and lifestyle education, supplementation of L-methyl folate, magnesium, essential fatty acids, and probiotics for all SG patients, with targeted supplementation of zinc, carnitine, and 25 OH-D. Because of small case occurrence rates of individual conditions in the study group, unreportable reductions were found, except GDM (SG vs CHCC, P value .046 with 95.38% confidence interval [CI]), and PIH (SG vs PP, P value .0505 with 94.95% CIl). The aggregated occurrence rate of the four conditions, however, was significantly lower in the study population than in either comparison population (PP P value .0154 with 98.46% CI, and CHCC P value .0265 with 97.35% CI). Customized nutritional intervention appears to have significantly reduced adverse perinatal outcomes. Prospective study within larger, at-risk populations is needed to determine whether customized nutrition improves conditions individually.

  14. Customized Nutritional Enhancement for Pregnant Women Appears to Lower Incidence of Certain Common Maternal and Neonatal Complications: An Observational Study

    PubMed Central

    Stone, P. Michael; Rydbom, Emily A.; Stone, Lucas A.; Stone, T. Elliot; Wilkens, Lindsey E.; Reynolds, Kathryn

    2014-01-01

    A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention. Intervention consisted of trimesterby-trimester nutrition and lifestyle education, supplementation of L-methyl folate, magnesium, essential fatty acids, and probiotics for all SG patients, with targeted supplementation of zinc, carnitine, and 25 OH-D. Because of small case occurrence rates of individual conditions in the study group, unreportable reductions were found, except GDM (SG vs CHCC, P value .046 with 95.38% confidence interval [CI]), and PIH (SG vs PP, P value .0505 with 94.95% CIl). The aggregated occurrence rate of the four conditions, however, was significantly lower in the study population than in either comparison population (PP P value .0154 with 98.46% CI, and CHCC P value .0265 with 97.35% CI). Customized nutritional intervention appears to have significantly reduced adverse perinatal outcomes. Prospective study within larger, at-risk populations is needed to determine whether customized nutrition improves conditions individually. PMID:25568832

  15. Customized nutritional enhancement for pregnant women appears to lower incidence of certain common maternal and neonatal complications: an observational study.

    PubMed

    Stone, Leslie P; Stone, P Michael; Rydbom, Emily A; Stone, Lucas A; Stone, T Elliot; Wilkens, Lindsey E; Reynolds, Kathryn

    2014-11-01

    A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention. Intervention consisted of trimesterby-trimester nutrition and lifestyle education, supplementation of L-methyl folate, magnesium, essential fatty acids, and probiotics for all SG patients, with targeted supplementation of zinc, carnitine, and 25 OH-D. Because of small case occurrence rates of individual conditions in the study group, unreportable reductions were found, except GDM (SG vs CHCC, P value .046 with 95.38% confidence interval [CI]), and PIH (SG vs PP, P value .0505 with 94.95% CIl). The aggregated occurrence rate of the four conditions, however, was significantly lower in the study population than in either comparison population (PP P value .0154 with 98.46% CI, and CHCC P value .0265 with 97.35% CI). Customized nutritional intervention appears to have significantly reduced adverse perinatal outcomes. Prospective study within larger, at-risk populations is needed to determine whether customized nutrition improves conditions individually. PMID:25568832

  16. Targeted alpha-particle immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G; Rosenblat, Todd L

    2014-01-01

    Because alpha-particles have a shorter range and a higher linear energy transfer (LET) compared with beta-particles, targeted alpha-particle immunotherapy offers the potential for more efficient tumor cell killing while sparing surrounding normal cells. To date, clinical studies of alpha-particle immunotherapy for acute myeloid leukemia (AML) have focused on the myeloid cell surface antigen CD33 as a target using the humanized monoclonal antibody lintuzumab. An initial phase I study demonstrated the safety, feasibility, and antileukemic effects of bismuth-213 ((213)Bi)-labeled lintuzumab. In a subsequent study, (213)Bi-lintuzumab produced remissions in some patients with AML after partial cytoreduction with cytarabine, suggesting the utility of targeted alpha-particle therapy for small-volume disease. The widespread use of (213)Bi, however, is limited by its short half-life. Therefore, a second-generation construct containing actinium-225 ((225)Ac), a radiometal that generates four alpha-particle emissions, was developed. A phase I trial demonstrated that (225)Ac-lintuzumab is safe at doses of 3 μCi/kg or less and has antileukemic activity across all dose levels studied. Fractionated-dose (225)Ac-lintuzumab in combination with low-dose cytarabine (LDAC) is now under investigation for the management of older patients with untreated AML in a multicenter trial. Preclinical studies using (213)Bi- and astatine-211 ((211)At)-labeled anti-CD45 antibodies have shown that alpha-particle immunotherapy may be useful as part conditioning before hematopoietic cell transplantation. The use of novel pretargeting strategies may further improve target-to-normal organ dose ratios. PMID:24857092

  17. Classification and genetic features of neonatal haemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism

    PubMed Central

    Kelly, A.; Lunt, P.; Rodrigues, F.; Berry, P; Flynn, D.; McKiernan, P.; Kelly, D.; Mieli-Vergani, G.; Cox, T.

