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Sample records for neonatal immunotherapy study

  1. Immunotherapy

    MedlinePlus

    ... boost your immune system to work better against cancer. Immunotherapy Can Cause Side Effects Immunotherapy can cause side ... work. Related Resources Targeted Therapy Biological Therapies for Cancer Immunotherapy: Using the Immune System to Treat Cancer Posted: ...

  2. Cancer immunotherapy.

    PubMed

    Bergman, Philip J

    2010-05-01

    The veterinary oncology profession is uniquely able to contribute to the many advances that are imminent in immunotherapy. However, what works in a mouse will often not reflect the outcome in human patients with cancer. Therefore, comparative immunotherapy studies using veterinary patients may be better able to bridge murine and human studies. Many cancers in dogs and cats seem to be stronger models for their counterpart human tumors than presently available murine model systems. This author looks forward to the time when immunotherapy plays a significant role in the treatment and/or prevention of cancer in human and veterinary patients.

  3. Factors influencing the prescription of allergen immunotherapy: the allergen immunotherapy decision analysis (AIDA) study.

    PubMed

    Frati, F; Incorvaia, C; Cadario, G; Fiocchi, A; Senna, G E; Rossi, O; Romano, A; Scala, E; Romano, C; Ingrassia, A; Zambito, M; Dell'albani, I; Scurati, S; Passalacqua, G; Canonica, G W

    2013-10-01

    The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy has been demonstrated by a number of meta-analyses. However, the daily practice of AIT is quite different from controlled trials, facing challenges in terms of selection of patients, practical performance, and, of particular importance, use of allergen extracts of inadequate quality. We here performed a survey, named the Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are used by specialists to choose a product for sublingual immunotherapy (SLIT) in patients with respiratory allergy. A questionnaire composed of 14 items to be ranked by each participant according to the importance attributed when choosing SLIT products was submitted to 444 Italian specialists. The responses of the 169 (38.1%) physicians, who answered all questions, were analysed. Most of the respondents were allergists (79%), followed by pulmonologists (10.8%), both allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of the respondents were males and 40.2% were females. The age distribution showed that 89.9% of the respondents were aged between 35 and 64 years. All respondents usually prescribed AIT products in their clinical practice: 31.4% used only SLIT, whereas 69.2% used both subcutaneous and sublingual administration. The rankings, expressed as means, attributed by physicians for each of the 14 items were as follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44), level of EBM validation of safety (4.30), standardization of the product (5.37), efficacy based on personal experience (5.82), defined content(s) of the major allergen(s) in micrograms (5.96), scientific evidence for each single allergen (6.17), safety based on personal experience (6.32), ease of administration protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose personalization (9.24), patient preference (9.25), ease of product storage (9.93), reimbursement

  4. 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.

  5. [Study of neonatal malnutrition risk in the Zaire milieu].

    PubMed

    Tandu-Umba, N F; Mputa Lobota, A; Bouillon, R

    1996-01-01

    This study is intended to assess neonatal risk of malnutrition owed to maternal energy intake lower than 2000 kcal/day among Zairian primiparae. Ninety-eight mother-neonate couples were classified according to the level of maternal energy intake. Neonatal albuminemia which previously showed itself as neonatal nutritional marker served for grouping neonates. Possibility of reaching optimal albuminemia value (29,34 g/l) was assessed according to different maternal energy profiles, using U-test and Chi 2. When maternal intake is lower than 2000 kcal/day, neonatal optimum is reached in 26% of cases; when maternal recommendation is lowered to 1675,21 kcal/day, neonatal optimum is reached in 63,43% of cases; with 2000 kcal/day as recommendation, this rate rises up to 71,4%. Under 2000 kcal/day neonatal risk of malnutrition is thus very high.

  6. Rush allergen specific immunotherapy protocol in feline atopic dermatitis: a pilot study of four cats.

    PubMed

    Trimmer, Ann M; Griffin, Craig E; Boord, Mona J; Rosenkrantz, Wayne S

    2005-10-01

    Rush immunotherapy has been shown to be as safe as conventional immunotherapy in canine atopic patients. Rush immunotherapy has not been reported in the feline atopic patient. The purpose of this pilot study was to determine a safe protocol for rush immunotherapy in feline atopic patients. Four atopic cats diagnosed by history, physical examination and exclusion of appropriate differential diagnoses were included in the study. Allergens were identified via liquid phase immunoenzymatic testing (VARL: Veterinary Allergy Reference Labs, Pasadena, CA). Cats were premedicated with 1.5 mg triamcinolone orally 24 and 2 h prior to first injection and 10 mg hydroxyzine PO 24, 12 and 2 h prior to first injection. An intravenous catheter was placed prior to first injection. Allergen extracts (Greer Laboratories, Lenoir, North Carolina) were all administered subcutaneously at increasing protein nitrogen units (pnu) every 30 minutes for 5 h to maintenance dose of 15,000 pnus ml-1. Vital signs were assessed every 15 minutes. Two cats developed mild pruritus and the subsequent injection was delayed 30 minutes. No changes in either cat's vital signs were noted, nor was there any further pruritus. All four cats successfully completed rush immunotherapy. Two cats developed a dermal swelling on the dorsal neck one week later. In these four cats, this protocol appeared to be a safe regimen to reach maintenance therapy. A larger sample of feline patients is needed to determine the incidence of adverse reactions and to follow the success of ASIT based upon this method of induction.

  7. 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

  8. 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.

  9. Cancer Immunotherapy

    MedlinePlus

    Immunotherapy is a cancer treatment that helps your immune system fight cancer. It is a type of biological therapy. Biological therapy uses substances ... t yet use immunotherapy as often as other cancer treatments, such as surgery, chemotherapy, and radiation therapy. ...

  10. Engineered Human Embryonic Stem Cell-Derived Lymphocytes to Study In Vivo Trafficking and Immunotherapy

    PubMed Central

    Knorr, David A.; Bock, Allison; Brentjens, Renier J.

    2013-01-01

    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. PMID:23421330

  11. 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.

  12. Neonatal brain image segmentation in longitudinal MRI studies.

    PubMed

    Shi, Feng; Fan, Yong; Tang, Songyuan; Gilmore, John H; Lin, Weili; Shen, Dinggang

    2010-01-01

    In the study of early brain development, tissue segmentation of neonatal brain MR images remains challenging because of the insufficient image quality due to the properties of developing tissues. Among various brain tissue segmentation algorithms, atlas-based brain image segmentation can potentially achieve good segmentation results on neonatal brain images. However, their performances rely on both the quality of the atlas and the spatial correspondence between the atlas and the to-be-segmented image. Moreover, it is difficult to build a population atlas for neonates due to the requirement of a large set of tissue-segmented neonatal brain images. To combat these obstacles, we present a longitudinal neonatal brain image segmentation framework by taking advantage of the longitudinal data acquired at late time-point to build a subject-specific tissue probabilistic atlas. Specifically, tissue segmentation of the neonatal brain is formulated as two iterative steps of bias correction and probabilistic-atlas-based tissue segmentation, along with the longitudinal atlas reconstructed by the late time image of the same subject. The proposed method has been evaluated qualitatively through visual inspection and quantitatively by comparing with manual delineations and two population-atlas-based segmentation methods. Experimental results show that the utilization of a subject-specific probabilistic atlas can substantially improve tissue segmentation of neonatal brain images.

  13. What Is Cancer Immunotherapy?

    MedlinePlus

    ... and Side Effects Treatment Types Immunotherapy What is cancer immunotherapy? Immunotherapy is treatment that uses certain parts of ... so that it will destroy them. Types of cancer immunotherapy The main types of immunotherapy now being used ...

  14. Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of Cancer Immunotherapies.

    PubMed

    Hambach, Lothar; Buser, Andreas; Vermeij, Marcel; Pouw, Nadine; van der Kwast, Theo; Goulmy, Els

    2016-01-01

    Cellular immunotherapy targeting human tumor antigens is a promising strategy to treat solid tumors. Yet clinical results of cellular immunotherapy are disappointing. Moreover, the currently available in vitro human tumor models are not designed to study the optimization of T-cell therapies of solid tumors. Here, we describe a novel assay for multiparametric in situ analysis of therapeutic effects on individual human three-dimensional (3D) tumors. In this assay, tumors of several millimeter diameter are generated from human cancer cell lines of different tumor entities in a collagen type I microenvironment. A newly developed approach for efficient morphological analysis reveals that these in vitro tumors resemble many characteristics of the corresponding clinical cancers such as histological features, immunohistochemical staining patterns, distinct tumor growth compartments and heterogeneous protein expression. To assess the response to therapy with tumor antigen specific T-cells, standardized protocols are described to determine T-cell infiltration and tumor destruction by monitoring soluble factors and tumor growth. Human tumors engineered in 3D collagen scaffolds are excellent in vitro surrogates for avascular tumor stages allowing integrated analyses of the antitumor efficacy of cancer specific immunotherapy in situ.

  15. Consanguinity and Neonatal Death: A Nested Case-Control Study

    PubMed Central

    Chaman, Reza; Gholami Taramsari, Mahshid; Khosravi, Ahmad; Amiri, Mohammad; Holakouie Naieni, Kourosh; Yunesian, Masoud

    2014-01-01

    Objective: Although numerous studies have found higher rates of abortion and still births following consanguinity (familial marriages), the question of whether consanguinity significantly increases the risk of neonatal death has inadequately been addressed.This study aims to evaluate familial marriage effects on neonatal death in rural areas in Iran. Materials and methods: In this nested case-control study, 6900 newbornswho were born in rural areas of Kohgiluyeh and Boyerahmad Province (South-West of Iran)were followed till the end of neonatal period, and neonatal death was the outcome of interest. Subsequently 97 cases and 97 controls were selected in study cohort by using risk set sampling model. Crude and adjusted odds ratios (OR) were estimated by usinga conditional logistic regression model. Results: In the final model, prematurity (OR = 5.57), low birthweight (LBW) (OR = 7.68), consanguinity (first cousins) (OR = 5.23), C-section (OR = 7.27), birth rank more than 3 (OR = 6.95) and birthsinterval less than 24 months (OR = 4.65) showed significant statistical association with neonatal mortality (p < 0.05). Conclusion: According to our findings, after adjusting the effects of other significant risk factors, familial marriageto first cousins is considered asan important risk factor for neonatal death. PMID:25530772

  16. 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

  17. Cancer immunotherapy

    PubMed Central

    Manjili, Masoud H.; Payne, Kyle K.

    2012-01-01

    Cancers utilize multiple mechanisms to overcome immune responses. Emerging evidence suggest that immunotherapy of cancer should focus on inducing and re-programming cells of the innate and adaptive immune systems rather than focusing solely on T cells. Recently, we have shown that such a multifaceted approach can improve immunotherapy of breast cancer. PMID:22720242

  18. Poliomyelitis, measles and neonatal tetanus: a hospital based epidemiological study.

    PubMed

    El Shazly, M K; Atta, H Y; Kishk, N A

    1997-01-01

    Vaccine-preventable diseases constitute a major health problem contributing to the morbidity and mortality in many developing countries including Egypt. WHO adopted resolutions to eradicate poliomyelitis by the year 2000, eliminate neonatal tetanus by the year 1995, and reduce measles mortality by 95% and morbidity by 90%, compared to the pre-immunization levels by 1995. Evaluation of preventive programs for these diseases necessitates availability of up to date information on their occurrence. The present study was undertaken to determine the current epidemiological features of poliomyelitis, neonatal tetanus and measles, to identify the trends of these diseases as well as to determine their outcomes and hospital loads. Data about the admitted cases of poliomyelitis, neonatal tetanus and measles were collected from the hospital register of Alexandria fever hospital for five successive years (1992-96). Available information on age, sex, residence, diagnosis, outcome of treatment, dates of admission and discharge were collected. The total number of cases of the three diseases admitted to the hospital during the period 1992-96 were 1406, measles represented 85.4%, neonatal tetanus 13.9% and poliomyelitis 0.7%. The results revealed that in the year 1994 only one case of poliomyelitis was admitted and since then no other cases were reported. The number of measles cases increased gradually in the latter years and about 78% of them were older than five years of age. A significant increase in the age of measles occurrence was observed. A gradual decline in the number of neonatal tetanus cases was observed. These cases were more apt to occur among early neonates but still clustered in certain geographical areas. The results of the study pinpoint the long term impact of the well run program aiming at eradicating poliomyelitis in Alexandria. However, for elimination of neonatal tetanus and controlling measles morbidity, further activities are required including strengthening

  19. A Survey of Neonatal Pharmacokinetic and Pharmacodynamic Studies in Pediatric Drug Development.

    PubMed

    Wang, J; Avant, D; Green, D; Seo, S; Fisher, J; Mulberg, A E; McCune, S K; Burckart, G J

    2015-09-01

    Conducting clinical trials in neonates is challenging, and knowledge gaps in neonatal clinical pharmacology exist. We surveyed the US Food and Drug Administration databases and identified 43 drugs studied in neonates or referring to neonates between 1998 and 2014. Twenty drugs were approved in neonates. For 10 drugs, approval was based on efficacy data in neonates, supplemented by pharmacokinetic data for four drugs. Approval for neonates was based on full extrapolation from older patients for six drugs, and partial extrapolation was the basis of approval for four drugs. Dosing recommendations differed from older patients for most drugs, and used body-size based adjustment in neonates. Trial failures were associated with various factors including inappropriate dose selection. Successful drug development in neonates could be facilitated by an improved understanding of the natural history and pathophysiology of neonatal diseases and identification and validation of clinically relevant biomarkers.

  20. Impact of oral immunotherapy on quality of life in children with cow milk allergy: a pilot study.

    PubMed

    Carraro, S; Frigo, A C; Perin, M; Stefani, S; Cardarelli, C; Bozzetto, S; Baraldi, E; Zanconato, S

    2012-01-01

    Quality of life is negatively affected in children with food allergy. Oral immunotherapy is an approach to food allergy that leads to patient desensitization by administering gradually increasing amounts of a given food allergen. The aim of this pilot study is to evaluate how oral immunotherapy affects quality of life in children allergic to cow milk proteins. Thirty children (aged 3-12 years) with cow milk allergy were recruited. Their parents were provided with a validated disease specific quality of life questionnaire (the food allergy quality of life questionnaire -- parent form, FAQLQ-PF) before and again 2 months after completing an oral immunotherapy protocol with cow milk. A significant improvement in all the investigated domains -- emotional impact, food anxiety and social and dietary limitations -- was found. The separate analysis of the different age groups demonstrated that the emotional impact and the food-related anxiety improved in children older than 4, while the social domains improved in each age group. In this pilot experience, oral immunotherapy significantly improves quality of life in children with cow milk allergy. The improvement seems particularly evident in children over 4 years old, who are most likely to benefit from the oral immunotherapy approach. Further placebo-controlled studies are needed to confirm these preliminary results.

  1. 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

  2. A study on neonatal calf diarrhea induced by rotavirus.

    PubMed

    Castrucci, G; Ferrari, M; Frigeri, F; Traldi, V; Angelillo, V

    1994-01-01

    This review summarizes the results of a study on rotaviruses isolated from calves affected by neonatal diarrhea. The results indicated that rotavirus infection is widespread and supported the evidence for an etiologic role of these viruses in neonatal diarrhea. Differences in virulence among bovine rotaviruses appeared also to be confirmed. Conventionally reared calves were fully susceptible to the experimental infection induced by rotaviruses originating from heterologous hosts, i.e. monkeys, pigs and rabbits. When rotavirus strains of bovine, simian and rabbit origin were compared by cross neutralization tests, it was found the simian and porcine strains were indistinguishable and both appeared to relate antigenically to the bovine strain. Finally, it was proven that feeding newborn calves with colostrum and first milk of their dams, previously vaccinated with an inactivated adjuvanted rotavirus vaccine, could prevent the neonatal diarrhea from occurring.

  3. Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study

    PubMed Central

    Wang, Chen-Hong; Du, Li-Zhong; Ma, Xiao-Lu; Shi, Li-Ping; Tong, Xiao-Mei; Liu, Hong; Ding, Guo-Fang; Yi, Bin; Pan, Xin-Nian; Zhong, Dan-Ni; Liu, Ling; Li, Mei; Liu, Cui-Qing; Xia, Shi-Wen; Wang, Hong-Yun; He, Ling; Liang, Kun; Zhou, Xiao-Yu; Han, Shu-Ping; Lyu, Qin; Qiu, Yin-Ping; Shan, Ruo-Bing; Mu, De-Zhi; Liu, Xiao-Hong; Zhuang, Si-Qi; Guo, Jing; Liu, Li; Zhu, Jia-Jun; Xiong, Hong

    2016-01-01

    Background: Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37–41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China. Methods: All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed. Results: A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents’ concern about the long-term outcomes was the main reason of medical care withdrawal. Conclusions: Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to

  4. Anti-Aß immunotherapy in Alzheimer's disease; relevance of transgenic mouse studies to clinical trials

    PubMed Central

    Wilcock, Donna M.; Colton, Carol A.

    2009-01-01

    Therapeutic approaches to the treatment of Alzheimer's disease are focused primarily on the Aß peptide which aggregates to form amyloid deposits in the brain. The amyloid hypothesis states that amyloid is the precipitating factor that results in the other pathologies of Alzheimer's, namely neurofibrillary tangles and neurodegeneration, as well as the clinical dementia. One such therapy that has attracted significant attention is anti-Aß immunotherapy. First described in 1999, immunotherapy uses anti-Aß antibodies to lower brain amyloid levels. Active immunization, in which Aß is combined with an adjuvant to stimulate an immune response producing antibodies and passive immunization, in which antibodies are directly injected, were shown to lower brain amyloid levels and improve cognition in multiple transgenic mouse models. Mechanisms of action were studied in these mice and revealed a complex set of mechanisms that depended on the type of antibody used. When active immunization advanced to clinical trials a subset of patients developed meningoencephalitis; an event not predicted in mouse studies. However, it was suspected that a T-cell response due to the type of adjuvant used was the cause of the meningoencephalitis and studies in mice indicated alternative methods of vaccination. Passive immunization has also advanced to phase III clinical trials on the basis of successful transgenic mouse studies. Reports from the active immunization clinical trial indicated that, indeed, amyloid levels in brain were reduced. While APP transgenic mouse models are useful in studying amyloid pathology these mice do not generate significant tau pathology or neuron loss. Continued development of new mouse models that do generate all of these pathologies will be critical in more accurately testing therapeutics and predicting the clinical outcome of such therapeutics. PMID:19096156

  5. Prospective study of percutaneous cryoablation combined with allogenic NK cell immunotherapy for advanced renal cell cancer.

    PubMed

    Lin, Mao; Xu, Kecheng; Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, LiZhi

    2017-03-05

    In this study, the clinical efficacy of cryosurgery combined with allogenic NK cell immunotherapy for advanced renal cell cancer was evaluated. From July to December 2016, we enrolled 60 patients who met the enrollment criteria and divided them into two groups: (1) the simple cryoablation group (n=30); and (2) the cryoablation combined with allogenic NK cells group (n=30). The clinical efficacy, quality of life, immune function, and other related indicators were evaluated. Combining allogeneic NK cells with cryoablation had a synergistic effect, not only enhancing the immune function and improving the quality of life of the patients, but also significantly exhibiting good clinical efficacy of the patients. This study is the first clinical trial that has evaluated the safety and efficacy of allogenic NK cells combined with cryosurgery for the treatment of renal cell cancer.

  6. Innovative Strategies for Breast Cancer Immunotherapy

    DTIC Science & Technology

    2014-09-01

    AWARD NUMBER: W81XWH-12-1-0223 TITLE: Innovative Strategies for Breast Cancer Immunotherapy ...studies (2). A promising approach in cancer treatment is adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells to redirect...multiple tissues. DISCUSSION Adoptive immunotherapy is a promising approach for the treatment of cancer , and observations from preclinical and

  7. Autoimmune Cardiotoxicity of Cancer Immunotherapy.

    PubMed

    Cheng, Feixiong; Loscalzo, Joseph

    2017-02-01

    Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.

  8. Anatomic variations of the coracoacromial ligament in neonatal cadavers: a neonatal cadaver study.

    PubMed

    Kopuz, Cem; Baris, Sancar; Yildirim, Mehmet; Gülman, Birol

    2002-10-01

    One of the most common causes of pain and disability in the upper limb is inflammation of the rotator cuff tendons. When no significant bony abnormality exists in the surrounding structures, the coracoacromial ligament has been implicated as a possible cause of impingement on the cuff tendons and various morphological variants of the ligament have so far been claimed to be either the cause or the result of impingement. In this study, 110 shoulders from 60 neonatal cadavers that were preserved in a preparation of formaldehyde were dissected. Anatomic variations of coracoacromial ligaments were investigated with metric and histologic analysis. Three main ligament types were identified: quadrangular, broad band and U-shaped. The multiple banded ligament was not found. Histologic analysis showed that in U-shaped ligaments a thin tissue existed in the central part of the ligament close to the coracoid. Comparing our data with the adult measurements of a previous study we suggest that the primordial ligament is broad shaped, but assumes a quadrangular shape due to the different growth rates of the coracoid and acromial ends. We also suggest that broad and U-shaped ligaments account for the primordial and quadrangular and Y-shaped ligaments account for the adult types of the single or double banded anatomic variants respectively. Our results show that various types of the coracoacromial ligament are present at the neonatal period and that the final shape of the ligament should be defined by developmental factors, rather than degenerative changes.

  9. Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study

    PubMed Central

    Phiri-Mazala, Grace; Guerina, Nicholas G; Kasimba, Joshua; Mulenga, Charity; MacLeod, William B; Waitolo, Nelson; Knapp, Anna B; Mirochnick, Mark; Mazimba, Arthur; Fox, Matthew P; Sabin, Lora; Seidenberg, Philip; Simon, Jonathon L; Hamer, Davidson H

    2011-01-01

    Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. Design Prospective, cluster randomised and controlled effectiveness study. Setting Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers’ homes, in rural village settings. Participants 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district. Interventions Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits). Main outcome measures The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data. Results Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by

  10. 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.

  11. Cancer immunotherapy.

    PubMed

    Bergman, Philip J

    2009-08-01

    The immune system is generally divided into 2 primary components: the innate immune response, and the highly specific but more slowly developing adaptive or acquired immune response. Immune responses can be further separated by whether they are induced by exposure to a foreign antigen (an "active" response) or whether they are transferred through serum or lymphocytes from an immunized individual (a "passive" response). The ideal cancer immunotherapy agent should be able to discriminate between cancer and normal cells (ie, specificity), be potent enough to kill small or large numbers of tumor cells (ie, sensitivity), and lastly be able to prevent recurrence of the tumor (ie, durability). Tumor immunology and immunotherapy is one of the most exciting and rapidly expanding fields at present.

  12. Development of a Model to Study the Abscopal Effect: Combining Image-Guided Radiation Therapy and Immunotherapy in Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Moretti, Amanda

    Distant metastases are a limiting factor in cancer patient survival as they are least accessible to conventional therapies. Effective therapy should treat primary tumours and metastatic disease. Use of image-guided radiation therapy (IGRx) enables high doses of radiation to be delivered for better tumour control while minimizing toxicity to healthy tissues. Systemic effects on distant non-irradiated tissues have been observed following IGRx. This phenomenon, termed the abscopal effect, is hypothesized to be mediated by the immune system. The inflammatory milieu generated following IGRx may activate immune cells to mount specific anti-tumour responses. The work described in this thesis aims to develop a model to study the abscopal effect, and evaluate the potential of combining IGRx and immunotherapy to enhance such distant tumour killing. Results from these studies may have clinical implications, where a combined IGRx and immunotherapy approach may prove useful in eliciting regression of local tumours and distant metastases.

  13. Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study.

    PubMed

    Ovali, E; Dikmen, T; Sonmez, M; Yilmaz, M; Unal, A; Dalbasti, T; Kuzeyli, K; Erturk, M; Omay, S B

    2007-06-01

    Cancer vaccine therapy represents a promising therapeutical option. Consistently, with these new treatment strategies, the use of dendritic cell vaccines is becoming increasingly widespread and currently in the forefront for cancer treatment. The purpose of this study was to evaluate the feasibility and safety of tumor lysate-pulsed dendritic cell (DC) vaccine in patients with advanced cancers. For this purpose, eighteen patients with relapsed or refractory cancer were vaccinated with peripheral monocyte-derived DCs generated with GM-CSF and IL-4, and pulsed consequently with 100 microg/ml of tumor lysate before maturation in culture in the presence of IL-1beta, PGE2 and TNF alpha for two days. The first two vaccinations were given intradermally every two weeks while further injections were given monthly. Tumor lysate-pulsed dendritic cell injections were well-tolerated in all patients with no more than grade 1 injection-related toxicity. Local inflammatory response was mainly erythematous which subsided in 48 hrs time. No end organ toxicity or autoimmune toxicity was identified. Clinical responses observed in our study were satisfactory for a phase I clinical study. We observed 4 (22%) objective clinical responses. These responses are significantly correlated with delayed type hypersensitivity testing (DTH) (p < 0.01). The results showed that this active immunotherapy is feasible, safe, and may be capable of eliciting immune responses against cancer.

  14. Epitope peptides and immunotherapy.

    PubMed

    Tanabe, Soichi

    2007-02-01

    Allergic diseases affect atopic individuals, who synthesize specific Immunoglobulins E (IgE) to environmental allergens, usually proteins or glycoproteins. These allergens include grass and tree pollens, indoor allergens such as house dust mites and animal dander, and various foods. Because allergen-specific IgE antibodies are the main effector molecules in the immune response to allergens, many studies have focused on the identification of IgE-binding epitopes (called B cell epitopes), specific and minimum regions of allergen molecules that binds to IgE. Our initial studies have provided evidence that only four to five amino acid residues are enough to comprise an epitope, since pentapeptide QQQPP in wheat glutenin is minimally required for IgE binding. Afterwards, various kinds of B cell epitope structures have been clarified. Such information contributes greatly not only to the elucidation of the etiology of allergy, but also to the development of strategies for the treatment and prevention of allergy. Allergen-specific T cells also play an important role in allergy and are obvious targets for intervention in the disease. Currently, the principle approach is to modify B cell epitopes to prevent IgE binding while preserving T cell epitopes to retain the capacity for immunotherapy. There is mounting evidence that the administration of peptide(s) containing immunodominant T cell epitopes from an allergen can induce T cell nonresponsiveness (immunotherapy). There have been clinical studies of peptide immunotherapy performed, the most promising being for bee venom sensitivity. Clinical trials of immunotherapy for cat allergen peptide have also received attention. An alternative strategy for the generation of an effective but hypoallergenic preparation for immunotherapy is to modify T cell epitope peptides by, for example, single amino acid substitution. In this article, I will present an overview of epitopes related to allergic disease, particularly stress on

  15. Immunotherapy for cancer.

    PubMed

    Leong, S P

    1993-10-01

    The study of the immune system on the cellular and molecular level has made significant strides over the past several decades. The role of immune system against infection is self-evident. Although the role of the immune system in the immune surveillance of cancer has not been proven, the immune system is believed to play an interactive role in the regulation of tumor growth. Immunotherapy is the application of the immune system to fight against the tumor. Although immunotherapeutic approaches have been tried in many types of cancer, both malignant melanoma and renal cell carcinoma seem to show occasional, but definitive response to immunotherapy. The fact that immune eradication of tumor is most efficient when the tumor burden is minimal speaks for the fact that immunotherapy may be most effective for control of microscopic disease. Therefore, to maximize the effect of immunotherapy, the tumor burden needs to be reduced, hopefully to microscopic level either by surgery or in combination with chemotherapy and radiation therapy. Also, new strategies are needed to develop more potent vaccines and stimulate effector cells to eradicate tumor cells under the most optimal conditions.

  16. [Immunotherapies for drug addictions].

    PubMed

    Montoya, Ivan

    2008-01-01

    Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders.

  17. Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: an in vivo study.

    PubMed

    Asadi-Ghalehni, Majid; Ghaemmaghami, Mohamad; Klimka, Alexander; Javanmardi, Masoud; Navari, Mohsen; Rasaee, Mohammad Javad

    2015-06-01

    To date, several small molecule inhibitors and monoclonal-antibodies (like ICR-62) have been used to treat tumors over-expressing epidermal growth factor receptor (EGFR). However, the limitations associated with these conventional applications accentuate the necessity of alternative approaches. Mimotopes as compelling molecular tools could rationally be employed to circumvent these drawbacks. In the present study, an M13 phage displaying ICR-62 binding peptide mimotope is exploited as a vaccine candidate. It exhibited high affinity towards ICR62 and polyclonal anti-P-BSA antibodies. Following the mice immunization, phage-based mimotope vaccine induced humoral immunity. Elicited anti-EGFR mimotope antibodies were detected using ELISA method. Moreover, the phage vaccine was tested on the Lewis lung carcinoma mice model to investigate the prophylactic and therapeutic effects. The tumor volume was measured and recorded in different animal groups to evaluate the anti-tumor effects of the vaccine. Our data indicate that the reported phage-based mimotope could potentially elicit specific antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor growth. However, in vivo experiments of prophylactic or therapeutic vaccination showed no specific advantage. Furthermore, phage-mimotope vaccine might be a promising approach in the field of cancer immunotherapy.

  18. 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.

  19. Feline immunotherapy.

    PubMed

    Trimmer, Ann M; Griffin, Craig E; Rosenkrantz, Wayne S

    2006-08-01

    Feline allergen specific immunotherapy (ASIT) is considered to be a safe and effective treatment for feline atopy. ASIT is defined as the practice of administering gradually increasing quantities of an allergen extract to an allergic subject. The purpose of which is to reduce or eliminate the symptoms associated with subsequent exposures to the causative allergen. ASIT offers an effective and safe treatment option for cats. Reported success rates range for 60 to 78% in feline atopic patients. Additionally, the reported incidence of side effects in feline atopic patients undergoing ASIT is very low and mainly anecdotal.

  20. 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.

  1. Electrophysiological properties of neonatal rat motoneurones studied in vitro.

    PubMed Central

    Fulton, B P; Walton, K

    1986-01-01

    The electroresponsive properties of neonatal lumbar spinal motoneurones were studied using isolated, hemisected spinal cords from neonatal rats aged 3-12 days. The extracellular and intracellular responses to electrical stimulation of the ventral and dorsal root were studied as well as the intracellular response to current injection. Field potentials recorded in the lateral motor area following electrical stimulation of lumbar ventral roots had a triphasic positive-negative-positive wave form. The negative component did not return to the base line smoothly but exhibited a 'shoulder' where the negativity increased in duration. Following electrical stimulation of the dorsal root, presynaptic field potentials were recorded upon activation of the afferent axons as well as following synaptic activation of interneurones and motoneurones. The input resistances of neonatal motoneurones determined from the slope of current-voltage plots were high compared with the adult. The resistance decreased with age with a mean of 18.1 M omega for animals 3-5 days old, 8.8 M omega for animals 6-8 days old and 5.4 M omega for animals 9-11 days old. Values for the membrane time constant were similar to those in the adult with a mean of 4.5 ms. Action potentials elicited by ventral or dorsal root stimulation or by intracellular current injection were marked by a pronounced after-depolarization (a.d.p.) and an after-hyperpolarization (a.h.p.). The amplitude of the a.h.p. varied with that of the a.d.p. The amplitude of excitatory post-synaptic potentials (e.p.s.p.s) elicited by electrical stimulation of the dorsal root was affected by intracellular current injection. Two types of e.p.s.p.s were distinguished: those with a biphasic reversal (early phase first) and those in which the early phase was unaffected by inward current injection while the later phase was reversed. Unlike in the adult, the reversals could be achieved with low current levels and the amplitude of both types of e

  2. Experimental and numerical studies on convective heat transfer in a neonatal incubator.

    PubMed

    Kim, Y H; Kwon, C H; Yoo, S C

    2002-01-01

    Thermo-neutrality is one of the major environmental factors affecting a premature or low-birth-weight neonate inside an incubator. Severe temperature differences inside an incubator lead to neonate heat loss, hypothermia and apnoea, which are closely related to air flow and air velocity. In the study, flow visualisations, hot-wire velocity measurements and computational fluid dynamics simulate the airflow inside a neonatal incubator. An anatomically correct neonate model is designed using a three-dimensional laser scanner system and a rapid prototyping machine. Flow visualisations demonstrate that large-scale rotating airflow is produced inside the chamber, and a number of small, stationary eddies are found in regions between the air inlet and the neonate. Hot-wire measurements show that air velocities along the long inlets are not uniform. Computational fluid dynamics show relatively uniform temperatures of about 34 degrees C on the neonate's anterior aspect and the highest temperature of 36.1 degrees C at the right armpit and the crotch. Flow fields from airflow visualisations, hot-wire measurements and computational fluid dynamics are very similar, both qualitatively and quantitatively. The small eddies produced between the neonate and the mattress could interfere with convective and evaporative heat transfers from the neonate. Therefore it is important to eliminate eddies around the neonate in future designs of neonatal incubators.

  3. 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.

  4. Epidemiologic study of neonatal jaundice. A survey of contributing factors.

    PubMed

    Bracci, R; Buonocore, G; Garosi, G; Bruchi, S; Berni, S

    1989-01-01

    In the attempt to detect factors influencing bilirubinemia in healthy full-term or near-term newborn infants, a statistical analysis was carried out on a population of 1,126 neonates to study the variables possibly associated with maximum bilirubin values reached in the first days of life. The following variables were studied: maximum bilirubin level (maxBIL), sex, mode of delivery, gestational age, birthweight, ratio of birthweight/weight on 5th day, Apgar score, Rh and ABO incompatibility. Blood glucose and calcium levels, haematocrit, intake of breast milk, formula and glucose solution were also evaluated during the first 5 days of life. Higher maxBIL was found in males compared to females, after spontaneous delivery vs. emergency caesarean section, after caesarean section without fetal distress vs. emergency caesarean section, and in ABO incompatibility vs. no ABO incompatibility. Statistically significant inverse correlations were observed between maxBIL and gestational age, birth weight, blood glucose, and SE-calcium. Significant positive correlations were found between maxBIL and haematocrit and breast milk intake. A multiple regression analysis between maxBIL and the significantly correlated parameters showed that only gestational age and birth weight remained significantly correlated with maxBIL. The results of the present investigation confirm that the factors most commonly reported as being responsible for neonatal hyperbilirubinemia do in fact play a role, although it can be considered almost negligible with the exception of gender, mode of delivery, ABO incompatibility, birthweight and gestational age.

  5. 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

  6. Physical Activity in Pregnancy and Neonatal Body Composition: The Healthy Start Study

    PubMed Central

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

    2014-01-01

    Objective To examine associations between pregnancy physical activity and neonatal fat mass and fat-free mass, birth weight and small for gestational age (SGA). Methods We analyzed 826 mother-neonate pairs (term births) participating in the longitudinal Healthy Start study. The Pregnancy Physical Activity Questionnaire was used to assess total energy expenditure and meeting American College of Obstetricians and Gynecologists (the College) guidelines for physical activity during early pregnancy, mid-pregnancy and late pregnancy. Models were adjusted for maternal and neonatal characteristics. Results Neonates had mean fat mass of 292.9 grams, fat-free mass of 2,849.8 g, and birth weight of 3,290.7 g. We observed 107 (12.9%) SGA and 30 (3.6%) large-for-gestational age (LGA) births. A significant inverse linear trend between total energy expenditure during late pregnancy and neonatal fat mass (Ptrend = 0.04) was detected. Neonates of mothers in the highest compared to lowest quartile of total energy expenditure during late pregnancy had 41.1 g less fat mass (249.4 vs. 290.5 g; P = 0.03). No significant trend was found with total energy expenditure and neonatal fat-free mass or birth weight. Early-pregnancy and mid-pregnancy total energy expenditure were not associated with neonatal outcomes. No significant trend was observed between late-pregnancy total energy expenditure and SGA (Ptrend = 0.07), but neonates of mothers in the highest compared to the lowest quartile had a 3.0 (95% CI 1.4–6.7) higher likelihood of SGA. Meeting the College’s physical activity guidelines during pregnancy was not associated with differences in neonatal outcomes. Conclusions Increasing levels of late-pregnancy total energy expenditure are associated with decreased neonatal adiposity without significantly reduced neonatal fat-free mass. PMID:25004346

  7. 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.

  8. Intraventricular hemorrhage in term neonates with hypoxic-ischemic encephalopathy: a comparison study between neonates treated with and without hypothermia

    PubMed Central

    Gorelik, Natalia; Daneman, Alan; Epelman, Monica

    2016-01-01

    Background To retrospectively determine the prevalence of intraventricular hemorrhage (IVH) in term neonates with hypoxic-ischemic encephalopathy (HIE) using head ultrasound (HUS) and MRI, and to compare the incidence of IVH in term babies with HIE treated by therapeutic hypothermia versus those managed conventionally. Methods A total of 61 term neonates from two institutions were diagnosed with HIE shortly after birth. Thirty infants from one institution were treated with whole body hypothermia. These infants had to satisfy the entry criteria for the neonatal hypothermia protocol of the institution. Thirty-one neonates underwent conventional treatment at the second institution. At that time, hypothermia was not yet a standard of care at that institution. All the neonates underwent HUS in their first 23 days of life. The 54 survivors also underwent MRI. The imaging studies were all reviewed for IVH. Results Amongst the 30 babies, who received whole body hypothermia, there were 18 males and 12 females, the mean birth weight was 3.5 kg (2.5 to 5.2 kg), and the HUS study was performed within 14.8 to 41 hours of life. The group of 31 infants treated conventionally was comprised of 12 boys and 19 girls, the infants had an average birth weight of 3.3 kg (2.3 to 4.2 kg), and they underwent HUS 1 to 23 days after birth, with only five children being older than 1 week at the time of the imaging studies. Four of the 61 infants (7%) were diagnosed with IVH on HUS. Three were confirmed with MRI. The fourth case showed a bilateral enlarged choroid plexus on HUS, but IVH could not be confirmed with MRI, as the infant did not survive. In the group of neonates treated with hypothermia, there were three cases (10%) of IVH, whereas in the group managed conventionally, IVH occurred in one infant (3%). Conclusions Our study shows that IVH remains uncommon in term infants with HIE. IVH was more prevalent in the group treated with hypothermia. PMID:27942469

  9. Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study

    PubMed Central

    2013-01-01

    Background Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. Methods/Design Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal post-partum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. Discussion This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring. PMID

  10. 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…

  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. Bio-immunotherapy for cancer in experimental studies and clinical application: current status and future challenges.

    PubMed

    Shen, R N; Lu, L; Kaiser, H E; Broxmeyer, H E

    1994-01-01

    Although successful treatment of patients with primary tumor by conventional surgery and radiotherapy is often possible, death frequently results from tumor metastases. Since metastasis has already occurred in many cancer patients at the time of diagnosis, a major emphasis of cancer treatment is and will continue to be the prevention or successful management of tumor metastases. Systemic chemotherapy has been widely used in the past in the hope of preventing or controlling micrometastases. The results of this treatment have been disappointing with little impact on survival in the vast majority of solid tumors. Bio-immunotherapy has emerged as another modality and is finding acceptance and use in treating patients with cancer. The role of bio-immunotherapy in traditional surgery, radiotherapy, chemotherapy and hyperthermia will be discussed. In order to evaluate new and innovative treatments, we and others have used murine models of erythroleukemia and solid tumors with metastatic potential to assess the effects in vivo of bio-immunotherapy. Tumor metastases can be dampened and immunosuppression restored by bio-immunotherapy, especially when used in combination with other forms of treatment. Most of the combination treatments used in animal models are encouraging but are by no means totally adequate or curative yet. The molecular basis of cancer is now understood to involve activation of dominant oncogenes and inactivation of tumor suppressor genes. These genetic events may represent novel targets for cancer treatment. The potential use and ethical implications of gene transfer to alter the behavior of somatic cells in patients with cancer has been noted. Also reported is genetic immunomodulation by introducting genes for cytokines into tumor cells or lymphocytes to stimulate a cytotoxic immune response against the tumor. As with bone marrow, human cord blood can be used for transplantation in the autologous, related allogeneic and unrelated allogeneic settings, and

  13. A study of neurosonogram abnormalities, clinical correlation with neurosonogram findings, and immediate outcome of high-risk neonates in Neonatal Intensive Care Unit

    PubMed Central

    Nagaraj, Niranjan; Berwal, Pramod Kumar; Srinivas, Anusha; Sehra, Ramnarayan; Swami, Sarika; Jeevaji, Prathyusha; Swami, Gotam; Choudary, Lokesh; Berwal, Ayush

    2016-01-01

    Background: Neonatal sonography of the brain is now an essential part of newborn care, particularly in high risk and unstable premature infants. Cranial ultrasound is the most available and easily repeatable imaging technique for the neonatal brain showing brain development and the most frequently occurring forms of cerebral injury in the preterm and terms. This study aims to assess the importance of cranial ultrasound as an investigatory modality for high-risk neonates and to find out the morphology of various cerebral lesions and correlate clinically. Methodology: An observational correlation clinical study was conducted at Sardar Patel Medical College, Bikaner involving 100 high-risk neonates admitted to Neonatal Intensive Care Unit (NICU) who was subjected to neurosonography on selected days as per protocol. Perinatal details were recorded, and clinical examination with appropriate investigations was done. The cranial ultrasound was done, and morphology of various findings was studied and recorded. Clinical correlation with cranial ultrasound findings and follow-up was done. Results: On cranial ultrasound, 38% of neonates had abnormal findings. Twelve percent of these had evidence of intracranial bleed, 13% periventricular echogenicity, 7% had ventriculomegaly, 2% had cerebral edema, and 1% had leukomalacia. Three neonates had findings suggestive of simple cyst in middle cranial fossa, agenesis of corpus callosum, and choroid plexus cyst. Conclusions: Cranial ultrasonography is the best point of care neuroimaging method available for high-risk neonates. It is critical as an investigatory modality in NICU and effectively documents morphology of cerebral damage. PMID:27857787

  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. Clinical characteristics and outcomes of neonatal pertussis: a comparative study.