    2001-01-01

    Neonatal haemochromatosis (NH) is a severe and newly recognised syndrome of uncertain aetiology, characterised by congenital cirrhosis or fulminant hepatitis and widespread tissue iron deposition. NH occurs in the context of maternal disease including viral infection, as a complication of metabolic disease in the fetus, and sporadically or recurrently, without overt cause, in sibs. Although an underlying genetic basis for NH has been suspected, no test is available for predictive analysis in at risk pregnancies.
  As a first step towards an understanding of the putative genetic basis for neonatal haemochromatosis, we have conducted a systematic study of the mode of transmission of this disorder in a total of 40 infants born to 27 families. We have moreover carried out a molecular analysis of candidate genes (β2-microglobulin, HFE, and haem oxygenases 1 and 2) implicated in iron metabolism. No pathogenic mutations in these genes were identified that segregate consistently with the disease phenotype in multiplex pedigrees. However, excluding four pedigrees with clear evidence of maternal infection associated with NH, a pedigree showing transmission of maternal antinuclear factor and ribonucleoprotein antibodies to the affected infants, and two families with possible matrilineal inheritance of disease in maternal half sibs, a large subgroup of the affected pedigrees point to the inheritance of an autosomal recessive trait. This included 14 pedigrees with affected and unaffected infants and a single pedigree where all four affected infants were the sole offspring of consanguineous but otherwise healthy parents.
  We thus report three distinct patterns of disease transmission in neonatal haemochromatosis. In the differentiation of a large subgroup showing transmission of disease in a manner suggesting autosomal recessive inheritance, we also provide the basis for further genome wide studies to define chromosomal determinants of iron storage disease in the

  18. Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: a Double-Blinded, Randomized Placebo Controlled Pilot Study in Critically Ill Neonates

    PubMed Central

    Calkins, Kara L.; Sanchez, Lauren A.; Tseng, Chi-Hong; Faull, Kym F.; Yoon, Alexander J.; Ryan, Christopher M.; Le, Thuc; Shew, Stephen B.

    2015-01-01

    Background This study’s objective was to determine if parenteral cysteine when compared to isonitrogenous non-cysteine supplementation increases erythrocyte reduced glutathione (GSH) in neonates at high risk for inflammatory injury. Material and Methods Neonates with a score for neonatal acute physiology (SNAP) > 10 requiring mechanical ventilation and parenteral nutrition (PN) were randomized in a double-blinded, placebo controlled study to receive parenteral cysteine-HCl (CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/day for ≥ seven days. A six-hour [13C2] glycine IV infusion was administered at study week one to determine fractional synthetic rate of glutathione (FSR-GSH). Results Baseline characteristics were similar between the CYS (n=17) and ISO groups (n=21). Erythrocyte GSH and total glutathione concentrations, GSH:oxidized glutathione (GSSG), and FSR-GSH after treatment were not different between groups. However, the CYS group had a larger individual positive change in GSH and total glutathione (infusion day – baseline) compared to the ISO group (p=0.02 for each). After adjusting for treatment, a lower enrollment weight and red blood cell (RBC) transfusion were associated with a decreased change in total glutathione and GSH (p< 0.05 for each). Conclusion When compared to isonitrogenous non-cysteine supplementation, high dose cysteine supplementation for at least one week in critically ill neonates resulted in a larger and more positive individual change in glutathione. Smaller infants and those who received transfused blood demonstrated less effective change in glutathione with cysteine supplementation. The benefit of cysteine remains promising and deserves further investigation. PMID:25139979

  19. Sox2-CreER mice are useful for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies

    PubMed Central

    Walters, Bradley J.; Yamashita, Tetsuji; Zuo, Jian

    2015-01-01

    Studies of hair cell regeneration in the postnatal cochlea rely on fate mapping of supporting cells. Here we characterized a Sox2-CreER knock-in mouse line with two independent reporter mouse strains at neonatal and mature ages. Regardless of induction age, reporter expression was robust, with CreER activity being readily detectable in >85% of supporting cells within the organ of Corti. When induced at postnatal day (P) 28, Sox2-CreER activity was exclusive to supporting cells demonstrating its utility for fate mapping studies beyond this age. However, when induced at P1, Sox2-CreER activity was also detected in >50% of cochlear hair cells, suggesting that Sox2-CreER may not be useful to fate map a supporting cell origin of regenerated hair cells if induced at neonatal ages. Given that this model is currently in use by several investigators for fate mapping purposes, and may be adopted by others in the future, our finding that current protocols are effective for restricting CreER activity to supporting cells at mature but not neonatal ages is both significant and timely. PMID:26108463

  20. Biomarkers for glioma immunotherapy: the next generation

    PubMed Central

    Ung, Timothy H.; Neira, Justin A.; Canoll, Peter; Bruce, Jeffrey N.