    PubMed

    Castagnini, Luis A; Munoz, Flor M

    2010-03-01

    We describe the features and outcomes of neonatal pertussis and compare these with neonates with non-pertussis acute respiratory illness from July 2000 through December 2007. Patients with pertussis had a more severe course of disease as evidenced by the clinical presentation, length of hospitalization, and oxygen requirement. Clinicians should have a high index of suspicion so that appropriate supportive care can be initiated promptly.

  16. [The effectiveness of specific immunotherapy of allergic diseases of respiratory organs from the standpoint of evidence-based medicine. The results of a 5-year retrospective study].

    PubMed

    Zabolotnyĭ, D I; Gogunskaia, I V; Zabolotnaia, D D; Zaritskaia, I S

    2013-01-01

    The objective of this first Ukrainian 5-year retrospective study was to subjectively evaluate the effectiveness of specific immunotherapy (sublingual and injection) of the upper respiratory tract in the patients presenting with seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR), SAR and PAR with polyvalent sensitization. The analysis of the results of sublingual, injection, and combined specific immunotherapy given to 750 patients allowed to describe them as "excellent" and "good" in the groups with PAR (83% of the total number), SAR (93%), SAR and PAR with polyvalent sensitization (84%).

  17. Refining human T-cell immunotherapy of cytomegalovirus disease: a mouse model with 'humanized' antigen presentation as a new preclinical study tool.

    PubMed

    Lemmermann, Niels A W; Reddehase, Matthias J

    2016-12-01

    With the cover headline 'T cells on the attack,' the journal Science celebrated individualized cancer immunotherapy by adoptive transfer of T cells as the 'Breakthrough of the Year' 2013 (J. Couzin-Frankel in Science 342:1432-1433, 2013). It is less well recognized and appreciated that individualized T cell immunotherapy of cytomegalovirus (CMV) infection is approaching clinical application for preventing CMV organ manifestations, interstitial CMV pneumonia in particular. This coincident medical development is particularly interesting as reactivated CMV infection is a major viral complication in the state of transient immunodeficiency after the therapy of hematopoietic malignancies by hematopoietic cell transplantation (HCT). It may thus be attractive to combine T cell immunotherapy of 'minimal residual disease/leukemia (MRD)' and CMV-specific T cell immunotherapy to combat both risks in HCT recipients simultaneously, and ideally with T cells derived from the respective HLA-matched HCT donor. Although clinical trials of human CMV-specific T cell immunotherapy were promising in that the incidence of virus reactivation and disease was found to be reduced with statistical significance, animal models are still instrumental for providing 'proof of concept' by directly documenting the prevention of viral multiple-organ histopathology and organ failure under controlled conditions of the absence versus presence of the therapy, which obviously is not feasible in an individual human patient. Further, animal models can make predictions regarding parameters that determine the efficacy of T cell immunotherapy for improved study design in clinical investigations, and they allow for manipulating host and virus genetics. The latter is of particular value as it opens the possibility for epitope specificity controls that are inherently missing in clinical trials. Here, we review a recently developed new mouse model that is more approximated to human CMV-specific T cell immunotherapy

  18. Maternal Substance Use and Neonatal Abstinence Syndrome: A Descriptive Study.

    PubMed

    McQueen, Karen A; Murphy-Oikonen, Jodie; Desaulniers, Lindsay

    2015-08-01

    Neonatal Abstinence Syndrome (NAS) is one of the primary negative effects of substance use during pregnancy. The exact statistics regarding NAS and substance use during pregnancy are difficult to determine due to underreporting, especially in the context of pregnancy. Similarly, little is known regarding whether the severity of NAS differs based on substance exposure. The purpose of this study was to evaluate the prevalence of NAS and types of substance use during pregnancy, and determine whether the presentation of NAS symptoms differ based on the type of substance. A retrospective chart review was conducted over a one year period at a tertiary care hospital. One hundred thirty-one mother-infant pairs met the inclusion criteria of documented NAS scores using the Modified Finnegan Scoring Tool and substance use during pregnancy. The results identified a high prevalence of NAS (8.7 %) primarily as a result of exposure to illicit opioids and/or to methadone as the treatment for opioid addiction. In addition, more than half the women on methadone maintenance treatment continued to use additional substances primarily opiates. Infants who were exposed to methadone experienced more severe NAS compared to infants not exposed to methadone including higher peak scores, prolonged NAS treatment, and length of stay. Given the severity of symptoms of the methadone exposed infants and the high rate of opioid use with methadone treatment, evidence-based interventions are required to decrease the negative effects of NAS.

  19. To Study the Correlation of Thompson Scoring in Predicting Early Neonatal Outcome in Post Asphyxiated Term Neonates

    PubMed Central

    Sharma, Manisha; Dolker, Stanzin; Kothapalli, Sharada

    2016-01-01

    Introduction Throughout the world each year, an estimated 23% of the 4 million neonatal deaths and 8% of all deaths in <5 years of age are associated with signs of asphyxia at birth. Aim To study the role of cord arterial blood gas analysis at birth and serial Thompson score in predicting the early neonatal outcome in post asphyxiated term neonates. Materials and Methods The study was conducted in Department of Paediatrics, in Neonatal Intensive Care Unit (NICU), Hindu Rao Hospital, New Delhi from May 2014 to February. 2015. This study was a prospective cross-sectional study. During this period, a total of 145 post asphyxiated term neonates born in labour room/obstetric operation theatre were recruited. An informed consent was taken from all the parents. The protocol was approved by the institutional ethical committee. Inclusion criteria were full-term babies with low-Apgar score i.e., 1 min score of ≤ 7 National Neonatal Perinatal Database 2010 (NNPD 2010). Statistical Analysis SPSS 17.0 Software has been used for data analysis. The data were expressed in terms of Means, Standard Deviation and Proportion, followed by comparison between groups through chi-square test or Fisher’s-exact test. A p-value of less than 0.05 was considered as statistically significant. Results The present study was carried out on 145 post asphyxiated full-term babies with low-Apgar score i.e., 1min score of ≤7mild Thompson score on day I,2,3 were 96 (66.2%), 119 (82.06%), 125 (86.20%), moderate Thompson score on day 1,3, 7 were 13 (8.9%), 6 (4.13%), 2 (1.37%) and severe Thompson score on day 1, 3, 7 were 36 (24.8%), 13 (8.96%), 7 (4.82%) respectively. Total 11 patients died out of 145 post asphyxiated full-term babies within 7 days, among 11 patients, 7 died within 3 days. There was clinical improvement among HIE patients as indicated by serial Thompson score done on day 1, 3 and 7. Among 145 patients 62(42.8%) had seizure and 83(57.2%) did not have seizure. Most common type of

  20. French retrospective multicentric study of neonatal hemochromatosis: importance of autopsy and autoimmune maternal manifestations.

    PubMed

    Collardeau-Frachon, Sophie; Heissat, Sophie; Bouvier, Raymonde; Fabre, Monique; Baruteau, Julien; Broue, Pierre; Cordier, Marie-Pierre; Debray, Dominique; Debiec, Hanna; Ronco, Pierre; Guigonis, Vincent

    2012-01-01

    Neonatal hemochromatosis is a rare disease that causes fetal loss and neonatal death in the 1st weeks of life and is one of the most common causes of liver failure in the neonate. The diagnosis is mostly made retrospectively, based on histopathologic features of severe liver fibrosis associated with hepatic and extrahepatic siderosis. Several etiologies may underlie this phenotype, including a recently hypothesized gestational alloimmune disease. Fifty-one cases of liver failure with intrahepatic siderosis in fetuses and neonates were analyzed retrospectively. Maternal and infant data were collected from hospitalization and autopsy reports. All available slides were reviewed independently by 3 pathologists. Immunologic studies were performed on maternal sera collected immediately after delivery. The diagnosis of neonatal haemochromatosis was retained in 33 cases, including 1 case with Down syndrome and 1 case with myofibromas. Liver siderosis was inversely proportional to fibrosis progression. In fetuses, iron storage was more frequent in the thyroid than in the pancreas. Perls staining in labial salivary glands was positive in 1 of 5 cases. Abnormal low signal intensity by magnetic resonance imaging was detected in the pancreas in 2 of 7 cases. Renal tubular dysgenesis was observed in 7 of 23 autopsy cases. Chronic villitis was seen in 7 of 15 placentas. Half of the mothers presented with an autoimmune background and/or autoantibodies in their sera. Our work highlights the importance of autopsy in cases of neonatal hemochromatosis and marshals additional data in support of the hypothesis that neonatal hemochromatosis could reflect maternal immune system dysregulation.

  1. The propylene glycol research project to illustrate the feasibility and difficulties to study toxicokinetics in neonates.

    PubMed

    Kulo, Aida; de Hoon, Jan N; Allegaert, Karel

    2012-10-05

    This paper aims to describe our propylene glycol (PG) research project to illustrate the feasibility and the difficulties encountered to perform excipient studies in neonates. PG is frequently co-administered excipient. PG accumulation potentially results in hyperosmolarity, lactic acidosis or hepato-renal toxicity in adults, reflecting issues related to pharmacokinetics (PKs) and -dynamics (PDs). Consequently, similar observations in neonates are urgently needed. Since newborns display 'physiological' impaired hepatic and renal elimination capacity, description of PG PK in neonates is warranted. The PG PD was assessed based on indicators of renal, hepatic and metabolic (in)tolerance earlier reported in adults and relating to osmolar changes. Based on the PK and PD data collected in neonates, we suggest that there is a lower limit of PG tolerance in neonates. In addition to preliminary data on PG disposition and tolerance in neonates, we mainly focus on the limitations of the current observations and the difficulties encountered during this PG project to further illustrate the specific setting of neonatal research.

  2. Molecular Imaging of Immunotherapy Targets in Cancer

    PubMed Central

    Ehlerding, Emily B.; England, Christopher G.; McNeel, Douglas G.

    2016-01-01

    Immunotherapy has emerged as a promising alternative in the arsenal against cancer by harnessing the power of the immune system to specifically target malignant tissues. As the field of immunotherapy continues to expand, researchers will require newer methods for studying the interactions between the immune system, tumor cells, and immunotherapy agents. Recently, several noninvasive imaging strategies have been used to map the biodistribution of immune checkpoint molecules, monitor the efficacy and potential toxicities of the treatments, and identify patients who are likely to benefit from immunotherapies. In this review, we outline the current applications of noninvasive techniques for the preclinical imaging of immunotherapy targets and suggest future pathways for molecular imaging to contribute to this developing field. PMID:27469363

  3. Microcephaly in north-east Brazil: a retrospective study on neonates born between 2012 and 2015

    PubMed Central

    Soares de Araújo, Juliana Sousa; Regis, Cláudio Teixeira; Gomes, Renata Grigório Silva; Tavares, Thiago Ribeiro; Rocha dos Santos, Cícera; Assunção, Patrícia Melo; Nóbrega, Renata Valéria; Pinto, Diana de Fátima Alves; Bezerra, Bruno Vinícius Dantas

    2016-01-01

    Abstract Objective To assess the number of children born with microcephaly in the State of Paraíba, north-east Brazil. Methods We contacted 21 maternity centres belonging to a paediatric cardiology network, with access to information regarding more than 100 000 neonates born between 1 January 2012 and 31 December 2015. For 10% of these neonates, nurses were requested to retrieve head circumference measurements data from delivery-room books. We used three separate criteria to classify whether a neonate had microcephaly: (i) the Brazilian Ministry of Health proposed criterion: term neonates (gestational age ≥ 37 weeks) with a head circumference of less than 32 cm; (ii) Fenton curves: neonates with a head circumference of less than −3 standard deviation for age and gender; or (iii) the proportionality criterion: neonates with a head circumference of less than ((height/2))+10) ± 2. Findings Between 1 and 31 December 2015, nurses obtained data for 16 208 neonates. Depending on which criterion we used, the number of neonates with microcephaly varied from 678 to 1272 (4.2–8.2%). Two per cent (316) of the neonates fulfilled all three criteria. We observed temporal fluctuations of microcephaly prevalence from late 2012. Conclusion The numbers of microcephaly reported here are much higher than the 6.4 per 10 000 live births reported by the Brazilian live birth information system. The results raise questions about the notification system, the appropriateness of the diagnostic criteria and future implications for the affected children and their families. More studies are needed to understand the epidemiology and the implications for the Brazilian health system. PMID:27821886

  4. Exosome-based immunotherapy.

    PubMed

    Chaput, Nathalie; Taïeb, Julien; Schartz, Noël E C; André, Fabrice; Angevin, Eric; Zitvogel, Laurence

    2004-03-01

    Exosomes are small membrane vesicles originating from late endosomes and secreted by hematopoietic and epithelial cells in culture. Exosome proteic and lipid composition is unique and might shed some light into exosome biogenesis and function. Exosomes secreted from professional antigen-presenting cells (i.e., B lymphocytes and dendritic cells) are enriched in MHC class I and II complexes, costimulatory molecules, and hsp70-90 chaperones, and have therefore been more extensively studied for their immunomodulatory capacities in vitro and in vivo. This review will present the main biological features pertaining to tumor or DC-derived exosomes, will emphasize their immunostimulatory function, and will discuss their implementation in cancer immunotherapy.

  5. Nonoliguric hyperkalemia in neonates: a case-controlled study.

    PubMed

    Yaseen, Hakam

    2009-03-01

    The objective of this study was to determine the incidence, risk factors, and morbidities associated with nonoliguric hyperkalemia (NOHK) in neonates. Infants were eligible for the study if they were born at Al Qassimi Hospital and fulfilled the diagnostic criteria of NOHK (serum potassium [SK] > or = 7 mmol/L during the first 72 hours of life with urinary output > or = 1 mL/kg/h). The next admitted infant with gestational age +/- 1 week and normal SK acted as control. Exclusion criteria were severe congenital malformation, renal failure, failure of adequate urinary collection, and early blood transfusion within the first 72 hours of life. Fluid intake and urinary output were monitored. Infants who developed hyperkalemia (SK > or = 6.5 mmol/L in two nonhemolysed venous or arterial blood samples) had serum potassium measured every 4 hours until it reached below 6 mmol/L. Hyperkalemia was identified between 6 and 36 hours of age in 45 infants (peak SK 7 to 9.3 mmol/L). During the time of the study, the prevalence of NOHK was 24% among extremely-low-birth-weight infants (with birth weight < 1000 g) who comprised 83% of those identified. Of infants with NOHK, 13% developed tachycardiac arrhythmia and 17% died. NOHK was significantly associated with fetal distress, early metabolic acidosis, early hyperglycemia, and absence of antenatal steroid administration. Hyperkalemic infants had significantly lower serum calcium and higher serum phosphorous, urea, and creatinine. Early polyuric episodes and high urinary output were also more common in hyperkalemic infants. NOHK affects mainly preterm infants. Electrolyte disturbance and increased serum urea and creatinine were associated with hyperkalemia. Infants with NOHK also had high incidence of cardiac arrhythmias and mortality.

  6. Active comparator-controlled, rater-blinded study of corticotropin-based immunotherapies for opsoclonus-myoclonus syndrome.

    PubMed

    Tate, Elizabeth D; Pranzatelli, Michael R; Verhulst, Steven J; Markwell, Stephen J; Franz, David Neal; Graf, William D; Joseph, S Anne; Khakoo, Yasmin N; Lo, Warren D; Mitchell, Wendy G; Sivaswamy, Lalitha

    2012-07-01

    To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.

  7. 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.

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

    PubMed Central

    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. Respiratory Viruses in Neonates: A Prospective, Community-based Birth Cohort Study.

    PubMed

    Sarna, Mohinder; Alsaleh, Asma; Lambert, Stephen B; Ware, Robert S; Mhango, Lebogang P; Mackay, Ian M; Whiley, David M; Sloots, Theo P; Grimwood, Keith

    2016-12-01

    A community-based birth cohort study collected weekly nasal swabs and recorded daily symptoms from 157 full-term infants. An average of 0.25 (95% confidence interval: 0.18, 0.34) respiratory virus infections per neonatal period were detected. Human rhinoviruses of diverse subtypes dominated; almost 50% were asymptomatic and continued rhinovirus detections may signify new genotypes. Respiratory viruses are common and often unrecognized in healthy neonates.

  10. Neonatal follow-up programs and follow-up studies: Historical and current perspectives

    PubMed Central

    Sauve, Reg; Lee, Shoo K

    2006-01-01

    The present report reviews some highlights in the history of neonatal intensive care and neonatal follow-up programs, particularly developments and reports that were based on experiences in Canada. Early outcomes reported from ‘preemie baby units’ were distressing, but attention has consistently been paid to preterm infant outcomes, even from the early days of neonatal intensive care units. Most current follow-up programs have goals related to ‘audit’ functions, education and clinical roles, but existing literature related to these functions is limited. Several reports have provided guidance in terms of neonatal follow-up research issues, and these strengthen the place of follow-up studies in outcomes research. PMID:19030284

  11. Neonatal mortality, risk factors and causes: a prospective population-based cohort study in urban Pakistan

    PubMed Central

    Jehan, Imtiaz; Harris, Hillary; Salat, Sohail; Zeb, Amna; Mobeen, Naushaba; Pasha, Omrana; Moore, Janet; Wright, Linda L; Goldenberg, Robert L

    2009-01-01

    Abstract Objective To evaluate the prevalence, sex distribution and causes of neonatal mortality, as well as its risk factors, in an urban Pakistani population with access to obstetric and neonatal care. Methods Study area women were enrolled at 20–26 weeks’ gestation in a prospective population-based cohort study that was conducted from 2003 to 2005. Physical examinations, antenatal laboratory tests and anthropometric measures were performed, and gestational age was determined by ultrasound to confirm eligibility. Demographic and health data were also collected on pretested study forms by trained female research staff. The women and neonates were seen again within 48 hours postpartum and at day 28 after the birth. All neonatal deaths were reviewed using the Pattinson et al. system to assign obstetric and final causes of death; the circumstances of the death were determined by asking the mother or family and by reviewing hospital records. Frequencies and rates were calculated, and 95% confidence intervals were determined for mortality rates. Relative risks were calculated to evaluate the associations between potential risk factors and neonatal death. Logistic regression models were used to compute adjusted odds ratios. Findings Birth outcomes were ascertained for 1280 (94%) of the 1369 women enrolled. The 28-day neonatal mortality rate was 47.3 per 1000 live births. Preterm birth, Caesarean section and intrapartum complications were associated with neonatal death. Some 45% of the deaths occurred within 48 hours and 73% within the first week. The primary obstetric causes of death were preterm labour (34%) and intrapartum asphyxia (21%). Final causes were classified as immaturity-related (26%), birth asphyxia or hypoxia (26%) and infection (23%). Neither delivery in a health facility nor by health professionals was associated with fewer neonatal deaths. The Caesarean section rate was 19%. Almost all (88%) neonates who died received treatment and 75% died in the

  12. Is Adjuvant Cellular Immunotherapy Essential after TACE-Predominant Minimally-Invasive Treatment for Hepatocellular Carcinoma? A Systematic Meta-Analysis of Studies Including 1774 Patients

    PubMed Central

    Chi, Jiachang; Wang, Tao; Tang, Xiaoyin; Cui, Dan; Qian, Qijun; Zhai, Bo

    2016-01-01

    Purpose Cellular immunotherapy has appeared to be a promising modality for the treatment of malignant tumor. The objective of this study was to evaluate the efficacy of cellular immunotherapy combined with minimally invasive therapy. Methods We searched PubMed, Web of Science and The Cochrane Library through March 2016 for relevant studies. Short-term efficacy (the disease control rate, the control rate of quality life and the AFP descent rate) and long-term efficacy (overall survival (OS) and progression-free survival (PFS) rate) were compared as the major outcome measures. The meta-analysis was performed using Review Manager 5.3. Results A total of 1174 references in 3 databases were found of which 19 individual studies with 1774 HCC patients enrolled in this meta-analysis. Meta-analysis results showed that cellular immunotherapy combined with minimally-invasive treatment significantly improved the measures of short-term response (the disease control rate (OR = 5.91, P = 0.007), the control rate of quality lift (OR = 3.38, P = 0.003) and the AFP descent rate (OR = 4.48, P = 0.02)). Also higher 6-month PFS (OR = 2.78, P = 0.05), ≥12-month PFS (OR = 3.56, P<0.00001) rate and 6-month OS (OR = 2.81, P = 0.0009), 12-month OS (OR = 3.05, P<0.00001) and 24-month OS (OR = 3.52, P<0.0001) rate were observed in patients undergoing cellular immunotherapy. Conclusions This meta-analysis suggested that cellular immunotherapy is a feasible adjuvant treatment that could be beneficial for the improvement of the clinical outcomes for hepatocellular carcinoma (HCC) patients after minimally invasive treatment, including short-term response and long-term survival. PMID:28006010

  13. Immunotherapy for lung cancer.

    PubMed

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W

    2016-07-01

    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

  14. Non-Specific Immunotherapies and Adjuvants

    MedlinePlus

    ... and Side Effects Treatment Types Immunotherapy Non-specific cancer immunotherapies and adjuvants Non-specific immunotherapies don’t target ... This makes BCG useful as a form of cancer immunotherapy. BCG was one of the earliest immunotherapies used ...

  15. Differences in organ dysfunctions between neonates and older children: a prospective, observational, multicenter study

    PubMed Central

    2010-01-01

    Introduction The multiple organ dysfunction syndrome (MODS) is a major cause of death for patients admitted to pediatric intensive care units (PICU). The Pediatric Logistic Organ Dysfunction (PELOD) score has been validated in order to describe and quantify the severity of organ dysfunction (OD). There are several physiological differences between neonates and older children. The objective of the study was to determine whether there are differences in incidence of ODs and mortality rate between full-term neonates (age <28 days) and older children. Methods In a prospective, observational study, 1806 patients, admitted to seven PICUs between September 1998 and February 2000 were included. The PELOD score, which includes six organ dysfunctions and 12 variables, was recorded daily. For each variable, the most abnormal value was used to define the daily OD. For each OD, the most abnormal value each day and that during the entire stay were used in calculating the daily PELOD and PELOD scores, respectively. The relationships between OD, daily OD, PELOD, daily PELOD and mortality were compared between the two strata (neonates, older children) based on the discrimination power, logistic and multiple regression analyses. Results Of the 1806 enrolled patients 171 (9.5%) were neonates. Incidence of MODS and mortality rate were higher among neonates than in older children (14.6% vs. 5.5%, P < 10-7; 75.4%, vs. 50.9%, P < 10-4; respectively). Daily PELOD scores were significantly higher in neonates from day 1 to day 4. Daily cardiovascular, respiratory and renal dysfunction scores from day 1 to day 4 as well as the PELOD score for the entire pediatric intensive care unit stay were also significantly higher in neonates. Neurological, cardiovascular, and hepatic dysfunctions were independent predictors of death among neonates while all ODs significantly contributed to the risk of mortality in older children. Conclusions Our data demonstrate that incidence of MODS and mortality rate

  16. Habituation of visual evoked responses in neonates and fetuses: a MEG study.

    PubMed

    Matuz, Tamara; Govindan, Rathinaswamy B; Preissl, Hubert; Siegel, Eric R; Muenssinger, Jana; Murphy, Pamela; Ware, Maureen; Lowery, Curtis L; Eswaran, Hari

    2012-07-01

    In this study we aimed to develop a habituation paradigm that allows the investigation of response decrement and response recovery and examine its applicability for measuring the habituation of the visually evoked responses (VERs) in neonatal and fetal magnetoencephalographic recordings. Two paradigms, one with a long and one with a short inter-train interval (ITI), were developed and tested in separate studies. Both paradigms consisted of a train of four light flashes; each train being followed by a 500Hz burst tone. Healthy pregnant women underwent two prenatal measurements and returned with their babies for a neonatal investigation. The amplitudes of the neonatal VERs in the long-ITI condition showed within-train response decrement. An increased response to the auditory dishabituator was found confirming response recovery. In the short-ITI condition, neonatal amplitude decrement could not be demonstrated while response recovery was present. In both ITI conditions, the response rate of the cortical responses was much lower in the fetuses than in the neonates. Fetal VERs in the long-ITI condition indicate amplitude decline from the first to the second flash with no further decrease. The long-ITI paradigm might be useful to investigate habituation of the VERs in neonates and fetuses, although the latter requires precaution.

  17. Habituation of visual evoked responses in neonates and fetuses: A MEG study

    PubMed Central

    Matuz, Tamara; Govindan, Rathinaswamy B.; Preissl, Hubert; Siegel, Eric R.; Muenssinger, Jana; Murphy, Pamela; Ware, Maureen; Lowery, Curtis L.; Eswaran, Hari

    2013-01-01

    In this study we aimed to develop a habituation paradigm that allows the investigation of response decrement and response recovery and examine its applicability for measuring the habituation of the visually evoked responses (VERs) in neonatal and fetal magnetoencephalographic recordings. Two paradigms, one with a long and one with a short inter-train interval (ITI), were developed and tested in separate studies. Both paradigms consisted of a train of four light flashes; each train being followed by a 500 Hz burst tone. Healthy pregnant women underwent two prenatal measurements and returned with their babies for a neonatal investigation. The amplitudes of the neonatal VERs in the long-ITI condition showed within-train response decrement. An increased response to the auditory dishabituator was found confirming response recovery. In the short-ITI condition, neonatal amplitude decrement could not be demonstrated while response recovery was present. In both ITI conditions, the response rate of the cortical responses was much lower in the fetuses than in the neonates. Fetal VERs in the long-ITI condition indicate amplitude decline from the first to the second flash with no further decrease. The long-ITI paradigm might be useful to investigate habituation of the VERs in neonates and fetuses, although the latter requires precaution. PMID:22483416

  18. Drug Utilization on Neonatal Wards: A Systematic Review of Observational Studies

    PubMed Central

    Rosli, Rosliana; Dali, Ahmad Fauzi; Abd Aziz, Noorizan; Abdullah, Amir Heberd; Ming, Long Chiau; Manan, Mohamed Mansor

    2017-01-01

    Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used. Publications written in English that described drug utilization in neonatal wards were selected. Assessment of the data was based on the category of the study design, the objective of study and the method used in reporting drug consumption. A total of 20 drug utilization studies were identified, 12 of which focused on all drug classes, while the other eight evaluated antimicrobials. Studies were reported in Europe (n = 7), the United States (n = 6), India (n = 5), Brazil (n = 1), and Iran (n = 1). Substantial variance with regard to study types (study design and methods), data source, and sample size were found among the selected studies. Of the studies included, 45% were cross-sectional or retrospective, 40% were prospective studies, and the remaining 15% were point prevalence surveys. More than 70% of the studies were descriptive studies, describing drug consumption patterns. Fifteen per cent of the descriptive studies evaluated changes in drug utilization patterns in neonates. Volume of units was the most prevalent method used for reporting all drug categories. The ATC/DDD system for reporting drug use was only seen in studies evaluating antimicrobials. The most commonly reported drugs across all studies are anti-infectives for systemic use, followed by drugs for the cardiovascular system, the nervous system and the respiratory system. Ampicillin and gentamicin were the most prescribed antimicrobials in hospitalized

  19. Drug Utilization on Neonatal Wards: A Systematic Review of Observational Studies.

    PubMed

    Rosli, Rosliana; Dali, Ahmad Fauzi; Abd Aziz, Noorizan; Abdullah, Amir Heberd; Ming, Long Chiau; Manan, Mohamed Mansor

    2017-01-01

    Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used. Publications written in English that described drug utilization in neonatal wards were selected. Assessment of the data was based on the category of the study design, the objective of study and the method used in reporting drug consumption. A total of 20 drug utilization studies were identified, 12 of which focused on all drug classes, while the other eight evaluated antimicrobials. Studies were reported in Europe (n = 7), the United States (n = 6), India (n = 5), Brazil (n = 1), and Iran (n = 1). Substantial variance with regard to study types (study design and methods), data source, and sample size were found among the selected studies. Of the studies included, 45% were cross-sectional or retrospective, 40% were prospective studies, and the remaining 15% were point prevalence surveys. More than 70% of the studies were descriptive studies, describing drug consumption patterns. Fifteen per cent of the descriptive studies evaluated changes in drug utilization patterns in neonates. Volume of units was the most prevalent method used for reporting all drug categories. The ATC/DDD system for reporting drug use was only seen in studies evaluating antimicrobials. The most commonly reported drugs across all studies are anti-infectives for systemic use, followed by drugs for the cardiovascular system, the nervous system and the respiratory system. Ampicillin and gentamicin were the most prescribed antimicrobials in hospitalized

  20. Urine metabolomics in neonates with late-onset sepsis in a case-control study

    PubMed Central

    Sarafidis, Kosmas; Chatziioannou, Anastasia Chrysovalantou; Thomaidou, Agathi; Gika, Helen; Mikros, Emmanouel; Benaki, Dimitra; Diamanti, Elisavet; Agakidis, Charalampos; Raikos, Nikolaos; Drossou, Vasiliki; Theodoridis, Georgios

    2017-01-01

    Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers. PMID:28374757

  1. Targeting CD47: the achievements and concerns of current studies on cancer immunotherapy.

    PubMed

    Huang, Yuting; Ma, Yuchi; Gao, Peng; Yao, Zhi

    2017-02-01

    Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction. This problem can be addressed by alternative animal models for better recapitulation of human CD47-SIRPα interaction. Both fragment crystallizable (Fc) fragment-dependent effects, like antibody-dependent cell-mediated cytotoxicity (ADCC), and Fc-independent CD47 intrinsic functions are involved in anti-CD47 therapy. The latter may be SIRPα-dependent or SIRPα-independent, such as the case of calreticulin. It has not reached a consensus which of the factors predominate the process, but the answer to this question will determine the optimal pharmaceutical and clinical design of CD47 targeting strategies.

  2. Targeting CD47: the achievements and concerns of current studies on cancer immunotherapy

    PubMed Central

    Huang, Yuting; Ma, Yuchi

    2017-01-01

    Targeting CD47 is in the spotlight of cancer immunotherapy. Blocking CD47 triggers the recognition and elimination of cancer cells by the innate immunity. There are three CD47 antagonists in phase I clinical trials, but their potential efficacies are highly controversial. We raise our concern that NOD-based xenograft hosts tend to overestimate, while syngeneic mouse models could substantially underestimate the efficacy of anti-CD47 therapy. Such discrepancy may be resulted from specific reagent that alters CD47 clustering, and the highly variable avidities of interspecies and intraspecies CD47-SIRPα interaction. This problem can be addressed by alternative animal models for better recapitulation of human CD47-SIRPα interaction. Both fragment crystallizable (Fc) fragment-dependent effects, like antibody-dependent cell-mediated cytotoxicity (ADCC), and Fc-independent CD47 intrinsic functions are involved in anti-CD47 therapy. The latter may be SIRPα-dependent or SIRPα-independent, such as the case of calreticulin. It has not reached a consensus which of the factors predominate the process, but the answer to this question will determine the optimal pharmaceutical and clinical design of CD47 targeting strategies. PMID:28275508

  3. 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.

  4. Determinants and Causes of Neonatal Mortality in Jimma Zone, Southwest Ethiopia: A Multilevel Analysis of Prospective Follow Up Study

    PubMed Central

    Debelew, Gurmesa Tura; Afework, Mesganaw Fantahun; Yalew, Alemayehu Worku

    2014-01-01

    Background Ethiopia is among the countries with the highest neonatal mortality with the rate of 37 deaths per 1000 live births. In spite of many efforts by the government and other partners, non-significant decline has been achieved in the last 15 years. Thus, identifying the determinants and causes are very crucial for policy and program improvement. However, studies are scarce in the country in general and in Jimma zone in particular. Objective To identify the determinants and causes of neonatal mortality in Jimma Zone, Southwest Ethiopia. Methods A prospective follow-up study was conducted among 3463 neonates from September 2012 to December 2013. The data were collected by interviewer-administered structured questionnaire and analyzed by SPSS V.20.0 and STATA 13. Verbal autopsies were conducted to identify causes of neonatal death. Mixed-effects multilevel logistic regression model was used to identify determinants of neonatal mortality. Results The status of neonatal mortality rate was 35.5 (95%CI: 28.3, 42.6) per 1000 live births. Though significant variation existed between clusters in relation to neonatal mortality, cluster-level variables were found to have non-significant effect on neonatal mortality. Individual-level variables such as birth order, frequency of antenatal care use, delivery place, gestation age at birth, premature rupture of membrane, complication during labor, twin births, size of neonate at birth and neonatal care practice were identified as determinants of neonatal mortality. Birth asphyxia (47.5%), neonatal infections (34.3%) and prematurity (11.1%) were the three leading causes of neonatal mortality accounting for 93%. Conclusions This study revealed high status of neonatal mortality in the study area. Higher-level variables had less importance in determining neonatal mortality. Individual level variables related to care during pregnancy, intra-partum complications and care, neonatal conditions and the immediate neonatal care practices

  5. 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.

  6. 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

  7. 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

  8. [Immunotherapy of melanoma].

    PubMed

    Dréno, Brigitte

    2010-10-01

    This article describes current concepts and future challenges in non specific immunotherapy, vaccination, and antigen-specific adoptive immunotherapy of melanoma. If these treatments are to realize their full potential, it will be essential to understand how the tumor induces immune tolerance.

  9. Neonatal Death

    MedlinePlus

    ... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...

  10. Maternal Smoking during Pregnancy and Neonatal Behavior: A Large-Scale Community Study

    PubMed Central

    Stroud, Laura R.; Paster, Rachel L.; Goodwin, Matthew S.; Shenassa, Edmond; Buka, Stephen; Niaura, Raymond; Rosenblith, Judy F.; Lipsitt, Lewis P.

    2009-01-01

    Objective To investigate the influence of prospectively-measured smoking during pregnancy on aspects of neonatal behavior in a large, community sample. Patients and Methods Participants were mothers and infants from the Providence Cohort of the National Collaborative Perinatal Project enrolled between 1960 and 1966. Mothers with pregnancy/medical complications and infants with medical complications and/or born premature or low birthweight were excluded. The final sample included 962 mother-infant pairs, of whom 23% were African-American. Maternal smoking was measured prospectively at each prenatal visit. Neonatal behavior was assessed using the Graham-Rosenblith Behavioral Examination of the Neonate. Items from the examination were reduced to three subscales: irritability, muscle tone, response to respiratory challenge. Results Sixty-two percent of the sample reported smoking during pregnancy with 24% of smokers reporting smoking a pack per day or more. We found a significant influence of maternal smoking exposure (none, moderate/less than a pack per day, heavy/pack a day or more) on irritability and muscle tone in the neonate (p's<.005), with exposed infants showing greater irritability and hypertonicity. Effects remained significant after controlling for significant covariates: maternal socioeconomic status, age and race, and infant birthweight and age (p's<.001). Post hoc tests suggested particular effects of heavy smoking on increased infant irritability, but both moderate and heavy smoking exposure on increased muscle tone. Conclusions In a large, community sample, exposure to maternal smoking was associated with increased irritability and hypertonicity in neonates. Exposure to maternal smoking did not influence neonatal response to respiratory challenge. This study is the largest-scale investigation to date of effects of maternal smoking (heavy and moderate) on examiner-assessed neonatal behavior. Given associations between both maternal smoking and infant

  11. 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.

  12. 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

  13. Observational study of haemostatic dysfunction and bleeding in neonates with hypoxic–ischaemic encephalopathy

    PubMed Central

    Pakvasa, Mitali A; Winkler, Anne M; Hamrick, Shannon E; Josephson, Cassandra D

    2017-01-01

    Objective Evaluate the relationship between initial haemostatic parameters and the frequency and severity of bleeding in neonates with hypoxic–ischaemic encephalopathy (HIE). Design Retrospective observational cohort study. Setting 2 academically affiliated level III neonatal intensive care units in Atlanta, Georgia. Participants 98 neonates with moderate-to-severe HIE who underwent haemostatic testing within 12 hours of birth and were born from 1 January 2008 to 31 December 2013. Primary and secondary outcome measures Initial haemostatic dysfunction was defined as one or more of the following: prothrombin time (PT) ≥18 s, platelet count <100×103/μL or fibrinogen <150 mg/dL. Bleeding assessed using the Neonatal Bleeding Assessment Tool and graded according to the WHO bleeding scale. The robust Poisson regression was used to evaluate the independent association between components of initial haemostatic dysfunction and bleeding. Results Among the 98 neonates evaluated, the prevalence of initial haemostatic dysfunction was 69% (95% CI 59% to 78%). 27 neonates (28%; 95% CI 19% to 38%) had abnormal bleeding events and 56 (57%) received at least 1 blood product transfusion. 3 neonates died from bleeding complications. The most common products transfused were fresh-frozen plasma (71%), followed by packed red blood cells (24%) and platelets (21%). In multivariable analysis, fibrinogen <150 mg/dL (adjusted relative risk 2.41, 95% CI 1.09 to 5.36) and platelet count <100×103/μL (adjusted relative risk 2.59, 95% CI 1.30 to 5.16), but not initial PT, were associated with an increased risk of bleeding. The most severe bleeding occurred in neonates with a fibrinogen <150 mg/dL. Conclusions Among neonates with moderate-to-severe HIE, haemostatic dysfunction is prevalent and associated with an increased risk of bleeding and high transfusion burden. Further studies are needed to determine the appropriate transfusion approaches in this population to prevent

  14. Level of maternal education is a significant determinant of neonatal survival: a PEARL study analysis.

    PubMed

    El Ansari, Walid; ur Rahman, Sajjad; Nimeri, Nuha; Latiph, Emirah; Yousafzai, Mohammad Tahir; Tohid, Hiba

    2015-02-01

    The study analyzed the demographic and socio-economic determinants of neonatal mortality. The variables included one fetal variable (gender), three maternal variables (level of education, occupation, age), three paternal variables (level of education, occupation, age), and seven household (family) variables (nationality, consanguinity, family income, house ownership, type of housing, family type, domestic help). One calendar year data (January to December 2011) was extracted from Qatar's National Perinatal Registry and analyzed using a univariate regression model. Qatar had a total of 20,583 live births and 102 neonatal deaths during 2011 (NMR 4.95/1000). Less than secondary school maternal education level, as compared to secondary school or above maternal education level, was the only variable significantly associated with neonatal mortality (OR 2.08, 95% CI 1.23 - 3.53, p=0.009). The association between the remaining thirteen variables and neonatal mortality was non-significant. Priority investment to raise female literacy above secondary school level may significantly improve neonatal survival.

  15. 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.

  16. Immunotherapy in Lung Cancer.

    PubMed

    Du, Lingling; Herbst, Roy S; Morgensztern, Daniel

    2017-02-01

    The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab. Because only a minority of patients benefit from this class of drugs, there has been an intense search for biomarkers.

  17. MAGE-A Antigens and Cancer Immunotherapy

    PubMed Central

    Zajac, Paul; Schultz-Thater, Elke; Tornillo, Luigi; Sadowski, Charlotte; Trella, Emanuele; Mengus, Chantal; Iezzi, Giandomenica; Spagnoli, Giulio C.