    2015-01-01

    The term “biomarker” historically refers to a single parameter, such as the expression level of a gene or a radiographic pattern, used to indicate a broader biological state. Molecular indicators have been applied to several aspects of cancer therapy: to describe the genotypic and phenotypic state of neoplastic tissue for prognosis, to predict susceptibility to anti-proliferative agents, to validate the presence of specific drug targets, and to evaluate responsiveness to therapy. For glioblastoma (GBM), immunohistochemical and radiographic biomarkers accessible to the clinical lab have informed traditional regimens, but while immunotherapies have emerged as potentially disruptive weapons against this diffusely infiltrating, heterogeneous tumor, biomarkers with strong predictive power have not been fully established. The cancer immunotherapy field, through the recently accelerated expansion of trials, is currently leveraging this wealth of clinical and biological data to define and revise the use of biomarkers for improving prognostic accuracy, personalization of therapy, and evaluation of responses across the wide variety of tumors. Technological advancements in DNA sequencing, cytometry, and microscopy have facilitated the exploration of more integrated, high-dimensional profiling of the disease system—incorporating both immune and tumor parameters—rather than single metrics, as biomarkers for therapeutic sensitivity. Here we discuss the utility of traditional GBM biomarkers in immunotherapy and how the impending transformation of the biomarker paradigm—from single markers to integrated profiles—may offer the key to bringing predictive, personalized immunotherapy to GBM patients. PMID:25724916

  1. Targeted immunotherapy for pediatric solid tumors

    PubMed Central

    Kopp, Lisa M.; Katsanis, Emmanuel

    2016-01-01

    ABSTRACT Metastatic and refractory pediatric solid tumor malignancies continue to have a poor outcome despite the > 80% cure rates appreciated in many pediatric cancers. Targeted immunotherapy is impacting treatment and survival in these aggressive tumors. We review current promising immunotherapeutic approaches in the pediatric oncology solid tumor setting. PMID:27141344

  2. Immunity to TB and targets for immunotherapy.

    PubMed

    Gonzalez-Juarrero, Mercedes

    2012-02-01

    For centuries the treatment of TB has presented an enormous challenge to global health. In the 20th century, the treatment of TB patients with long-term multidrug therapy gave hope that TB could be controlled and cured; however, contrary to these expectations and coinciding with the emergence of AIDS, the world has witnessed a rampant increase in hard-to-treat cases of TB, along with the emergence of highly virulent and multidrug-resistant Mycobacterium tuberculosis strains. Unfortunately, these bacteria are now circulating around the world, and there are few effective drugs to treat them. As a result, the prospects for improved treatment and control of TB in the 21st century have worsened and we urgently need to identify new therapies that deal with this problem. The potential use of immunotherapy for TB is now of greater consideration than ever before, as immunotherapy could potentially overcome the problem of drug resistance. TB immunotherapy targets the already existing host anti-TB immune response and aims to enhance killing of the bacilli. For this purpose, several approaches have been used: the use of anti-Mycobacteria antibodies; enhancing the Th1 protective responses by using mycobacterial antigens or increasing Th1 cytokines; interfering with the inflammatory process and targeting of immunosuppressive pathways and targeting the cell activation/proliferation pathways. This article reviews our current understanding of TB immunity and targets for immunotherapy that could be used in combination with current TB chemotherapy.

  3. Maternal experiences of caring for an infant with neurological impairment after neonatal encephalopathy in Uganda: a qualitative study

    PubMed Central

    Nakamanya, Sarah; Siu, Godfrey E.; Lassman, Rachel; Seeley, Janet; Tann, Cally J.

    2015-01-01

    Abstract Purpose: The study investigated maternal experiences of caring for a child affected by neurological impairment after neonatal encephalopathy (NE) (“birth asphyxia”) in Uganda. Methods: Between September 2011 and October 2012 small group and one-on-one in-depths interviews were conducted with mothers recruited to the ABAaNA study examining outcomes from NE in Mulago hospital, Kampala. Data were analysed thematically with the aid of Nvivo 8 software. Findings: Mothers reported caring for an infant with impairment was often complicated by substantial social, emotional and financial difficulties and stigma. High levels of emotional distress, feelings of social isolation and fearfulness about the future were described. Maternal health-seeking ability was exacerbated by high transport costs, lack of paternal support and poor availability of rehabilitation and counselling services. Meeting and sharing experiences with similarly affected mothers was associated with more positive maternal caring experiences. Conclusion: Mothering a child with neurological impairment after NE is emotionally, physically and financially challenging but this may be partly mitigated by good social support and opportunities to share caring experiences with similarly affected mothers. A facilitated, participatory, community-based approach to rehabilitation training may have important impacts on maximising participation and improving the quality of life of affected mothers and infants.Implications for RehabilitationCaring for an infant with neurological impairment after NE in Uganda has substantial emotional, social and financial impacts on families and is associated with high levels of emotional stress, feelings of isolation and stigma amongst mothers.Improved social support and the opportunity to share experiences with other similarly affected mothers are associated with a more positive maternal caring experience. High transport costs, lack of paternal support and poor availability