    2017-01-01

    MAGE-A antigens are expressed in a variety of cancers of diverse histological origin and germinal cells. Due to their relatively high tumor specificity, they represent attractive targets for active specific and adoptive cancer immunotherapies. Here, we (i) review past and ongoing clinical studies targeting these antigens, (ii) analyze advantages and disadvantages of different therapeutic approaches, and (iii) discuss possible improvements in MAGE-A-specific immunotherapies. PMID:28337438

  18. Evolution of end points for cancer immunotherapy trials.

    PubMed

    Hoos, A

    2012-09-01

    The effect of cancer immunotherapies is on the immune system and not directly on the tumour. The kinetics of immunotherapy are characterised by a cellular immune response followed by potential changes in tumour burden or patient survival. To adequately investigate immunotherapies in clinical trials, a new development paradigm including reconsideration of established end points addressing this biology is needed. Over the last 7 years, several initiatives across the cancer immunotherapy community were facilitated by the Cancer Research Institute Cancer Immunotherapy Consortium. They systematically evolved an immunotherapy-focused clinical development paradigm and proposed to redefine trial end points. On that basis, analysis of several large datasets generated throughout the immunotherapy community supports three novel end point proposals. First, results from T-cell immune response assays are highly variable and often nonreproducible. Harmonisation of assays can minimise this variability and support the investigation of the cellular immune response as a biomarker and testing it for clinical surrogacy. Secondly, immunotherapy induces novel patterns of the antitumour response not captured by World Health Organisation criteria or Response Evaluation Criteria in Solid Tumours. New immune-related response criteria were defined which more comprehensively capture all response patterns. Thirdly, survival curves in randomised immunotherapy trials can show a delayed separation, which can impact study results. Altered statistical models are needed to describe the hazard ratios as a function of time, and differentiate them before and after separation of curves to improve planning of phase III trials. Taken together, these recommendations may improve our tools for cancer immunotherapy investigations.

  19. 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

  20. Immunotherapy for food allergies in children.

    PubMed

    Martinolli, Francesco; Carraro, Silvia; Berardi, Mariangela; Ferraro, Valentina; Baraldi, Eugenio; Zanconato, Stefania

    2014-01-01

    Food allergy is an increasingly prevalent problem all over the world and especially in westernized countries, and there is an unmet medical need for an effective form of therapy. During childhood natural tolerance development is frequent, but some children with cow's milk or hen's egg allergy and the majority of children with peanut allergy will remain allergic until adulthood, limiting not only the diet of patients but also their quality of life. Within the last several years, the usefulness of immunotherapy for food allergies has been investigated in food allergic patients. Several food immunotherapies are being developed; these involve oral, sublingual, epicutaneous, or subcutaneous administration of small amounts of native or modified allergens to induce immune tolerance. The approach generally follows the same principles as immunotherapy of other allergic disorders and involves administering small increasing doses of food during an induction phase followed by a maintenance phase with regular intake of a maximum tolerated amount of food. Oral immunotherapy seems to be a promising approach for food allergic patients based on results from small uncontrolled and controlled studies. Diet containing heated milk and egg may represent an alternative approach to oral immunomodulation for cow's milk and egg allergic subjects. However, oral food immunotherapy remains an investigational treatment to be further studied before advancing into clinical practice. Additional bigger, multicentric and hopefully randomized-controlled studies must answer multiple questions including optimal dose, ideal duration of immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment.

  1. 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…

  2. 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…

  3. Immunotherapy for Alzheimer disease.

    PubMed

    Gouras, Gunnar K

    2009-01-01

    Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque pathology and improve behavior in transgenic mouse models of the disease. Several ongoing immunotherapy clinical trials for Alzheimer disease are in progress. The background and ongoing challenges for these immunological approaches for the treatment of Alzheimer disease are discussed.

  4. Providing immediate neonatal care and resuscitation at birth beside the mother: clinicians’ views, a qualitative study

    PubMed Central

    Yoxall, Charles W; Ayers, Susan; Sawyer, Alexandra; Bertullies, Sophia; Thomas, Margaret; D Weeks, Andrew; Duley, Lelia

    2015-01-01

    Objectives The aims of this study were to assess clinicians’ views and experiences of providing immediate neonatal care at birth beside the mother, and of using a mobile trolley designed to facilitate this bedside care. Design Qualitative interview study with semistructured interviews. Results The results were analysed using thematic analysis. Setting A large UK maternity unit. Participants Clinicians (n=20) from a range of disciplines who were present when the trolley was used to provide neonatal care at birth at the bedside. Five clinicians provided/observed advanced resuscitation by the bedside. Results Five themes were identified: (1) Parents’ involvement, which included ‘Contact and involvement’, ‘Positive emotions for parents’ and ‘Staff communication’; (2) Reservations about neonatal care at birth beside the mother, which included ‘Impact on clinicians’ and ‘Impact on parents’; (3) Practical challenges in providing neonatal care at the bedside, which included ‘Cord length’ and ‘Caesarean section’; (4) Comparison of the trolley with usual resuscitation equipment and (5) Training and integration of bedside care into clinical routine, which included ‘Teething problems’ and ‘Training’. Conclusions Overall, most clinicians were positive about providing immediate neonatal care at the maternal bedside, particularly in terms of the clinicians’ perceptions of the parents’ experience. Clinicians also perceived that their close proximity to parents improved communication. However, there was some concern about performing more intensive interventions in front of parents. Providing immediate neonatal care and resuscitation at the bedside requires staff training and support. PMID:26423852

  5. 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

  6. 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

  7. Neonatal Cholestasis

    PubMed Central

    Feldman, Amy G.; Sokol, Ronald J.

    2013-01-01

    Cholestatic jaundice is a common presenting feature of neonatal hepatobiliary and metabolic dysfunction. Any infant who remains jaundiced beyond age 2 to 3 weeks should have the serum bilirubin level fractionated into a conjugated (direct) and unconjugated (indirect) portion. Conjugated hyperbilirubinemia is never physiologic or normal. The differential diagnosis of cholestasis is extensive, and a step-wise approach based on the initial history and physical examination is useful to rapidly identify the underlying etiology. Early recognition of neonatal cholestasis is essential to ensure timely treatment and optimal prognosis. Even when specific treatment is not available, infants who have cholestasis benefit from early medical management and optimization of nutrition. Future studies are necessary to determine the most reliable and cost-effective method of universal screening for neonatal cholestasis. PMID:24244109

  8. The iron status at birth of neonates with risk factors for developing iron deficiency: a pilot study

    PubMed Central

    MacQueen, BC; Christensen, RD; Ward, DM; Bennett, ST; O’Brien, EA; Sheffield, MJ; Baer, VL; Snow, GL; Lewis, KA Weaver; Fleming, RE; Kaplan, J

    2016-01-01

    OBJECTIVE Small-for-gestational-age (SGA) neonates, infants of diabetic mothers (IDM) and very-low-birth weight premature neonates (VLBW) are reported to have increased risk for developing iron deficiency and possibly associated neurocognitive delays. STUDY DESIGN We conducted a pilot study to assess iron status at birth in at-risk neonates by measuring iron parameters in umbilical cord blood from SGA, IDM, VLBW and comparison neonates. RESULTS Six of the 50 infants studied had biochemical evidence of iron deficiency at birth. Laboratory findings consistent with iron deficiency were found in one SGA, one IDM, three VLBW, and one comparison infant. None of the infants had evidence of iron deficiency anemia. CONCLUSIONS Evidence of biochemical iron deficiency at birth was found in 17% of screened neonates. Studies are needed to determine whether these infants are at risk for developing iron-limited erythropoiesis, iron deficiency anemia or iron-deficient neurocognitive delay. PMID:27977019

  9. 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

  10. 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.

  11. 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…

  12. DNA methylome profiling using neonatal dried blood spot samples: a proof-of-principle study.

    PubMed

    Hollegaard, Mads Vilhelm; Grauholm, Jonas; Nørgaard-Pedersen, Bent; Hougaard, David Michael

    2013-04-01

    DNA methylation is the most common DNA modification and perhaps the best described epigenetic modification. It is believed to be important for genomic imprinting and gene regulation and has been associated with the development of diseases such as schizophrenia and some types of cancer. Neonatal dried blood spot samples, commonly known as Guthrie cards, are routinely collected worldwide to screen newborns for diseases. Some countries, including Denmark, have been storing the excess neonatal dried blood spot samples in biobanks for decades. Representing a high percentage of the population under a certain age, the neonatal dried blood spot samples are a potential alternative to collecting new samples to study diseases. As such, neonatal dried blood spot samples have previously been used for DNA genotyping studies with excellent results. However, the amount of material available for research is often limited, challenging researchers to generate the most data from a limited quantity of material. In this proof-of-principle study, we address whether two 3.2mm disks punched from a neonatal dried blood spot sample contain enough DNA for genome-wide methylome profiling, measuring 27,578 loci at the same time. We selected two subjects and carried out the following with each: 1) collected an adult whole-blood sample as reference, 2) spotted a fraction of the whole-blood sample onto a similar type of filter paper as used in the newborn screening and stored it for 3years to serve as a dried blood spot reference, and 3) identified the archived neonatal dried blood spot samples, stored for 26-28years, in the Danish Newborn Screening Biobank as a representative of the archived samples. For comparison, we used two different kits for DNA extraction. The DNA, extracted using the Extract-N-Amp Blood PCR kit, was analyzed, and no statistically significant differences were observed (P<0.001) when we compared the methylation profile of the reference whole-blood samples to the dried blood

  13. Immunotherapy for cancer.

    PubMed

    Streilein, J W

    1978-11-01

    It seems nonetheless reasonable to take a skeptical view of immunotherapy for cancer. If the immunologic response can be brought to bear meaningfully and effectively upon the tumorhost relationship so that the host is spared, then let it be proved by appropriate clinical trials. Without unrealistic expectations, it may be easier to tolerance the gradual realization that immunotherapy may be only peripherally important in the control of malignant disease.

  14. 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

  15. 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.

  16. Relationship of EEG sources of neonatal seizures to acute perinatal brain lesions seen on MRI: a pilot study.

    PubMed

    Despotovic, Ivana; Cherian, Perumpillichira J; De Vos, Maarten; Hallez, Hans; Deburchgraeve, Wouter; Govaert, Paul; Lequin, Maarten; Visser, Gerhard H; Swarte, Renate M; Vansteenkiste, Ewout; Van Huffel, Sabine; Philips, Wilfried

    2013-10-01

    Even though it is known that neonatal seizures are associated with acute brain lesions, the relationship of electroencephalographic (EEG) seizures to acute perinatal brain lesions visible on magnetic resonance imaging (MRI) has not been objectively studied. EEG source localization is successfully used for this purpose in adults, but it has not been sufficiently explored in neonates. Therefore, we developed an integrated method for ictal EEG dipole source localization based on a realistic head model to investigate the utility of EEG source imaging in neonates with postasphyxial seizures. We describe here our method and compare the dipole seizure localization results with acute perinatal lesions seen on brain MRI in 10 full-term infants with neonatal encephalopathy. Through experimental studies, we also explore the sensitivity of our method to the electrode positioning errors and the variations in neonatal skull geometry and conductivity. The localization results of 45 focal seizures from 10 neonates are compared with the visual analysis of EEG and MRI data, scored by expert physicians. In 9 of 10 neonates, dipole locations showed good relationship with MRI lesions and clinical data. Our experimental results also suggest that the variations in the used values for skull conductivity or thickness have little effect on the dipole localization, whereas inaccurate electrode positioning can reduce the accuracy of source estimates. The performance of our fused method indicates that ictal EEG source imaging is feasible in neonates and with further validation studies, this technique can become a useful diagnostic tool.

  17. 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

  18. Epidemiological Study of Hospital-Acquired Bacterial Conjunctivitis in a Level III Neonatal Unit

    PubMed Central

    Dias, Catarina; Gonçalves, Márcia; João, Anabela

    2013-01-01

    Background. Conjunctivitis is one of the most frequently occurring hospital-acquired infections among neonates, although it is less studied than potentially life-threatening infections, such as sepsis and pneumonia. Objectives. The aims of our work were to identify epidemiologic characteristics, pathogens, and susceptibility patterns of bacterial hospital-acquired conjunctivitis (HAC) in a level III neonatal unit. Materials and Methods. Data were collected retrospectively from patient charts and laboratory databases. Hospital-acquired conjunctivitis was defined in accordance with the Centers for Disease Control/National Healthcare Safety Network (CDC/NHSN) diagnostic criteria. Results. One or more episodes of HAC were diagnosed in 4,0% (n = 60) of 1492 neonates admitted during the study period. Most of the episodes involved premature (75,4%) and low birth weight (75,4%) neonates. Infection rates were higher among patients undergoing noninvasive mechanical ventilation (46,7%), parenteral nutrition (13,6%), and phototherapy (6,8%). Predominant pathogens included Serratia marcescens (27,9%), Escherichia coli (23%), and Pseudomonas aeruginosa (18%). Susceptibility patterns revealed bacterial resistances to several antibiotic classes. Gentamicin remains the adequate choice for empirical treatment of HAC in our NICU. Conclusion. It is important to know the local patterns of the disease in order to adjust prevention strategies. Our work contributes to the epidemiological characterization of a sometimes overlooked disease. PMID:23766676

  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. 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.

  2. Retrospective study of neonatal ligation during 2002 in the United Kingdom of persistently patent arterial ducts.

    PubMed

    Venkatesh, Vidheya; Lee, Lleona; White, Deborah; Kelsall, Wilf

    2009-08-01

    Our aim was to ascertain the number of neonatal ligations of the patent arterial duct performed in the United Kingdom in 2002, and to determine the survival of the neonates after 30 days. A postal questionnaire was sent to the lead paediatician in every hospital in the United Kingdom possessing a special care or neonatal intensive care unit, requesting information on the number of babies referred for ligation of a persistently patent arterial duct. A separate questionnaire was sent to the paediatric cardiothoracic centres for information on babies who underwent the procedure. Cross-referencing the responses identified neonates who were not reported in the separate questionnaires. Additional information was requested from the central cardiac audit database. The overall response rate was 74%, with 172 forms returned of 234 distributed. From the combined responses, we ascertained that ligation has been performed in 244, with survival at 30 days of 94%. There were problems in identifying some babies because of the incomplete nature of the information received from both referring hospitals and specialist cardiothoracic centres. We would recommend a joint prospective study is conducted by paediatricians and paediatric cardiologists to determine the short and long term outcomes in this population known to be at high risk.

  3. Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study.

    PubMed

    Babatz, J; Röllig, C; Oelschlägel, U; Zhao, S; Ehninger, G; Schmitz, M; Bornhäuser, M

    2003-10-01

    Dendritic cells (DC) are professional antigen-presenting cells that are widely used in the experimental immunotherapy of cancer. For clinical use GMP-like protocols for the preparation of functionally active dendritic cells (DC) in large numbers and at high purity are needed. However, the currently available protocols have certain disadvantages. In this study we tested the generation and clinical applicability of DC from monocyte preparations produced by immunomagnetic CD14(+) selection using a semiautomated clinical scale immunomagnetic column. Peripheral blood mononuclear cells (PBMC) of 10 patients with metastatic solid tumors were used. With the immunomagnetic separation, we obtained a cell suspension of high CD14(+) purity (median 97.4%, range 94.9-99.0) with a high monocyte yield (median 82.3%, range 63.9-100.0). Differentiation of CD14(+) cells into mature monocyte-derived DC was induced by incubation with IL-4, GM-CSF, TNF-alpha, PGE(2), IL-1 beta, and IL-6. Mature DC showed a high expression of CD83, HLA-DR, and the co-stimulatory molecules CD80 and CD86. Overall CD83(+) yield was 12.1% (range 4.0-29.4). Allogeneic T stimulatory capacity could be demonstrated for all DC preparations in proliferation assays. No significant differences in marker expression or T cell stimulation was detected between fresh DC and those derived from cryopreserved immature DC. Clinical administration of autologous DC by three different parenteral routes was tolerated by all 10 patients without systemic signs of toxicity. Our results indicate that immunomagnetic isolation of CD14(+) monocytes using the CliniMACS device is a suitable method for clinical-scale generation of functional DC under GMP-grade conditions. The selection can be performed in a closed system. Therefore, immunomagnetic CD14(+) selection can be seen as an alternative way to generate DC for clinical tumor vaccination protocols.

  4. Immunotherapy in gastric cancer.

    PubMed

    Matsueda, Satoko; Graham, David Y

    2014-02-21

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.

  5. Neonatal sepsis

    PubMed Central

    Shah, Birju A; Padbury, James F

    2014-01-01

    Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW <1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount. PMID:24185532

  6. 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

  7. Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design

    PubMed Central

    Tremoulet, Adriana; Le, Jennifer; Poindexter, Brenda; Sullivan, Janice E.; Laughon, Matthew; Delmore, Paula; Salgado, Andrea; Ian-U Chong, Sandy; Melloni, Chiara; Gao, Jamie; Benjamin, Daniel K.; Capparelli, Edmund V.

    2014-01-01

    Although ampicillin is the most commonly used drug in neonates, developmental pharmacokinetic (PK) data to guide dosing are lacking. Ampicillin is primarily renally eliminated, and developmental changes are expected to influence PK. We conducted an open-label, multicenter, opportunistic, prospective PK study of ampicillin in neonates stratified by gestational age (GA) (≤34 or >34 weeks) and postnatal age (PNA) (≤7 or >7 days). Drug concentrations were measured by tandem mass spectrometry. PK data were analyzed using population nonlinear mixed-effects modeling in NONMEM 7.2. Monte Carlo simulations were conducted to determine the probability of target attainment for the time in which the total steady-state ampicillin concentrations remained above the MIC (T>MIC) for 50%, 75%, and 100% of the dosing interval. A total of 142 PK samples from 73 neonates were analyzed (median [range] GA, 36 [24 to 41] weeks; PNA, 5 [0 to 25] days). The median ampicillin dose was 200 (100 to 350) mg/kg/day. Postmenstrual age and serum creatinine were covariates for ampicillin clearance (CL). A simplified dosing regimen of 50 mg/kg every 12 h for GA of ≤34 weeks and PNA of ≤7 days, 75 mg/kg every 12 h for GA of ≤34 weeks and PNA of ≥8 and ≤28 days, and 50 mg/kg every 8 h for GA of >34 weeks and PNA of ≤28 days achieved the prespecified surrogate efficacy target in 90% of simulated subjects. Ampicillin CL was associated with neonatal development. A simplified dosing regimen stratified by GA and PNA achieves the desired surrogate therapeutic target in the vast majority of neonates. PMID:24614374

  8. Systematic Review and Meta-analysis: Gene Association Studies in Neonatal Sepsis.

    PubMed

    Srinivasan, Lakshmi; Swarr, Daniel T; Sharma, Megha; Cotten, C Michael; Kirpalani, Haresh

    2016-12-13

    Background Association studies of various gene variants in neonatal sepsis show conflicting results. Objective We performed a systematic review of candidate gene association studies in neonatal sepsis to provide pooled estimates of risk for selected gene variants. Methods We performed a search using MeSH terms "infection," "sepsis," "infant," "genetic variation," "polymorphism," and "genetic association studies." We included studies evaluating associations between neonatal sepsis and genetic variants (2000-2015). We excluded case reports/series, commentaries, narrative reviews, and nonhuman research. We assessed quality of studies using STREGA guidelines. Following estimation of odds ratios (ORs), data were pooled using random effects models. Results Twenty eight of 1,404 identified studies were included. Meta-analyses were performed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 as these gene variants were tested in multiple studies. TNF-α 308GG genotype demonstrated trends toward increased sepsis risk in the primary analysis of culture-proven sepsis (OR 1.18, 95% confidence interval [CI] 0.97-1.44). IL-10 1082GG genotype was associated with lower sepsis odds in very low-birth-weight (VLBW) infants (OR 0.51, 95% CI 0.29-0.91). Conclusion We uncovered an association between IL-10 1082 gene variation and sepsis in VLBW infants but did not identify associations between neonatal sepsis and TNF-α 308 or IL-6 gene variation. Larger cohort replication studies are required to validate these findings.

  9. 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

  10. 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

  11. HTLV-1-targeted immunotherapy.

    PubMed

    Suehiro, Youko

    Adult T-cell leukemia/lymphoma (ATL) is a HTLV-1 induced T-cell malignancy with an extremely poor prognosis. There is a long latency period between HTLV-1 infection and the onset of ATL, which indicates the existence of multistep mechanisms of leukemogenesis in the infected cells. Tax, which is encoded by the HTLV-1 pX region, plays a crucial role in HTLV-1 leukemogenesis and is a major target of CTL. We developed an anti-ATL therapeutic vaccine consisting of autologous dendritic cells that is pulsed with Tax peptides (Tax-DC). The vaccination protocol was completed with three injections at a 2-week interval, within one month. Good quality of life and long-term treatment-free survival were observed for more than 3 years in two of the three patients enrolled in the pilot study. Furthermore, the proviral load remained mostly around the carrier level, with minor fluctuation, after vaccination. Tax-specific proliferative CTL responses were observed in all cases and sporadically augmented responses were also subsequently detected. The Tax-DC vaccine might be a well-tolerated and long-lasting maintenance therapy that is acceptable even for elderly patients. Based on the encouraging results, we are now conducting a clinical trial of Tax-DC vaccine combined with anti-CCR4 antibody to enhance the efficacy of the vaccine as next-generation immunotherapy.

  12. 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

  13. Mechanisms of sublingual immunotherapy.

    PubMed

    Scadding, Guy; Durham, Stephen R

    2011-05-01

    Sublingual immunotherapy (SLIT) has been shown to be effective in the treatment of seasonal allergic rhinoconjunctivitis. Despite comparable clinical efficacy to traditional subcutaneous immunotherapy, the mechanisms of SLIT have yet to be fully established. This article considers the role of the local oral mucosa and regional lymphoid tissues in the processing of allergen during SLIT and the subsequent effects on T-cell and B-cell immune compartments and at mucosal sites. The likely time course of events and the evidence for long-lasting tolerance following SLIT are discussed.

  14. Immunotherapy in veterinary oncology.

    PubMed

    Bergman, Philip J

    2014-09-01

    Tumor immunology and immunotherapy is one of the most exciting and rapidly expanding fields. The immune system is divided into 2 primary components: the innate immune response and the highly specific, but more slowly developing, adaptive or acquired immune response. Immune responses are separated by whether they are induced by exposure to a foreign antigen (active response) or transferred through serum or lymphocytes from an immunized individual (passive response). The ideal cancer immunotherapy agent should discriminate between cancer and normal cells (specificity), be potent enough to kill small or large numbers of tumor cells (sensitivity), and prevent recurrence of a tumor (durability).

  15. Evaluation of a sublingual immunotherapy solution in olive-induced respiratory allergy in Jordan: a retrospective observational study

    PubMed Central

    Al-Asad, Khaled; Al-Nazer, Sayed; Al-Faqih, Anan; Hashem, Mohammad Jamil

    2017-01-01

    Background Olive pollen is an important cause of respiratory allergy in the Middle East. In this study, the clinical characteristics of adults and children with confirmed allergic rhinitis (AR; with or without asthma) in Jordan were described, and the use of sublingual immunotherapy (SLIT) in a real-life clinical setting was assessed. Methods This retrospective observational study evaluated the clinical features of olive-induced allergy and the use of an SLIT solution of standardized extracts toward Ole e 1 given in a pre- and coseasonal scheme with a daily dose of 300 index of reactivity for two consecutive seasons. Inclusion criteria were as follows: ≥5 years of age, AR, proven olive sensitization, and at least 2 years follow-up after SLIT initiation. The following data were recorded at SLIT initiation: clinical characteristics, rhinitis and asthma symptom scores, and concomitant symptomatic medications. During follow-up and at the end of each season, the following data were recorded: symptom progression/scores, any changes to symptomatic medications, and treatment compliance. The secondary objective was to determine any effect on quality of life, use of concomitant AR medications, and treatment compliance. Results Eighty-six patients with seasonal AR were included in this analysis (52.3% with coexisting asthma). Between the initiation of treatment and the end of second pollen season, symptoms of AR and asthma were decreased by 79.5% and 41.7%, respectively, with an improvement in quality of life score in 71.5% of the patients (P<0.0001 for all). Physicians reported that after 2 years of SLIT, there was an improvement in the symptoms of both AR (95.2%) and asthma (93.3%), with 98.8% of the patients showing good treatment compliance. A reduction in symptomatic medications was also found. SLIT was well tolerated with no systemic reactions being reported. Conclusion In children and adults with olive-associated respiratory allergy in Jordan, the use of a pre- and

  16. Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double-blind, placebo-controlled study.

    PubMed

    Bahçeciler, N N; Işik, U; Barlan, I B; Başaran, M M

    2001-07-01

    To evaluate the efficacy of specific sublingual immunotherapy (SLIT), we enrolled 15 children with asthma and rhinitis (7 girls, 8 boys, mean +/- SD age of 11.7 +/- 3.3) allergic to house dust mite (HDM) into a double-blind, placebo-controlled study. After a run-in period, patients were randomized to receive either placebo (n = 7) or SLIT (n = 8) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus) + Dermatophagoides farinea (D. farinea) 50/50 extract. They received increasing doses up to 100 index units of reactivity (IR) every day for 4 weeks, then 100 IR/day for another 4 weeks, followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months. Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores, serum total IgE levels, results of lung function tests, methacholine provocation tests, and skin prick tests. Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group (P = 0.05, P = 0.028, respectively), whereas no such difference was observed in the placebo group. At the end of follow-up, mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group (P = 0.04). Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups, whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group (P = 0.026). At the end of 6 months, peak expiratory flow (PEF) values in the placebo group was significantly lower than in the SLIT group (P = 0.049). Throughout the treatment period, the SLIT group was found to have less asthma exacerbations than the placebo group (P = 0.007). The provocation concentration causing a 20% drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups. None of the patients reported local or systemic side

  17. Use of hyperbaric oxygenation in neonatal patients: a pilot study of 8 patients.

    PubMed

    Sánchez, E Cuauhtémoc

    2013-01-01

    This article presents a pilot study to determine the value of hyperbaric oxygenation (HBO₂) in the acute management of neonatal hypoxia (hypoxic ischemic encephalopathy) and necrotizing enterocolitis. Neonates with hypoxic-ischemic encephalopathy and NE were treated in a Sechrist monoplace chamber. Electroencephalogram, evoked potential, ophthalmic evaluation, ultrasonograph, laboratory exams, and radiographs were obtained before and after HBO₂. Treatment protocol was 2.0 atm abs/45 minutes. Preventive myringotomies were conducted in all patients. A follow-up was done at 3 and 6 months. All patients (n = 8) were ventilator-dependent and required bag-valve-mask ventilation by a neonatologist during the treatment. All showed a resolution after HBO₂. There was also a dramatic improvement (P < .05) in hemoglobin, hematocrit, total proteins, serum sodium, triglycerides, and pH. There were favorable changes in all other studies although they did not meet statistical significance. There was a marked reduction of the morbidity and mortality. There were no adverse effects on the ophthalmologic or Central Nervous System. When used promptly, HBO₂ can modify the local and systemic inflammatory response caused by intestinal inflammation or cerebral or systemic hypoxia. It helps to preserve the marginal tissue and recover the ischemic and metabolic penumbra. This pilot study suggests that HBO₂ could be a safe and effective treatment in the acute management of neonatal necrotizing enterocolitis or hypoxic ischemic encephalopathy. There is a need for a prospective, randomized, controlled, and double-blinded study to determine the real use of HBO₂ in these cases.

  18. 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.

  19. Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells.

    PubMed

    Mazumder, A; Eberlein, T J; Grimm, E A; Wilson, D J; Keenan, A M; Aamodt, R; Rosenberg, S A

    1984-02-15

    In previous in vitro studies, the authors showed that phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL) from cancer patients to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. Thus, after IRB approval, a phase I clinical protocol was instituted in cancer patients who had failed all other therapy to determine the toxicity and effects, in vivo, of the infusion of large numbers of such PHA activated autologous PBL. Ten patients were treated on the protocol, six with sarcoma, one with melanoma, and three with colorectal cancer. Up to a total of 1.7 X 10(11) PBL were obtained from 7 to 15 successive leukaphereses, the cells from each leukapheresis being incubated in vitro in medium containing PHA and human AB serum for 2 days and then reinfused following the next leukapheresis 2 days later. Toxicity encountered included fever and chills in 10/10 patients, headaches in 5/10, nausea and vomiting in 3/10, and requirement for erythrocyte transfusion in 8/10. No evidence for autoimmune disease, abnormal serum chemical or coagulation studies, or pulmonary emboli was found. 111Indium trafficing studies showed distribution of infused cells mainly to the spleen and liver, with some accumulation in the lungs and tumor especially after repeated infusions. In 9/10 patients, activated PBL were detected in the peripheral circulation by the sixth leukapheresis. Evidence for this was found by assaying the incorporation of tritiated thymidine (3H-Tdr) into, and lysis of fresh tumor cells by, unstimulated PBL from successive leukaphereses. No tumor regression was seen in these patients with bulk disease. These studies demonstrated that large numbers of PHA-activated PBL can be safely obtained and infused into humans, achieving an increase in the number of circulating activated cells with evidence of migration of cells to tumor, lungs, liver and spleen. Further studies of the use of activated lymphocyte infusion in

  20. Open questions for Alzheimer's disease immunotherapy.

    PubMed

    Golde, Todd E

    2014-01-01

    Perhaps more definitively than any other class of novel Alzheimer's disease (AD) therapy, pre-clinical studies in mouse models of amyloid β (Aβ) deposition have established the disease-modifying potential of anti-Aβ immunotherapy. Despite disappointing results to date from anti-Aβ immunotherapy therapeutic trials, there is continued hope that such immunotherapies, especially if used in the preclinical stages, could prove to be the first disease-modifying therapies available for AD. The general optimism that Aβ-targeting and emerging tau-targeting immunotherapies may prove to be disease modifying is tempered by many unanswered questions regarding these therapeutic approaches, including but not limited to i) lack of precise understanding of mechanisms of action, ii) the factors that regulate antibody exposure in the brain, iii) the optimal target epitope, and iv) the mechanisms underlying side effects. In this review I discuss how answering these and other questions could increase the likelihood of therapeutic success. As passive immunotherapies are also likely to be extremely expensive, I also raise questions relating to cost-benefit of biologic-based therapies for AD that could limit future impact of these therapies by limiting access due to economic constraints.

  1. Computer-controlled stimulation for functional magnetic resonance imaging studies of the neonatal olfactory system

    PubMed Central

    Arichi, T; Gordon-Williams, R; Allievi, A; Groves, AM; Burdet, E; Edwards, AD

    2013-01-01

    Aim Olfactory sensation is highly functional early in human neonatal life, with studies suggesting that odours can influence behaviour and infant–mother bonding. Due to its good spatial properties, blood oxygen level–dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) has the potential to rapidly advance our understanding of the neural activity which underlies the development of olfactory perception in this key period. We aimed to design an ‘olfactometer’ specifically for use with neonatal subjects for fMRI studies of odour perception. Methods We describe a fully automated and programmable, fMRI compatible system capable of presenting odorant liquids. To prevent contamination of the system and minimize between-subject infective risk, the majority of the olfactometer is constructed from single-use, readily available clinical equipment. The system was used to present the odour of infant formula milk in a validation group of seven neonatal subjects at term equivalent postmenstrual age (median age 40 weeks). Results A safe, reliable and reproducible pattern of stimulation was delivered leading to well-localized positive BOLD functional responses in the piriform cortex, amygdala, thalamus, insular cortex and cerebellum. Conclusions The described system is therefore suitable for detailed studies of the ontology of olfactory sensation and perception during early human brain development. PMID:23789919

  2. Value of postmortem studies in deceased neonatal and pediatric intensive care unit patients.

    PubMed

    Widmann, Raphael; Caduff, Rosmarie; Giudici, Luca; Zhong, Qing; Vogetseder, Alexander; Arlettaz, Romaine; Frey, Bernhard; Moch, Holger; Bode, Peter K

    2017-02-01

    Worldwide, various autopsy studies have shown a decrease in the diagnostic error rate over the last years. The cause of this positive development is mainly due to the improvement of modern medicine. However, intensive care unit patients are thought to have a higher risk for diagnostic errors, which is documented in several studies in the adult population. In contrast, there is only limited information about diagnostic errors in pediatrics, particularly in pediatric and neonatal intensive care units. The aims of this study were to analyze the spectrum of childhood death, determine the prevalence and distribution of autopsy-confirmed diagnostic errors, and describe patient characteristics that might have influenced the discordance between antemortem and postmortem findings. We analyzed 143 autopsy reports from 2004 to 2013 and correlated these with clinical reports. The overall autopsy rate during this interval was 20.3%. The leading causes of death were congenital malformations (28%), diseases closely associated with perinatal disorders (25%), disorders of the cardiovascular system (18%), and infections (15%). Additional findings were obtained in 23% of the autopsies. Major diagnostic errors were found in 6%, the lowest reported value in a developed country as yet. Most cases (75%) showed complete concordance between clinical diagnoses and postmortem findings, in line with improvements in diagnostic and therapeutic processes over the last decades. In conclusion, autopsy of neonates, infants, and children represents an important tool for monitoring the quality of pediatric and neonatal medical care.

  3. Do cry features reflect pain intensity in preterm neonates? A preliminary study.

    PubMed

    Johnston, C C; Sherrard, A; Stevens, B; Franck, L; Stremler, R; Jack, A

    1999-08-01

    The purpose of this study was to investigate if cries from preterm neonates would reflect changes in pain intensity following interventions. The cries from 25 preterm neonates from an original sample of 122 were audiorecorded while the infant was undergoing heelstick during a randomized crossover design testing the efficacy of: pacifier with sucrose or water, or prone position as compared to standard care. Both pacifier conditions reduced procedural pain according to a validated composite pain measure (the Premature Infant Pain Profile). There were proportionately fewer cries in the two pacifier groups compared to the prone positioning and standard care groups, and cry duration was positively correlated with PIPP scores. However, neither cry duration nor fundamental frequency reflected group differences. Further research is needed to determine if cry is a sensitive and valid indicator of pain in preterm infants.

  4. A Pilot Study of Antithrombin Replacement Prior to Cardiopulmonary Bypass in Neonates.

    PubMed

    Niebler, Robert A; Woods, Katherine J; Murkowski, Kathleen; Ghanayem, Nancy S; Hoffman, George; Mitchell, Michael E; Punzalan, Rowena C; Scott, J Paul; Simpson, Pippa; Tweddell, James S

    2016-01-01

    Neonates have low levels of antithrombin. Inadequate anticoagulation during cardiopulmonary bypass (CPB) due to low antithrombin activity may result in a poor preservation of the coagulation system during bypass. We hypothesize that antithrombin replacement to neonates prior to CPB will preserve the hemostatic system and result in less postoperative bleeding. A randomized, double-blinded, placebo-controlled pilot study of antithrombin replacement to neonates prior to CPB was conducted. Preoperative antithrombin levels determined the dose of recombinant antithrombin or placebo to be given. Antithrombin levels were measured following the dosing of the antithrombin/placebo, after initiation of bypass, near the completion of bypass, and upon intensive care unit admission. Eight subjects were enrolled. No subject had safety concerns. Mediastinal exploration occurred in two antithrombin subjects and one placebo subject. Antithrombin activity levels were significantly higher in the treated group following drug administration; levels continued to be higher than preoperatively but not different from the placebo group at all other time points. Total heparin administration was less in the antithrombin group; measurements of blood loss were similar in both groups. A single dose of recombinant antithrombin did not maintain 100% activity levels throughout the entire operation. Although no safety concerns were identified in this pilot study, a larger trial is necessary to determine clinical efficacy.

  5. Providing immediate neonatal care and resuscitation at birth beside the mother: parents’ views, a qualitative study

    PubMed Central

    Sawyer, Alexandra; Ayers, Susan; Bertullies, Sophia; Thomas, Margaret; Weeks, Andrew D; Yoxall, Charles W; Duley, Lelia

    2015-01-01

    Objectives The aims of this study were to assess parents’ views of immediate neonatal care and resuscitation at birth being provided beside the mother, and their experiences of a mobile trolley designed to facilitate this bedside care. Design Qualitative study with semistructured interviews. Results were analysed using thematic analysis. Setting Large UK maternity hospital. Participants Mothers whose baby received initial neonatal care in the first few minutes of life at the bedside, and their birth partners, were eligible. 30 participants were interviewed (19 mothers, 10 partners and 1 grandmother). 5 babies required advanced neonatal resuscitation. Results 5 themes were identified: (1) Reassurance, which included ‘Baby is OK’, ‘Having baby close’, ‘Confidence in care’, ‘Knowing what's going on’ and ‘Dad as informant’; (2) Involvement of the family, which included ‘Opportunity for contact’, ‘Family involvement’ and ‘Normality’; (3) Staff communication, which included ‘Communication’ and ‘Experience’; (4) Reservations, which included ‘Reservations about witnessing resuscitation’, ‘Negative emotions’ and ‘Worries about the impact on staff’ and (5) Experiences of the trolley, which included ‘Practical issues’ and ‘Comparisons with standard resuscitation equipment’. Conclusions Families were positive about neonatal care being provided at the bedside, and felt it gave reassurance about their baby's health and care. They also reported feeling involved as a family. Some parents reported experiencing negative emotions as a result of witnessing resuscitation of their baby. Parents were positive about the trolley. PMID:26384723

  6. 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.

  7. Basics of cancer immunotherapy.

    PubMed

    Fujioka, Yuki; Nishikawa, Hiroyoshi

    The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19(+) acute lymphocytic leukemia. In sharp contrast to conventional anti-cancer reagents which directly kill cancer cells, cancer immunotherapy activates various types of immune effector cells to attack cancer cells. However, more than half of the treated patients showed no activation of anti-tumor CD8(+) killer T cells and CD4(+) helper T cells and failed to respond to immune therapies such as immune checkpoint blockade, even when administered in combination regimens. Thus, development of novel immunotherapies to achieve more effective activation of anti-cancer immunity and immuno-monitoring of biomarkers, allowing proper evaluation of immune responses in cancer patients in order to detect responders, are urgent issues. Additionally, we must pay attention to characteristic immunological side effects not observed following treatment with conventional anti-cancer reagents. Herein, we present a summary outline and discuss the future direction of cancer immunotherapy.

  8. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of 10455 patients

    PubMed Central

    da Cunha-Bang, C; Simonsen, J; Rostgaard, K; Geisler, C; Hjalgrim, H; Niemann, C U

    2016-01-01

    The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer Register between 1978 and 2013. We identified 10 455 CLL patients and 508 995 CLL-free control persons from the general population. Compared with the latter, the relative mortality rate between CLL patients and their controls decreased from 3.4 (95% CI 3.2–3.6) to 1.9 (95% CI 1.7–2.1) for patients diagnosed in 1978–1984 and 2006–2013, respectively. The improved survival corresponded to a decreasing risk of death from malignant hematological diseases, whereas the risk of death from infections was stable during the study period. These population-based data substantiate the improved survival for patients treated with chemo-immunotherapy demonstrated in clinical studies. PMID:27834937

  9. Potential for immunotherapy in soft tissue sarcoma

    PubMed Central

    Tseng, William W; Somaiah, Neeta; Engleman, Edgar G

    2015-01-01

    Soft tissue sarcomas (STS) are rare, heterogeneous tumors of mesenchymal origin. Despite optimal treatment, a large proportion of patients will develop recurrent and metastatic disease. For these patients, current treatment options are quite limited. Significant progress has been made recently in the use of immunotherapy for the treatment of other solid tumors (e.g. prostate cancer, melanoma). There is a strong rationale for immunotherapy in STS, based on an understanding of disease biology. For example, STS frequently have chromosomal translocations which result in unique fusion proteins and specific subtypes have been shown to express cancer testis antigens. In this review, we discuss the current status of immunotherapy in STS, including data from human studies with cancer vaccines, adoptive cell therapy, and immune checkpoint blockade. Further research into STS immunology is needed to help design logical, subtype-specific immunotherapeutic strategies. PMID:25625925

  10. [Immunotherapies and targeted therapies in medical oncology].

    PubMed

    Rousseau, Benoît; Champiat, Stéphane; Loirat, Delphine; Arrondeau, Jennifer; Lemoine, Nathalie; Soria, Jean-Charles

    2014-01-01

    New immunotherapies, also called "immune checkpoints", are promising and showed interesting antitumoral activities in particular in advanced setting of melanoma, clear cell renal cancer or non-small cell lung carcinoma. These treatments include ipilimumab, anti-PD-1 and anti-PD-L1. There is a strong rational for combination of immunotherapies and targeted therapies. This review is dedicated to expose the theorical issues and preclinical data of such combinations. This review examined the impact of immunotherapies on transduction pathways and modification of immunity related to targeted therapies. First clinical data form early drug development studies showed the difficulties observed with such combination and limitating toxicities. Finally, potential interesting combinations are overviewed with an emphasis on sequential treatments.

  11. [Pharmacokinetic and clinical studies of latamoxef (moxalactam) in neonates and premature infants].