  4. Does smoking in pregnancy modify the impact of antenatal steroids on neonatal respiratory distress syndrome? Results of the Epipage study

    PubMed Central

    Burguet, A; Kaminski, M; Truffert, P; Menget, A; Marpeau, L; Voyer, M; Roze, J; Escande, B; Cambonie, G; Hascoet, J; Grandjean, H; Breart, G; Larroque, B; on, b

    2005-01-01

    Objectives: To assess the relation between cigarette smoking during pregnancy and neonatal respiratory distress syndrome (RDS) in very preterm birth, and to analyse the differential effect of antenatal steroids on RDS among smokers and non-smokers. Design: A population based cohort study (the French Epipage study). Setting: Regionally defined births in France. Methods: A total of 858 very preterm liveborn singletons (27–32 completed weeks of gestation) of the French Epipage study were included in this analysis. The odds ratio for RDS in relation to smoking in pregnancy was estimated using a logistic regression to control for gestational age. The odds ratio for RDS in relation to antenatal steroids was estimated taking into account an interaction between antenatal steroids and cigarette smoking, using multiple logistic regression to control for gestational age, birthweight ratio, main causes of preterm birth, mode of delivery, and sex. Results: The odds ratio for RDS in relation to smoking in pregnancy adjusted for gestational age (aOR) was 0.59 (95% confidence interval (CI) 0.44 to 0.79). The aOR for RDS in relation to antenatal steroids was 0.31 (95% CI 0.19 to 0.49) in babies born to non-smokers and 0.63 (95% CI 0.38 to 1.05) in those born to smokers; the difference was significant (p = 0.04). Conclusions: Cigarette smoking during pregnancy is associated with a decrease in the risk of RDS in very preterm babies. Although antenatal steroids reduce the risk of RDS in babies born to both smokers and non-smokers, the reduction is smaller in those born to smokers. PMID:15613572

  5. Do Sustained Lung Inflations during Neonatal Resuscitation Affect Cerebral Blood Volume in Preterm Infants? A Randomized Controlled Pilot Study

    PubMed Central

    Schwaberger, Bernhard; Pichler, Gerhard; Avian, Alexander; Binder-Heschl, Corinna; Baik, Nariae; Urlesberger, Berndt

    2015-01-01

    Background Sustained lung inflations (SLI) during neonatal resuscitation may promote alveolar recruitment in preterm infants. While most of the studies focus on respiratory outcome, the impact of SLI on the brain hasn’t been investigated yet. Objective Do SLI affect cerebral blood volume (CBV) in preterm infants? Methods Preterm infants of gestation 28 weeks 0 days to 33 weeks 6 days with requirement for respiratory support (RS) were included in this randomized controlled pilot trial. Within the first 15 minutes after birth near-infrared spectroscopy (NIRS) measurements using ‘NIRO-200-NX’ (Hamamatsu, Japan) were performed to evaluate changes in CBV and cerebral tissue oxygenation. Two groups were compared based on RS: In SLI group RS was given by applying 1–3 SLI (30 cmH2O for 15 s) continued by respiratory standard care. Control group received respiratory standard care only. Results 40 infants (20 in each group) with mean gestational age of 32 weeks one day (±2 days) and birth weight of 1707 (±470) g were included. In the control group ΔCBV was significantly decreasing, whereas in SLI group ΔCBV showed similar values during the whole period of 15 minutes. Comparing both groups within the first 15 minutes ΔCBV showed a tendency toward different overall courses (p = 0.051). Conclusion This is the first study demonstrating an impact of SLI on CBV. Further studies are warranted including reconfirmation of the present findings in infants with lower gestational age. Future investigations on SLI should not only focus on respiratory outcome but also on the consequences on the developing brain. Trial Registration German Clinical Trials Register DRKS00005161 https://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do PMID:26406467

  6. Emerging Opportunities and Challenges in Cancer Immunotherapy.

    PubMed

    Whiteside, Theresa L; Demaria, Sandra; Rodriguez-Ruiz, Maria E; Zarour, Hassane M; Melero, Ignacio