    PubMed

    Fujii, R; Hashira, S; Takimoto, M; Oka, T; Yoshioka, H; Tsuchida, A; Sanae, N; Maruyama, S; Tojo, M; Sunakawa, K

    1984-06-01

    Studies were carried out on the in vivo kinetics and clinical efficacy of latamoxef (LMOX) in neonates and premature infants. The results are summarized below. Serum concentration and T1/2 following intravenous injection of LMOX to neonates LMOX was intravenously administered to neonates as one shot doses of 10 mg/kg and 20 mg/kg. The serum concentration of LMOX showed a dose-response to the 10 and 20 mg/kg doses in each of the 0--3 day-old group, 4--7 day-old group and 8--28 day-old group. The T 1/2 values were as follows; for the 10 mg/kg dose, 5.17 hours in the 0--3 day-old group, 3.28 hours in the 4--7 day-old group and 2.79 hours in the 8--28 day-old group; for the 20 mg/kg dose, 5.58 hours in the 0--3 day-old group, 3.46 hours in the 4--7 day-old group and 3.14 hours in the 8--28 day-old group. Thus, it is seen that the half-life of both dosages decreased as the infants became older. Serum concentration and T 1/2 following intravenous injection of LMOX to premature infants Similar to the case of neonates described above, the concentration of LMOX in the serum of the premature infants showed a dose-response to the 10 mg/kg and 20 mg/kg dosages. The T 1/2 values for the 0--3, 4--7 day-old and 8--28 day-old groups were 7.54, 3.93 hours and 6.25 hours, respectively, for the 10 mg/kg dose, and 10.8, 4.05 hours and 3.23 hours, respectively, for the 20 mg/kg dose. Again, it is seen that the half-life of both dosages decreased as the age of the prematurely-born infants increased. Serum concentration and T1/2 following 1-hour intravenous drip infusion of LMOX to neonates LMOX was administered to neonates in doses of 10 mg/kg and 20 mg/kg, by i.v. drip infusion over a 1-hour period. With both dosages, the peak serum concentration of LMOX occurred at the time of completion of the infusion. The T1/2 values for the 0--3, 4--7 day-old and 8--28 day-old groups were 5.41, 3.68 hours and 1.92 hours, respectively, for the 10 mg/kg dose, and 5.31, 2.67 hours and 4.86 hours

  12. 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.

  13. 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.

  14. [A pilot study on establishment of human/pig hematopoietic chimera model in fetal and neonatal pigs].

    PubMed

    Tan, Ying-Xia; Wang, Jie-Xi; Li, Ming; Zhang, Yang-Pei

    2005-08-01

    This study was aimed to explore the feasibility of transplanting human cord blood stem cells (HSC) into pre-immune fetal and neonatal pigs, and to investigate the self-renewal of HSC in the recipient pigs. The fetus and neonate were manipulated in sterile separated room and human donor cells were injected into fetus via fetus muscle or umbilical vein (dissectted womb) or into neonate via umbilical vein before cutting it. Human CD45(+) cells s were detected by labeling with human anti-CD45 antibody and analyzed by fluorescence activated cell sorting (FACS). The results showed that tested pigs developed as well as control and a definite proportion of human cells existed in peripheral blood of chimeric pig on day 60 after transplantation. In conclusion, the fetus and neonate pigs can tolerate a definite proportion of human antigens, and to establish the human/pig model of hematopoietic chimerism is possible.

  15. [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

  16. [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.

  17. Immunotherapy of Childhood Sarcomas

    PubMed Central

    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. PMID:26301204

  18. 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.

  19. [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.

  20. A Bayesian approach to the creation of a study-customized neonatal brain atlas.

    PubMed

    Zhang, Yajing; Chang, Linda; Ceritoglu, Can; Skranes, Jon; Ernst, Thomas; Mori, Susumu; Miller, Michael I; Oishi, Kenichi

    2014-11-01

    Atlas-based image analysis (ABA), in which an anatomical "parcellation map" is used for parcel-by-parcel image quantification, is widely used to analyze anatomical and functional changes related to brain development, aging, and various diseases. The parcellation maps are often created based on common MRI templates, which allow users to transform the template to target images, or vice versa, to perform parcel-by-parcel statistics, and report the scientific findings based on common anatomical parcels. The use of a study-specific template, which represents the anatomical features of the study population better than common templates, is preferable for accurate anatomical labeling; however, the creation of a parcellation map for a study-specific template is extremely labor intensive, and the definitions of anatomical boundaries are not necessarily compatible with those of the common template. In this study, we employed a volume-based template estimation (VTE) method to create a neonatal brain template customized to a study population, while keeping the anatomical parcellation identical to that of a common MRI atlas. The VTE was used to morph the standardized parcellation map of the JHU-neonate-SS atlas to capture the anatomical features of a study population. The resultant "study-customized" T1-weighted and diffusion tensor imaging (DTI) template, with three-dimensional anatomical parcellation that defined 122 brain regions, was compared with the JHU-neonate-SS atlas, in terms of the registration accuracy. A pronounced increase in the accuracy of cortical parcellation and superior tensor alignment were observed when the customized template was used. With the customized atlas-based analysis, the fractional anisotropy (FA) detected closely approximated the manual measurements. This tool provides a solution for achieving normalization-based measurements with increased accuracy, while reporting scientific findings in a consistent framework.

  1. 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.

  2. Laser immunotherapy in treatment of metastatic prostate tumors in rats

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Ritchey, Jerry W.; Bartles, Kenneth E.; Lucroy, Michael D.; Liu, Hong; Nordquist, Robert E.

    2002-07-01

    Laser immunotherapy is a special cancer treatment modality using an intratumor injection of a special formulation consisting of a novel immunoadjuvant and a laser-absorbing dye, followed by a non-invasive near-IR laser irradiation. Our early experiments using a metastatic mammary rat tumor model showed that laser immunotherapy could cause acute selective photothermal tumor destruction and induce a systemic, long-term specific anti-tumor immunity. In the current study, laser immunotherapy was used to treat metastatic prostate tumors in Copenhagen male rats. The transplantable tumors metastasize mainly to the lung and the lung cancer is usually the cause of death. Two experimental were performed in our study. The first was to study the effect of laser immunotherapy on the tumor burdens, both the primary and the metastasis in the lung. The second was to study the effect of laser immunotherapy on the long-term survival of the tumor-bearing rats. For comparison, some rat tumors were also treated by the laser-dye combination to study the photothermal effect. Tour results showed that both the photothermal effect and the laser immunotherapy could slow the growth of primary tumors and the metastatic tumors. The laser-dye-immunoadjuvant treatment resulted in more than 20 percent long-term survival rate in tumor-bearing rats. Our experimental results indicate that the laser immunotherapy has a great potential in treating metastatic tumors.

  3. 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…

  4. Nanoparticulate immunotherapy for cancer.

    PubMed

    Kapadia, Chintan H; Perry, Jillian L; Tian, Shaomin; Luft, J Christopher; DeSimone, Joseph M

    2015-12-10

    Although surgery, radiation therapy, and chemotherapy have significantly improved as treatments for cancer, they can rarely control metastatic disease and cures remain scarce. Promising recent developments suggest that cancer immunotherapy may become a powerful new therapy that clinicians can offer cancer patients. The opportunity to orchestrate the body's own immune system to target, fight, and eradicate cancer cells without destroying healthy cells makes this an extremely attractive treatment modality. Our increased knowledge in anti-tumor immunity and the immunosuppressive tumor microenvironment (TME) has provided many therapeutic strategies to battle cancer. That combined with advancements in the field of particulate delivery systems provide a mechanism to deliver these immunotherapeutics to their specific targeted cells and the TME. In this review we will focus on the current status of immunotherapy and the potential advantages of utilizing nanocarriers within the field.

  5. 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.

  6. Immunotherapy in food allergy

    PubMed Central

    Kamdar, Toral; Bryce, Paul J

    2010-01-01

    Food allergies are caused by immune responses to food proteins and represent a breakdown of oral tolerance. They can range from mild pruritis 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. PMID:20543886

  7. Neonatal sepsis.

    PubMed

    Stefanovic, Iva Mihatov

    2011-01-01

    Neonatal sepsis is the most common cause of neonatal deaths with high mortality despite treatment. Neonatal sepsis can be classified into two subtypes depending upon onset of symptoms. There are many factors that make neonates more susceptable to infection. Signs of sepsis in neonates are often non-specific and high degree of suspicion is needed for early diagnosis. Some laboratory parameters can be helpful for screening of neonates with neonatal sepsis, but none of it is specific and sensitive enough to be used singly. Diagnostic approach mostly focuses on history and review of non specific signs and symptoms. Antibiotic treatment is the mainstay of treatment and supportive care is equally important. The aim of this review is to give an overview of neonatal sepsis, including incidence, etiology, clinical picture, diagnostics and therapy.

  8. 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 ...

  9. Integrated Immunotherapy for Breast Cancer

    DTIC Science & Technology

    2014-09-01

    2 AD_________________ Award Number: W81XWH-12-1-0366 TITLE: Integrated Immunotherapy for Breast Cancer PRINCIPAL...31Aug2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Integrated Immunotherapy for Breast Cancer 5b. GRANT NUMBER W81XWH-12-1-0366 5c. PROGRAM... immunotherapy , tumor microenvironment, dendritic cells, metastasis, cancer stroma. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18

  10. Sexual violence and neonatal outcomes: a Norwegian population-based cohort study

    PubMed Central

    Henriksen, Lena; Schei, Berit; Vangen, Siri; Lukasse, Mirjam

    2014-01-01

    Objective The objective of this study was to explore the association between sexual violence and neonatal outcomes. Design National cohort study. Setting Women were recruited to the Norwegian Mother and Child Cohort Study (MoBa) while attending routine ultrasound examinations from 1999 to 2008. Population A total of 76 870 pregnant women. Methods Sexual violence and maternal characteristics were self-reported in postal questionnaires during pregnancy. Neonatal outcomes were retrieved from the Medical Birth Registry of Norway (MBRN). Risk estimations were performed with linear and logistic regression analysis. Outcome measures: gestational age at birth, birth weight, preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Results Of 76 870 women, 18.4% reported a history of sexual violence. A total of 4.7% delivered prematurely, 2.7% had children with a birth weight <2500 g and 8.1% children were small for their gestational age. Women reporting moderate or severe sexual violence (rape) had a significantly reduced gestational length (2 days) when the birth was provider-initiated in an analysis adjusted for age, parity, education, smoking, body mass index and mental distress. Those exposed to severe sexual violence had a significantly reduced gestational length of 0.51 days with a spontaneous start of birth. Crude estimates showed that severe sexual violence was associated with PTB, LBW and SGA. When controlling for the aforementioned sociodemographic and behavioural factors, the association was no longer significant. Conclusions Sexual violence was not associated with adverse neonatal outcomes. Moderate and severe violence had a small but significant effect on gestational age; however, the clinical influence of this finding is most likely limited. Women exposed to sexual violence in this study reported more of the sociodemographic and behavioural factors associated with PTB, LBW and SGA compared with non-abused women. PMID:25763796

  11. 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.

  12. Immunotherapy of cancer in 2012.

    PubMed

    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.

  13. 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

  14. Specific immunotherapy in children.

    PubMed

    Bufe, A; Roberts, G

    2011-09-01

    Subcutaneous immunotherapy (SCIT) with allergen extracts in children with allergic rhinitis, with or without co-seasonal asthma, has developed into a routine treatment although the scientific evidence for its efficacy is not as strong as for adults. In the hands of experienced allergists, this treatment has been proven to be safe. The development of allergen tablets for sublingual immunotherapy (SLIT) may open a new age of more convenient, safer SIT. In children, in particular, the evidence for the long-term efficacy of SLIT, its ability to prevent the development of asthma and polysensitization and its comparability to SCIT will be required before it will replace the traditional subcutaneous route. Issues of compliance represent an important drawback of SLIT. We need ways of improving this. Treatment of asthma by immunotherapy is still restricted to clearly defined patients with mild to moderate asthma with symptoms that are related to the specific allergen sensitization. In these patients, symptoms and use of anti-inflammatory therapy can be reduced by SIT.

  15. Immunotherapy of Fungal Infections.

    PubMed

    Datta, Kausik; Hamad, Mawieh

    2015-01-01

    Fungal organisms are ubiquitous in the environment. Pathogenic fungi, although relatively few in the whole gamut of microbial pathogens, are able to cause disease with varying degrees of severity in individuals with normal or impaired immunity. The disease state is an outcome of the fungal pathogen's interactions with the host immunity, and therefore, it stands to reason that deep/invasive fungal diseases be amenable to immunotherapy. Therefore, antifungal immunotherapy continues to be attractive as an adjunct to the currently available antifungal chemotherapy options for a number of reasons, including the fact that existing antifungal drugs, albeit largely effective, are not without limitations, and that morbidity and mortality associated with invasive mycoses are still unacceptably high. For several decades, intense basic research efforts have been directed at development of fungal immunotherapies. Nevertheless, this approach suffers from a severe bench-bedside disconnect owing to several reasons: the chemical and biological peculiarities of the fungal antigens, the complexities of host-pathogen interactions, an under-appreciation of the fungal disease landscape, the requirement of considerable financial investment to bring these therapies to clinical use, as well as practical problems associated with immunizations. In this general, non-exhaustive review, we summarize the features of ongoing research efforts directed towards devising safe and effective immunotherapeutic options for mycotic diseases, encompassing work on antifungal vaccines, adoptive cell transfers, cytokines, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), and other agents.

  16. Immunotherapy of melanoma.

    PubMed

    Kee, D; McArthur, G

    2017-03-01

    Immunotherapy for advanced melanoma has progressed dramatically in the last five years with the approval of immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Inhibition of these targets can break cancer-immune tolerance and result in durable objective responses with significantly improved tolerability over cytokine-based immunotherapy. Ipilimumab is an inhibitor of CTLA-4 and the first-in-class immune checkpoint inhibitor to demonstrate an improvement in overall survival in melanoma. Pembrolizumab and nivolumab target PD-1 and have improved single agent activity and tolerability in comparison to ipilimumab. The combination of nivolumab and ipilimumab results in even better response rates, reductions in tumor volume and progression free survival but at the expense of considerable autoimmune effects. Autoimmune side-effects and non-standard response kinetics represent a new challenge associated with cancer therapies that practitioners will have to become more familiar with as checkpoint inhibitors increasingly become part of mainstream oncological practice. Ongoing areas of investigation include drug development against novel immune targets; alternative treatment modalities, such as genetically modified oncolytic viruses; optimization of immunotherapy combination strategies; and the identification of reliable biomarkers to better guide treatment selection.

  17. 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.

  18. [Immunotherapy in uropathology].

    PubMed

    Verkarre, Virginie; Roussel, Hélène; Granier, Clémence; Tartour, Eric; Allory, Yves

    2017-02-01

    The algorithms for treatment of metastatic cancers are evolving due to positive results obtained with immunotherapy. Therapeutics approaches to stimulate the immune system have already been used in the treatment of kidney and bladder cancer, such as the administration of cytokines and BCG therapy, confirming the immunogenicity of these tumors. The aim of immunotherapies is not only to activate the immune system against tumor cells, but also to take into account the tumor-induced suppressive microenvironment, in particular by removing the anergy of T-cell lymphocytes, and by targeting the co-stimulation inhibitors molecules. Among the genito-urinary cancers, second-line clinical trials have clearly shown that kidney and bladder cancers are sensitive to the inhibition of PD-1/PD-L1 axis and have already achieved FDA approvals for some molecules. Numerous other clinical trials are underway, particularly in first-line treatment in bladder and renal cancers. Refractory testicular cancer could also benefit from these treatments. Other approaches using vaccine therapy especially in castration-resistant prostate cancer are also of interest. We will see, in this chapter dedicated to the urogenital cancers, the benefit of the immunotherapy by resituating it in the genetic and immunological context of each organ. We will also present briefly the therapeutic outlines and the place of biomarkers.

  19. 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.

  20. Parenting roles and knowledge in neonatal intensive care units: protocol of a mixed methods study

    PubMed Central

    Alves, Elisabete; Amorim, Mariana; Fraga, Sílvia; Barros, Henrique; Silva, Susana

    2014-01-01

    Introduction There is a strong focus on the translation of scientific knowledge into evidence-based practice when dealing with very preterm births. The aim is to standardise and rationalise healthcare. The incorporation of parents’ perspectives with respect to the organisation of care and technical interventions in neonatal intensive care units (NICUs) is needed. This study aims to analyse the repertoire of meanings, knowledge and emotions actualised by the parents of very preterm infants hospitalised in NICUs in the decision process regarding parental care, treatment options and uses of information sources. Methods and analysis This is a mixed-methods, observational study. The methodological strategy will rely on: (1) Ethnographic observation, carried out in a level III NICU located in the North of Portugal, during 6 months; (2) NICU-based surveys of mothers and fathers of very preterm infants born between July 2013 and June 2014 and admitted at the seven public level III NICUs of the Northern Health Region of Portugal; (3) Single and couple semistructured interviews to a subsample of mothers and fathers of very preterm infants, 4 months after birth. Inferential statistics will be used to analyse the quantitative data and content analysis, with an iterative and reflexive process and will be implemented to assess qualitative data. Ethics and dissemination The study protocol was approved by the National Data Protection Commission and the Ethics Committee of all the hospitals involved. The current project will contribute to develop resources for enriched good medical practices in the context of neonatal services through integrating insights from social sciences, public health, epidemiology and ethics. The expected dissemination actions are effective tools in designing strategies that aim to develop family-centred care and to improve medical practices in the context of neonatal services. PMID:25011994

  1. Electrical Impedance Tomography: a new study method for neonatal Respiratory Distress Syndrome?

    PubMed

    Chatziioannidis, I; Samaras, T; Nikolaidis, N

    2011-07-01

    Treatment of cardiorespiratory system diseases is a procedure that usually demands data collection on terms of the anatomy and the operation of the organs that are under study. Electrical Impedance Tomography (EIT) is an alternative approach, in comparison to existing techniques. With EIT electrodes are placed in the perimeter of the human body and images of the estimated organ are reconstructed, using the measurement of its impendence (or resistance) distribution and determining its alteration through time, while at the same time the patient is not exposed to ionizing radiation. Its clinical use presupposes the correct placement of the electrodes over the perimeter of the human body, the rapid data collection and electrical safety. It is a low cost technique and it is implemented near the patient. It is able to determine the distribution of ventilation, blood supply, diffused or localized lung defects, but it can also estimate therapeutic interventions or alteration to assisted ventilation of the neonate. EIT was developed at the beginning of the 1980s, but it has only recently begun to be implemented on neonates, and especially in the study of their respiratory system function. The low rate of image analysis is considered to be a drawback, but it is offset by the potential offered for the estimation of lungs' function (both under normal and pathological conditions), since ventilation and resistance are two quite similar concepts. In this review the most important studies about EIT are mentioned as a method of estimating respiratory distress syndrome in neonates. In terms of the above mentioned development, it is supposed that this technique will offer a great amount of help to the doctor in his / her estimations of the cardiorespiratory system and to his / her selection of the best intervening strategies.

  2. Immunotherapies to prevent mother-to-child transmission of HIV.

    PubMed

    Hicar, Mark D

    2013-03-01

    Although pharmacological interventions have been successful in reducing prevention of maternal to child transmission (PMTCT) of HIV, there is concern that complete elimination through this mode of transmission will require other measures. Immunotherapies in infants or pregnant mothers may be able to eradicate this form of transmission. A recent vaccine trial in adults showed encouraging results, but as in most HIV safety and efficacy vaccine trials, the question of MTCT was not addressed. Concentrating transmission studies and vaccine studies in the setting of MTCT offers several advantages. MTCT has a generally reproducible known transmission rate and has been successfully used to assess pharmacological interventions on decreasing transmission. Even in resource poor settings, the infrastructure for neonatal vaccination is already in place. Although rare, both passive and active vaccination trials have been successfully completed in pediatric populations. Unfortunately, little success in affecting MTCT has been shown. Largely, a correlate of protection in any type of transmission, including MTCT, is unknown. Data supports a role for antibodies in effecting strain and transmission during MTCT. The role of antibodies in MTCT is reviewed with a focus on recent passive immunization and considerations for future studies.

  3. Allergen Immunotherapy in Allergic Respiratory Diseases

    PubMed Central

    Viswanathan, Ravi K.

    2012-01-01

    Allergen-specific immunotherapy (SIT) involves the repeated administration of allergenic extracts to atopic individuals over a period of 3 to 5 years either subcutaneously (SCIT) or sublingually (SLIT) for the treatment of allergic respiratory diseases, including asthma and allergic rhinitis (AR). In studies, SCIT and SLIT have been shown to improve existing symptoms of asthma and AR and to also have the capability to cause disease-modifying changes of the underlying atopic condition so as to prevent new allergic sensitization as well as arrest progression of AR to asthma. Recent evidence suggests that immunotherapy brings about these effects through actions that use T-regulatory cells and blocking antibodies such as IgG4 and IgA2, which can then result in an “immune deviation” from a T-helper (Th) 2 cell pattern to a Th1 cell pattern. Numerous meta-analyses and studies have been performed to evaluate the existing data among these studies, with the consensus recommendation favoring the use of immunotherapy because of its potential to modify existing diseases. Significant adverse reactions can occur with immunotherapy, including anaphylaxis and, very rarely, death. A primary factor in considering SIT is its potential to provide long-lasting effects that are able to be sustained well after its discontinuation. Given the significant burden these allergic diseases impose on the health-care system, SIT appears to be a cost-effective adjunctive treatment in modifying the existing disease state. PMID:22553263

  4. Susceptibility of neonatal T cells and adult thymocytes to peripheral tolerance to allogeneic stimuli

    PubMed Central

    do Canto, Fábio B; Lima, Celso; Teixeira, Ivan A; Bellio, Maria; Nóbrega, Alberto; Fucs, Rita

    2008-01-01

    We studied the tolerization of neonatal thymocytes (NT), neonatal splenocytes (NS) and adult thymocytes (AT), transferred to syngeneic nude (nu/nu) hosts previously injected with semi-allogeneic splenocytes, without any supportive immunosuppressive treatment. This protocol allows the study of peripheral tolerance in the absence of the thymus. BALB/c neonatal T cells and ATs were able to expand in syngeneic BALB/c nu/nu mice and functionally reconstituted an allogeneic response, rejecting (BALB/c × B6.Ba) F1 splenocytes transferred 3–4 weeks after injection of BALB/c cells. However, if (BALB/c × B6.Ba) F1 cells were injected into BALB/c nude hosts 30 days before transfer of NT, NS or AT cells, the F1 population was preserved and specific tolerance to B6 allografts was established. Furthermore, transfer to lymphopenic F1 nu/nu showed that tolerance could be established only for neonatal populations, showing that unique properties of neonatal T cells allow their tolerization in both lymphopenic and non-lymphopenic conditions, in the absence of suppressive immunotherapy. These results bring empirical support to the possibility of T-cell engraftment in immunodeficient patients showing partial identity with donor major histocompatibility complex (MHC) genes; the manipulation of immunological maturity of donor T cells may be the key for successful reconstitution of immunocompetence without induction of graft-versus-host disease. PMID:18462348

  5. Immune mechanisms of sublingual immunotherapy.

    PubMed

    Jay, David C; Nadeau, Kari C

    2014-11-01

    Sublingual immunotherapy (SLIT) is a well-established allergen-specific immunotherapy and a safe and effective strategy to reorient inappropriate immune responses in allergic patients. SLIT takes advantage of the tolerogenic environment of the oral mucosa to promote tolerance to the allergen. Several clinical studies have investigated the complex interplay of innate and adaptive immune responses that SLIT exploits. The oral immune system is composed of tolerogenic dendritic cells that, following uptake of allergen during SLIT, support the differentiation of T helper cell type 1 (Th1) and the induction of IL-10-producing regulatory T cells. Following SLIT, allergic disease-promoting T helper cell type 2 (Th2) responses shift to a Th1 inflammatory response, and IL-10 and transforming growth factor (TGF)-β production by regulatory T cells and tolerogenic dendritic cells suppress allergen-specific T cell responses. These immune changes occur both in the sublingual mucosa and in the periphery of a patient following SLIT. SLIT also promotes the synthesis of allergen-specific IgG and IgA antibodies that block allergen-IgE complex formation and binding to inflammatory cells, thus encouraging an anti-inflammatory environment. Several of these revealing findings have also paved the way for the identification of biomarkers of the clinical efficacy of SLIT. This review presents the emerging elucidation of the immune mechanisms mediated by SLIT.

  6. Novel Immunotherapies for Autoimmune Hepatitis

    PubMed Central

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

  7. The expanding role of immunotherapy.

    PubMed

    Martin-Liberal, Juan; Ochoa de Olza, María; Hierro, Cinta; Gros, Alena; Rodon, Jordi; Tabernero, Josep

    2017-02-11

    The use of agents able to modulate the immune system to induce or potentiate its anti-tumour activity is not a new strategy in oncology. However, the development of new agents such as immune checkpoint inhibitors has achieved unprecedented efficacy results in a wide variety of tumours, dramatically changing the landscape of cancer treatment in recent years. Ipilimumab, nivolumab, pembrolizumab or atezolizumab are now standard of care options in several malignancies and new indications are being approved on a regular basis in different tumours. Moreover, there are many other novel immunotherapy strategies that are currently being assessed in clinical trials. Agonists of co-stimulatory signals, adoptive cell therapies, vaccines, virotherapy and others have raised interest as therapeutic options against cancer. In addition, many of these novel approaches are being developed both in monotherapy and as part of combinatory regimes in order to synergize their activity. The results from those studies will help to define the expanding role of immunotherapy in cancer treatment in a forthcoming future.

  8. Novel Immunotherapies for Autoimmune Hepatitis.

    PubMed

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects.

  9. [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.

  10. A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units

    PubMed Central

    Isaacs, D

    2003-01-01

    Objective: To study late onset systemic infections with coagulase negative staphylococci. Methods: Prospective longitudinal study of coagulase negative staphylococcal infection in 18 Australasian neonatal nurseries. Results: From 1991 to 2000 inclusive, there were 1281 cases of coagulase negative staphylococcal (CoNS) sepsis, comprising 57.1% of all late onset infections. The male/female ratio was 1.27:1 (p < 0.05). The incidence of CoNS sepsis was 3.46 episodes per 1000 live births. Most infected babies (71%) were 24–29 weeks gestation at birth (mode 26 weeks). The first positive culture was day 7–14 in 49% of babies (mode 10 days). Five cases of meningitis were reported, an incidence of 0.4% of all CoNS infections. Twenty nine babies (2.3%) had concurrent necrotising enterocolitis and CoNS septicaemia. Four babies (0.3%) died from CoNS infection, but CoNS infection possibly contributed to the death of an additional 20 babies (1.6%). The mortality directly attributable to CoNS infection was significantly lower than that from late onset infections with Staphylococcus aureus (13.1%; relative risk (RR) = 36.1 (95% confidence interval (CI) 13.0 to 100.2) or with Gram negative bacilli (14.2%; RR = 45.5 (95% CI 16.8 to 123.3)). Conclusions: CoNS are currently responsible for most late onset neonatal infections. Most infected babies are < 30 weeks gestation at birth, and usually present between 7 and 14 days of age. CoNS infections may be associated with necrotising enterocolitis, although causality is unproven. Neonatal CoNS infections are relatively benign: meningitis is rare and mortality low compared with infection from other organisms. Over-vigorous attempts to reduce the incidence of CoNS infections using prophylactic antibiotics are not advisable. PMID:12598493

  11. Adapting conventional cancer treatment for immunotherapy.

    PubMed

    Qiao, Jian; Liu, Zhida; Fu, Yang-Xin

    2016-05-01

    The efficacy of directly killing tumors by conventional cancer therapies, such as chemotherapy and radiotherapy, has been for several decades well established. But, a suppressed immune response might become a lethal side effect after repeated cycles of intensive treatment. Recently, achievements in immune checkpoint inhibitors and adoptive T cell-mediated immunotherapies have resulted in changes in frontline management of advanced cancer diseases. However, accumulated evidence indicates that immunotherapeutic and conventional strategies alone are often ineffective to eradicate big tumors or metastasis. To improve the outcomes of treatment for advanced cancer diseases, the combination of conventional cancer treatment with various immunotherapeutic approaches has been attempted and has shown potential synergistic effects. Recent studies have unexpectedly demonstrated that some strategies of conventional cancer treatment can regulate the immune response positively, thus the understanding of how to adapt conventional treatment for immunotherapy is crucial to the design of effective combination therapy of conventional treatment with immunotherapy. Here, we review both experimental and clinical studies on the therapeutic effect and its mechanisms of combining conventional therapy with immunotherapy in treatment of cancer.

  12. Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion

    PubMed Central

    Nio, Y; Nagami, H; Tamura, K; Tsubono, M; Nio, M; Sato, M; Kawabata, K; Hayashi, H; Shiraishi, T; Imai, S; Tsuchitani, T; Mizuta, J; Nakagawa, M; Fukumoto, M

    1999-01-01

    The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of

  13. Neonatal risk factors for cerebral palsy in very preterm babies: case-control study.

    PubMed Central

    Murphy, D. J.; Hope, P. L.; Johnson, A.

    1997-01-01

    OBJECTIVE: To identify neonatal risk factors for cerebral palsy among very preterm babies and in particular the associations independent of the coexistence of antenatal and intrapartum factors. DESIGN: Case-control study. SETTING: Oxford health region. SUBJECTS: Singleton babies born between 1984 and 1990 at less than 32 weeks' gestation who survived to discharge from hospital: 59 with cerebral palsy and 234 randomly selected controls without cerebral palsy. MAIN OUTCOME MEASURES: Adverse neonatal factors expressed as odds ratios and 95% confidence intervals. RESULTS: Factors associated with an increased risk of cerebral palsy after adjustment for gestational age and the presence of previously identified antenatal and intrapartum risk factors were patent ductus arteriosus (odds ratio 2.3; 95% confidence interval 1.2 to 4.5), hypotension (2.3; 1.3 to 4.7), blood transfusion (4.8; 2.5 to 9.3), prolonged ventilation (4.8; 2.5 to 9.0), pneumothorax (3.5; 1.6 to 7.6), sepsis (3.6; 1.8 to 7.4), hyponatraemia (7.9; 2.1 to 29.6) and total parenteral nutrition (5.5; 2.8 to 10.5). Seizures were associated with an increased risk of cerebral palsy (10.0; 4.1 to 24.7), as were parenchymal damage (32; 12.4 to 84.4) and appreciable ventricular dilatation (5.4; 3.0 to 9.8) detected by cerebral ultrasound. CONCLUSION: A reduction in the rate of cerebral palsy in very preterm babies requires an integrated approach to management throughout the antenatal, intrapartum, and neonatal periods. PMID:9040385

  14. Sublingual (SLIT) Versus Oral Immunotherapy (OIT) for Food Allergy

    PubMed Central

    McGowan, Emily C.

    2016-01-01

    Food allergy is a common condition for which the only currently approved treatments are avoidance of the allergenic food and the administration of emergency medications upon accidental exposure. Over the past 10 years, significant advances have been made in the field of food immunotherapy, with efforts focusing on allergen exposure via the oral mucosa. Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are the two modalities that have been most extensively studied, and this article will review recent advances in our knowledge of the efficacy and safety of these treatments. PMID:25297805

  15. Brain Ultrasonography Findings in Neonatal Seizure; a Cross-sectional Study

    PubMed Central

    Nabavi, Seyed Saeed; Partovi, Parinaz

    2017-01-01

    Introduction: Screening of newborns with seizure, who have curable pathologic brain findings, might be able to improve their final outcome by accelerating treatment intervention. The present study aimed to evaluate the brain ultrasonography findings of newborns hospitalized with complaint of seizure. Methods: The present cross-sectional study designed to evaluate brain ultrasonography findings of hospitalized newborns complaining seizure. Neonatal seizure was defined as presence of tonic, clonic, myoclonic, and subtle attacks in 1 - 28 day old newborns. Results: 100 newborns with the mean age of 5.82 ± 6.29 days were evaluated (58% male). Most newborns were in the < 10 days age range (76%), term (83%) and with normal birth weight (81%). 22 (22%) of the ultrasonography examinations showed a pathologic finding. A correlation was only found between birth age and probability of the presence of a pathologic problem in the brain as the frequency of these problems was significantly higher in pre-term newborns (p = 0.023). Conclusion: Based on the findings of the present study, frequency of pathologic findings in neonatal brain ultrasonography was 22%. Hemorrhage (12%) and hydrocephaly (7%) were the most common findings. The only factor correlating with increased probability of positive findings was the newborns being pre-term. PMID:28286848

  16. Sublingual Immunotherapy for Allergic Fungal Sinusitis.

    PubMed

    Melzer, Jonathan M; Driskill, Brent R; Clenney, Timothy L; Gessler, Eric M

    2015-10-01

    Allergic fungal sinusitis (AFS) is a condition that has an allergic basis caused by exposure to fungi in the sinonasal tract leading to chronic inflammation. Despite standard treatment modalities, which typically include surgery and medical management of allergies, patients still have a high rate of recurrence. Subcutaneous immunotherapy (SCIT) has been used as adjuvant treatment for AFS. Evidence exists to support the use of sublingual immunotherapy (SLIT) as a safe and efficacious method of treating allergies, but no studies have assessed the utility of SLIT in the management of allergic fungal sinusitis. A record review of cases of AFS that are currently or previously treated with sublingual immunotherapy from 2007 to 2011 was performed. Parameters of interest included serum IgE levels, changes in symptoms, Lund-McKay scores, decreased sensitization to fungal allergens associated with AFS, and serum IgE levels. Ten patients with diagnosed AFS were treated with SLIT. No adverse effects related to the use of SLIT therapy were identified. Decreases in subjective complaints, exam findings, Lund-McKay scores, and serum IgE levels were observed. Thus, sublingual immunotherapy appears to be a safe adjunct to the management of AFS that may improve patient outcomes.

  17. 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.

  18. Immunotherapy and gene therapy.

    PubMed

    Simpson, Elizabeth

    2004-02-01

    The Immunotherapy and Gene Therapy meeting of the Academy of Medical Sciences reviewed the state-of-the-art and translational prospects for therapeutic interventions aimed at killing tumor cells, correcting genetic defects and developing vaccines for chronic infections. Crucial basic science concepts and information about dendritic cells, the structure and function of T-cell receptors, and manipulation of the immune response by cytokine antagonists and peptides were presented. This information underpins vaccine design and delivery, as well as attempts to immunomodulate autoimmune disease. Results from studies using anticancer DNA vaccines, which include appropriate signals for both the innate and adaptive immune response, were presented in several talks. The vaccines incorporated helper epitopes and cancer target epitopes such as immunoglobulin idiotypes (for lymphomas and myelomas), melanoma-associated antigens (for melanoma and other solid tumors) and minor histocompatibility antigens (for leukemia). The results of using vaccines employing similar principles and designed to reduce viral load in HIV/AIDS patients were also presented. The introduction of suicide genes incorporating the bacterial enzyme nitroreductase gene (ntr) targeted at tumor cells prior to administration of the prodrug CB-1954, converted by ntr into a toxic alkylating agent, was discussed against the background of clinical trials and improved suicide gene design. The introduction into hematopoietic stem cells of missing genes for the common gamma-chain, deficiency of which causes severe combined immunodeficiency (SCID), used similar retroviral transduction. The outcome of treating six SCID patients in the UK, and ten in France was successful immune reconstitution in the majority of patients, but in two of the French cases a complication of lymphoproliferative disease due to insertional mutagenesis was observed. The adoptive transfer of T-cells specific for minor histocompatibility antigens (for

  19. 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

  20. Comparative Study in Early Neonates with Septicemia by Blood Culture, Staining Techniques and C – Reactive Protein (CRP)

    PubMed Central

    Dhanalakshmi, V.

    2015-01-01

    Aim: The aim of this study was to compare and evaluate the pathogenic bacteria in neo-natal septicemia by using various diagnostic techniques. Setting and Design: Our study was designed to evaluate a feasible method to diagnose neonatal septicemia even at primary health centre level. Materials and Methods: Blood samples were collected aseptically from 70 neonates. The specimens were inoculated into brain heart infusion broth and subcultures were performed with specific media. Antibiotic sensitivity pattern of isolates was studied by Modified Kirby Bauer Disc diffusion technique and differentiate the isolates by staining methods. C-reactive protein (CRP) was evaluated by using standard kit method. Results: Out of 70 cases of childhood septicemia of age group 1-30 days, 37 had positive CRP, 36 were positive for BCS and blood culture was positive only in 41 cases, where predominant organism being Klebsiella species (n=28, 68.29%) followed by Escherichia coli (n=4, 9.76%), Pseudomonas aeruginosa (n=3,7.31%), Proteus mirabilis (n=2,4.88%) and Coagulase negative staphylococcus (n=4,9.76%). Conclusion: Our findings suggest that Klebsiella species as an important cause of neonatal septicemia. The isolated organisms were found to be highly sensitive to cefatoxime and amikacin. Hence, these antibiotics can be considered as the first drug of choice for neonatal septicemia. PMID:25954618

  1. 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.

  2. Neonates in Ahmedabad, India, during the 2010 Heat Wave: A Climate Change Adaptation Study

    PubMed Central

    Kakkad, Khyati; Barzaga, Michelle L.; Wallenstein, Sylvan; 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. PMID:24734050

  3. Stress Management among Parents of Neonates Hospitalized in NICU: A Qualitative Study

    PubMed Central

    Heidari, Haydeh; Hasanpour, Marzieh; Fooladi, Marjan

    2017-01-01

    Introduction: Infant hospitalization is stressful event for parent in NICU. Parents think that they have lost control because of unfamiliar environment. Therefore, stress management is very important in this period. The family as the main factor of strength and protection for infant is required as the bases of standard care in NICU. Therefore the aim of this study was to investigate stress management in Iranian NICU Parents. Methods: Using qualitative content analysis approach helped to collect and analysis data for open coding, classification, and theme abstraction. Twenty one parents with hospitalized neonates, physicians and nurses in the city of Isfahan were purposely recruited and selected for in-depth interviews. Results: The analyzed content revealed unique stress management approaches among the parents. The main themes were: 1) spirituality, 2) seeking information, 3) Seeking hope, 4) maintaining calm, 5) attachment to infant, and 6) communicating with the medical team Conclusion: Findings of this study highlights the importance of medical team’s attention to stressed parents who are trying to make adjustment or adapt to the hospitalization of their infant. A revised management approach to address the emotional needs of parents of neonates in Iran seems essential for improving communication with physicians and nurses. PMID:28299295

  4. 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.

  5. Sublingual immunotherapy in allergic rhinitis

    PubMed Central

    Han, Doo Hee

    2011-01-01

    Current treatment options for allergic rhinitis (AR) include allergen avoidance and environmental control, pharmacotherapy, nasal surgery and immunotherapy. Among these, immunotherapy is the only therapeutic option that modifies fundamental immunologic mechanism by inducing desensitization. Specific allergen immunotherapy has been used for 1 century since 1911 and subcutaneous immunotherapy (SCIT) has been demonstrated to be effective in asthma and AR. However, SCIT has several disadvantages such as inconvenience, invasiveness and potentially severe systemic reactions. Thus, sublingual immunotherapy (SLIT) has recently received much attention around the world as a treatment for AR and is now widely used to replace the subcutaneous route. SLIT has recently been introduced in Korea and is now available for AR treatment in the Asia-Pacific region. This review offers better understanding of SLIT for AR by summarizing published articles and our previous works regarding proposed mechanisms, indication and efficacy, safety and adverse events, and compliance. PMID:22053308

  6. Survival Outcomes of Sipuleucel-T Phase III Studies: Impact of Control-Arm Cross-Over to Salvage Immunotherapy.

    PubMed

    George, Daniel J; Nabhan, Chadi; DeVries, Todd; Whitmore, James B; Gomella, Leonard G

    2015-09-01

    Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic/minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). After disease progression, control-arm patients on three double-blind, randomized phase III sipuleucel-T trials were offered, in nonrandomized open-label protocols, APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control manufacture. These exploratory analyses evaluated potential effects on survival outcomes associated with such treatment. Of 249 control-treated patients, 165 (66.3%) received APC8015F. We explored the effects of APC8015F on the overall survival (OS; Cox regression) of control-arm patients and treatment effects of sipuleucel-T versus control adjusted for APC8015F treatment [iterative parameter estimation model (IPE)]. The median time to first APC8015F infusion was 5.2 months (range, 1.8-33.1) after randomization and 2.2 months (0.5-14.6) after progression. After disease progression, median survival was longer for APC8015F-treated versus control-only treated patients [20.0 vs. 9.8 months; HR, 0.53; 95% confidence interval (CI), 0.38-0.74; P < 0.001]; however, baseline characteristics were more favorable for APC8015F-treated patients. Multivariate regression analyses identified lactate dehydrogenase, alkaline phosphatase, hemoglobin, ECOG status, age, and number of bone metastases as potential (P < 0.1) independent predictors of postprogression survival. After adjusting for these predictors, APC8015F (HR, 0.78; 95% CI, 0.54-1.11; P = 0.17) treatment trended toward improved survival. Estimated median OS benefit for sipuleucel-T versus control adjusted for APC8015F treatment was 3.9 months if APC8015F had no effect and was 8.1 months if APC8015F was equally as effective as sipuleucel-T. Exploratory analyses indicate that APC8015F treatment may have extended patient survival, suggesting the sipuleucel-T OS advantage in CRPC may be more robust than previously estimated.