    2016-04-15

    Immunotherapy strategies against cancer are emerging as powerful weapons for treatment of this disease. The success of checkpoint inhibitors against metastatic melanoma and adoptive T-cell therapy with chimeric antigen receptor T cells against B-cell-derived leukemias and lymphomas are only two examples of developments that are changing the paradigms of clinical cancer management. These changes are a result of many years of intense research into complex and interrelated cellular and molecular mechanisms controling immune responses. Promising advances come from the discovery of cancer mutation-encoded neoantigens, improvements in vaccine development, progress in delivery of cellular therapies, and impressive achievements in biotechnology. As a result, radical transformation of cancer treatment is taking place in which conventional cancer treatments are being integrated with immunotherapeutic agents. Many clinical trials are in progress testing potential synergistic effects of treatments combining immunotherapy with other therapies. Much remains to be learned about the selection, delivery, and off-target effects of immunotherapy used alone or in combination. The existence of numerous escape mechanisms from the host immune system that human tumors have evolved still is a barrier to success. Efforts to understand the rules of immune cell dysfunction and of cancer-associated local and systemic immune suppression are providing new insights and fuel the enthusiasm for new therapeutic strategies. In the future, it might be possible to tailor immune therapy for each cancer patient. The use of new immune biomarkers and the ability to assess responses to therapy by noninvasive monitoring promise to improve early cancer diagnosis and prognosis. Personalized immunotherapy based on individual genetic, molecular, and immune profiling is a potentially achievable future goal. The current excitement for immunotherapy is justified in view of many existing opportunities for harnessing

  7. Use of pulsed-field gel electrophoresis typing to study an outbreak of infection due to Serratia marcescens in a neonatal intensive care unit.

    PubMed Central

    Miranda, G; Kelly, C; Solorzano, F; Leanos, B; Coria, R; Patterson, J E

    1996-01-01

    Serratia marcescens is a well-known cause of nosocomial infections and outbreaks, particularly in critically ill neonates and immunocompromised patients. Numerous methods have been proposed for typing. We used pulsed-field gel electrophoresis (PFGE) typing to analyze an outbreak in a neonatal intensive care unit (NICU). We included 23 patient isolates from an outbreak (March to July 1995), and 10 patient isolates from different wards during the same time period. PFGE of whole-cell DNA digested by SpeI was used as a marker of strain identity. The most common presentation of the infection was sepsis in 18 of 23 (78%) neonates. Only four different biotypes were identified; biotype A8d accounted for 84% of the strains. PFGE typing revealed two clones responsible for two different clonal strain dissemination outbreaks from March to July, with 24 patient isolates being pattern A and 4 patient isolates being pattern E. PFGE typing suggests cross transmission between patients in the NICU and other wards. The isolates from 5 other patients showed distinct PFGE patterns. Extensive investigation and cultures failed to identify any environmental or staff reservoir of S. marcescens. This is one of the first reports applying PFGE to the study of S. marcescens, and this method was a useful marker of strain identity. PFGE typing distinguished strains which appeared to be the same by biotyping. PMID:8940460

  8. Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges.

    PubMed

    Han, Ethan Q; Li, Xiu-ling; Wang, Chun-rong; Li, Tian-fang; Han, Shuang-yin

    2013-01-01

    Recent years have witnessed much progress in both basic research and clinical trials regarding cancer immunotherapy with chimeric antigen receptor (CAR)-engineered T cells. The unique structure of CAR endows T cell tumor specific cytotoxicity and resistance to immunosuppressive microenvironment in cancers, which helps patients to better tackle the issue of immunological tolerance. Adoptive immunotherapy (AIT) using this supernatural T cell have gained momentum after decades of intense debates because of the promising results obtained from preclinical models and clinical trials. However, it is very important for us to evaluate thoroughly the challenges/obstacles before widespread clinical application, which clearly warrants more studies to improve our understanding of the mechanism underlying AIT. In this review, we focus on the critical issues related to the clinical outcomes of CAR-based adoptive immunotherapy and discuss the rationales to refine this new cancer therapeutic modality. PMID:23829929

  9. Cellular immunotherapy for refractory hematological malignancies

    PubMed Central

    2013-01-01

    Background Acute myeloid leukemia (AML) and other aggressive refractory hematological malignancies unresponsive to upfront therapy remain difficult conditions to treat. Often, the focus of therapy is centered on achieving complete remission of disease in order to proceed with a consolidative stem cell transplant. At issue with this paradigm is the multitude of patients who are unable to achieve complete remission with standard chemotherapeutic options. A major benefit of transplantation is the graft versus tumor effect that follows successful engraftment. However, with this graft versus tumor effect comes the risk of graft versus host disease. Therefore, alternative treatment options that utilize immunotherapy while minimizing toxicity are warranted. Herein, we propose a novel treatment protocol in which haploidentical peripheral blood stem cells are infused into patients with refractory hematological malignancies. The end goal of cellular therapy is not engraftment but instead is the purposeful rejection of donor cells so as to elicit a potent immune reaction that appears to break host tumor tolerance. Methods/design The trial is a FDA and institutional Rhode Island Hospital/The Miriam Hospital IRB approved Phase I/II study to determine the efficacy and safety of haploidentical peripheral blood cell infusions into patients with refractory hematological malignancies. The primary objective is the overall response rate while secondary objectives will assess the degree and duration of response as well as safety considerations. Patients with refractory acute leukemias and aggressive lymphomas over the age of 18 are eligible. Donors will be selected amongst family members. Full HLA typing of patients and donors will occur as will chimerism assessments. 1-2x108 CD3+ cells/kilogram will be infused on Day 0 without preconditioning. Patients will be monitored for their response to therapy, in particular for the development of a cytokine release syndrome (CRS) that has been