  7. Is there a Place for Prebiotics in the Management of Neonatal Inguinal Hernia? A Preliminary Study

    PubMed Central

    Dhaou, Mahdi Ben; Zouari, Mohamed; Ammar, Saloua; Bouraoui, Amira; Gassara, Imene; Feki, Ines; Zitouni, , Hayet; Jallouli, Mohamed; Masmoudi, Jawaher; Gargouri, Abdellatif; Mhiri, Riadh

    2017-01-01

    The objective of this study was to assess the place of prebiotics in the management of neonatal inguinal hernia. Boys with a diagnosis of unilateral non-complicated inguinal hernia, aged less than 40 days, were prospectively followed from January 2012 to December 2014. Clinical and psychiatric data and outcomes were collected before and after prebiotics (Primalac AC) administration. Ninety-eight patients were included. There were 75 inguinal hernias and 23 inguino-scrotal hernias. Before prebiotics administration 72.2% of infants had abdominal distention and 98% had colic. After prebiotics, abdominal distention and colic regressed in 85.2% and 73.2% of patients, respectively. Hernias disappeared clinically in 66.3% of cases. The factors associated with the disappearance of hernias were the type of the hernia (p<0.001), colic (p<0.001), and abdominal distention (p<0.001). Prebiotics would be a new adjunct in the management of neonatal inguinal hernia. They decrease colic and abdominal distention, which seems helpful to prevent strangulation and probably get spontaneous resolution of small hernias. PMID:28083493

  8. Is there a Place for Prebiotics in the Management of Neonatal Inguinal Hernia? A Preliminary Study.

    PubMed

    Dhaou, Mahdi Ben; Zouari, Mohamed; Ammar, Saloua; Bouraoui, Amira; Gassara, Imene; Feki, Ines; Zitouni, Hayet; Jallouli, Mohamed; Masmoudi, Jawaher; Gargouri, Abdellatif; Mhiri, Riadh

    2017-01-01

    The objective of this study was to assess the place of prebiotics in the management of neonatal inguinal hernia. Boys with a diagnosis of unilateral non-complicated inguinal hernia, aged less than 40 days, were prospectively followed from January 2012 to December 2014. Clinical and psychiatric data and outcomes were collected before and after prebiotics (Primalac AC) administration. Ninety-eight patients were included. There were 75 inguinal hernias and 23 inguino-scrotal hernias. Before prebiotics administration 72.2% of infants had abdominal distention and 98% had colic. After prebiotics, abdominal distention and colic regressed in 85.2% and 73.2% of patients, respectively. Hernias disappeared clinically in 66.3% of cases. The factors associated with the disappearance of hernias were the type of the hernia (p<0.001), colic (p<0.001), and abdominal distention (p<0.001). Prebiotics would be a new adjunct in the management of neonatal inguinal hernia. They decrease colic and abdominal distention, which seems helpful to prevent strangulation and probably get spontaneous resolution of small hernias.

  9. 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.

  10. Neonatal Infection with Neisseria meningitidis: Analysis of a 97-Year Period Plus Case Study

    PubMed Central

    Bülbül, Ali; Cömert, Serdar; Uslu, Sinan; Arslan, Selda; Nuhoglu, Asiye

    2014-01-01

    Neisseria meningitidis is one of the major causes of meningitis in children and adolescents, but it is rarely found during the neonatal period. Here, we describe a neonate with meningococcal sepsis who was admitted to the hospital on postnatal day 10, and we discuss the clinical features of neonatal infection with N. meningitidis in relation to the literature (analysis of a 97-year period). PMID:25031437

  11. Adoptive immunotherapy for cancer.

    PubMed

    Ruella, Marco; Kalos, Michael

    2014-01-01

    Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T-cell and tumor biology and the broader systemic immune response.

  12. Neuropathologic study of border disease virus in naturally infected fetal and neonatal small ruminants and its association with apoptosis.

    PubMed

    Toplu, N; Oguzoglu, T Ç; Epikmen, E T; Aydogan, A

    2011-05-01

    The present study describes the pathologic changes and cellular apoptosis in the central nervous system (CNS) of fetal and neonatal small ruminants infected with border disease virus (BDV), as demonstrated by immunohistochemistry and in situ hybridization. Abortions of ewes and goats were observed, as were births of lambs and kids with poor survival rates and nervous signs. Lesions included cerebellar hypoplasia, porencephaly, hydranencephaly, and nonsuppurative meningoencephalomyelitis with hypomyelinogenesis. Viral antigens and RNA were present in neuropil, glial, and neuronal cells, especially in periventricular areas, cerebellum, and brainstem. TUNEL positivity and labeling of anti-bax and anti-caspases 3, 8, and 9 were detected in BDV-infected CNSs, especially in glial and neuronal cells. The double immunostaining and TUNEL assay revealed that in BDV-infected animals, not only were BDV-infected glial and neuronal cells undergoing apoptosis, but so were uninfected cells in close vicinity of BDV-infected cells. The expression of activated caspases 3, 8, 9; bax; and TUNEL in glial and neuronal cells of the infected fetal and neonatal kids were significantly (P < .05) higher than those of the infected fetal and neonatal lambs. Yet, the expression of bcl-2 in the CNSs of the infected fetal and neonatal lambs was higher (P < .05) in neuronal and glial cells than in those of the infected fetal and neonatal kids. The results suggest that cell death in the BDV-infected CNS is induced by intrinsic and extrinsic cascades of apoptotic pathways.

  13. 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.

  14. 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

  15. Safety and effect on reported symptoms of depigmented polymerized allergen immunotherapy: a retrospective study of 2927 paediatric patients

    PubMed Central

    Pfaar, Oliver; Sager, Angelika; Robinson, Douglas S

    2015-01-01

    Background Allergen immunotherapy (AIT) is effective treatment for allergic diseases, and subcutaneous use of depigmented polymerized extracts may allow rapid up-dosing and safe therapy. To date, there is little information on their safety and clinical effects for children and adolescents with allergic disease. Methods We performed a retrospective survey of patient notes of 2927 children and adolescents across 136 centres who had received subcutaneous AIT (SCIT) with depigmented polymerized extracts to pollen or mite allergens for at least 1 yr to collect documentation on safety and clinical symptoms. Results 16.3% percent of patients had local reactions, of these 148 were larger than 12 cm in diameter. Systemic reactions were documented in 1.6% of children and in 0.8% of adolescents. There were no documented cases of anaphylactic shock. There were significant reductions in the frequency of patients with recorded nasal symptoms over time of treatment. Moreover, the prescribing rate of rescue medication was reduced over the course of SCIT. Conclusion These ‘real-life’ data from a large retrospective analysis including 2927 children and adolescents with pollen- and/or mite-induced allergic rhinoconjunctivitis with/or without allergic asthma indicate that AIT with depigmented polymerized extracts is well tolerated, and they are compatible with clinical response. PMID:25640879

  16. Immunotherapy with yellow jacket venom. A comparative study including three different extracts, one adsorbed to aluminium hydroxide and two unmodified.

    PubMed

    Mosbech, H; Malling, H J; Biering, I; Böwadt, H; Søborg, M; Weeke, B; Løwenstein, H

    1986-02-01

    Thirty-two patients with previous systemic allergic reaction to yellow jacket stings were randomly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom: 1) extract adsorbed to aluminium hydroxide (Alutard-SQ), 2) Pharmalgen extract or 3) non-adsorbed extract from Allergologisk Laboratorium (ALK aq.). Regular examinations showed a decrease in skin prick test size in nearly all patients. Specific IgE-antibody (RAST and CRIE scores) showed a similar, but not significant tendency to decrease in all three groups. Specific IgG-antibody increased considerably in the Alutard group only; after 2 years, however, no difference could be detected between the three groups. During dose increase, patients treated with ALK aq. generally had smaller local reactions to injections than those treated with Pharmalgen. Few systemic reactions occurred in all three groups. Nineteen patients treated for 2 1/2-3 1/2 years were challenged in-hospital with stings from yellow jackets. No systemic and only minor local reactions occurred. Consequently, with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated.

  17. 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…

  18. Innovation in Bladder Cancer Immunotherapy.

    PubMed

    Grossman, H Barton; Lamm, Donald L; Kamat, Ashish M; Keefe, Stephen; Taylor, John A; Ingersoll, Molly A

    2016-10-01

    Bladder cancer is understudied despite its high prevalence and its remarkable response to immunotherapy. Indeed, funding for studies to explore mechanisms of tumor immunity and novel new therapeutics is disproportionately lower for bladder cancer in comparison with malignancies of the breast, prostate, or lung. However, the recent successes of checkpoint blockade therapy suggest that new therapeutic strategies are on the horizon for bladder cancer. Here, we give a perspective into the evolution of bladder cancer therapy, focusing on strategies to treat high-risk nonmuscle invasive disease, followed by a discussion of recent advances in the treatment of muscle invasive bladder cancer and their potential applicability to lower stage disease. Finally, we explore immunotherapeutic strategies, which have been demonstrated to be successful in the treatment of other malignancies, for their potential to treat and cure patients with nonmuscle and muscle invasive bladder cancer.

  19. Use of Colistin in a Neonatal Intensive Care Unit: A Cohort Study of 65 Patients

    PubMed Central

    Çağan, Eren; Baş, Evrim Kıray; Asker, Hüseyin Selim

    2017-01-01

    Background The emergence of infections related to multidrug-resistant Gram-negative bacilli (MDR-GNB) reintroduced the use of colistin, an antibiotic that was previously abandoned due to adverse effects. However, because of its limited use in neonatal intensive care units, there is very little data about the effectiveness and safety of colistin in children and newborns. In this study, which will be the largest case study in the literature, we aimed to evaluate the effectiveness and safety of colistin in full-term and preterm newborns. Material/Methods The study included patients admitted into 2 level 3 neonatal intensive care units between January 2013 and June 2015. The medical records of patients diagnosed with sepsis, meningitis, pneumonia, and urinary tract infection based on the diagnostic culture results and treated with colistin were analyzed retrospectively. The patients whose infections were not verified were excluded from the study. Results The study included 65 patients (18 term, 47 preterm). The most frequently isolated pathogens were Klebsiella pneumoniae and Acinetobacter baumannii followed by Pseudomonas aeruginosa and Enterobacter cloacae. Mean colistin treatment time was 15±3.5 days. All patients treated with colistin were being treated with at least 1 other antibiotic. While a complete clinical response was achieved in 51 (72.3%) patients, 14 (21.5%) patients died during treatment. Four (7.7%) patients died during as a result of another infection. Three patients developed renal toxicity, another 3 patients had seizures, and apnea was observed in 3 patients. Conclusions Colistin was found to be effective and safe for treatment of MDR-GNB infections in preterms and infants with very low birth weight. Given the severity of the infection, the adverse effects of colistin were at acceptable levels. PMID:28135233

  20. 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.

  1. Neonatal jaundice.

    PubMed

    McKiernan, Pat

    2012-06-01

    Neonatal jaundice lasting greater than 2 weeks should be investigated. Pale stools and dark or yellow urine are evidence of liver disease, which should be urgently investigated. The neonatal hepatitis syndrome has many causes, and a structured approach to investigation is mandatory. It should be possible to confirm or exclude biliary atresia within one week, so that definitive surgery is not delayed unnecessarily. Babies with the neonatal hepatitis syndrome should have vigorous fat-soluble vitamin supplementation, including parenteral vitamin K if coagulation is abnormal. The prognosis for infants with idiopathic neonatal hepatitis and multifactorial cholestasis is excellent.

  2. Oral lyophilisate and food immunotherapy: from research to clinical practice.

    PubMed

    Tabar, A I

    2008-01-01

    Thanks to its excellent safety profile, sublingual immunotherapy has served as a basis for launching two important lines of research in current allergology: sublingual immunotherapy with pharmaceutical registry (oral lyophilizates or tablets), and sublingual immunotherapy with food. At present, clinical trials are being conducted which use rapid dissolution oral lyophilizates. The results of the clinical trials carried out in large patient groups and based on a double-blind methodological design have allowed pharmaceutical registry of this form of treatment, with the therapeutic indications of rhinitis and allergy to grasses. Phleum lyophilizate indicated for the treatment of rhinoconjunctivitis will be marketed in Spain in the coming months. In parallel to development of the sublingual route, advances in our knowledge of pollen allergy and its relationship to plant food allergies have facilitated the conducting of studies involving sublingual immunotherapy for allergy to kiwifruit, hazelnut and peach - thus giving rise to promising future perspectives for affected patients.

  3. 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.

  4. 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.

  5. Neonatal and infantile erythroderma: a clinical and follow-up study of 42 cases.

    PubMed

    Al-Dhalimi, Muhsin A A

    2007-05-01

    Erythroderma in neonates and infants is a frequently encountered problem in the daily practice of pediatric dermatology. The objective of this study was to determine the frequency of various causes of this clinical entity, as well as which clinical and laboratory findings are useful in the differentiation of these causes, and to assess the evolution of this disease in this age group. Forty-two patients with erythroderma under 1 year of age were included in this study. A follow-up period of 3-5 years was completed. The study was performed in the Department of Dermatology, Al-Sadr and Alhakeem teaching hospitals and a private section in Najaf governorate, Iraq during the period 1998-2006. The diagnosis was made at an average of 3 months after the onset of the disease. The underlying causes included seborrheic dermatitis in 21.4%, atopic dermatitis in 14.3%, different types of Ichthyoses in 31.5%, psoriasis in 4.7%, pityriasis rubra pilaris in 2.4%, Staphylococcal scalded skin syndrome in 7.14%, Netherton syndrome in 4.7%, immune deficiency syndromes in 4.8% and undetermined erythroderma in 9.5% of the patients. Of 29 cases, histopathological examination of skin biopsy showed non-specific features in 58.7% and could confirm the diagnosis in 41.3% cases. The prognosis was poor with a mortality rate of 26.2% and severe dermatoses persisted in 60% of the survivors. It is difficult to make the etiological diagnosis of neonatal erythroderma from the first examination. Associated immune deficiency should be suspected if the condition associated with skin indurations, severe alopecia, failure to thrive and/or have infectious complications. The prognosis is poor especially in those with immune deficiency or a chronic persistent course.

  6. Provision of Therapeutic Hypothermia in Neonatal Transport: A Longitudinal Study and Review of Literature

    PubMed Central

    2015-01-01

    Background: Worldwide, a significant proportion of infants needing therapeutic hypothermia for hypoxia-ischaemia are transported to a higher-level facility for neonatal intensive care. They pose technical challenges to transport teams in cooling them. Concerns exist about the efficacy of passive cooling in neonatal transport to achieve a neurotherapeutic temprature. Servo-controlled cooling in the standard of care on the neonatal unit. The key question is whether the same standard of care in the neonatal unit can be safely used for therapeutic hypothermia during transport of neonates with suspected hypoxia-ischaemia. Methods: A prospective cross-sectional survey of United Kingdom (UK) neonatal transport services (n=21) was performed annually from 2011-2014 with a 100% response. The survey ascertained information about service provision and the method of cooling used during transport. Results: In 2011, all UK neonatal transport services provided therapeutic hypothermia during transport. Servo-control cooling machines were used by only 6 of the 21 teams (30%) while passive cooling was used by 15 of the 21 (70%) teams. In 2012 9 of the 21 teams (43%) were using servo-control. By 2014 the number of teams using servo-control cooling had more than doubled to 15 of the 21 (62%) services. Teams have done this through modification of transport trolleys and dedicated ambulances. Conclusion: Servo-controlled cooling in neonatal transport is becoming more common in the UK. The question remains whether it should be endorsed as a standard of care. Some teams continue to passively cool neonates with hypoxia-ischaemia during transport. This article reviews the drivers, current evidence, safety and processes involved in provision of therapeutic hypothermia during neonatal transport to enable teams to decide what would be the right option for them. PMID:26180694

  7. 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.

  8. 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…

  9. A quick snip - A study of the impact of outpatient tongue tie release on neonatal growth and breastfeeding.

    PubMed

    Miranda, Benjamin H; Milroy, Catherine J

    2010-09-01

    A prospective study (62 neonates) of ankyloglossia and breastfeeding difficulty is presented. At 2 weeks post-frenulotomy, there were significant improvements in weight (15+/-1.2 centiles) and breastfeeding, including number of sessions/24h (19%) and bottle top-ups/24h (81%) (p<0.0001).

  10. Breaking New Ground: An Exploratory Study of the Role and Education of the Advanced Neonatal Nurse Practitioner. Researching Professional Education. Research Reports Series Number 4.

    ERIC Educational Resources Information Center

    Redshaw, M. E.; Harris, A.

    A British research study documented and defined the level of functioning of advanced neonatal nurse practitioners (ANNPs) in comparison with qualified nurses and junior pediatric medical staff working in the same neonatal units. Subjects were ANNPs, ANNP students, and clinician mentors in 10 units. Data were collected through interviews,…

  11. Immune targets and neoantigens for cancer immunotherapy and precision medicine.

    PubMed

    Wang, Rong-Fu; Wang, Helen Y

    2017-01-01

    Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA-4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer. Current success of cancer immunotherapy is built upon the work of cancer antigens and co-inhibitory signaling molecules identified 20 years ago. Among the large numbers of target antigens, CD19 is the best target for CAR T cell therapy for blood cancer, but CAR-engineered T cell immunotherapy does not yet work in solid cancer. NY-ESO-1 is one of the best targets for TCR-based immunotherapy in solid cancer. Despite the great success of checkpoint blockade therapy, more than 50% of cancer patients fail to respond to blockade therapy. The advent of new technologies such as next-generation sequencing has enhanced our ability to search for new immune targets in onco-immunology and accelerated the development of immunotherapy with potentially broader coverage of cancer patients. In this review, we will discuss the recent progresses of cancer immunotherapy and novel strategies in the identification of new immune targets and mutation-derived antigens (neoantigens) for cancer immunotherapy and immunoprecision medicine.

  12. 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.

  13. Genetic immunotherapy for cancer.

    PubMed

    Elmslie, R E; Dow, S W

    1997-08-01

    The application of gene therapy to the treatment of human and veterinary diseases offers an innovative addition to the clinician's treatment options. Gene therapy can potentially be used to (1) replace defective or missing genes, (2) treat cancer, and (3) deliver drugs. The focus of this paper is the use of gene therapy in the treatment of cancer. To be effective, genes must be delivered to target cells which can then serve as the factory to produce the gene product. Delivery systems include retroviral vectors, adenoviral vectors, and direct introduction of plasmid DNA into cells. In the case of cancer immunotherapy, introduced genes produce products that enhance tumor immunosurveillance and tumor cell killing by immune mechanisms.

  14. Mutanome directed cancer immunotherapy.

    PubMed

    Vormehr, Mathias; Diken, Mustafa; Boegel, Sebastian; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2016-04-01

    Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the repertoire of mutations ('the mutanome') in every patient's tumor. This review highlights insights into immune recognition of neo-epitopes and novel concepts for comprehensive identification and immunotherapeutic exploitation of individual mutations.

  15. Immunotherapy of hepatocellular carcinoma

    PubMed Central

    Pardee, Angela D.; Butterfield, Lisa H.

    2012-01-01

    Current therapies for advanced hepatocellular carcinoma (HCC) are marginally effective and exacerbate underlying liver disease. The ability of immunotherapy to elicit nontoxic, systemic, long-lived anti-tumor activity makes it particularly well-suited for use in the setting of HCC. While therapeutic benefit has been achieved in early clinical trials, the efficacy of immune-based therapies is limited by several unique properties of HCC, most notably the inherently tolerogenic character of the liver in both healthy and diseased (chronically-infected or tumor-bearing) states. Therapeutic regimens that both counteract these immunosuppressive mechanisms and amplify tumor-specific immunity are expected to profoundly improve clinical outcomes for HCC patients. PMID:22720211

  16. 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

  17. Cancer immunotherapy products

    PubMed Central

    Camarero, Jorge; Ruiz, Sol

    2012-01-01

    Active immunotherapy products (widely known as “cancer vaccines”) are products intended to stimulate an immune response to mediate tumor destruction or reduce the progression of disease in patients where cancer has been diagnosed. Some quality attributes of these products are very difficult to characterize or present a high variability (especially if they are for autologous use), further complicating the interpretation of some of the clinical data. Furthermore, questions arise in the evaluation of efficacy and safety data in comparison with current chemical or biological treatments for the same indications. Some of these aspects are discussed in this paper in relationship with the regulatory requirements in the European Union and as applied to two recently assessed medicinal products, Oncophage and Provenge, both considered therapeutic “cancer vaccines” for renal cell carcinoma and prostate cancer, respectively. PMID:22863755

  18. T cell responses induced by allergen-specific immunotherapy

    PubMed Central

    Maggi, E

    2010-01-01

    Allergen-specific immunotherapy is recognized as a highly effective practice in the treatment of patients with severe allergic rhinitis and/or asthma and is recommended by World Health Organization as an integrated part of allergy management strategy. Several studies have shown that allergen-specific immunotherapy, based on the administration of increasing doses of allergen, achieves a hyposensitization and reduces both early and late responses occurring during the natural exposure to the allergen itself. This is the unique antigen-specific immunomodulatory treatment in current use for human diseases. Successful immunotherapy is associated with reductions in symptoms and medication scores and improved quality of life. After interruption it usually confers long-term remission of symptoms and prevents the onset of new sensitizations in children up to a number of years. Subcutaneous immunotherapy usually suppresses the allergen-induced late response in target organs, likely due to the reduction of the infiltration of T cells, eosinophils, basophils, mast cells and neutrophils. In addition to the reduction of cells of allergic inflammation, immunotherapy also decreases inflammatory mediators at the site of allergen exposure. This review provides an update on the immunological T cell responses induced by conventional subcutaneous and sublingual immunotherapy, and gives a unifying view to reconciling the old dualism between immunoredirecting and immunoregulating mechanisms. PMID:20408857

  19. Development of new immunotherapy treatments in different cancer types.

    PubMed

    Stanculeanu, D L; Daniela, Zob; Lazescu, A; Bunghez, R; Anghel, R

    2016-01-01

    Cancer immunotherapy involves the use of therapeutic modalities that determine a manipulation of the immune system by using immune agents such as cytokines, vaccines, cell therapies and humoral, transfection agents. Immunotherapy of cancer has to stimulate the host's anti-tumor response by increasing the effector cell number and the production of soluble mediators and decrease the host's suppressor mechanisms by inducing tumor killing environment and by modulating immune checkpoints. Immunotherapy seems to work better in more immunogenic tumors. Making a review of literature, the article presents the new immunologic treatments in cancers less presented in the latest conferences, cancers in which, immunotherapy is still under investigation. Bladder cancer was the first indication for which immunotherapy was used in 1970. A promising clinical research in bladder cancer is the use of immune checkpoint inhibitors. Although breast cancer is considered immunologically silent, several preclinical and clinical studies suggested that immunotherapy has the potential to improve the clinical outcomes for patients with breast cancer. Cervical cancer, brain cancer, head and neck cancer and colorectal and esophageal cancers are cancer types for which new immune-based cancer treatments are currently under development. Recent agents used in clinical trials will be described in before mentioned cancers.

  20. Development of new immunotherapy treatments in different cancer types

    PubMed Central

    Stanculeanu, DL; Daniela, Zob; Lazescu, A; Bunghez, R; Anghel, R

    2016-01-01

    Cancer immunotherapy involves the use of therapeutic modalities that determine a manipulation of the immune system by using immune agents such as cytokines, vaccines, cell therapies and humoral, transfection agents. Immunotherapy of cancer has to stimulate the host’s anti-tumor response by increasing the effector cell number and the production of soluble mediators and decrease the host’s suppressor mechanisms by inducing tumor killing environment and by modulating immune checkpoints. Immunotherapy seems to work better in more immunogenic tumors. Making a review of literature, the article presents the new immunologic treatments in cancers less presented in the latest conferences, cancers in which, immunotherapy is still under investigation. Bladder cancer was the first indication for which immunotherapy was used in 1970. A promising clinical research in bladder cancer is the use of immune checkpoint inhibitors. Although breast cancer is considered immunologically silent, several preclinical and clinical studies suggested that immunotherapy has the potential to improve the clinical outcomes for patients with breast cancer. Cervical cancer, brain cancer, head and neck cancer and colorectal and esophageal cancers are cancer types for which new immune-based cancer treatments are currently under development. Recent agents used in clinical trials will be described in before mentioned cancers. PMID:27974927

  1. Recent advances in the field of anti-cancer immunotherapy

    PubMed Central

    Neves, Henrique; Kwok, Hang Fai

    2015-01-01

    Background The main goal of anti-cancer therapy is to specifically inhibit the malignant activity of cancer cells, while leaving healthy cells unaffected. As such, for every proposed therapy, it is important to keep in mind the therapeutic index — the ratio of the toxic dose over the therapeutic dose. The use of immunotherapy has allowed a means to both specifically block protein–protein interaction and deliver cytotoxic events to a tumor-specific antigen. Review scope It is the objective of this review to give an overview on current immunotherapy treatment for cancers using monoclonal antibodies. We demonstrate three exciting targets for immunotherapy, TNF-α Converting Enzyme (TACE), Cathepsin S and Urokinase Plasmogen Activator and go over the advances made with one of the most used monoclonal antibodies in cancer therapy, Rituximab; as well as Herceptin, which is used for breast cancer therapy. Furthermore, we touch on other venues of immunotherapy, such as adaptive cell transfer, the use of nucleic acids and the use of dendritic cells. Finally, we summarize some ongoing studies that spell tentative advancements for anti-cancer immunotherapy. General significance Immunotherapy is at the forefront of anti-cancer therapies, allying both a high degree of specificity to general high effectiveness and fewer side-effects. PMID:26673349

  2. 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.

  3. Subcutaneous and sublingual immunotherapy for allergic rhinitis: What is the evidence?

    PubMed Central

    Wise, Sarah K.

    2012-01-01

    Background: Increasing interest in sublingual immunotherapy (SLIT) among practitioners and patients has resulted in numerous publications and clinical trials in recent years. With the clinical growth of SLIT, discussions of its efficacy, safety, and immunologic effects have intensified, as have comparisons to subcutaneous immunotherapy (SCIT). In the United States, SCIT has been the traditional form of immunotherapy for inhalant allergy and is the only immunotherapy method approved by the U.S. Food and Drug Administration at this time. The similarities and differences between SLIT and SCIT are often discussed, yet clinical studies directly comparing these immunotherapy methods are scarce. Methods: A literature review of specific issues and controversies between SLIT and SCIT for allergic rhinitis was conducted. Results: Safety, efficacy, and immunologic effects of these two immunotherapy techniques are reviewed. Conclusion: Unanswered questions relating to SLIT are examined. PMID:22391071

  4. 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.

  5. 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

  6. The study on clinical value of the detection about serum and Unconjugated Bilirubin in diagnosis of neonatal jaundice.

    PubMed

    Wang, Guangzhou; Wang, Jiefei; Huang, Nannan; Yu, Fengqin

    2016-01-01

    In this paper, the clinical value of the detection about serum and unconjugated bilirubin (UCB) in neonatal jaundice was studied to found an effective and rapid method for diagnose of neonatal jaundice. ALB (Serum Albumin), total serum bilirubin (TSB) and UCB were detected by ELISA method among the 100 cases with neonatal jaundice selected for the study. The values of ALB, UCB and TSB in moderate jaundice patients were (42.83±3.87) g/L, (287.35±44.38) μm/L, (304.16±43.40) μm/L, respectively; as for the severe jaundice patients, the values were (38.41±4.82) g/L, (354.38±48.75) μm/L, (375.20±47.51) μm/L. The results showed significant differences with the p< 0.05 between moderate and severe jaundice patients. The level of ALB, UCB, TSB in hemolytic jaundice, obstructive jaundice and jaundice caused by other infections also had significant differences, and the difference was statistically significant (p<0.05). The detection of ALB and UCB provides a useful method for the diagnosis and assessment of neonatal jaundice.

  7. Immunotherapy of Congenital SIV Infection.

    DTIC Science & Technology

    1996-10-01

    TITLE: Immunotherapy of Congenital SIV Infection PRINCIPAL INVESTIGATOR: Ruth M. Ruprecht, M.D., Ph.D. CONTRACTING ORGANIZATION: Dana-Farber Cancer...SUBTITLE Immunotherapy of Congenital SIV 5. FUNDING NUMBERS Infection DAMD17-94-J-4431 6. AUTHOR(S) Ruth M. Ruprecht. M.D-. Ph.D 7. PERFORMING...period of several weeks, this strategy was adopted to avoid potential bias because of season or other factors. Because the staff at the Yerkes Regional

  8. Mechanism of Anti-α-Synuclein Immunotherapy

    PubMed Central

    Lee, Jun Sung; Lee, Seung-Jae

    2016-01-01

    Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson’s disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy. PMID:26828212

  9. 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.

  10. Accounting for Multiple Births in Neonatal and Perinatal Trials: Systematic Review and Case Study

    PubMed Central

    Hibbs, Anna Maria; Black, Dennis; Palermo, Lisa; Cnaan, Avital; Luan, Xianqun; Truog, William E; Walsh, Michele C; Ballard, Roberta A

    2010-01-01

    Objectives To determine the prevalence in the neonatal literature of statistical approaches accounting for the unique clustering patterns of multiple births. To explore the sensitivity of an actual trial to several analytic approaches to multiples. Methods A systematic review of recent perinatal trials assessed the prevalence of studies accounting for clustering of multiples. The NO CLD trial served as a case study of the sensitivity of the outcome to several statistical strategies. We calculated odds ratios using non-clustered (logistic regression) and clustered (generalized estimating equations, multiple outputation) analyses. Results In the systematic review, most studies did not describe the randomization of twins and did not account for clustering. Of those studies that did, exclusion of multiples and generalized estimating equations were the most common strategies. The NO CLD study included 84 infants with a sibling enrolled in the study. Multiples were more likely than singletons to be white and were born to older mothers (p<0.01). Analyses that accounted for clustering were statistically significant; analyses assuming independence were not. Conclusions The statistical approach to multiples can influence the odds ratio and width of confidence intervals, thereby affecting the interpretation of a study outcome. A minority of perinatal studies address this issue. PMID:19969305

  11. Gold Nanoparticle Mediated Cancer Immunotherapy

    PubMed Central

    Almeida, Joao Paulo Mattos; Figueroa, Elizabeth Raquel; Drezek, Rebekah Anna

    2013-01-01

    Significant progress has been made in the field of cancer immunotherapy, where the goal is to activate or modulate the body’s immune response against cancer. However, current immunotherapy approaches exhibit limitations of safety and efficacy due to systemic delivery. In this context, the use of nanotechnology for the delivery of cancer vaccines and immune adjuvants presents a number of advantages such as targeted delivery to immune cells, enhanced therapeutic effect, and reduced adverse outcomes. Recently, gold nanoparticles (AuNP) have been explored as immunotherapy carriers, creating new AuNP applications that merit a critical overview. This review highlights recent advances in the development of AuNP mediated immunotherapies that harness AuNP biodistribution, optical properties and their ability to deliver macromolecules such as peptides and oligonucleotides. It has been demonstrated that the use of AuNP carriers can improve the delivery and safety of immunotherapy agents, and that AuNP immunotherapies are well suited for synergistic combination therapy with existing cancer therapies like photothermal ablation. PMID:24103304

  12. 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

  13. 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

  14. Neonatal care in the home in northern rural Honduras: a qualitative study of the role of traditional birth attendants.

    PubMed

    Sacks, Emma; Bailey, Joanne Motiño; Robles, Chayla; Low, Lisa Kane

    2013-01-01

    Traditional birth attendants (TBAs) have limited ability to reduce maternal mortality, but may be able to have a significant impact on neonatal survival. This qualitative study explores TBAs' (possessive) experience with neonatal care in a rural Honduran community. In 6 semistructured focus groups, TBAs described services they routinely provide to newborns. Using Atlas.ti, Version 6.0. (ATLAS.ti Scientific Software Development GmbH, University of Berlin), transcripts were coded by bilingual researchers and analyzed by thematic content. TBAs demonstrated limited knowledge of newborn physiology, yet were aware of many internationally recommended practices. Despite attempts to follow recommendations, all TBAs expressed difficulty due to resource constraints. TBAs were strong advocates of immediate breast-feeding and skin-to-skin care, but they did not demonstrate knowledge regarding delayed bathing and thermal care. Most TBAs stated that a sick neonate could be identified immediately at birth; thus, infections or other illnesses developed in later days may be missed. TBAs did not believe they could have averted neonatal complications or deaths that had occurred under their care. For most healthy newborns, TBAs are the primary providers until the 2-month vaccine visit at the healthcare clinic. Improved TBA training focused on infection symptomotology, physiology, and thermoregulation for newborns may increase opportunities for improved health and timely referrals to healthcare facilities.

  15. Maternal, neonatal and community factors influencing neonatal mortality in Brazil.

    PubMed

    Machado, Carla Jorge; Hill, Kenneth

    2005-03-01

    Child mortality (the mortality of children less than five years old) declined considerably in the developing world in the 1990s, but infant mortality declined less. The reductions in neonatal mortality were not impressive and, as a consequence, there is an increasing percentage of infant deaths in the neonatal period. Any further reduction in child mortality, therefore, requires an understanding of the determinants of neonatal mortality. 209,628 birth and 2581 neonatal death records for the 1998 birth cohort from the city of São Paulo, Brazil, were probabilistically matched. Data were from SINASC and SIM, Information Systems on Live Births and Deaths of Brazil. Logistic regression was used to find the association between neonatal mortality and the following risk factors: birth weight, gestational age, Apgar scores at 1 and 5 minutes, delivery mode, plurality, sex, maternal education, maternal age, number of prior losses, prenatal care, race, parity and community development. Infants of older mothers were less likely to die in the neonatal period. Caesarean delivery was not found to be associated with neonatal mortality. Low birth weight, pre-term birth and low Apgar scores were associated with neonatal death. Having a mother who lives in the highest developed community decreased the odds of neonatal death, suggesting that factors not measured in this study are behind such association. This result may also indicate that other factors over and above biological and more proximate factors could affect neonatal death.

  16. Sublingual Immunotherapy with a Five-Grass Pollen Tablet in Adult Patients with Allergic Rhinitis: An Open, Prospective, Noninterventional, Multicenter Study

    PubMed Central

    Pfaar, Oliver; Richter, Heinz-Gerd; Klimek, Ludger; Sieber, Jochen; Hadler, Meike; Karagiannis, Efstrathios

    2015-01-01

    Background. Although the safety and efficacy of sublingual immunotherapy (SLIT) with a five-grass pollen tablet have been demonstrated in randomized clinical trials (RCTs), these outcomes must always be evaluated in real-life medical practice. Methods. In a prospective, open-label, noninterventional, “real-life” study in Germany, we evaluated the safety, tolerability, and effectiveness of SLIT with a five-grass pollen tablet in adults with grass-pollen-induced allergic rhinoconjunctivitis. Results. 808 adults were enrolled between September 2008 and December 2009. 35.3% of the participants experienced at least one adverse drug reaction (ADR), the most common of which were mild-to-moderate gastrointestinal and respiratory disorders. Serious ADRs considered causally related to SLIT treatment occurred in four patients. Overall, the five-grass pollen tablet was considered to have good or very good tolerability by most investigators and patients. Treatment was associated with the relief of nasal, ocular, and bronchial symptoms and decreased symptomatic medication use. However, interpretation of clinical improvements was limited by lower atmospheric grass pollen levels during the study season (relative to the preceding season). Conclusions. In a large population of patients treated in real-life medical practice, SLIT with a five-grass pollen tablet was safe and well tolerated. The patient-reported symptom relief suggests that SLIT was associated with clinical benefits. PMID:26351635

  17. Macrosomic Neonates Carry Increased Risk of Dental Caries in Early Childhood: Findings from a Cohort Study, the Okinawa Child Health Study, Japan

    PubMed Central

    Yokomichi, Hiroshi; Tanaka, Taichiro; Suzuki, Kohta; Akiyama, Tomoki; Yamagata, Zentaro

    2015-01-01

    Background Although many studies have discussed health risks in neonates with a low birth weight, few studies have focused on the risks in neonates with a high birth weight. The objective of this study was to determine whether differences in the incidence of dental caries in early childhood are associated with birth weight status. Methods A total of 117,175 children born in Okinawa Prefecture, Japan from 1997 to 2007 were included in this study. Medical professionals collected information about birth records, growth and development, parental child-rearing practices and dental health at 3 months, 18 months and 3 years of age. The risk of dental caries among neonates with macrosomia (birth weight ≥4000 g) was compared with that among neonates with normal weight (2500–3999 g). Sensitivity analyses included ‘large for gestational age’ (LGA, birth weight above the 90th percentile for gestational age), which was relative to ‘appropriate for gestational age’ (birth weight between 10th and 90th percentiles). Relative risks and relative risk increases were estimated by multivariate Poisson regression. Results At 3 years of age, the relative risk increases for dental caries after adjusting for confounding factors were 19% [95% confidence interval (CI), 11%–28%, P < 0.001] for macrosomic neonates and 12% (95% CI, 9%–16%, P < 0.001) for LGA neonates. Conclusion Macrosomia and LGA were associated with an increased risk of dental caries in early childhood. Particular attention should be paid to abnormally large neonates. PMID:26207737

  18. Alternative Abeta immunotherapy approaches for Alzheimer's disease.

    PubMed

    Town, Terrence

    2009-04-01

    In a seminal report in 1999, Schenk and colleagues demonstrated that vaccination of a mouse model of Alzheimer's disease (AD) with amyloid-beta(1-42) peptide (Abeta(1-42)) and adjuvant resulted in striking mitigation of AD-like pathology - giving rise to the field of AD immunotherapy. Later studies confirmed this result in other mouse models of AD and additionally showed cognitive improvement after Abeta vaccination. Based on these results, early developmental clinical trials ensued to immunize AD patients with Abeta(1-42) plus adjuvant (so-called "active" Abeta immunotherapy; trade name AN-1792; Elan Pharmaceuticals, Dublin, Ireland). However, the phase IIa trial was halted after 6 % of patients developed aseptic meningoencephalitis. Despite occurrence of this adverse event, many individuals demonstrated high serum antibody titres to Abeta and histological evidence of clearance of the hallmark AD pathology, beta-amyloid plaques. While raising justifiable safety concerns, these important results nonetheless demonstrated the feasibility of the active Abeta immunotherapy approach. This review focuses on alternative approaches to active Abeta vaccination that are currently in various stages of development - from pre-clinical studies in animal models to current clinical trials. Specifically, the focus is on those strategies that target inflammatory and immune aspects of AD, and can therefore be classified as immunotherapeutic in a broad sense.

  19. Durations of second stage of labor and pushing, and adverse neonatal outcomes: a population-based cohort study

    PubMed Central

    Sandström, A; Altman, M; Cnattingius, S; Johansson, S; Ahlberg, M; Stephansson, O

    2017-01-01

    Objective: The associations between duration of second stage of labor, pushing time and risk of adverse neonatal outcomes are not fully established. Therefore, we aimed to examine such relationships. Study design: A population-based cohort study including 42 539 nulliparous women with singleton infants born in cephalic presentation at ⩾37 gestational weeks, using the Stockholm-Gotland Obstetric Cohort, Sweden, and the Swedish Neonatal Quality Register, 2008 to 2013. Poisson regression was used to analyze estimated adjusted relative risks (RRs), with 95% confidence intervals (CIs). Outcome measures were umbilical artery acidosis (pH <7.05 and base excess <−12), birth asphyxia-related complications (including any of the following conditions: hypoxic ischemic encephalopathy, hypothermia treatment, neonatal seizures, meconium aspiration syndrome or advanced resuscitation after birth) and admission to neonatal intensive care unit (NICU). Results: Overall rates of umbilical artery acidosis, birth asphyxia-related complications and admission to NICU were 1.08, 0.63 and 6.42%, respectively. Rate of birth asphyxia-related complications gradually increased with duration of second stage: from 0.42% at <1 h to 1.29% at ≥4 h (adjusted RR 2.46 (95% CI 1.66 to 3.66)). For admission to NICU, corresponding rates were 4.97 and 9.45%, and adjusted RR (95% CI) was 1.80 (95% CI 1.58 to 2.04). Compared with duration of pushing <15 min, a duration of pushing ⩾60 min increased rates of acidosis from 0.57 to 1.69% (adjusted RR 2.55 (95% CI 1.51 to 4.30)). Conclusion: Prolonged durations of second stage of labor and pushing are associated with increased RRs of adverse neonatal outcomes. Clinical assessment of fetal well-being is essential when durations of second stage and pushing increases. PMID:27929527

  20. 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

  1. 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

  2. Neonatal mortality in Utah.

    PubMed

    Woolley, F R; Schuman, K L; Lyon, J L

    1982-09-01

    A cohort study of neonatal mortality (N = 106) in white singleton births (N = 14,486) in Utah for January-June 1975 was conducted. Using membership and activity in the Church of Jesus Christ of Latter-day Saints (LDS or Mormon) as a proxy for parental health practices, i.e., tobacco and alcohol abstinence, differential neonatal mortality rates were calculated. The influence of potential confounding factors was evaluated. Low activity LDS members were found to have an excess risk of neonatal death five times greater than high activity LDS, with an upper bound of a two-sided 95% confidence interval of 7.9. The data consistently indicate a lower neonatal mortality rate for active LDS members. Non-LDS were found to have a lower rate than either medium or low activity LDS.

  3. Comparative Study of Virulence Traits of Escherichia coli Clinical Isolates Causing Early and Late Neonatal Sepsis▿

    PubMed Central

    Soto, S. M.; Bosch, J.; Jimenez de Anta, M. T.; Vila, J.

    2008-01-01

    Neonatal meningitis and septicemia caused by Escherichia coli are still major health problems in industrialized countries. Forty-seven E. coli strains causing neonatal sepsis were analyzed. Twenty-two and 25 strains caused early (detected from 0 to 3 days after birth) and late (detected from 4 to 28 days after birth) infections, respectively. Only the ibeA gene was significantly more prevalent in the strains causing early infections. PMID:18160454

  4. Neonatal medications.

    PubMed

    Ward, Robert M; Stiers, Justin; Buchi, Karen

    2015-04-01

    Neonatal abstinence syndrome (NAS) is reaching epidemic proportions related to perinatal use of opioids. There are many approaches to assess and manage NAS, including one we have outlined. A standardized approach is likely to reduce length of stay and variability in practice. Circumcision is a frequent, painful procedure performed in the neonatal period. The rationale for providing analgesia is presented as well as a review of methods. Pharmacogenomics and pharmacogenetics have expanded our understanding of diseases and their drug therapy. Some applications of pharmacogenomics to the neonatal period are presented, along with pediatric challenges of developmental expression of drug-metabolizing enzymes.

  5. Development of rituximab-resistant B-NHL clones: an in vitro model for studying tumor resistance to monoclonal antibody-mediated immunotherapy.

    PubMed

    Jazirehi, Ali R; Bonavida, Benjamin

    2011-01-01

    Therapeutic strategies for cancer include chemotherapy, immunotherapy, and radiation. Such therapies result in significant short-term clinical responses; however, relapses and recurrences occur with no treatments. Targeted therapies using monoclonal antibodies have improved responses with minimal toxicities. For instance, Rituximab (chimeric anti-CD20 monoclonal antibody) was the first FDA-approved monoclonal antibody for the treatment of patients with non-Hodgkin's lymphoma (NHL). The clinical response was significantly improved when used in combination with chemotherapy. However, a subset of patients does not respond or becomes resistant to further treatment. Rituximab-resistant (RR) clones were used as a model to address the potential mechanisms of resistance. In this chapter, we discuss the underlying molecular mechanisms by which rituximab signals the cells and modifies several intracellular survival/antiapoptotic pathways, leading to its chemo/immunosensitizing activities. RR clones were developed to mimic in vivo resistance observed in patients. In comparison with the sensitive parental cells, the RR clones are refractory to rituximab-mediated cell signaling and chemosensitization. Noteworthy, interference with the hyperactivated survival/antiapoptotic pathways in the RR clones with various pharmacological inhibitors mimicked rituximab effects in the parental cells. The development of RR clones provides a paradigm for studying resistance by other anticancer monoclonal antibodies in various tumor models.

  6. Immunotherapy for nasopharyngeal cancer-a review.

    PubMed

    Jain, Amit; Chia, Whay Kuang; Toh, Han Chong

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV) and characterized by peritumoral immune infiltrate. Advanced NPC has high lethality. Immunotherapy directed against EBV antigen targets has been previously explored in clinical trials, and is likely to be validated as an important target in NPC as randomized data emerges in the future. Cancer vaccines and adoptive T cell therapy have been explored in the clinic, with the latter showing the greatest success. Recent advances in gene sequencing technology now allow personalized tumor epitope mapping, whilst the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis offers the opportunity to activate adaptive T cell response in vivo. Anti-PD1 antibodies have shown promising activity in early phase clinical trials, and randomized studies against chemotherapy are underway. As immunotherapy is incorporated into standard treatment paradigms, issues of optimal combinations with targeting agents, immune adjuvants, and sequence with chemotherapy and radiation therapy will need to be addressed. Effective strategies to increase tumor antigenicity, improve immunological memory and reduce immune escape, will need to be developed to improve treatment outcomes. Here we present a brief history of the evolution of immunotherapy in NPC, and highlight key concepts relevant to its further development in the clinic.

  7. 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.

  8. Sublingual vs Oral Immunotherapy for Food Allergy

    PubMed Central

    Narisety, Satya D.; Keet, Corinne A.

    2013-01-01

    The incidence of food allergy in developed countries has increased in recent years, escalating the need to find a suitable form of treatment as an alternative to current management, which includes strict avoidance and ready availability of injectable epinephrine (adrenaline). Allergen immunotherapy is currently being studied for use in the treatment of IgE-mediated food allergy to the most common foods, including peanut, tree nut, milk and egg. Two modalities, oral immunotherapy (OIT) and sublingual immunotherapy (SLIT), have shown great promise. Both OIT and SLIT have been able to desensitize subjects to varying degrees, but the two treatment methods differ in doses that can be achieved, duration of treatment, safety profile and ease of use outside the research setting, among other aspects. More research is needed to conclude which mode of treatment is more effective in inducing long-term tolerance with the least amount of serious adverse reactions. However, OIT and SLIT show great promise, and a widespread treatment for food allergy may be within reach. PMID:23009174

  9. 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

  10. 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 ...

  11. Cerebral Cortical Folding Analysis with Multivariate Modeling and Testing: Studies on Gender Differences and Neonatal Development

    PubMed Central

    Awate, Suyash P.; Yushkevich, Paul A.; Song, Zhuang; Licht, Daniel J.; Gee, James C.

    2010-01-01

    This paper presents a novel statistical framework for human cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding by a single number, the proposed descriptor unifies multiple characteristics of surface geometry in a high-dimensional space (hundreds/thousands of dimensions). In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. This paper presents new mathematical insights into the relationship of cortical complexity with intra-cranial volume (ICV). It shows that conventional complexity descriptors implicitly handle ICV Differences in Different ways, thereby lending Different meanings to “complexity”. The paper proposes a new application of a non-parametric permutation-based approach for rigorous statistical hypothesis testing with multivariate cortical descriptors. The paper presents two cross-sectional studies applying the proposed framework to study folding Differences between genders and in neonates with complex congenital heart disease. Both studies lead to novel interesting results. PMID:20630489

  12. Video Laryngoscopy vs. Direct Laryngoscopy in Teaching Neonatal Endotracheal Intubation: A Simulation-Based Study

    PubMed Central

    Thomas, Eric J; Katakam, Lakshmi

    2017-01-01

    Background Neonatal endotracheal intubation is a life-saving procedural skill where best practices have been developed from expert opinion. Few empirical studies have examined how this skill should be taught. Objective To determine whether a video laryngoscope (VL) assisted intubation training curriculum compared to a traditional direct laryngoscope (DL) assisted curriculum improves neonatal intubation performance of novice intubators in a simulated setting. Methods A randomized trial of novice intubators was conducted at the University of Texas-Houston from 6/2013–8/2013. Eligible candidates were randomly assigned to control group (DL curriculum) or intervention group (VL curriculum). Those in the intervention group received instruction with VL videos and practice with Storz C-MAC® VL (Karl Storz, Tuttlingen, Germany) in addition to a traditional curriculum. Intubation performance was evaluated in a simulated setting using a SimNewB® (Laerdal, NY, USA) manikin and traditional intubation equipment. The number of intubation attempts, outcome of each attempt, and time to successful intubation were recorded. The data was analyzed using Fisher's exact test and logistic regression where appropriate. Results One hundred twenty-three trainees were enrolled, 62 (50%) in DL group and 61 (50%) in the VL group. Intubation success on first attempt was achieved by 69% (43/62) of the DL group vs. 61% (37/61) of the VL group, P=0.35. Time to successful intubation was 25 sec (interquartile range (IQR) 18, 32) in the DL group and 26.5 sec (IQR 20, 43) in the VL group, P=0.27. Those in the VL group were more likely to need more than two attempts to achieve intubation success, OR=3.09 (95% CI 1.03–9.28). Conclusions In a simulated setting, teaching with a VL curriculum did not improve intubation performance compared to teaching with DL. Further studies are needed to determine if VL-based teaching has an impact on clinical intubation performance. PMID:28168139

  13. LMA Supreme for neonatal resuscitation: study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background The most important action in the resuscitation of a newborn in the delivery room is to establish effective assisted ventilation. The face mask and endotracheal tube are the devices used to achieve this goal. Laryngeal mask airways that fit over the laryngeal inlet have been shown to be effective for ventilating newborns at birth and should be considered as an alternative to facemask ventilation or endotracheal intubation among newborns weighing >2,000 g or delivered ≥34 weeks’ gestation. A recent systematic review and meta-analysis of supraglottic airways in neonatal resuscitation reported the results of four randomized controlled trials (RCTs) stating that fewer infants in the group using laryngeal mask airways required endotracheal intubation (1.5%) compared to the group using face masks (12.0%). However, there were methodological concerns over all the RCTs including the fact that the majority of the operators in the trials were anesthesiologists. Our hypothesis is based on the assumption that ventilating newborns needing positive pressure ventilation with a laryngeal mask airway will be more effective than ventilating with a face mask in a setting where neonatal resuscitation is performed by midwives, nurses, and pediatricians. The primary aim of this study will be to assess the effectiveness of the laryngeal mask airway over the face mask in preventing the need for endotracheal intubation. Methods/design This will be an open, prospective, randomized, single center, clinical trial. In this study, 142 newborns weighing >1,500 g or delivered ≥34 weeks gestation needing positive pressure ventilation at birth will be randomized to be ventilated with a laryngeal mask airway (LMA SupremeTM, LMA Company, UK - intervention group) or with a face mask (control group). Primary outcome: Proportion of newborns needing endotracheal intubation. Secondary outcomes: Apgar score at 5 minutes, time to first breath, onset of the first cry, duration of

  14. Immunotherapy: Disrupting the Cancer Treatment World

    MedlinePlus

    ... Research Immunotherapy Treatment Immunotherapy: Disrupting the Cancer Treatment World Jun 16, 2014 This story is part of ... Research We Conduct Back To Top Imagine a world free from cancer. Help make it a reality. ...

  15. Biologic Therapy (Immunotherapy) for Kidney Cancer

    MedlinePlus

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  16. 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

  17. Auditory habituation in the fetus and neonate: an fMEG study.

    PubMed

    Muenssinger, Jana; Matuz, Tamara; Schleger, Franziska; Kiefer-Schmidt, Isabelle; Goelz, Rangmar; Wacker-Gussmann, Annette; Birbaumer, Niels; Preissl, Hubert

    2013-03-01

    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 auditory habituation paradigm consisting of 100 trains of five 500 Hz tones, one 750 Hz tone (dishabituator) and two more 500 Hz tones, respectively, were presented to 41 fetuses (gestational age 30-39 weeks) and 22 newborns or babies (age 6-89 days). A response decrement between the first and fifth tones (habituation), an increment between the fifth tone and the dishabituator (stimulus specificity) and an increment between the fifth (last tone before the dishabituator) and seventh tones (first tone after the dishabituator) (dishabituation) were expected. Fetuses showed weak responses to the first tone. However, a significant response decrement between the second and fifth tones (habituation) and a significant increment between the fifth tone and the dishabituator (stimulus specificity) were found. No significant difference was found for dishabituation nor was a developmental trend found at the group level. From the neonatal data, significant values for stimulus specificity were found. Sensory fatigue or adaptation was ruled out as a reason for the response decrement due to the strong reactions to the dishabituator. Taken together, the current study used fMEG to directly show fetal habituation and provides evidence of fetal learning in the last trimester of pregnancy.

  18. Calcium Chloride in Neonatal Parenteral Nutrition: Compatibility Studies Using Laser Methodology

    PubMed Central

    Huston, Robert K.; Christensen, J. Mark; Karnpracha, Chanida; Rosa, Jill E.; Clark, Sara M.; Migaki, Evelyn A.; Wu, YingXing

    2014-01-01

    Introduction We have previously reported results of precipitation studies for neonatal parenteral nutrition solutions containing calcium chloride and sodium phosphate using visual methods to determine compatibility. The purpose of this study was to do further testing of compatibility for solutions containing calcium chloride using more sensitive methods. Methods Solutions of Trophamine (Braun Medical Inc, Irvine, CA) and Premasol (Baxter Pharmaceuticals, Deerfield, IL) were compounded with calcium chloride and potassium phosphate. Controls contained no calcium or phosphate. After incubation at 37° for 24 hours solutions without visual precipitation were analyzed to determine mean particle size using dynamic light scattering from a laser light source. Results Particle sizes were similar for control solutions and those without visual precipitation and a mean particle size <1000 nm. Compatible solutions were defined as those with added calcium and phosphate with no visual evidence of precipitation and mean particle size <1000 nm. In solutions containing 2.5–3% amino acids and 10 mmol/L of calcium chloride the maximum amount of potassium phosphate that was compatible was 7.5 mmol/L. Conclusion Maximum amounts of phosphate that could be added to parenteral nutrition solutions containing Trophamine and calcium chloride were about 7.5–10 mmol/L less for a given concentration of calcium based upon laser methodology compared to visual techniques to determine compatibility. There were minor differences in compatibility when adding calcium chloride and potassium phosphate to Premasol versus Trophamine. PMID:25192060

  19. 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.

  20. 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

  1. Chapter 3: Allergen immunotherapy: definition, indication, and reactions.

    PubMed

    Georgy, Mary S; Saltoun, Carol A

    2012-01-01

    Specific allergen immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. It is a disease modifying therapy, indicated for the treatment of allergic rhinitis, allergic asthma, and hymenoptera hypersensitivity. Specific IgE antibodies for appropriate allergens for immunotherapy must be documented. Indications for allergen immunotherapy include (1) inadequate symptom control despite pharmacotherapy and avoidance measures, (2) a desire to reduce the morbidity from allergic rhinitis and/or asthma or reduce the risk of anaphylaxis from a future insect sting, (3) when the patient experiences undesirable side effects from pharmacotherapy, and (4) when avoidance is not possible. Furthermore, patients may seek to benefit from economic savings of allergen immunotherapy compared with pharmacotherapy over time. Several studies have reported that immunotherapy in children with allergic rhinitis appears to prevent the development of new allergic sensitizations and/or new-onset asthma. Humoral, cellular, and tissue level changes occur with allergen immunotherapy including large increases in antiallergen IgG(4) antibodies, a decrease in the postseasonal rise of antiallergen IgE antibodies, reduced numbers of nasal mucosal mast cells and eosinophils, induction of Treg cells, and suppression of Th2 more than Th1 lymphocytes. There is a corresponding increase in IL-10 and transforming growth factor beta. In the United States, allergen immunotherapy is administered by the subcutaneous route in the physician's office, whereas primarily in some countries in Europe, it is administered for allergic rhinitis and asthma by the sublingual route by the patient at home.

  2. 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

  3. Neonates with Cystic Fibrosis Have a Reduced Nasal Liquid pH; A Small Pilot Study

    PubMed Central

    Abou Alaiwa, Mahmoud H.; Beer, Alison M.; Pezzulo, Alejandro A.; Launspach, Janice L.; Horan, Rebecca A.; Stoltz, David A.; Starner, Timothy D.; Welsh, Michael J.; Zabner, Joseph

    2014-01-01

    Background Disrupted HCO3- transport and reduced airway surface liquid (ASL) pH in cystic fibrosis (CF) may initiate airway disease. We hypothesized that ASL pH is reduced in neonates with CF. Methods In neonates with and without CF, we measured pH of nasal ASL. We also measured nasal pH in older children and adults. Results In neonates with CF, nasal ASL (pH 5.2±0.3) was more acidic than in non-CF neonates (pH 6.4±0.2). In contrast, nasal pH of CF children and adults was similar to values measured in people without CF. Conclusions At an age when infection, inflammation and airway wall remodeling are minimal, neonates with CF had an acidic nasal ASL compared to babies without CF. The CF:non-CF pH difference disappeared in older individuals, perhaps because secondary manifestations of disease increase ASL pH. These results aid understanding of CF pathogenesis and suggest opportunities for therapeutic intervention and monitoring of disease. PMID:24418186

  4. 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

  5. Hypopituitarism in a neonate with hyperbilirubinemia and decreased level of consciousness: a case report study.

    PubMed

    Mousavi, Hadi; Bakhtiyari, Salar

    2014-01-01

    Decreased level of consciousness in neonates may result from different etiologies, including rare metabolic and hormonal disorder due to anterior pituitary insufficiency. In this case report, a five-day-old newborn boy was referred to the neonatal intensive care unit of Mustafa Khomeini hospital of Ilam, Iran. He had an open anterior fontanel with no history of prenatal and familial diseases. Clinical examination showed decreased level of consciousness so that this patient responded only to painful stimuli. Furthermore, unconsciousness, hyperbilirubinemia, and hypotonia were fully evident. Given the clinical findings and decreased level of consciousness, hormonal diagnostic tests and brain CT scan were performed for any evidence of hypopituitarism. Clinical and experimental findings were consistent with the generalized edema and pituitary insufficiency secondary to central hypothyroidism and cortisol deficiency. Based on the findings, the neonate was put on the hormonal replacement therapy and, as the result, all of the abnormal clinical symptoms disappeared. In conclusion, fatal neonatal diseases may be mistaken with unimportant clinical findings at the first examination. Therefore, comprehensive attention to all potential causes of such symptoms in the neonates should be given for early diagnosis and treatment, and to prevent any fatal and irreversible complications.

  6. Comparative Assessment of Cytokines and Other Inflammatory Markers for the Early Diagnosis of Neonatal Sepsis–A Case Control Study

    PubMed Central

    Prashant, Akila; Vishwanath, Prashant; Kulkarni, Praveen; Sathya Narayana, Prashanth; Gowdara, Vijaykumar; Nataraj, Suma M.; Nagaraj, Rashmi

    2013-01-01

    Objective Cytokines (IL-6, IL-8 and TNF-α), sCD163, and C-reactive protein were serially measured in an attempt to identify a set of tests which can reliably confirm or refute the diagnosis of neonatal sepsis at an early stage. Methods One hundred neonates suspected to have sepsis on clinical grounds and who met the inclusion criteria were enrolled for the study. Based on the positive or negative blood culture reports they were classified as infected (n = 50) and non-infected (n = 50) neonates respectively. Fifty healthy neonates without any signs of sepsis were also included in the study as control group. The initial blood sample was taken on day 0 (at the time of sepsis evaluation) and two further samples were taken on days 1 and 2 for monitoring the clinical progress and response to treatment. In the control group the cord blood and 48 hours venous sample was collected. Plasma CRP (ng/ml), IL-6 (pg/ml), IL-8 (pg/ml), TNF-α (ng/ml) and sCD163 (ng/ml) were determined by double antibody method Enzyme Linked Immunosorbent Assay in all the three blood samples. Results The cut of levels for CRP at >19,689 ng/ml had a sensitivity of 68%, specificity of 92%, for IL-6 at >95.32 pg/ml had a sensitivity of 54%, specificity of 96%, for IL-8 at >70.86 pg/ml had a sensitivity of 78%, specificity of 70%, for sCD163 at >896.78 ng/ml had a sensitivity of 100%, specificity of 88% for the diagnosis of infection before antibiotics. TNF-α levels of >12.6 ng/ml showed 100% sensitivity and 72% specificity for the diagnosis of inflammation. Conclusion The most powerful predictor to differentiate between the non-infected and infected neonates before antibiotics was sCD163. The most powerful indicator for evaluation of prognosis is IL-6. sCD163 can be used alone to screen for sepsis in neonates before the results of blood culture are received. PMID:23869218

  7. 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.

  8. 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

  9. Restrictive management of neonatal polycythemia.

    PubMed

    Morag, Iris; Strauss, Tzipora; Lubin, Daniel; Schushan-Eisen, Irit; Kenet, Gili; Kuint, Jacob

    2011-10-01

    Partial exchange transfusion (PET) is traditionally suggested as treatment for neonates diagnosed with polycythemia. Nevertheless, justification of this treatment is controversial. We evaluated the risk for short-term complications associated with a restrictive treatment protocol for neonatal polycythemia. A retrospective cross-sectional analytical study was conducted. Three treatment groups were defined and managed according to their degree of polycythemia, defined by capillary tube filled with venous blood and manually centrifuged hematocrit: group 1, hematocrit 65 to 69% and no special treatment was recommended; group 2, hematocrit 70 to 75% and intravenous fluids were given and feedings were withheld until hematocrit decreased to < 70%; and group 3, hematocrit ≥ 76% or symptomatic neonates and PET was recommended. During the study period, 190 neonates were diagnosed with polycythemia. The overall rate of short-term complications was 15% (28 neonates). Seizures, proven necrotizing enterocolitis, or thrombosis did not occur in any participating neonates. PET was performed in 31 (16%) neonates. The groups did not differ in their rate of early neonatal morbidities or length of hospitalization. Restrictive treatment for neonatal asymptomatic polycythemia is not associated with an increased risk of short-term complications.

  10. A piglet model for studies of gastrointestinal uptake of cadmium in neonates.

    PubMed

    Eklund, Gunilla; Tallkvist, Jonas; Oskarsson, Agneta

    2004-02-02

    Newborns are believed to have a higher gastrointestinal uptake of inorganic cadmium (Cd) than adults. However, relevant models for investigations of absorption of dietary Cd in neonates are lacking. In the present study, piglets were exposed to 2 or 20 microg Cd/kg body weight (b wt) per day by repeated oral administrations of CdCl2 dissolved in deionized water or infant follow-up formula from days 0 to 10. Elevated and dose-dependent Cd retention in blood and tissues resulted from this low-dose Cd exposure, as determined at day 11. Follow-up formula reduced Cd uptake in comparison to deionized water. However, Cd distribution to the kidneys was higher when Cd was given in formula than in water. Metallothionein (MT) levels in liver, kidney and duodenum were six, three and two times higher, respectively compared to an un-exposed control. Differences in bioavailability and distribution of low-dose Cd given in various diets to newborns could be detected by the proposed piglet model.

  11. 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.

  12. A Retrospective Study of the Health Profile of Neonates of Mothers with Anemia in Pregnancy and Pregnancy Induced Hypertension in Lagos, Nigeria

    PubMed Central

    Sanni, Silifat Ajoke; Onabanjo, Oluseye Olusegun; Olayiwola, Ibiyemi O.; Agbonlahor, Mure

    2014-01-01

    Our study assessed the health profile of neonates in relation to anemia in pregnancy and pregnancy induced hypertension (PIH). This was a retrospective study where a systematic random sampling technique was used to select a total of 1046 case records of pregnant women registered for ante-natal care at Lagos Island Maternity Hospital, Lagos, Nigeria, between 2005 and 2009. Socio-demographic characteristics of the mothers, prevalence of anemia and PIH, and neonatal health profile were obtained from the case records and were analyzed using both descriptive and inferential statistics. Pearson product moment correlation was used to show the relationship (P≤0.05) between maternal complications and neonatal health profile. Majority (68.8%) of the mothers had anemia and 6.7 % had PIH. Majority (97.12%) of the neonates were live births and 2.88% of the neonates were still births, 65.4% of the women with still birth pregnancy outcome had anemia, and 34.6% had PIH. Majority (74%) of the neonates had birth weight within normal range (2.5-4.0 kg) and majority (68%) had normal Apgar score at 5 min of birth (7-10). A positive correlation existed between the packed cell volume of the mother and the birth weight of the neonates (r=0.740, P≤0.05). A negative correlation existed between the incidence of PIH and the birth weight of the neonates (r= 0.781, P≤0.05), head circumference (r=–0.491, P≤0.05) and the length of the neonates(r=–0.480, P≤0.05). We conclude that nutritional and health care intervention programmes for pregnant women should be intensified especially during ante-natal visits to hospitals. PMID:28299124

  13. Immunotherapy and mast cell activation.

    PubMed

    Carlos, A G; Carlos, M L; Santos, M A; Pedro, E; Santos, S; Lopes-Pregal, A

    1998-10-01

    Tryptase is the more specific markers for mast cell activation and mediators release and can be used as an index of mast cell activation after challenge. Nasal provocation tests have been done in patients allergic to the pollen of Parietaria (pellitory wall) before and after specific systemic immunotherapy and tryptase release evaluated in nasal lavage fluid. After specific immunotherapy the concentration of tryptase in nasal lavage was significantly decreased to all the concentrations used in challenge and the peack of tryptase release was delayed. These results confirm that assays of tryptase in nasal fluid after nasal provocation are a reliable markers of mast cell activation. Immunotherapy with specific allergen decreases mast cell reactivity to the same allergen.

  14. Emerging nanotechnologies for cancer immunotherapy

    PubMed Central

    Steinmetz, Nicole F

    2016-01-01

    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. PMID:27190253

  15. Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study

    PubMed Central

    Nie, Jing-Jing; Liang, Xiao-Feng; Yan, Ling; Wang, Fu-Zhen; Zhai, Xiang-Jun; Liu, Jian-Xun; Zhu, Feng-Cai; Chang, Zhan-Jun; Li, Jie

    2016-01-01

    Objective Occult HBV infection (OBI) has been reported in infants born to HBsAg-positive mothers despite immunization. This study aims to determine the maintenance of this status in a prospective birth cohort. Methods A total of 158 neonates born to HBsAg-positive mothers were enrolled. All received passive-active immunization against HBV according to a 0-1-6 schedule. Sera were collected at 7 months of age. Those diagnosed with OBI were serially followed up at 12, 24 and 36 months of age. HBV serological markers were determined by Abbott i2000 system. HBV DNA was quantitated by Abbott m2000 system. Standard PCR followed by direct sequencing were applied for mother-child HBV pairs. Homology and phylogenetic comparisons were done by BLAST and Mega 5. Results All the 158 neonates were HBsAg-negative and anti-HBs-positive at 7 months of age, and 32 (20.3%) of them were diagnosed with OBI, with a median HBV DNA level of 1.97 (1.20–3.71) log IU/mL. Of them, HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively. HBV DNA disappeared at one of the follow-up points in 31 neonates, however, rebounded to low levels in 6 of them thereafter. HBV DNA persisted at low levels during follow-ups in the other one neonate apart from the above 31. All remained negative for HBsAg. Only two (6.3%) neonates were positive for anti-HBc after 24 months of age. HBV showed close homology and phylogenetic relationships for mother-child pairs. S-escape mutant, G145R, was not discovered. The first vaccine dose within 6 hours of birth significantly reduced the occurrence of OBI (59.4% vs. 83.3%, p = 0.003). Conclusions HBV may be controlled in immunized neonates of HBsAg-positive mothers, after being diagnosed with OBI. Timely vaccination against HBV may provide the utmost protection. Long-term and close monitorings are needed. PMID:27835694

  16. 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

  17. Immunotherapy for Alzheimer's Disease

    PubMed Central

    Wisniewski, Thomas; Goni, Fernando

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD the normal soluble amyloid β (sAβ) peptide is converted into oligomeric/fibrillar Aβ. The oligomeric forms of Aβ are thought to be the most toxic, while fibrillar Aβ becomes deposited as amyloid plaques and congophilic angiopathy, which serve as neuropathological markers of the disease. In addition the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles is a critical part of the pathology. Numerous therapeutic interventions are under investigation to prevent and treat AD. Among the more exciting and advanced of these approaches is vaccination. Active and passive Immunotherapy targeting only Aβ has been successful in many AD model animal trials; however, the more limited human data has shown much less benefit so far, with encephalitis occurring in a minority of patients treated with active immunization and vasogenic edema or amyloid-related imaging abnormalities (ARIA) being a complication in some passive immunization trials. Therapeutic intervention targeting only tau has been tested only in mouse models; and no approaches targeting both pathologies concurrently has been attempted, until very recently. The immune approaches tried so far were targeting a self-protein, albeit in an abnormal conformation; however, effective enhanced clearance of the disease associated conformer has to be balanced with the potential risk of stimulating excessive toxic inflammation. The design of future more effective immunomodulatory approaches will need to target all aspects of AD pathology, as well as specifically targeting pathological oligomeric conformers, without the use of any self-antigen. PMID:24412277

  18. Maternal diet quality in pregnancy and neonatal adiposity: The Healthy Start Study

    PubMed Central

    Shapiro, Allison L B; Kaar, Jill L; Crume, Tessa L; Starling, Anne P; Siega-Riz, Anna Maria; Ringham, Brandy M; Glueck, Deborah H; Norris, Jill M; Barbour, Linda A; Friedman, Jacob E (Jed); Dabelea, Dana

    2017-01-01

    Background and Objective Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass, %FM) at birth by increasing the fat mass (FM) component of neonatal body composition. Methods Our analysis was conducted using a pre-birth observational cohort of 1,079 mother-offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-hour dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores ≤ 57 and scores > 57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 hours after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for pre-pregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex, and gestational age. Results Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, SD: 13.6). An HEI-2010 score ≤ 57 was significantly associated with higher neonatal %FM (β = 0.58, 95% CI 0.07, 1.1, p<0.05) and FM (β=20.74; 95% CI 1.49, 40.0; p<0.05) but no difference in FFM. Conclusions Poor diet quality during pregnancy increases neonatal adiposity independent of maternal pre-pregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity. PMID:27133623

  19. Maternal Anaemia and Neonatal Outcome: A Prospective Study on Urban Pregnant Women

    PubMed Central

    Kaur, Manpreet; Chauhan, Aarti; Manzar, Md Dilshad

    2015-01-01

    Introduction Maternal anaemia is a major contributor of adverse neonatal outcomes, particularly compromised birth weight and head circumference. Objective To assess the relationship between maternal anaemia and neonatal measures in a sample of low-middle income group urban mothers. Materials and Methods One hundred pregnant women with population representative prevalence of anaemia were enrolled. Socio-demographic, anthropometry, obstetric profile (parity, abortion history, food habits, gap period with last pregnancy etc), and systolic/diastolic blood pressure were documented. Neonatal outcomes (gestational age and type of delivery), and birth anthropometry (weight, length, and head circumference) were measured at delivery. Univariate and multivariate regression analysis for associating maternal haemoglobin levels and neonatal outcomes were performed. Results The anaemic and non-anaemic pregnant women differed significantly in interval between previous & index pregnancy (p=0.031), parity (p=0.009), systolic blood pressure (p=0.026), diastolic blood pressure (p=0.042), maternal Hb (p<0.01). The mean gestational age (p<0.01), weight (p<0.01), length (p<0.01) and head circumference (p<0.01) of the neonates differed significantly between the two groups. On using maternal haemoglobin as a continuous variable, these anthropometric birth outcomes were positively correlated with maternal haemoglobin (p<0.05). Further, univariate linear regression showed similar associations between maternal haemoglobin (g/dL) and birth weight (p=0.004), length (p=0.010) and head circumference (p=0.003). Conclusion Maternal haemoglobin has a positive relationship with the neonatal measures of weight, length and head circumference. PMID:26816949

  20. 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.

  1. 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.

  2. Th1 cytokine-based immunotherapy for cancer.

    PubMed

    Xu, Hong-Mei

    2014-10-01

    Cytokine-based immunotherapy is executed by harnessing cytokines to activate the immune system to suppress tumors. Th1-type cytokines including IL-1, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor are potent stimulators of Th1 differentiation and Th1-based antitumor response. Many preclinical studies demonstrated the antitumor effects of Th1 cytokines but their clinical efficacy is limited. Multiple factors influence the efficacy of immunotherapy for tumors. For instance immunosuppressive cells in the tumor microenvironment can produce inhibitory cytokines which suppress antitumor immune response. Most studies on cytokine immunotherapy focused on how to boost Th1 response; many studies combined cytokine-based therapy with other treatments to reverse immunosuppression in tumor microenvironment. In addition, cytokines have pleiotropic functions and some cytokines show paradoxical activities under different settings. Better understanding the physiological and pathological functions of cytokines helps clinicians to design Th1-based cancer therapy in clinical practice.

  3. Neonatal pain

    PubMed Central

    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. PMID:24330444

  4. 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.

  5. Clinical characteristics of fetal and neonatal outcomes in twin pregnancy with preeclampsia in a retrospective case–control study

    PubMed Central

    Yuan, Ting; Wang, Wei; Li, Xue-Lan; Li, Chun-Fang; Li, Chao; Gou, Wen-Li; Han, Zhen

    2016-01-01

    Abstract The aim of our study was to compare the clinical characteristics of fetal and neonatal outcomes in twin pregnancies between women with preeclampsia (PE) and those with normotension in a Chinese population. There were 143 preeclamptic women and 367 normotensive women with twin pregnancies included in this retrospective case–control study. The baseline characteristics and perinatal outcomes were collected and compared between the groups. Multiple logistic regression and linear regression were used to assess the correlations between PE and the outcomes. Significant increases were observed in the frequencies of preterm delivery (OR = 2.75, P < 0.001), iatrogenic preterm birth (OR = 3.52, P < 0.001), and IUGR (OR = 2.94, P = 0.001) in the PE group, and the PE group had more than a 2-fold risk of adverse neonatal outcomes. Preeclamptic twin neonates had lower birth weights (β = −147.34, P = 0.005; β = −169.47, P = 0.001). The comparison on the discordance of intertwin weight was not significantly different. Twin pregnancies with PE are associated with worse perinatal outcomes. The adverse outcomes of preeclamptic twin pregnancies may be associated with lower birth weights rather than the discordance of the intertwin weight, which requires further confirmation. The results may provide helpful references for better clinical assessments, evaluations of prognosis, and a deeper understanding of preeclamptic twin pregnancies. PMID:27787375

  6. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study.

    PubMed

    Hohmeister, Johanna; Kroll, Alexander; Wollgarten-Hadamek, Iris; Zohsel, Katrin; Demirakça, Süha; Flor, Herta; Hermann, Christiane

    2010-08-01

    Due to maturation-related plasticity of the developing nociceptive system, neonatal nociceptive input, as induced by medical procedures in the neonatal intensive care unit (NICU), may cause long-term alterations in pain processing. Using functional magnetic resonance imaging, this study investigated the cerebral pain response in school-aged children and adolescents (11-16 yr) with experience in a NICU after preterm (or=37 weeks gestational age, N=9) as compared to fullterm control children without early hospitalization (N=9). NICU children had been recruited retrospectively among former patients of the Children's University Hospital Mannheim. All children had participated in our previous studies [46,49] entailing psychophysical measurements. In response to tonic (30s) heat stimuli of individually adjusted moderate pain intensity, which were of comparable temperature across groups, the preterm but not the fullterm NICU children exhibited significant activations in a number of brain regions (thalamus, anterior cingulate cortex, cerebellum, basal ganglia, and periaquaeductal gray) that were not significantly activated in controls. The preterms showed significantly higher activations than controls in primary somatosensory cortex, anterior cingulate cortex, and insula. This exaggerated brain response was pain-specific and was not observed during non-painful warmth stimulation. Preterms' continuous pain ratings revealed a tendency for increased sensitization within and a lack of habituation across trials. In highly vulnerable children such as preterms, neonatal nociceptive input may, aside from other neurodevelopmental consequences, persistently increase the gain within pain pathways.

  7. Maternal and neonatal health impact of obstetrical risk insurance scheme in Mauritania: a quasi experimental before-and-after study.

    PubMed

    Philibert, Aline; Ravit, Marion; Ridde, Valéry; Dossa, Inès; Bonnet, Emmanuel; Bedecarrats, Florent; Dumont, Alexandre

    2017-04-01

    A variety of health financing schemes shaped on pre-payment scheme have been implemented across Sub-Saharan Africa (SSA) to address the Millennium Development Goals (MDGs). In Mauritania, the Obstetric Risk Insurance package (ORI) focusing on maternal and perinatal health has been progressively implemented at the health district level since 2002. Here, our main objective was to assess the effectiveness of the ORI in increasing facility-based delivery rates, as well as increases in family planning, antenatal and postnatal care, caesarean delivery and neonatal health, from demographic and health survey data between 2002 and 2011. We also examined whether the effects of the ORI varied between strata of the population. The study was based on a quasi-experimental before-and-after design to assess the causal link between availability of ORI and increase in use of maternal health services and neonatal mortality. In combination with geographical information system, difference-in-differences and odd ratio approaches were used to address our objectives. Indicators of access to care for pregnant women and neonatal health and improved in both non-intervention and intervention groups during the study period. There was no global effect of the availability of ORI on facility-based delivery rates, nor on the use of antenatal and postnatal care services, except for qualified antenatal services. However, delivery rates in local health centres with ORI increased more rapidly than in those with no ORI, the contrary was shown for hospitals. Caesarean delivery and family planning decreased with ORI. Although late neonatal mortality rates remained low in the country, a significant decrease was seen in districts without ORI. Except for some strata of the population, ORI has not really met its objective of attracting more pregnant women towards facility-based health care.

  8. Clinical Effectiveness of Hymenoptera Venom Immunotherapy: A Prospective Observational Multicenter Study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity

    PubMed Central

    Ruëff, Franziska; Przybilla, Bernhard; Biló, Maria Beatrice; Müller, Ulrich; Scheipl, Fabian; Seitz, Michael J.; Aberer, Werner; Bodzenta-Lukaszyk, Anna; Bonifazi, Floriano; Campi, Paolo; Darsow, Ulf; Haeberli, Gabrielle; Hawranek, Thomas; Küchenhoff, Helmut; Lang, Roland; Quercia, Oliviero; Reider, Norbert; Schmid-Grendelmeier, Peter; Severino, Maurizio; Sturm, Gunter Johannes; Treudler, Regina; Wüthrich, Brunello

    2013-01-01

    Background Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Objective Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. Methods In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. Results 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. Interpretation It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy. PMID:23700415

  9. Immunotherapy for patients with advanced pancreatic carcinoma: a promising treatment

    PubMed Central

    Liu, Jing; Lian, Zhouyang; Liang, Long; Chen, Wenbo; Luo, Xiaoning; Pei, Shufang; Mo, Xiaokai; Zhang, Lu; Huang, Wenhui; Ouyang, Fusheng; Guo, Baoliang; Liang, Changhong; Zhang, Shuixing

    2017-01-01

    There are limited data on the safety and efficacy of immunotherapy for patients with advanced pancreatic cancer (APC). A meta-analysis of single-arm trials is proposed to assess the efficacy and safety of immunotherapy for APC. Eighteen relevant studies involving 527 patients were identified. The pooled disease control rate (DCR), overall survival (OS), progression free survival (PFS), and 1-year survival rate were estimated as 59.32%, 7.90 months, 4.25 months, and 30.12%, respectively. Subgroup analysis showed that the pooled OS, PFS, and 1-year survival rate were significantly higher for autologous activated lymphocyte therapy compared with peptide-based vaccine therapy (OS: 8.28 months vs. 7.40 months; PFS: 6.04 months vs. 3.86 months; 1-year survival rate: 37.17% vs. 19.74%). Another subgroup analysis demonstrated that the pooled endpoints were estimated as obviously higher for immunotherapy plus chemotherapy compared with immunotherapy alone (DCR: 62.51% vs. 47.63%; OS: 8.67 months vs. 4.91 months; PFS: 4.91 months vs. 3.34 months; 1-year survival rate: 32.32% vs. 21.43%). Of the included trials, seven trials reported no treatment related adverse events , five trials reported (16.6 3.9) % grade 3 adverse events and no grade 4 adverse events. In conclusion, immunotherapy is safe and effective in the treatment of APC. PMID:27992378

  10. Multiallergen-specific immunotherapy in polysensitized patients: where are we?

    PubMed

    Bahceciler, Nerin Nadir; Galip, Nilufer; Cobanoglu, Nazan

    2013-02-01

    Allergen-specific immunotherapy administered by the subcutaneous route was introduced a century ago and has been shown to be effective in the management of allergic rhinitis and asthma. More recently, the sublingual administration of allergen extracts has become popular, especially in European countries, and has also demonstrated efficacy in respiratory allergic diseases. Both modes of allergen administration during immunotherapy have been shown not only to reduce symptoms and the need for medication, but also to prevent the development of additional sensitivities in monosensitized patients, as well as asthma development in patients with allergic rhinitis, with a long-lasting effect after the completion of several years of treatment. Almost all of the well-designed and double-blinded, placebo-controlled studies evaluated treatment with single-allergen extracts. Therefore, most meta-analyses published to date evaluated immunotherapy with single allergen or extracts containing several cross-reactive allergens. As a result, in general, multiallergen immunotherapy in polysensitized patients (mixture of noncross-reactive allergens) is not recommended owing to lack of evidence. Although some guidelines have recommended against the use of multiallergen mixtures, allergists commonly use mixtures to which the patient is sensitive with the rationale that effective immunotherapy should include all major sensitivities. Literature on this subject is scarce in spite of the widespread use worldwide. Here, this issue will be extensively discussed based on currently available literature and future perspectives will also be explored.