  10. Production of Monoclonal Antibodies in Plants for Cancer Immunotherapy

    PubMed Central

    Moussavou, Ghislain; Ko, Kisung; Lee, Jeong-Hwan; Choo, Young-Kug

    2015-01-01

    Plants are considered as an alternative platform for recombinant monoclonal antibody (mAb) production due to the improvement and diversification of transgenic techniques. The diversity of plant species offers a multitude of possibilities for the valorization of genetic resources. Moreover, plants can be propagated indefinitely, providing cheap biomass production on a large scale in controlled conditions. Thus, recent studies have shown the successful development of plant systems for the production of mAbs for cancer immunotherapy. However, their several limitations have to be resolved for efficient antibody production in plants. PMID:26550566

  11. Carbohydrate modified ultrafine ceramic nanoparticles for allergen immunotherapy.

    PubMed

    Pandey, Ravi Shankar; Sahu, Satish; Sudheesh, M S; Madan, Jitender; Kumar, Manoj; Dixit, Vinod Kumar

    2011-08-01

    The uses of drug-delivery systems in allergen specific immunotherapy appear to be a promising approach due to their ability to act as adjuvants, transport the allergens to immune-competent cells and tissues and reduce the number of administrations. The aim of this work was to evaluate the carbohydrate modified ultrafine ceramic core based nanoparticles (aquasomes) as adjuvant/delivery vehicle in specific immunotherapy using ovalbumin (OVA) as an allergen model. Prepared nanoparticles were characterized for size, shape, zeta potential, antigen integrity, surface adsorption efficiency and in vitro release. The humoral and cellular-induced immune responses generated by OVA adsorbed aquasomes were studied by two intradermal immunizations in BALB/c mice. OVA sensitized mice were treated with OVA adsorbed aquasomes and OVA adsorbed aluminum hydroxide following established protocol. Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated. Developed aquasomes possessed a negative zeta potential (-11.3 mV) and an average size of 47 nm with OVA adsorption efficiency of ~60.2 μg mg(-1) of hydroxyapatite core. In vivo immune response after two intradermal injections with OVA adsorbed aquasomes resulted in a mixed Th1/Th2-type immune response. OVA-sensitized mice model, treatment with OVA adsorbed aquasomes elicited lower levels of IgE (p<0.05), serum histamine and higher survival rate in comparison with alum adsorbed OVA. Symptoms of anaphylactic shock in OVA aquasome-treated mice were weaker than the one induced in the alum adsorbed OVA group. Results from this study demonstrate the valuable use of aquasomes in allergen immunotherapy. PMID:21333772

  12. Update on Neonatal Hypoglycemia

    PubMed Central

    Rozance, Paul J.

    2014-01-01

    Purpose of Review Neonatal hypoglycemia is one of the most common biochemical abnormalities encountered in the newborn. However, controversy remains surrounding its definition and management especially in asymptomatic patients. Recent Findings New information has been published that describes the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study failed to find an association between repetitive low glucose concentrations and poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to hyperinsulinism, especially genetic causes, continued to be associated with brain injury. New advances were made in the diagnosis and management of hyperinsulinism, including acquired hyperinsulinism in small for gestational age infants and others. Continuous glucose monitoring remains an attractive strategy for future research in this area. Summary The fundamental question of how best to manage asymptomatic newborns with low glucose concentrations remains unanswered. Balancing the risks of over treating newborns with low glucose concentrations who are undergoing a normal transition following birth against the risks of under treating those in whom low glucose concentrations are pathological, dangerous, and/or a harbinger of serious metabolic disease remains a challenge. PMID:24275620

  13. Immunologic special forces: anti-pathogen cytotoxic T-lymphocyte immunotherapy following hematopoietic stem cell transplantation

    PubMed Central

    Keller, Michael D; Bollard, Catherine M

    2014-01-01

    Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naïve sources, and reduce the time requirement for production. Early studies suggest that anti-fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T-cells with resistance to pharmacologic immunosuppression. PMID:27274983

  14. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue. [Mice

    SciTech Connect

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-04-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy.

  15. Maternal macronutrient intake during pregnancy is associated with neonatal abdominal adiposity: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study1-4

    PubMed Central

    Chen, Ling-Wei; Tint, Mya-Thway; Fortier, Marielle V.; Aris, Izzuddin M.; Bernard, Jonathan Y.; Colega, Marjorelee; Gluckman, Peter D.; Saw, Seang-Mei; Chong, Yap-Seng; Yap, Fabian; Godfrey, Keith M.; Kramer, Michael S.; van Dam, Rob M.; Chong, Mary Foong-Fong; Lee, Yung Seng