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

    PubMed

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

    2014-03-01

    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.

  12. Gestational diabetes mellitus treatment reduces obesity-induced adverse pregnancy and neonatal outcomes: the St. Carlos gestational study

    PubMed Central

    Assaf-Balut, Carla; Familiar, Cristina; García de la Torre, Nuria; Rubio, Miguel A; Bordiú, Elena; del Valle, Laura; Lara, Miriam; Ruiz, Teresa; Ortolá, Ana; Crespo, Irene; Duran, Alejandra; Herraiz, Miguel A; Izquierdo, Nuria; Perez, Noelia; Torrejon, Maria J; Runkle, Isabelle; Montañez, Carmen; Calle-Pascual, Alfonso L

    2016-01-01

    Background Obesity and gestational diabetes mellitus (GDM) increase the morbidity of the mother and newborn, which could increase further should they coexist. We aimed to determine the risk of adverse pregnancy and neonatal outcomes associated with excess weight (EW), and within this group identify potential differences between those with and without GDM. Methods We carried out a post-hoc analysis of the St. Carlos Gestational Study which included 3312 pregnant women, arranged in 3 groups: normal-weight women (NWw) (2398/72.4%), overweight women (OWw) (649/19.6%) and obese women (OBw) (265/8%). OWw and OBw were grouped as EW women (EWw). We analyzed variables related to adverse pregnancy and neonatal outcomes. Results The relative risk (95% CI) for GDM was 1.82 (1.47 to 2.25; p<0.0001) for OWw, and 3.26 (2.45 to 4.35; p<0.0001) in OBw. Univariate analysis showed associations of EW to higher rates of prematurity, birth weight >90th centile, newborns admitted to neonatal intensive care unit (NICU), instrumental delivery and cesarean delivery (all p<0.005). Multivariate analysis, adjusted for parity and ethnicity, showed that EW increased the risk of prematurity, admission to NICU, cesarean and instrumental delivery, especially in EWw without GDM. NWw with GDM had a significantly lower risk of admission to NICU and cesarean delivery, compared with NWw without GDM. Conclusions EW is detrimental for pregnancy and neonatal outcomes, and treatment of GDM contributes to lowering the risk in EWw and NWw. Applying the same lifestyle changes to all pregnant women, independent of their weight or GDM condition, could improve these outcomes. PMID:28074143

  13. 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

  14. Effect of neonatal sublingual vaccination with native or denatured ovalbumin and adjuvant CpG or cholera toxin on systemic and mucosal immunity in mice.

    PubMed

    Huang, C-F; Wu, T-C; Chu, Y-H; Hwang, K-S; Wang, C-C; Peng, H-J

    2008-11-01

    Sublingual immunotherapy has been applied for allergic diseases, but whether sublingual immunization in neonates can prevent sensitization has not been studied. In this study, we evaluate the effect of neonatal sublingual vaccination with native or denatured allergens alone or plus adjuvant on allergy prevention. Newborn BALB/c mice were sublingually vaccinated daily for the first 3 days with native or denatured ovalbumin (OVA) only, or combined adjuvant CpG or cholera toxin (CT). They were sensitized with OVA adsorbed onto alum 7 weeks after the last vaccination. Specific secretory IgA antibody responses were readily induced by neonatal vaccination with antigen plus CpG or CT, but not with antigen alone. Whereas vaccination with denatured OVA plus CpG markedly enhanced T helper 1 (Th1) responses and inhibited IgE production, vaccination with denatured OVA plus CT increased cervical lymph node cell production of interleukin-4 (IL-4), IL-5, IL-6, and serum IgG1 responses. These data demonstrate that neonatal sublingual vaccination with denatured OVA and CpG not only preferentially induces systemic Th1 responses and mucosal immunity, but also simultaneously abrogates IgE production. Neonatal sublingual vaccines may play a role for the strategy of allergy prevention.

  15. Allergen-Specific Immunotherapy in Food Anaphylaxis

    PubMed Central

    2008-01-01

    Specific immunotherapy (SIT) protocols for nutritional allergens have only recently been established with a focus on oral allergy syndrome because of pollen cross-reacting antibodies. For these patients, a substantial number of studies have been published suggesting benefits from SIT. The situation in true anaphylaxis to food allergens such as peanut allergy is more complex, and therapeutic strategies are based on individual protocols rather than controlled studies. However, in defined cases, SIT represents a promising approach for a durable protection from life-threatening risks after accidental ingestion. PMID:23283385

  16. 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

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

    PubMed Central

    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. PMID:26500653

  18. 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.

  19. 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

  20. Engineering opportunities in cancer immunotherapy

    PubMed Central

    Jeanbart, Laura; Swartz, Melody A.

    2015-01-01

    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. PMID:26598681

  1. Economic evaluation of therapeutic cancer vaccines and immunotherapy: a systematic review.

    PubMed

    Geynisman, Daniel M; Chien, Chun-Ru; Smieliauskas, Fabrice; Shen, Chan; Shih, Ya-Chen Tina

    2014-01-01

    Cancer immunotherapy is a rapidly growing field in oncology. One attractive feature of cancer immunotherapy is the purported combination of minimal toxicity and durable responses. However such treatments are often very expensive. Given the wide-spread concern over rising health care costs, it is important for all stakeholders to be well-informed on the cost and cost-effectiveness of cancer immunotherapies. We performed a comprehensive literature review of cost and cost-effectiveness research on therapeutic cancer vaccines and monoclonal antibodies, to better understand the economic impacts of these treatments. We summarized our literature searches into three tables by types of papers: systematic review of economic studies of a specific agent, cost and cost-effectiveness analysis. Our review showed that out of the sixteen immunotherapy agents approved, nine had relevant published economic studies. Five out of the nine studied immunotherapy agents had been covered in systematic reviews. Among those, only one (rituximab for non-Hodgkin lymphoma) was found to be cost-effective. Of the four immunotherapy drugs not covered in systematic reviews (alemtuzumab, ipilimumab, sipuleucel-T, ofatumumab), high incremental cost-effectiveness ratio (ICER) was reported for each. Many immunotherapies have not had economic evaluations, and those that have been studied show high ICERs or frank lack of cost-effectiveness. One major hurdle in improving the cost-effectiveness of cancer immunotherapies is to identify predictive biomarkers for selecting appropriate patients as recipients of these expensive therapies. We discuss the implications surrounding the economic factors involved in cancer immunotherapies and suggest that further research on cost and cost-effectiveness of newer cancer vaccines and immunotherapies are warranted as this is a rapidly growing field with many new drugs on the horizon.

  2. Cinacalcet Monotherapy in Neonatal Severe Hyperparathyroidism: A Case Study and Review

    PubMed Central

    Gannon, Anthony W.; Monk, Heather M.

    2014-01-01

    Context: Neonatal severe hyperparathyroidism (NSHPT) is a severe form of familial hypocalciuric hypercalcemia characterized by severe hypercalcemia and skeletal demineralization. In most cases, NSHPT is due to biallelic loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR), but some patients have heterozygous mutations. Conventional treatment consists of iv saline, bisphosphonates, and parathyroidectomy. Objective: The aim of this project was to characterize the molecular basis for NSHPT in an affected newborn and to describe the response to monotherapy with cinacalcet. Methods: Clinical and biochemical features were monitored as cinacalcet therapy was initiated and maintained. Genomic DNA was obtained from the proband and parents. The CASR gene was amplified by PCR and sequenced directly. Results: The patient was a full-term male who developed hypotonia and respiratory failure soon after birth. He was found to have multiple fractures and diffuse bone demineralization, with a marked elevation in serum ionized calcium (1.99 mmol/L) and elevated serum levels of intact PTH (1154 pg/mL); serum 25-hydroxyvitamin D was low, and fractional excretion of calcium was reduced. The serum calcium level was not reduced by iv saline infusion. Based on an extensive family history of autosomal dominant hypercalcemia, a diagnosis of NSHPT was made, and cinacalcet therapy was initiated with a robust and durable effect. Molecular studies revealed a heterozygous R185Q missense mutation in the CASR in the patient and his father, whereas normal sequences for the CASR gene were present in the patient's mother. Conclusions: We describe the first use of cinacalcet as monotherapy for severe hypercalcemia in a newborn with NSHPT. The rapid and durable response to cinacalcet suggests that a trial of calcimimetic therapy should be considered early in the course of NSHPT. PMID:24203066

  3. Video recording of neonatal resuscitation: A feasibility study to inform widespread adoption

    PubMed Central

    Shivananda, Sandesh; Twiss, Jennifer; el-Gouhary, Enas; el-Helou, Salhab; Williams, Connie; Murthy, Prashanth; Suresh, Gautham

    2017-01-01

    AIM To determine the feasibility of introducing video recording (VR) of neonatal resuscitation (NR) in a perinatal centre. METHODS This was a prospective cohort quality improvement study on preterm infants and their caregivers. Based on evidence and experience of other centers using VR intervention, a contextually relevant implementation and evaluation strategy was designed in the planning phase. The components of intervention were pre-resuscitation team huddle, VR of NR and video debriefing (VD), all occurring on the same day. Various domains of feasibility and sustainability as well as feasibility criteria were predefined. Data for analysis was collected using quantitative and qualitative methods. RESULTS Seventy-one caregivers participated in VD of 14 NRs facilitated by six trained instructors. Ninety-one percent of caregivers perceived enhanced learning and patient safety and, 48 issues were identified related to policy, caregiver roles, and latent safety threats. Ninety percent of caregivers expressed their willingness to participate in VD activity and supported the idea of integrating it into a resuscitation team routine. Eighty-three percent and 50% of instructors expressed satisfaction with video review software and quality of audio VR. No issues about maintenance of infant or caregivers’ confidentiality and erasure of videos were reported. Criteria for feasibility were met (refusal rate of < 10%, VR performed on > 50% of occasions, and < 20% caregivers’ perceiving a negative impact on team performance). Necessary adaptations to enhance sustainability were identified. CONCLUSION VR of NR as a standard of care quality assurance activity to enhance caregivers’ learning and create opportunities that improve patient safety is feasible. Despite its complexity with inherent challenges in implementation, the intervention was acceptable, implementable, and potentially sustainable with adaptations. PMID:28224098

  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. Prostate cancer as a model for tumour immunotherapy

    PubMed Central

    Drake, Charles G.

    2011-01-01

    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. PMID:20651745

  6. Interleukin-13 Receptor Alpha 2-Targeted Glioblastoma Immunotherapy

    PubMed Central

    Crawford, Andrew C.

    2014-01-01

    Glioblastoma (GBM) is the most lethal primary brain tumor, and despite several refinements in its multimodal management, generally has very poor prognosis. Targeted immunotherapy is an emerging field of research that shows great promise in the treatment of GBM. One of the most extensively studied targets is the interleukin-13 receptor alpha chain variant 2 (IL13Rα2). Its selective expression on GBM, discovered almost two decades ago, has been a target for therapy ever since. Immunotherapeutic strategies have been developed targeting IL13Rα2, including monoclonal antibodies as well as cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-expressing T cells. Advanced therapeutic development has led to the completion of several clinical trials with promising outcomes. In this review, we will discuss the recent advances in the IL13Rα2-targeted immunotherapy and evaluate the most promising strategy for targeted GBM immunotherapy. PMID:25247196

  7. 2003-2013, a valuable study: Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in stage IV breast cancer.

    PubMed

    Lin, Mao; Liang, Shuzhen; Jiang, Feng; Xu, Jiongyuan; Zhu, Weibing; Qian, Wei; Hu, Yong; Zhou, Zhanchun; Chen, Jibing; Niu, Lizhi; Xu, Kecheng; Lv, Youyong

    2017-03-01

    Dendritic cells (DCs) and cytokine-induced killer (CIK) cells have both shown activity as immunotherapy in some malignancies. Our aim was to prospective assess the effect of this immunotherapy in patients with stage IV breast cancer. Between Aug 2003 and Dec 2013, we collected 368 patients who met inclusion criteria and divided into immunotherapy group (treatment group: 188 patients) and chemotherapy group (control group: 180 patients). DCs were prepared from the mononuclear cells isolated from patients in the treatment group using IL-2/GM-CSF and were loaded with tumour antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. After the patients had received low-dose chemotherapy, those in the treatment group also received the DC-CIK therapy, which was repeated four times in a fortnight to form one cycle. At least three cycles of DC-CIK therapy were given. Immune function was measured in treatment group patients' sera. Disease-free survival (DFS) and Overall survival (OS) after the diagnosis of stage IV breast cancer was assessed after a 10-year follow-up. The result demonstrated that immune function is obviously enhanced after DC-CIK therapy. By Cox regression analysis, DC-CIK therapy reduced the risk of disease progression (p<0.01) with an increased OS (p<0.01). After low-dose chemotherapy, active immunization with DC-CIK immunotherapy is a potentially effective approach for the control of tumour growth in stage IV breast cancer patients.

  8. 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

  9. Treatment of respiratory allergy with allergy immunotherapy tablets.

    PubMed

    Bachert, C

    2011-07-01

    Allergy immunotherapy tablets (AIT) have expanded the treatment options for patients suffering from respiratory allergies. Efficacy is established in adults and children for two different commercially available grass AITs. The ALK grass AIT has an efficacy comparable to subcutaneous immunotherapy (SCIT), with a proven disease-modifying effect after treatment completion. Safety profiles favour AIT over SCIT. Studies suggest that tablets in all aspects are superior to sublingual drops. AITs for other allergies including house dust mite and birch and ragweed pollen are in development.

  10. A pilot cohort analytic study of Family Integrated Care in a Canadian neonatal intensive care unit

    PubMed Central

    2013-01-01

    Background We have developed a Family Integrated Care (FIC) model for use in a neonatal intensive care unit (NICU) where parents provide most of the care for their infant, while nurses teach and counsel parents. The objective of this pilot prospective cohort analytic study was to explore the feasibility, safety, and potential outcomes of implementing this model in a Canadian NICU. Methods Infants born ≤35 weeks gestation, receiving continuous positive airway pressure or less respiratory support, with a primary caregiver willing and able to spend ≥8 hours a day with their infant were eligible. Families attended daily education sessions and were mentored at the bedside by nurses. The primary outcome was weight gain, as measured by change in z-score for weight 21 days after enrolment. For each enrolled infant, we identified two matched controls from the previous year’s clinical database. Differences in weight gain between the two groups were analyzed using a linear mixed effects multivariable regression model. We also measured parental stress levels using the Parental Stress Survey: NICU, and interviewed parents and nurses regarding their experiences with FIC. Results This study included 42 mothers and their infants. Of the enrolled infants, matched control data were available for 31 who completed the study. The rate of change in weight gain was significantly higher in FIC infants compared with control infants (p < 0.05). There was also a significant increase in the incidence of breastfeeding at discharge (82.1 vs. 45.5%, p < 0.05). The mean Parental Stress Survey: NICU score for FIC mothers was 3.06 ± 0.12 at enrolment, which decreased significantly to 2.30 ± 0.13 at discharge (p < 0.05). Feedback from the parents and nurses indicated that FIC was feasible and appropriately implemented. Conclusions This study suggests that the FIC model is feasible and safe in a Canadian healthcare setting and results in improved weight gain among preterm infants. In addition

  11. Cancer immunotherapy: sipuleucel-T and beyond.

    PubMed

    Hammerstrom, Aimee E; Cauley, Diana H; Atkinson, Bradley J; Sharma, Padmanee

    2011-08-01

    In April 2010, sipuleucel-T became the first anticancer vaccine approved by the United States Food and Drug Administration. Different from the traditional chemotherapy agents that produce widespread cytotoxicity to kill tumor cells, anticancer vaccines and immunotherapies focus on empowering the immune system to overcome the tumor. The immune system consists of innate and adaptive components. The CD4(+) and CD8(+) T cells are the most crucial components of the adaptive arm of the immune system that act to mediate antitumor responses. However, T-cell responses are regulated by intrinsic and extrinsic mechanisms, which may interfere with effective antitumor responses. Many anticancer immunotherapies use tumor-associated antigens as vaccines in order to stimulate an immune response against tumor cells. Sipuleucel-T is composed of autologous mononuclear cells incubated with a fusion protein consisting of a common prostate cancer antigen (prostatic acid phosphatase) linked to an adjuvant (granulocyte-macrophage colony-stimulating factor). It is postulated that when the vaccine is infused into the patient, the activated antigen-presenting cells displaying the fusion protein will induce an immune response against the tumor antigen. In a recent randomized, double-blind, placebo-controlled, phase III clinical trial, sipuleucel-T significantly improved median overall survival by 4.1 months in men with metastatic castration-resistant prostate cancer compared with placebo. Although overall survival was improved, none of the three phase III clinical trials found a significant difference in time to disease progression. This, along with cost and logistic issues, has led to an active discussion. Although sipuleucel-T was studied in the metastatic setting, its ideal place in therapy is unknown, and clinical trials are being conducted in patients at different stages of disease and in combination with radiation therapy, antiandrogen therapy, and chemotherapy. Various other anticancer

  12. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

    Synopsis 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. The following chapter reviews recent trends in epidemiology, and provides an update on risk factors, diagnostic methods and management of neonatal sepsis. PMID:23481106

  13. 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.

  14. Functional Laterality of Task-Evoked Activation in Sensorimotor Cortex of Preterm Infants: An Optimized 3 T fMRI Study Employing a Customized Neonatal Head Coil

    PubMed Central

    Smith-Collins, Adam PR; Müller, Nicole; Stegmann-Woessner, Gaby; Jankowski, Jacob; Gieseke, Jürgen; Born, Mark; Seitz, Hermann; Bartmann, Peter; Schild, Hans H.; Pruessmann, Klaas P.; Boecker, Henning

    2017-01-01

    Background Functional magnetic resonance imaging (fMRI) in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD) responses in sensorimotor cortex (SMC). Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level. Patients / methods Here, we employed a custom-designed neonatal MR-coil adapted and optimized to the head size of a newborn in order to improve robustness, reliability and validity of neonatal sensorimotor fMRI. Thirteen preterm infants with a median gestational age of 26 weeks were scanned at term-corrected age using a prototype 8-channel neonatal head coil at 3T (Achieva, Philips, Best, NL). Sensorimotor stimulation was elicited by passive extension/flexion of the elbow at 1 Hz in a block design. Analysis of temporal signal to noise ratio (tSNR) was performed on the whole brain and the SMC, and was compared to data acquired with an ‘adult’ 8 channel head coil published previously. Task-evoked activation was determined by single-subject SPM8 analyses, thresholded at p < 0.05, whole-brain FWE-corrected. Results Using a custom-designed neonatal MR-coil, we found significant positive BOLD responses in contralateral SMC after unilateral passive sensorimotor stimulation in all neonates (analyses restricted to artifact-free data sets = 8/13). Improved imaging characteristics of the neonatal MR-coil were evidenced by additional phantom and in vivo tSNR measurements: phantom studies revealed a 240% global increase in tSNR; in vivo studies revealed a 73% global and a 55% local (SMC) increase in tSNR, as compared to the ‘adult’ MR

  15. Insect sting allergy. A study from 1980 to 2003 of patients who started treatment with venom immunotherapy between 1980 and 1998

    PubMed Central

    Haye, Rolf; Døsen, Liv Kari

    2005-01-01

    Background Previously we treated patients with insect sting allergy with venom immunotherapy (IT) using whole body insect extracts. From 1980 we changed to insect venoms. The purpose of this study was to analyse data from the patients in order to improve our treatment. Methods This is an open, single centre study on patients treated with venom IT 14 years or older with a history of a systemic allergic reaction to an insect sting, a positive skin prick test (SPT) or a positive RAST and willingness to comply with five years of IT. Clinical and laboratory data were registered prospectively at the start of IT and after five years of treatment until 2003 on patients who started IT between 1980 and 1998. Questionnaires were answered in 1989, 1993 and 2003. Statistical analysis was done with Pearson's chi square, Fisher's exact or the t-test. Results Of 315 patients treated, 44 were given bee, 248 common wasp and 23 both venoms. Of the common wasp sting incidents 5.5 % resulted in a severe allergic reaction (SAR) during adequate IT and 22% after cessation. Seventy-one per cent of the patients carried epinephrine. Precautionary steps were taken by 77% of the patients during or after inadequate IT. On or after adequate IT 83% felt completely or substantially safe. Surprisingly 29 % of those inadequately treated felt safer and 50% were satisfied with having had the opportunity to be treated. The SPT became negative in 68% of the wasp allergic patients after five years of adequate IT. Increased risk of experiencing SAR to a future sting in wasp allergic patients after cessation of adequate IT was significantly associated with a SAR due to IT during the rush regimen. SAR due to IT occurred very rarely during maintenance dosing. Conclusion Adequate venom IT is very effective while ongoing but somewhat less effective after cessation, while inadequate treatment gives poor results. More of our patients should complete five years of IT and some should continue IT. The type of

  16. Specific immunotherapy in renal cancer: a systematic review

    PubMed Central

    Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I.; Rezaei, Nima

    2016-01-01

    Background: Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. Methods: We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). Results: We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58–0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients

  17. 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

  18. [Immunotherapy in radical surgery of colorectal carcinoma].

    PubMed

    Brivio, Fernando; Fumagalli, Luca; Chiarelli, Marco; Denova, Marianna; Bertolini, Aimone; Cetta, Marco; Nespoli, Angelo

    2007-01-01

    Cancer-associated immunodeficiency is seriously worsened by surgical trauma. Short-term preoperative interleukin-2 (IL-2) immunotherapy abolishes postoperative immunodeficiency and can induce immunological control of the growth of minimal residual disease. Growth factors play an important role in oncological practice in treating neutropenia (G-CSF) or associated anaemia during chemotherapy (erythropoietin). Unfortunately, lymphocytopenia is not considered a biological marker with regard to survival. On the other hand, the role of the immune response to surgical trauma has been emphasised by many surgeons, and to counteract it immune nutrition (omega 3 fatty acid, mRNA, arginine) or thymic hormone have been tried. We believe that the obvious method of counteracting postoperative lymphocytopenia is the administration of the specific growth factor for T lymphocytes, i.e. IL-2. The aim of this study was to report on our experience with IL-2 preoperative immunoactivation in colorectal cancer and the long-term outcome of patients treated in comparison with a control group operated on without immunotherapy. In order to obtain activated lymphocytosis at the time of operation administration of IL-2 (6 million I.U. twice daily subcutaneously) for 3 preoperative days is sufficient, starting 4 days before surgery. The inclusion/exclusion criteria were histologically documented colorectal cancer, elective surgery, laparotomic surgery, no second tumour, age 20-80 years, no cardiovascular, hepatic or renal failure. From June 1992 to December 2005, 67 patients were treated (Dukes B/C: 46/21) with IL-2 immunotherapy. The clinical and biological results were compared with those of a control group of 173 patients (Dukes B/C 114/59) operated on in the same period and recruited with the same criteria. Dukes stage-C patients in both groups underwent adjuvant chemotherapy plus radiotherapy for rectal cancer. Data were statistically analysed using Fisher's exact test, Student's T-test and

  19. Costs and Cost-Effectiveness of Training Traditional Birth Attendants to Reduce Neonatal Mortality in the Lufwanyama Neonatal Survival Study (LUNESP)

    PubMed Central

    Sabin, Lora L.; Knapp, Anna B.; MacLeod, William B.; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H.; Gill, Christopher J.

    2012-01-01

    Background The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. Methods and Findings We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Conclusions Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care. PMID:22545117

  20. Anti-programmed cell death protein 1 tolerance and efficacy after ipilimumab immunotherapy: observational study of 39 patients.

    PubMed

    Amode, Reyhan; Baroudjian, Barouyr; Kowal, Anita; Jebali, Majdi; Allayous, Clara; Bagot, Martine; Madjlessi, Nika; Roux, Jennifer; Viguier, Manuelle; Basset Seguin, Nicole; Porcher, Raphaël; Pagès, Cécile; Lebbé, Céleste

    2017-04-01

    In patients with ipilimumab (IPI)-refractory melanoma, the anti-programmed cell death proteins 1 (PD1s) nivolumab (NIV) and pembrolizumab (PEM) are considered to be a new standard of treatment. Few data are available on anti-PD1 safety in patients who develop IPI-related severe adverse events (AEs) (grade≥3). The aim of this study was to compare the anti-PD1 safety and efficacy in patients with previous severe toxicity to IPI versus in those showing moderate and no previous IPI-related AEs. This single institution-based observational study included all patients treated with anti-PD1 (PEM or NIV) and previously treated with IPI for unresectable stage III or IV melanoma. The patients enrolled were classified according to the occurrence of IPI-related AEs: group A: no previous IPI-related AEs; group B: mild to moderate IPI-related AEs; and group C: severe to life-threatening IPI-related AEs. The main outcome measure was safety of the anti-PD1 among the three groups. The secondary endpoints included response parameters. Groups A, B, and C included, respectively, 16, 13, and 10 patients. The incidence of severe anti-PD1-related AEs (grades 3-4) was 12, 23, and 10% in groups A, B, and C, respectively. One-year estimates of survival were 52.2, 73.4, and 66.7% among the patients in groups A, B, and C, respectively. The number of patients was too small to enable a meaningful statistical comparison. We did not observe any difference in anti-PD1 toxicity onset incidence according to the occurrence of previous IPI AEs. These reassuring real-life data should be confirmed in a wider analysis.

  1. Hypernatremia in the Neonate: Neonatal Hypernatremia and Hypernatremic Dehydration in Neonates Receiving Exclusive Breastfeeding

    PubMed Central

    Mujawar, Nilofer Salim; Jaiswal, Archana Nirmal

    2017-01-01

    Aims and Objectives: Evaluation of neonatal hypernatremia and hypernatremic dehydration in neonates receiving exclusive breastfeeding. Introduction: Neonatal hypernatremia is a serious condition in the newborn period. We present infants with hypernatremic dehydration due to breast milk (BM) hypernatremia. Hypernatremic dehydration in breast-fed newborns is usually secondary to insufficient lactation. We present the neonatal hypernatremia and hypernatremic dehydration encountered between January and December, 2012, its causes and treatment. Methodology: This was a retrospective study. We analyzed records of babies admitted to the Neonatal Intensive Care Unit who were investigated and found to have hypernatremia and whose mother's BM sodium (BM Na) was done. Inclusion Criteria: (1) Babies with serum Na >145 meq/l, (2) euglycemia, (3) normocalcemic, (4) no clinical and lab evidence of sepsis, (5) exclusive breast feeds. Exclusion Criteria: Neonates not satisfying any mentioned criterion. Results: BM Na correlated strongly with neonatal hypernatremia in exclusively breast-fed babies who did not otherwise have any risk factor. Conclusion: Elevated BM Na is an important etiological factor in neonatal hypernatremia. PMID:28197048

  2. [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.

  3. Population-Based Incidence and Etiology of Community-Acquired Neonatal Bacteremia in Mirzapur, Bangladesh: An Observational Study

    PubMed Central

    Darmstadt, Gary L.; Saha, Samir K.; Choi, Yoonjoung; El Arifeen, Shams; Ahmed, Nawshad Uddin; Bari, Sanwarul; Rahman, Syed M.; Mannan, Ishtiaq; Crook, Derrick; Fatima, Kaniz; Winch, Peter J.; Seraji, Habibur Rahman; Begum, Nazma; Rahman, Radwanur; Islam, Maksuda; Rahman, Anisur; Black, Robert E.; Santosham, Mathuram; Sacks, Emma; Baqui, Abdullah H.

    2010-01-01

    Background To devise treatment strategies for neonatal infections, the population-level incidence and antibiotic susceptibility of pathogens must be defined. Methods Surveillance for suspected neonatal sepsis was conducted in Mirzapur, Bangladesh, from February 2004 through November 2006. Community health workers assessed neonates on postnatal days 0, 2, 5, and 8 and referred sick neonates to a hospital, where blood was collected for culture from neonates with suspected sepsis. We estimated the incidence and pattern of community-acquired neonatal bacteremia and determined the antibiotic susceptibility profile of pathogens. Results The incidence rate of community-acquired neonatal bacteremia was 3.0 per 1000 person–neonatal periods. Among the 30 pathogens identified, the most common was Staphylococcus aureus (n = 10); half of all isolates were gram positive. Nine were resistant to ampicillin and gentamicin or to ceftiaxone, and 13 were resistant to cotrimoxazole. Conclusion S. aureus was the most common pathogen to cause community-acquired neonatal bacteremia. Nearly 40% of infections were identified on days 0–3, emphasizing the need to address maternal and environmental sources of infection. The combination of parenteral procaine benzyl penicillin and an aminoglycoside is recommended for the first-line treatment of serious community-acquired neonatal infections in rural Bangladesh, which has a moderate level of neonatal mortality. Additional population-based data are needed to further guide national and global strategies. Trial registration ClinicalTrials.gov identifier: NCT00198627. PMID:19671016

  4. [Neonatal intussusception].

    PubMed

    Cuervo, J L

    2015-01-13

    Intussusception in infants and young children is a relatively common entity with a well defined clinical picture and a favorable outcome in most cases.The neonatal intussusceptions is extremely rare and does not have a well-defined clinical picture since its clinical manifestations vary according to the gestational time it occurs, the response of the injured intestine and the gestational age of the child concerned. Two new cases of neonatal intussusceptions are presented and a review of the world literature is performed. Given the stage of intussusceptions (pre- or postnatal) occurs and gestational age of the affected infant (preterm or term), there are three entities with clinical characteristics, topography and evolution rather different: prenatal or intrauterine intussusception, postnatal intussusception in the preterm and postnatal intussusception in the term infant.

  5. Neonatal hemochromatosis.

    PubMed

    Feldman, Amy G; Whitington, Peter F

    2013-12-01

    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.

  6. Neonatal glucocorticosteroid treatment causes systolic dysfunction and compensatory dilation in early life: studies in 4-week-old prepubertal rats.

    PubMed

    Bal, Miriam P; de Vries, Willem B; van der Leij, Feike R; van Oosterhout, Matthijs F M; Berger, Rolf M F; Baan, Jan; van der Wall, Ernst E; van Bel, Frank; Steendijk, Paul

    2005-07-01

    Glucocorticosteroid treatment is widely used to prevent chronic lung disease in premature infants. Recent studies in adult rats, treated with dexamethasone in the neonatal period, report negative long-term effects on the heart and severely reduced life expectancy. We treated neonatal rats with dexamethasone and studied cardiac function after 4 wk (prepubertal age) to investigate whether the late effects as previously described are preceded by detectable alterations in cardiac function at a younger age. Male rat pups (n = 12) were injected intraperitoneally with dexamethasone on d 1, 2, and 3 (0.5, 0.3, and 0.1 mug/g) of life. Control pups (n = 10) received saline. At 4 wk the animals were anesthetized, and a pressure-conductance catheter was introduced into the left ventricle to measure pressure-volume loops. Cardiac function was measured and pressure-volume relations were determined to quantify intrinsic systolic and diastolic function. Subsequently, hearts were excised for histologic examination. Compared with saline-treated animals, dexamethasone-treated rats had a reduced ventricular weight (270 +/- 40 versus 371 +/- 23 mg, p < 0.001) and reduced systolic function (end-systolic elastance: 1.24 +/- 0.43 versus 2.50 +/- 1.39 mm Hg/muL, p = 0.028). Cardiac output was maintained and end-diastolic volume was increased (84 +/- 23 versus 59 +/- 19 microL, p = 0.012) indicating a state of compensatory dilatation. Heart rate, diastolic function, and systemic vascular resistance were unchanged. Neonatal dexamethasone treatment causes cardiac alterations that can be detected in the prepubertal period and that may precede severe cardiac dysfunction later in life. If our findings are confirmed in humans, this may have consequences for a large patient population and cardiac screening at young age may be indicated to enable secondary prevention.

  7. 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

  8. New checkpoints in cancer immunotherapy.

    PubMed

    Ni, Ling; Dong, Chen

    2017-03-01

    Immune responses must be fine-tuned to allow effective clearance of invading pathogens, while maintain tolerance to self-antigens. T cells are the major effector cells for fighting and killing tumor cells. Immune checkpoints play a pivotal role in T cell activation, and determine the functional outcome of T cell receptor (TCR) signaling. The blockade of immune checkpoints CTLA-4 and PD-1 has already been one of the most successful cancer immunotherapies. In this review, we will focus on three novel inhibitory B7 family checkpoint molecules, B7-H3, B7S1 and VISTA. The aim of this article is to summarize their expressions in tumors as well as their roles in controlling and suppressing T cell immune responses and anti-tumor immunity. These pathways may be explored in future cancer immunotherapy.

  9. Multifunctional nanoparticles for cancer immunotherapy

    PubMed Central

    Saleh, Tayebeh; Shojaosadati, Seyed Abbas

    2016-01-01

    ABSTRACT During the last decades significant progress has been made in the field of cancer immunotherapy. However, cancer vaccines have not been successful in clinical trials due to poor immunogenicity of antigen, limitations of safety associated with traditional systemic delivery as well as the complex regulation of the immune system in tumor microenvironment. In recent years, nanotechnology-based delivery systems have attracted great interest in the field of immunotherapy since they provide new opportunities to fight the cancer. In particular, for delivery of cancer vaccines, multifunctional nanoparticles present many advantages such as targeted delivery to immune cells, co-delivery of therapeutic agents, reduced adverse outcomes, blocked immune checkpoint molecules, and amplify immune activation via the use of stimuli-responsive or immunostimulatory materials. In this review article, we highlight recent progress and future promise of multifunctional nanoparticles that have been applied to enhance the efficiency of cancer vaccines. PMID:26901287

  10. Immunotherapy of Congenital SIV Infection.

    DTIC Science & Technology

    1997-10-01

    is to develop DNA vaccine strategies to treat and/or prevent primate lentivirus infection in infant rhesus macaques . As outlined in the year 02...natural vaginal birth, and the dams were returned to their breeding colonies. The neonatal macaques were given the DNA vaccines as outlined (Table 2...involving neonatal rhesus macaques has been initiated at the Yerkes Regional Primate Research Center. The course of DNA inoculations has been completed

  11. 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.

  12. Advances in personalized cancer immunotherapy.

    PubMed

    Kakimi, Kazuhiro; Karasaki, Takahiro; Matsushita, Hirokazu; Sugie, Tomoharu

    2017-01-01

    There are currently three major approaches to T cell-based cancer immunotherapy, namely, active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Recently, this latter approach has demonstrated remarkable clinical benefits, putting cancer immunotherapy under the spotlight. Better understanding of the dynamics of anti-tumor immune responses (the "Cancer-Immunity Cycle") is crucial for the further development of this form of treatment. Tumors employ multiple strategies to escape from anti-tumor immunity, some of which result from the selection of cancer cells with immunosuppressive activity by the process of cancer immunoediting. Apart from this selective process, anti-tumor immune responses can also be inhibited in multiple different ways which vary from patient to patient. This implies that cancer immunotherapy must be personalized to (1) identify the rate-limiting steps in any given patient, (2) identify and combine strategies to overcome these hurdles, and (3) proceed with the next round of the "Cancer-Immunity Cycle". Cancer cells have genetic alterations which can provide the immune system with targets by which to recognize and eradicate the tumor. Mutated proteins expressed exclusively in cancer cells and recognizable by the immune system are known as neoantigens. The development of next-generation sequencing technology has made it possible to determine the genetic landscape of human cancer and facilitated the utilization of genomic information to identify such candidate neoantigens in individual cancers. Future immunotherapies will need to be personalized in terms of the identification of both patient-specific immunosuppressive mechanisms and target neoantigens.

  13. Radiation and immunotherapy: a synergistic combination

    PubMed Central

    Kalbasi, Anusha; June, Carl H.; Haas, Naomi; Vapiwala, Neha

    2013-01-01

    Immunotherapy can be an effective treatment for metastatic cancer, but a significant subpopulation will not respond, likely due to the lack of antigenic mutations or the immune-evasive properties of cancer. Likewise, radiation therapy (RT) is an established cancer treatment, but local failures still occur. Clinical observations suggest that RT may expand the therapeutic reach of immunotherapy. We examine the immunobiologic and clinical rationale for combining RT and immunotherapy, two modalities yet to be used in combination in routine practice. Preclinical data indicate that RT can potentiate the systemic efficacy of immunotherapy, while activation of the innate and adaptive immune system can enhance the local efficacy of RT. PMID:23863633

  14. 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

  15. Immunotherapy for Acute Myelogenous Leukaemia

    PubMed Central

    Powles, R. L.; Crowther, D.; Bateman, C. J. T.; Beard, M. E. J.; McElwain, T. J.; Russell, J.; Lister, T. A.; Whitehouse, J. M. A.; Wrigley, P. F. M.; Pike, M.; Alexander, P.; Fairley, G. Hamilton

    1973-01-01

    One hundred and seven untreated patients with acute myelogenous leukaemia (AML) were admitted to St Bartholomew's Hospital between 10 October 1970 and 31 January 1973. Before receiving drugs to induce remission they were allocated alternatively into 2 groups to decide their remission treatment—a group to receive chemotherapy alone and a group to receive the same chemotherapy with immunotherapy. The patients were then given induction chemotherapy and 45 of them attained complete remission. All patients in remission then received chemotherapy consisting of 5 days treatment every 28 days. Patients receiving immunotherapy were also given multiple weekly intradermal injections of irradiated stored AML cells and Glaxo B.C.G. using a Heaf gun. There were 19 patients in the group which received only chemotherapy during remission; 7 of these patients remain alive (median survival after attaining remission 303 days) and only 5 are still in their first remission (median remission length 188 days). Twenty-three patients were allocated to receive immunotherapy during remission in addition to chemotherapy and 16 remain alive (median 545 days) and 8 are in their first remission (median 312 days). The difference in survival of the two groups is significant with a P value of 0·003. PMID:4271320

  16. [Melanoma immunotherapy: dendritic cell vaccines].

    PubMed

    Lozada-Requena, Ivan; Núñez, César; Aguilar, José Luis

    2015-01-01

    This is a narrative review that shows accessible information to the scientific community about melanoma and immunotherapy. Dendritic cells have the ability to participate in innate and adaptive immunity, but are not unfamiliar to the immune evasion of tumors. Knowing the biology and role has led to generate in vitro several prospects of autologous cell vaccines against diverse types of cancer in humans and animal models. However, given the low efficiency they have shown, we must implement strategies to enhance their natural capacity either through the coexpression of key molecules to activate or reactivate the immune system, in combination with biosimilars or chemotherapeutic drugs. The action of natural products as alternative or adjuvant immunostimulant should not be ruled out. All types of immunotherapy should measure the impact of myeloid suppressor cells, which can attack the immune system and help tumor progression, respectively. This can reduce the activity of cellular vaccines and/or their combinations, that could be the difference between success or not of the immunotherapy. Although for melanoma there exist biosimilars approved by the Food and Drug Administration (FDA), not all have the expected success. Therefore it is necessary to evaluate other strategies including cellular vaccines loaded with tumor antigenic peptides expressed exclusively or antigens from tumor extracts and their respective adjuvants.

  17. Immunotherapy and immunoescape in colorectal cancer

    PubMed Central

    Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348

  18. Advances in Cancer Immunotherapy in Solid Tumors

    PubMed Central

    Menon, Smitha; Shin, Sarah; Dy, Grace

    2016-01-01

    Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field. PMID:27886124

  19. 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

  20. 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.