    2016-01-01

    Background Infant body composition has been associated with later metabolic risk, but few studies have examined the association between maternal macronutrient intake and neonatal body composition. Furthermore, most of those studies have used proxy measures of body composition that may not reflect body fat distribution, particularly abdominal internal adiposity. Objective We investigated the relation between maternal macronutrient intake and neonatal abdominal adiposity measured using magnetic resonance imaging (MRI) in a multi-ethnic Asian mother-offspring cohort. Methods Macronutrient intakes of mothers were ascertained using a 24-h dietary recall at 26-28 weeks gestation. Neonatal abdominal adiposity was assessed using MRI in the second week of life. Mother-offspring dyads with complete macronutrient intake and adiposity information (n= 320) were included in the analysis. Associations were assessed by both substitution and addition models using multivariable linear regressions. Results Mothers [mean age: 30 y; 44% Chinese, 38% Malay, 18% Indians] consumed 15.5 ± 4.3% (mean ± SD) of their energy intakes from protein, 32.4 ± 7.7% from fat, and 52.1 ± 9.0% from carbohydrate. A higher protein, lower carbohydrate/fat diet during pregnancy was associated with lower abdominal internal adipose tissue (IAT) in the neonates [β (95% CI): -0.18 (-0.35, -0.001) mL per 1% protein to carbohydrate substitution and -0.25 (-0.46, -0.04) mL per 1% protein to fat substitution]. These associations were stronger in boys than in girls (P-interactions <0.05). Higher maternal intake of animal protein [-0.26 (-0.47, -0.05) mL for fat substitution], but not plant protein, was associated with lower offspring IAT. In contrast, maternal macronutrient intake was not consistently associated with infant anthropometric measurements, including abdominal circumference and subscapular skinfold thickness. Conclusions Higher maternal protein intake (at the expense of carbohydrate or fat intake

  16. Social autopsy study identifies determinants of neonatal mortality in Doume, Nguelemendouka and Abong–Mbang health districts, Eastern Region of Cameroon

    PubMed Central

    Koffi, Alain K.; Libite, Paul–Roger; Moluh, Seidou; Wounang, Romain; Kalter, Henry D.

    2015-01-01

    Background Reducing preventable medical causes of neonatal death for faster progress toward the MGD4 will require Cameroon to adequately address the social factors contributing to these deaths. The objective of this paper is to explore the social, behavioral and health systems determinants of newborn death in Doume, Nguelemendouka and Abong–Mbang health districts, in Eastern Region of Cameroon, from 2007–2010. Methods Data come from the 2012 Verbal/Social Autopsy (VASA) study, which aimed to determine the biological causes and social, behavioral and health systems determinants of under–five deaths in Doume, Nguelemendouka and Abong–Mbang health districts in Eastern Region of Cameroon. The analysis of the data was guided by the review of the coverage of key interventions along the continuum of normal maternal and newborn care and by the description of breakdowns in the care provided for severe neonatal illnesses within the Pathway to Survival conceptual framework. Results One hundred sixty–four newborn deaths were confirmed from the VASA survey. The majority of the deceased newborns were living in households with poor socio–economic conditions. Most (60–80%) neonates were born to mothers who had one or more pregnancy or labor and delivery complications. Only 23% of the deceased newborns benefited from hygienic cord care after birth. Half received appropriate thermal care and only 6% were breastfed within one hour after birth. Sixty percent of the deaths occurred during the first day of life. Fifty–five percent of the babies were born at home. More than half of the deaths (57%) occurred at home. Of the 64 neonates born at a health facility, about 63% died in the health facility without leaving. Careseeking was delayed for several neonates who became sick after the first week of life and whose illnesses were less serious at the onset until they became more severely ill. Cost, including for transport, health care and other expenses, emerged as main

  17. Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011

    PubMed Central

    2012-01-01

    Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and “perceived” business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace

  18. Immunotherapy for pythiosis: Effect on NTPDase activity in lymphocytes of an experimental model.

    PubMed

    Bach, Barbara Charlotte; Leal, Daniela Bitencourt Rosa; Ruchel, Jader Betsch; Souza, Viviane do Carmo Gonçalves; Maboni, Grazieli; Dal Pozzo, Marcelo; Schlemmer, Karine Bizzi; Alves, Sydney Hartz; Santurio, Janio Morais

    2010-12-01

    NTPDase (EC 3.6.1.5) occurs in lymphocytes and plays an important role in immune function, in that hydrolyzes extracellular nucleoside tri- and/or diphosphates to form AMP. Pythium insidiosum causes the disease pythiosis, a pyogranulomatous disease of horses, dogs, cattle, cats and humans. Most antifungal drugs are ineffective against this pathogen, and immunotherapy, a treatment approach that relies on the injection of P. insidiosum antigen, has been successfully used in humans and horses to manage this disease. In this study, we investigated NTPDase activity in lymphocytes from rabbits inoculated with zoospores of P. insidiosum. After immunotherapy, we investigated the relationship between enzymatic activity and the pattern of the immune response. One milliliter of zoospores was inoculated subcutaneously into the coastal region of each rabbit. An average of 17,500 viable mobile zoospores/mL of induction medium was administered. Inoculated rabbits were checked weekly, and the subcutaneous nodular area (cm²) was measured 28 days after inoculation. Rabbits that developed lesions received four doses of immunotherapy at intervals of 14 days. Blood samples were collected by heart puncture twice a month for the determination of NTPDase activity. The results demonstrated that NTPDase activity in lymphocytes was increased in relation to ATP hydrolysis (by about 100%) in pythiosis and returned to normal values after immunotherapy. The data demonstrating NTPDase activity before and after immunotherapy reinforce the previously elaborated hypothesis that the change from a Th2 to a Th1 immune response is responsible for the curative properties of immunotherapy. PMID:20970953

  19. Animal studies of neonatal hypothermic neuroprotection have translated well in to practice.

    PubMed

    Gunn, Alistair J; Thoresen, Marianne

    2015-12-01

    The discovery that mild, induced hypothermia can improve neurological recovery after global moderate to severe hypoxia-ischemia has been a dramatic validation of the strong foundation of preclinical studies that informed current protocols. The major challenge is to find ways to further improve outcomes. As discussed in this review, the findings from large clinical trials of extended cooling are highly concordant with recent animal studies. These findings support the use of precise, carefully selected animal models to refine our strategies to protect babies with moderate to severe encephalopathy before instigating further large trials. PMID:25930163

  20. The Role of Prenatal Care and Social Risk Factors in the Relationship between Immigrant Status and Neonatal Morbidity: A Retrospective Cohort Study

    PubMed Central

    Sarabia-Lavín, Raquel; Bolumar, Francisco; Rioja, Luis; Delgado, Abraham

    2015-01-01

    Background and Aim Literature evaluating association between neonatal morbidity and immigrant status presents contradictory results. Poorer compliance with prenatal care and greater social risk factors among immigrants could play roles as major confounding variables, thus explaining contradictions. We examined whether prenatal care and social risk factors are confounding variables in the relationship between immigrant status and neonatal morbidity. Methods Retrospective cohort study: 231 pregnant African immigrant women were recruited from 2007–2010 in northern Spain. A Spanish population sample was obtained by simple random sampling at 1:3 ratio. Immigrant status (Spanish, Sub-Saharan and Northern African), prenatal care (Kessner Index adequate, intermediate or inadequate), and social risk factors were treated as independent variables. Low birth weight (LBW < 2500 grams) and preterm birth (< 37 weeks) were collected as neonatal morbidity variables. Crude and adjusted odds ratios (OR) were estimated by unconditional logistic regression with 95% confidence intervals (95% CI). Results Positive associations between immigrant women and higher risk of neonatal morbidity were obtained. Crude OR for preterm births in Northern Africans with respect to nonimmigrants was 2.28 (95% CI: 1.04–5.00), and crude OR for LBW was 1.77 (95% CI: 0.74–4.22). However, after adjusting for prenatal care and social risk factors, associations became protective: adjusted OR for preterm birth = 0.42 (95% CI: 0.14–1.32); LBW = 0.48 (95% CI: 0.15–1.52). Poor compliance with prenatal care was the main independent risk factor associated with both preterm birth (adjusted OR inadequate care = 17.05; 95% CI: 3.92–74.24) and LBW (adjusted OR inadequate care = 6.25; 95% CI: 1.28–30.46). Social risk was an important independent risk factor associated with LBW (adjusted OR = 5.42; 95% CI: 1.58–18.62). Conclusions Prenatal care and social risk factors were major confounding variables in

  1. Neuroendocrine (NE) cells in rat neonatal lungs. A histochemical and immunocytochemical study.

    PubMed

    Gomez-Pascual, A; Martin-Lacave, I; Moreno, A M; Fernandez, A; Galera, H

    1990-06-01

    A study has been carried out to determine the presence of NE cells in the newborn rat lung. The localization of these cell was achieved by an argyrophil method. Both single NE and NEB, were found. Immunoperoxidase techniques were performed to determine NSE, serotonin and calcitonin production in these NE formations.

  2. Auditory Habituation in the Fetus and Neonate: An fMEG Study

    ERIC Educational Resources Information Center

    Muenssinger, Jana; Matuz, Tamara; Schleger, Franziska; Kiefer-Schmidt, Isabelle; Goelz, Rangmar; Wacker-Gussmann, Annette; Birbaumer, Niels; Preissl, Hubert

    2013-01-01

    Habituation--the most basic form of learning--is used to evaluate central nervous system (CNS) maturation and to detect abnormalities in fetal brain development. In the current study, habituation, stimulus specificity and dishabituation of auditory evoked responses were measured in fetuses and newborns using fetal magnetoencephalography (fMEG). An…

  3. Combinations of Radiotherapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    PubMed Central

    Barker, Christopher A.; Postow, Michael A.

    2015-01-01

    Radiotherapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiotherapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiotherapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiotherapy. The cytokines interferon-alpha and interleukin-2 have been combined with radiotherapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiotherapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested radiotherapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiotherapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study. PMID:24661650

  4. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    SciTech Connect

    Barker, Christopher A.; Postow, Michael A.

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study