  1. Longitudinal changes in maternal and neonatal anthropometrics: a case study of the Helsinki Birth Cohort, 1934-1944.

    PubMed

    Moltchanova, E; Eriksson, J G

    2015-08-01

    Changes in anthropometrics often reflect changes in living conditions, and one's characteristics at birth may be associated with future health. The aim of this study was to investigate the secular trends in maternal and neonatal anthropometrics in the Helsinki Birth Cohort Study. The study participants, thus, comprised all 13,345 live births recorded in Helsinki, Finland, between 1934 and 1944. Adult characteristics of the clinical subsample comprised of 2003 individuals, alive during 2003, were also analyzed. Linear Regression analysis with seasonal terms was applied to see whether clinically and statistically significant trends can be found in maternal age, height and body mass index (BMI) at pregnancy; gestational age, birth weight, ponderal index and sex ratio; and adult height, BMI and fat percentage. Statistically significant trends were found in maternal age and maternal BMI with abrupt changes between 1941 and 1944. Gestational age increased by an average of 0.11% per year (P<0.0001), and the proportion of premature births dropped from 7.9% in 1934 to 4.5% in 1944 (P<0.0001). In the clinical sample, a statistically significant, although small, average annual increase of 0.1% in adult heights was detected (P=0.0012 for men and P=0.0035 for women). In conclusion, although no significant changes were found in either neonatal or adult anthropometrics of babies born in Helsinki between 1934 and 1944, there were abrupt changes in the characteristics of their mothers.

  2. 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.

  3. Towards Curative Cancer Immunotherapy: Overcoming Posttherapy Tumor Escape

    PubMed Central

    Zhou, Gang; Levitsky, Hyam

    2012-01-01

    The past decade has witnessed the evolvement of cancer immunotherapy as an increasingly effective therapeutic modality, evidenced by the approval of two immune-based products by the FDA, that is, the cancer vaccine Provenge (sipuleucel-T) for prostate cancer and the antagonist antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4) ipilimumab for advanced melanoma. In addition, the clinical evaluations of a variety of promising immunotherapy drugs are well under way. Benefiting from more efficacious immunotherapeutic agents and treatment strategies, a number of recent clinical studies have achieved unprecedented therapeutic outcomes in some patients with certain types of cancers. Despite these advances, however, the efficacy of most cancer immunotherapies currently under clinical development has been modest. A recurring scenario is that therapeutic maneuvers initially led to measurable antitumor immune responses in cancer patients but ultimately failed to improve patient outcomes. It is increasingly recognized that tumor cells can antagonize therapy-induced immune attacks through a variety of counterregulation mechanisms, which represent a fundamental barrier to the success of cancer immunotherapy. Herein we summarize the findings from some recent preclinical and clinical studies, focusing on how tumor cells advance their survival and expansion by hijacking therapy-induced immune effector mechanisms that would otherwise mediate their destruction. PMID:22778760

  4. Thrombocytopenia and platelet transfusion in the neonate.

    PubMed

    Cremer, Malte; Sallmon, Hannes; Kling, Pamela J; Bührer, Christoph; Dame, Christof

    2016-02-01

    Neonatal thrombocytopenia is widespread in preterm and term neonates admitted to neonatal intensive care units, with up to one-third of infants demonstrating platelet counts <150 × 10(9)/L. Thrombocytopenia may arise from maternal, placental or fetal/neonatal origins featuring decreased platelet production, increased consumption, or both mechanisms. Over the past years, innovations in managing neonatal thrombocytopenia were achieved from prospectively obtained clinical data on thrombocytopenia and bleeding events, animal studies on platelet life span and production rate and clinical use of fully automated measurement of reticulated platelets (immature platelet fraction). This review summarizes the pathophysiology of neonatal thrombocytopenia, current management including platelet transfusion thresholds and recent developments in megakaryopoietic agents. Furthermore, we propose a novel index score for bleeding risk in thrombocytopenic neonates to facilitate clinician's decision-making when to transfuse platelets.

  5. 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.

  6. Oxidative stress in the neonate.

    PubMed

    Robles, R; Palomino, N; Robles, A

    2001-11-01

    The aim of this study is to determine the oxidative state of term and preterm neonates at the moment of birth and during the first days of life, and the influence of exposure to oxygen on the premature neonates.A total of 20 neonates were selected. Group A: 10 healthy full-term neonates, and Group B: 10 preterm neonates with no other pathology associated, requiring oxygen therapy. Venous samples were taken in cord at 3 and 72 h in Group A, and in cord at 3, 24 and 72 h and 7 days in Group B.Hydroperoxides, Q10 coenzyme (Co Q10) and alpha-tocopherol were measured within the erythrocyte membrane. Levels of hydroperoxides present in erythrocyte membrane were higher than normal both in Group A and in Group B at birth. This increase was greater in the group of premature neonates. Levels of alpha-tocopherol at birth increase significantly at 72 h in term neonates. Among the premature newborns, alpha-tocopherol levels are two to three times lower at birth and do not rise to higher levels as in the term neonate group. Fall in levels of Co Q10 in erythrocyte membranes is observed, and perhaps is due to the role of Co Q10 in maintaining the pool of reduced tocopherol. At birth, the neonate presents an increase of markers of oxidative stress and a decrease of their antioxidant defenses. This difference is greater as gestational age decreases. The application of oxygen therapy resulted in these levels which remain low throughout the study period.

  7. [Selected clinical and laboratory tests during specific immunotherapy of patients hypersensitive to insect bites].

    PubMed

    Szymański, W; Kazberuk, M; Michalska, I; Chyrek-Borowska, S

    The study aimed at determining selected immunologic parameters of the cellular histamine secretion and skin reactivity in the group of 9 patients hypersensitive to insect poison with effective immunotherapy following 2 years of maintenance treatment. It has been shown that the continuation of the specific immunotherapy for 2 years maintains and even increases favourable changes in humoral and cellular immunity induced already in the early phase of desensitization. An assay of the specific IgE and IgG4, cellular histamine secretion, and skin reactivity is of value in monitoring specific allergy to insect poison immunotherapy.

  8. FAK-inhibition opens the door to checkpoint immunotherapy in Pancreatic Cancer.

    PubMed

    Symeonides, Stefan N; Anderton, Stephen M; Serrels, Alan

    2017-01-01

    Immunotherapy has had remarkable success in the treatment of some cancer types. However, pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors. Recently, Jiang and colleagues identified a key role for FAK in regulating the composition of the fibrotic and immuno-suppressive pancreatic tumour niche, and showed that FAK inhibitors can be used in combination with immune checkpoint blockade and gemcitabine chemotherapy to significantly delay pancreatic tumour progression. This study further supports the use of FAK inhibitors in combination with immunotherapy.

  9. Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis.

    PubMed

    Rosewich, Martin; Lee, Denise; Zielen, Stefan

    2013-07-01

    The prevalence of seasonal allergic rhinitis in the western world is high and increasing. Besides considerably affecting physical and psychosocial aspects of patients' lives, allergic rhinitis is often associated with allergic asthma and may aggravate this condition over time. Specific immunotherapy is currently the only approved therapy that can modify the underlying disease process and induce long-term tolerance to allergens. Pollinex Quattro is a subcutaneous four injections immunotherapy consisting of tyrosine-absorbed specific allergoids and enhanced with the adjuvant monophosphoryl lipid A (MPL(®)). MPL(®) induces a significant Th 1-type immune response, characterized by an increase of allergen-specific IgG antibody levels and dampening of the IgE response during allergen exposure. Due to this dual action of stimulating the immune system, Pollinex Quattro is clinically effective after only four injections given pre-seasonally. A large clinical program has demonstrated efficacy and tolerability of Pollinex Quattro in children, adolescents and adults with grass and tree pollen allergy. A health economics study concluded that an immunotherapy with only 4 injections might be more cost-beneficial than other application forms of immunotherapy.

  10. Interleukin-2 and interleukin-15: immunotherapy for cancer.

    PubMed

    Fehniger, Todd A; Cooper, Megan A; Caligiuri, Michael A

    2002-04-01

    Interleukin (IL)-2 and IL-15 are two cytokine growth factors that regulate lymphocyte function and homeostasis. Early clinical interest in the use of IL-2 in the immunotherapy of renal cell carcinoma and malignant melanoma demonstrated the first efficacy for cytokine monotherapy in the treatment of neoplastic disease. Advances in our understanding of the cellular and molecular biology of IL-2 and its receptor complex have provided rationale to better utilize IL-2 to expand and activate immune effectors in patients with cancer. Exciting new developments in monoclonal antibodies recognizing tumor targets and tumor vaccines have provided new avenues to combine with IL-2 therapy in cancer patients. IL-15, initially thought to mediate similar biological effects as IL-2, has been shown to have unique properties in basic and pre-clinical studies that may be of benefit in the immunotherapy of cancer. This review first summarizes the differences between IL-2 and IL-15 and highlights that better understanding of normal physiology creates new ideas for the immunotherapy of cancer. The application of high, intermediate, and low/ultra low dose IL-2 therapy in clinical trials of cancer patients is discussed, along with new avenues for its use in neoplastic diseases. The growing basic and pre-clinical evidence demonstrating that IL-15 may be useful in immunotherapy approaches to cancer is also presented.

  11. Conference overview: Cancer Immunotherapy and Immunomonitoring (CITIM): moving forward.

    PubMed

    Malyguine, Anatoli; Umansky, Victor; Kotlan, Beatrix; Aptsiauri, Natalia; Shurin, Michael R

    2012-01-01

    The immune system is a critical element involved in the control of tumor development and progression. While professionals have learned how to manipulate the immune system to generate tumor-specific immune responses, cancer immunotherapy has not yet delivered substantial clinical benefits. It has become increasingly clear that tumor-induced abnormalities in the immune system not only hamper tumor immunosurveillance, but also limit the efficacy of cancer immunotherapy. Meanwhile, the results of recent studies allow the belief that one is on the edge of a real breakthrough in this promising direction in cancer therapy. The 2(nd) International Conference 'Cancer Immunotherapy and Immunomonitoring (CITIM)' was the second meeting in Eastern Europe to specifically focus on the issue of immune regulation in the tumor environment, cancer immunotherapy, and immunomonitoring of immunotherapeutic clinical trials. This CITIM Conference held in Budapest, Hungary, was comprised from 12 plenary sessions, Best Abstract Award session, Poster session, and four Keynote lectures. Outstanding presentations and numerous productive discussions summarized the current place of the field and opened new directions for improving monitoring and therapy for patients with cancer.

  12. 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

  13. A comparison study of multishot vs. single-shot DWI-EPI in the neonatal brain: reduced effects of ghosting compared to adults.

    PubMed

    van Pul, Carola; Roos, F George; Derksen, O Sjoerd; Buijs, Jan; Vlaardingerbroek, Marinus T; Kopinga, Klaas; Wijn, Pieter F F

    2004-11-01

    In the neonatal brain, it is important to use a fast imaging technique to acquire all diffusion weighted images (DWI) for apparent diffusion coefficient (ADC) calculation. Taking into account the occurrence of typical echo planar imaging (EPI) artifacts, we have investigated whether single-shot (SSh) or multishot (MSh) DWI-EPI should be preferred. In 14 neonates, 17 adult patients and 5 adult volunteers, DWIs are obtained both with SSh and MSh EPI. The occurrence of artifacts and their influence on the ADC are explored and further quantified using simulations and phantom studies. Two radiologists scored overall image quality and diagnosability of all images. Single-shot and MSh DWI-EPI scored equally well in neonates with respect to overall image quality and diagnosability. In newborns, more motion artifacts in MSh can be noticed while N/2-ghost artifacts in SSh occur less frequently than in adults. Both N/2-ghost and motion artifacts result in significant ADC abnormalities. There is a serious risk that these artifacts will be mistaken for genuine diffusion abnormalities. N/2-ghost artifacts are hardly noticed in the neonatal brain, which might be due to smaller cerebrospinal fluid (CSF) velocity than in adults. Apparent diffusion coefficient values in MSh are unreliable if motion occurs. We conclude that for ADC calculations in neonates SSh DWI-EPI is more reliable than MSh.

  14. 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

  15. 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

  16. Parent Experience of Neonatal Encephalopathy.

    PubMed

    Lemmon, Monica E; Donohue, Pamela K; Parkinson, Charlamaine; Northington, Frances J; Boss, Renee D

    2017-03-01

    We aimed to characterize the parent experience of caring for an infant with neonatal encephalopathy. In this mixed-methods study, we performed semistructured interviews with parents whose infants were enrolled in an existing longitudinal cohort study of therapeutic hypothermia between 2011 and 2014. Thematic saturation was achieved after 20 interviews. Parent experience of caring for a child with neonatal encephalopathy was characterized by 3 principal themes. Theme 1: Many families described cumulative loss and grief throughout the perinatal crisis, critical neonatal course, and subsequent missed developmental milestones. Theme 2: Families experienced entangled infant and broader family interests. Theme 3: Parents evolved into and found meaning in their role as an advocate. These data offer insight into the lived experience of parenting an infant with neonatal encephalopathy. Primary data from parents can serve as a useful framework to guide the development and interpretation of parent-centered outcomes.

  17. Frequency and Characteristics of Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Organisms in Neonates: A Prospective Cohort Study

    PubMed Central

    Vijayakanthi, Nandini; Bahl, Dheeraj; Kaur, Nirmaljit; Maria, Arti; Dubey, Nand Kishore

    2013-01-01

    This prospective cohort study was conducted to determine the frequency of infections caused by extended-spectrum beta-lactamase- (ESBL-) producing organisms, various bacteria producing ESBL, antibiotic susceptibility of these organisms, and the risk factors associated with these infections in a neonatal intensive care unit in a tertiary care hospital in North India. Of the 150 neonates enrolled in the study, 47 culture-positive neonates were included in the study cohort and were divided into two groups: ESBL-positive (8 neonates) and ESBL-negative (39 neonates) cohorts. Various organisms were isolated from 72 culture samples in these 47 neonates. Of these, 10 culture samples grew ESBL-positive organisms and 62 samples grew ESBL-negative organisms. The frequency of ESBL-producing organisms was found to be 5.3%. ESBL infection incidence densities were found to be 3.4 per 1000 patient-days. Klebsiella (60%) was the most common organism producing ESBL followed by Escherichia coli (30%) and Pseudomonas (10%). Eighty percent of the ESBL-producing organisms were sensitive to piperacillin-tazobactam. Risk factors found significant by univariate analysis (P < 0.05) were preterm, low birthweight, perinatal asphyxia, respiratory distress syndrome, anaemia, metabolic acidosis, prolonged mechanical ventilation (>7 days), length of hospitalization, length of level 3 stay, prior antibiotic use, central venous catheter duration, peripherally inserted central venous catheter duration, and total parenteral nutrition duration. Factors that retained significance in the logistic regression model were duration of hospital stay (adjusted OR: 0.958, CI: 0.920–0.997, and P value = 0.037) and gestational age (adjusted OR: 1.39, CI: 1.037–1.865, and P value = 0.028). There was no significant difference in the mortality between the two groups. PMID:24175299

  18. 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

  19. [Sublingual immunotherapy with cat epithelial extract. Personal experience].

    PubMed

    Sánchez Palacios, A; Schamann, F; García, J A

    2001-01-01

    Because cats are a common pet in many houses and tourist complexes in the Canary Islands, sensitization to cat epithelium is a frequent problem. A total of 19.2% of patients with intrinsic asthma are sensitized to cat epithelium. In the Canary Islands, the percentage of sensitization among patients with a household cat is 18.1%, which higher is higher than in the rest of Spain (11.9). Many patients with extrinsic asthma sensitized to house dust mites undergo conventional subcutaneous immunotherapy but evolution is unsatisfactory due to sensitization to cat epithelium (whether a cat is present or not). The aim of this study was to evaluate the clinical effectiveness of sublingual immunotherapy with extract of cat epithelium in monosensitized patients with perennial allergic rhinitis and/or bronchial asthma. Forty patients monosensitized to cat epithelium were selected. Of these, 20 were administered sublingual immunotherapy and another 20 received placebo. The following evaluation was carried out in both groups: in vivo and in vitro: symptom score, skin tests, nasal challenge with cat epithelium, specific IgE determination, specific IgG4 and eosinophilic cationic protein. After 1 year of treatment the cumulative dose was 3.6 micrograms of Fe ld I, equivalent to 10 ng/drop. Duration of treatment was 365 days. Our conclusions, based on our patients in the Canary Islands, were the following: 1. Sublingual Fel d I therapy is effective after 1 year of treatment. 2. There were no modifications in IgE, eosinophilic cationic protein or skin tests. 3. An increase in IgG4 occurred which was related to clinical improvement. 4. In general, tolerance was good, except in one patient who presented urticaria and sublingual pruritus. 5. In polysensitized patients, sublingual immunotherapy to cat epithelium is complementary to immunotherapy to dermatophagoides.

  20. IMMUNOTHERAPY FOR PORCINE CYSTICERCOSIS: IMPLICATIONS FOR PREVENTION OF HUMAN DISEASE

    PubMed Central

    EVANS, CARLTON A. W.; GONZALEZ, ARMANDO E.; GILMAN, ROBERT H.; VERASTEGUI, MANUELA; GARCIA, HECTOR H.; CHAVERA, ALFONSO; PILCHER, JOY B.; TSANG, VICTOR C. W.

    2010-01-01

    Taenia solium cysticercosis is an important cause of human disease in many developing countries. Porcine cysticercosis is a vital link in the transmission of this disease and impairs meat production. A treatment for porcine cysticercosis may be an effective way of preventing human disease that would also benefit pig farmers, facilitating control programs in disease-endemic regions. Previous research suggests that reinfection with cysticercosis or immunotherapy with cysticercal antigens may cause degeneration of cysticerci, potentially curing porcine cysticercosis. Therefore, a blinded, randomized, controlled study to assess the efficacy and safety of immunotherapy in 28 naturally parasitized pigs was performed. Four groups of pigs with similar weights were inoculated twice with membrane-enriched cysticercal antigens (MA), saline, aqueous-soluble crude cysticercal antigens (AA) in adjuvant (Freund's complete then incomplete), or adjuvant alone. Immunotherapy was well tolerated but had no consistent effect on the macroscopic appearance of cysticerci or eosinophil count. Histopathologic findings were variable, with both severe and minimal inflammatory reactions seen in adjacent cysticerci in all pigs. Nine (64%) of 14 pigs given immunotherapy developed new antibody bands on electroimmunotransfer blot compared with one (7%) of 14 control pigs (P < 0.01). Treatment with AA in adjuvant caused a significant increase in the proportion of cysticerci that failed to evaginate and were, therefore, not viable for infecting humans (34% for pigs given AA in adjuvant compared with 10% for adjuvant alone; P < 0.04). Although immunotherapy caused a statistically significant decrease in the viability of cysticerci, this immunologic reaction was not great enough to prevent human disease. PMID:9063358

  1. Cytotoxic immunotherapy strategies for cancer: mechanisms and clinical development.

    PubMed

    Aguilar, Laura K; Guzik, Brian W; Aguilar-Cordova, Estuardo

    2011-08-01

    Traditional therapies for cancer include surgery, chemotherapy, and radiation. Chemotherapy has widespread systemic cytotoxic effects against tumor cells but also affects normal cells. Radiation has more targeted local cytotoxicity but is limited to killing cells in the radiation field. Immunotherapy has the potential for systemic, specific killing of tumor cells. However, if the immune response is specific to a single antigen, tumor evasion can occur by down-regulation of that antigen. An immunotherapy approach that induces polyvalent immunity to autologous tumor antigens can provide a personalized vaccine with less potential for immunologic escape. A cytotoxic immunotherapy strategy creates such a tumor vaccine in situ. Immunogenic tumor cell death provides tumor antigen targets for the adaptive immune response and stimulates innate immunity. Attraction and activation of antigen presenting cells such as dendritic cells is important to process and present tumor antigens to T cells. These include cytotoxic T cells that kill tumor cells and T cells which positively and negatively regulate immunity. Tipping the balance in favor of anti-tumor immunity is an important aspect of an effective strategy. Clinically, immunotherapies may be most effective when combined with standard therapies in a complimentary way. An example is gene-mediated cytotoxic immunotherapy (GMCI) which uses an adenoviral vector, AdV-tk, to deliver a cytotoxic and immunostimulatory gene to tumor cells in vivo in combination with standard therapies creating an immunostimulatory milieu. This approach, studied extensively in animal models and early stage clinical trials, is now entering a definitive Phase 3 trial for prostate cancer.

  2. Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions.

    PubMed

    Gupta, Shilpa; Gill, David; Poole, Austin; Agarwal, Neeraj

    2017-01-27

    Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.

  3. Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions

    PubMed Central

    Gupta, Shilpa; Gill, David; Poole, Austin; Agarwal, Neeraj

    2017-01-01

    Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for first-line platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC. PMID:28134806

  4. Active Idiotypic Vaccination Versus Control Immunotherapy for Follicular Lymphoma

    PubMed Central

    Levy, Ronald; Ganjoo, Kristen N.; Leonard, John P.; Vose, Julie M.; Flinn, Ian W.; Ambinder, Richard F.; Connors, Joseph M.; Berinstein, Neil L.; Belch, Andrew R.; Bartlett, Nancy L.; Nichols, Craig; Emmanouilides, Christos E.; Timmerman, John M.; Gregory, Stephanie A.; Link, Brian K.; Inwards, David J.; Freedman, Arnold S.; Matous, Jeffrey V.; Robertson, Michael J.; Kunkel, Lori A.; Ingolia, Diane E.; Gentles, Andrew J.; Liu, Chih Long; Tibshirani, Robert; Alizadeh, Ash A.; Denney, Dan W.

    2014-01-01

    Purpose Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study. PMID:24799467

  5. Tau immunotherapy for Alzheimer's disease.

    PubMed

    Pedersen, Jan Torleif; Sigurdsson, Einar M

    2015-06-01

    Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive deficits become evident in AD. Several complementary mechanisms of antibody-mediated removal of tau aggregates are likely to act in concert and the importance of each one may depend on antibody properties, the disease, and its stage. Clinical trials of tau immunotherapy are already underway and several more are likely to be initiated in the near future.

  6. 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

  7. Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study

    PubMed Central

    Tann, Cally J.; Nakakeeto, Margaret; Hagmann, Cornelia; Webb, Emily L.; Nyombi, Natasha; Namiiro, Flaviah; Harvey-Jones, Kelly; Muhumuza, Anita; Burgoine, Kathy; Elliott, Alison M.; Kurinczuk, Jennifer J.; Robertson, Nicola J.; Cowan, Frances M.

    2016-01-01

    Background: In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. Methods: Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. Results: Scans were performed at median age 11.5 (interquartile range (IQR): 5.2–20.2) and 8.4 (IQR: 3.6–13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98–9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61–6.95)). Conclusion: In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia–ischemia (HI). Early abnormalities were a significant predictor of death. PMID:27064242

  8. Cross-fostering study of methyl mercury retention, demethylation and excretion in the neonatal hamster.

    PubMed

    Nordenhäll, K; Dock, L; Vahter, M

    1998-03-01

    The cross-fostering technique was used in order to compare methyl mercury (MeHg) metabolism in hamsters following prenatal (in utero) and neonatal (lactational) exposure. Pregnant Syrian golden hamsters were administered radiolabeled MeHg on day 12 of gestation. The offspring was nursed by foster mothers unexposed to MeHg, while the pups from the unexposed animals were nursed by the MeHg-administered animals. Under these conditions, each pup in the litter received a dose of MeHg in utero corresponding to 0.9% of the maternal dose. The average amount of mercury found in the pups exposed via milk corresponded to 4.5% of the total body burden of the foster dam at the onset of lactation. This was about half the amount received by the pups exposed in utero. The total body burden of mercury, and the amount of mercury in the liver, brain and kidney of the pups exposed in utero began to decrease at seven days of age. The rate of decrease differed among the tissues and was lowest in the kidney. The amount of mercury in pups exposed via milk reached a peak level when the pups were 10-15 days old. The total body burden of mercury showed a slow decrease while the liver, brain and kidney levels decreased rapidly. In both groups of animals, up to 80% of the total body burden of mercury was found in the pelt. These data show that milk may be a significant exposure route for mercury and that neonatal hamsters are unable to demethylate MeHg and excrete mercury in urine and faeces.

  9. Sublingual immunotherapy in southern Africa: lessons learned.

    PubMed

    Potter, Paul

    2013-07-01

    Sublingual immunotherapy (SLIT) is recommended in South Africa for the treatment of allergic rhinitis (with or without asthma) to house dust mites or grass pollens. Recent local studies have confirmed efficacy and safety but have also shown heterogeneity in clinical responses to the European SLIT vaccines used in the region. It has been found that regular follow-up with standardized rhinitis quality-of-life questionnaires improves compliance and encourages the patients to complete the 3-year SLIT course. Patients who discontinue usually do so in the first year because of logistic and financial reasons rather than adverse side effects. Further studies are in progress at the Allergy Diagnostic & Clinical Research Unit to identify immunologic markers of the SLIT responder phenotype.

  10. Improving the Context Supporting Quality Improvement in a Neonatal Intensive Care Unit Quality Collaborative: An Exploratory Field Study.

    PubMed

    Grooms, Heather R; Froehle, Craig M; Provost, Lloyd P; Handyside, James; Kaplan, Heather C

    2016-04-26

    Successful quality improvement (QI) requires a supportive context. The goal was to determine whether a structured curriculum could help QI teams improve the context supporting their QI work. An exploratory field study was conducted of 43 teams participating in a neonatal intensive care unit QI collaborative. Using a curriculum based on the Model for Understanding Success in Quality, teams identified gaps in their context and tested interventions to modify context. Surveys and self-reflective journals were analyzed to understand how teams developed changes to modify context. More than half (55%) targeted contextual improvements within the microsystem, focusing on motivation and culture. "Information sharing" interventions to communicate information about the project as a strategy to engage more staff were the most common interventions tested. Further study is needed to determine if efforts to modify context consistently lead to greater outcome improvements.

  11. Characterization of the MUC1.Tg/MIN Transgenic Mouse as a Model for Studying Antigen-Specific Immunotherapy of Adenomas

    PubMed Central

    Akporiaye, Emmanuel T.; Bradley-Dunlop, Deborah; Gendler, Sandra J.; Mukherjee, Pinku; Madsen, Cathy S.; Hahn, Tobias; Besselsen, David G.; Dial, Sharon M.; Cui, Haiyan; Trevor, Katrina

    2007-01-01

    A bigenic MUC1.Tg/MIN mouse model was developed by crossing Apc/MIN/+ (MIN) mice with human MUC1 transgenic mice to evaluate MUC1 antigen-specific immunotherapy of intestinal adenomas. The MUC1.Tg/MIN mice developed adenomas at a rate comparable to that of MIN mice and had similar levels of serum MUC1 antigen. A MUC1-based vaccine consisting of MHC class I-restricted MUC1 peptides, a MHC class II-restricted pan-helper peptide, unmethylated CpG oligodeoxynucleotide and GM-CSF caused flattening of adenomas and significantly reduced the number of large adenomas. Immunization was successful in generating a MUC1-directed immune response evidenced by increased MUC1 peptide-specific anti-tumor cytotoxicity and IFN-γ secretion by lymphocytes. PMID:17707958

  12. Immunology in the Clinic Review Series; focus on allergies: immunotherapy for food allergy.

    PubMed

    Mousallem, T; Burks, A W

    2012-01-01

    There is no approved therapy for food allergy. The current standard of care is elimination of the triggering food from the diet and accessibility to epinephrine. Immunotherapy is a promising treatment approach. While desensitization to most foods seems feasible, it remains unclear if a permanent state of tolerance is achievable. The research team at Duke is pioneering immunotherapy for food allergies. Work here has evolved over time from small open-label pilot studies to larger randomized designs. Our data show that immunological changes associated with immunotherapy include reduction in mast cell reactivity, decreased basophil responses, decreased specific-immunoglobulin (Ig)E, increased IgG4 and induction of regulatory T cells. Immunotherapy has generated much excitement in the food allergy community; however, further studies are needed before it is ready for clinical use.

  13. Immunology in the Clinic Review Series; focus on allergies: immunotherapy for food allergy

    PubMed Central

    Mousallem, T; Burks, A W

    2012-01-01

    OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic Diseases, Host Responses, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses. There is no approved therapy for food allergy. The current standard of care is elimination of the triggering food from the diet and accessibility to epinephrine. Immunotherapy is a promising treatment approach. While desensitization to most foods seems feasible, it remains unclear if a permanent state of tolerance is achievable. The research team at Duke is pioneering immunotherapy for food allergies. Work here has evolved over time from small open-label pilot studies to larger randomized designs. Our data show that immunological changes associated with immunotherapy include reduction in mast cell reactivity, decreased basophil responses, decreased specific-immunoglobulin (Ig)E, increased IgG4 and induction of regulatory T cells. Immunotherapy has generated much excitement in the food allergy community; however, further studies are needed before it is ready for clinical use. PMID:22132881

  14. Secretory phospholipase A2 pathway in various types of lung injury in neonates and infants: a multicentre translational study

    PubMed Central

    2011-01-01

    Background Secretory phospholipase A2 (sPLA2) is a group of enzymes involved in lung tissue inflammation and surfactant catabolism. sPLA2 plays a role in adults affected by acute lung injury and seems a promising therapeutic target. Preliminary data allow foreseeing the importance of such enzyme in some critical respiratory diseases in neonates and infants, as well. Our study aim is to clarify the role of sPLA2 and its modulators in the pathogenesis and clinical severity of hyaline membrane disease, infection related respiratory failure, meconium aspiration syndrome and acute respiratory distress syndrome. sPLA2 genes will also be sequenced and possible genetic involvement will be analysed. Methods/Design Multicentre, international, translational study, including several paediatric and neonatal intensive care units and one coordinating laboratory. Babies affected by the above mentioned conditions will be enrolled: broncho-alveolar lavage fluid, serum and whole blood will be obtained at definite time-points during the disease course. Several clinical, respiratory and outcome data will be recorded. Laboratory researchers who perform the bench part of the study will be blinded to the clinical data. Discussion This study, thanks to its multicenter design, will clarify the role(s) of sPLA2 and its pathway in these diseases: sPLA2 might be the crossroad between inflammation and surfactant dysfunction. This may represent a crucial target for new anti-inflammatory therapies but also a novel approach to protect surfactant or spare it, improving alveolar stability, lung mechanics and gas exchange. PMID:22067747

  15. Serum immunoglobulins in Nigerian neonates.

    PubMed

    Akinwolere, O A; Akinkugbe, F M; Oyewole, A I; Salimonu, L S

    1989-01-01

    Serum immunoglobulins G, M and A levels were studied in 187 Nigerian neonates. Estimations were done by the radial immunodifusion method of Mancini. Immunoglobulin G shows a fall in value in the first few days of life to about 62% of the value in the last days of the neonatal period. There is however a gradual increase in the level of IgM to about double at the end of the neonatal period. IgA level remained relatively constantly low throughout this period. The effect of maternal education on the levels of immunoglobulins of their neonates was also investigated. This had a positive influence at the secondary educational level, affecting only the IgG and IgA.

  16. 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…

  17. Prostate cancer immunotherapy, particularly in combination with androgen deprivation or radiation treatment. Customized pharmacogenomic approaches to overcome immunotherapy cancer resistance

    PubMed Central

    ALBERTI, C.

    2016-01-01

    Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation. Unlike afore said immune check point inhibitors, both cell-based (by the use of prostate specific antigen carriers autologous dendritic cells or even whole cancer cells) and recombinant viral vector vaccines are able to induce immune-mediated focused killing of specific antigen-presenting prostate cancer cells. Such vaccines, either used alone or concurrently/sequentially combined with above-mentioned conventional therapies, led to generally reach, in the field of various clinical trials, reasonable results particularly as regards the patient’s overall survival. Adoptive trasferred T-cells, as adoptive T-cell passive immunotherapy, and monoclonal antibodies against specific antigen-endowed prostate cancer cells can improve immune micro-environmental conditions. On the basis of a preliminary survey about various immunotherapy strategies, are here also outlined their effects when combined with androgen deprivation therapy or radiation. What’s more, as regard the immune-based treatment effectiveness, it has to be pointed out that suitable personalized epigenetic/gene profile-achieved pharmacogenomic approaches to target identified gene aberrations, may lead to overcome – as well as for conventional therapies

  18. Genetic engineering of allergens for immunotherapy.

    PubMed

    Bonura, Angela; Colombo, Paolo

    2009-06-01

    Allergen-specific immunotherapy was introduced into clinical practice at the beginning of the 20(th) century and its efficacy in the treatment of seasonal allergic rhinitis has been confirmed in many clinical studies which have shown that it can prevent the onset of new sensitizations to different allergens and reduces the development of asthma in patients with allergic rhinitis. Progress in molecular cloning and characterization of allergens have made it possible to produce single recombinant allergens whose immunological properties have been tested in vitro and in vivo and have demonstrated that they retain properties resembling their natural counterpart. Several rational approaches are being developed to improve the efficacy of SIT by reducing immunoglobulin IgE-mediated adverse reactions. Some of these molecules have been tested in the clinic, demonstrating the feasibility of using biotechnology-derived products as new standardized, improved and safer therapeutic compositions.

  19. 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.

  20. [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.

  1. 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

  2. Novel approaches in cancer immunotherapy.

    PubMed

    Subramaniam, Deepa S; Liu, Stephen V; Giaccone, Giuseppe

    2016-04-01

    Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccines, tumor cell vaccines and immune cell vaccines. The pros and cons of nucleic acid-based vaccines including DNA and RNA vaccines will be discussed. Adoptive cell therapy has made significant progress utilizing chimeric antigen-receptor transduced T cells, especially in hematologic malignancies. We will also consider the key targets in checkpoint inhibition, and summarize some of the preclinical and clinical data with respect to checkpoint inhibition. Progress made in the novel immunotherapeutic approach of oncolytic viral therapy will be analyzed. PDL-1 expression by tumor cells and tumor infiltrating lymphocytes has been looked at as a biomarker in clinical trials. Limitations to such an approach and potential candidates for future predictive biomarkers of response to immunotherapy and biomarkers of autoimmunity and adverse reactions will be considered.

  3. 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.

  4. 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.

  5. 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.

  6. Neonatal screening for sickle cell diseases in Camberwell: results and recommendations of a two year pilot study.

    PubMed Central

    Horn, M E; Dick, M C; Frost, B; Davis, L R; Bellingham, A J; Stroud, C E; Studd, J W

    1986-01-01

    The sickle cell diseases are a major health problem for Afro-Caribbean peoples. Neonatal detection and prophylactic management can reduce mortality and morbidity in childhood. A study was therefore conducted analysing the results of the first two years of cord blood screening in the Camberwell health area. Thirteen cases of sickle cell disease and two of haemoglobin (Hb)C disease were identified among 2202 non-white infants screened. The carrier state, sickle cell trait (HbAS), was present in 11.9% and HbC trait (HbAC) in 4.1% of Afro-Caribbean infants. The incidence of disease and of carrier states was much higher in West Africans than in Caribbeans. The wider implications of screening and the need for a comprehensive plan of care are emphasised. PMID:3082419

  7. 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.

  8. 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.

  9. 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

  10. [Criteria of efficacy of adjuvant immunotherapy of surface cancer of the urinary bladder].

    PubMed

    Loran, O B; Medvedev, V L; Budnik, N V

    2005-01-01

    Assessment of prognostic significance of interleukine-8 (L-8) urine levels was made in 12 patients with verified surface cancer of the urinary bladder (SCUB) on adjuvant intravesical immunotherapy. Quantitative enzyme immunoassay identified IL-8 in the urine before intravesical injection of BCG vaccine and 6 hours later. A total of 192 urine samples were studied ("Multiskan-Jems", 405 nm). Adjuvant immunotherapy raises an L-8 level in the urine of the patients. After 8-week immunotherapy IL-8 elevated from 169.4 pg/ml to 326 pg/ml. Four patients with minimal difference in IL-8 urine levels (120 pg/ml, on the average) before and 6 hours after intravesical injection of BCG vaccine developed recurrence. Thus, quantitative assessment of IL-8 in urine of SCUB patients given intravesical BCG therapy can serve as one of prognostic criteria of adjuvant immunotherapy efficacy.

  11. From "magic bullets" to specific cancer immunotherapy.

    PubMed

    Riether, Carsten; Schürch, Christian; Ochsenbein, Adrian F

    2013-01-23

    The immune system is able to specifically target antigen-expressing cancer cells. The promise of immunotherapy was to eliminate cancer cells without harming normal tissue and, therefore, with no or very few side effects. Immunotherapy approaches have, for several decades, been tested against several tumours, most often against malignant melanoma. However, although detectable immune responses have regularly been induced, the clinical outcome has often been disappointing. The development of molecular methods and an improved understanding of tumour immunosurveillance led to novel immunotherapy approaches in the last few years. First randomised phase III trials proved that immunotherapy can prolong survival of patients with metastatic melanoma or prostate cancer. The development in the field is very rapid and various molecules (mainly monoclonal antibodies) that activate the immune system are currently being tested in clinical trials and will possibly change our treatment of cancer. The ultimate goal of any cancer therapy and also immunotherapy is to cure cancer. However, this depends on the elimination of the disease originating cancer stem cells. Unfortunately, cancer stem cells seem resistant to most available treatment options. Recent developments in immunotherapy may allow targeting these cancer stem cells specifically in the future. In this review, we summarise the current state of immunotherapy in clinical routine and the expected developments in the near future.

  12. Neonatal jaundice is associated with a small increase in the risk of childhood type 1 diabetes: a meta-analysis of observational studies.

    PubMed

    McNamee, Maria B; Cardwell, Chris R; Patterson, Chris C

    2012-02-01

    Published data on the role of neonatal jaundice as a risk factor for childhood type 1 diabetes mellitus is inconsistent. We aimed to review systematically, the evidence for an increased risk of type 1 diabetes in children diagnosed with neonatal jaundice. A comprehensive search of the published literature was performed to identify studies that had recorded the occurrence of neonatal jaundice in a group of children with type 1 diabetes and in a group of control children. Odds ratios (ORs) were extracted from reports or derived from tabulated data and then combined using a random effects meta-analysis. Data were available from 12 case-control studies and one retrospective cohort study. Overall, there was only weak evidence of an increase in the risk of type 1 diabetes in children who had neonatal jaundice (OR 1.14, 95% CI 0.99-1.32; P = 0.07), and there was some evidence of heterogeneity (I(2) = 53%, P = 0.01) mainly attributable to one study. An analysis restricted to studies not relying on parental recall showed a stronger, significant relationship (OR = 1.25, 95% CI 1.03-1.51; P = 0.02), although heterogeneity remained. This analysis found evidence of a small but statistically significant increase in childhood type 1 diabetes risk associated with neonatal jaundice but only for studies which used data from obstetric records. Jaundice caused by blood group incompatibility or requiring phototherapy may be associated with a greater increase in type 1 diabetes risk and deserves further study.

  13. 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.

  14. Evaluation of neonatal jaundice in the Makkah region.

    PubMed

    Alkhotani, Abdulaziz; Eldin, Essam Eldin Mohamed Nour; Zaghloul, Amal; Mujahid, Shakil

    2014-04-25

    The aims of this study were to detect the frequency at which the different types of neonatal jaundice occur in Makkah and to estimate the malondialdehyde (MDA) levels. This study included 239 neonates with neonatal jaundice, 20 anemic neonates and 21 healthy neonates. ABO incompatibility was observed in 31.6% of neonates with indirect hyperbilirubinemia, in 14.3% of those with early onset jaundice, in 9.5% of those with persistent jaundice, in 8.5% of those with physiological jaundice, in 5% of anemic neonates and in 12% of all neonates. glucose-6-phosphate dehydrogenase (G6PD) deficiency was observed in 10.5% of neonates with indirect hyperbilirubinemia, in 3.9% of those with physiological jaundice, in 11.1% of those with direct hyperbilirubinemia, in 12% of those with persistent jaundice, in 10% of anemic neonates and in 6.6% of all neonates. Rh incompatibility and polycythemia were found in 2.6% of neonates with indirect hyperbilirubinemia and in 0.4% of all neonates. In comparison to control group, MDA was significantly higher in all groups except for the anemic group. In conclusion, ABO incompatibility and G6PD deficiency frequently result in neonatal jaundice in Makkah, whereas Rh incompatibility and polycythemia are rare. The MDA level may serve as an indicator of oxidative stress.

  15. Immunotherapy of systemic sclerosis

    PubMed Central

    Manno, Rebecca; Boin, Francesco

    2011-01-01

    Scleroderma is a multisystem autoimmune disease characterized by an abnormal immune activation associated with the development of underlying vascular and fibrotic disease manifestations. This article highlights the current use of drugs targeting the immune system in scleroderma. Nonselective immunosuppression, and in particular cyclophosphamide, remains the main treatment for progressing skin involvement and active interstitial lung disease. Mycophenolate mofetil is a promising alternative to cyclophosphamide. The use of cyclosporine has been limited by modest efficacy and serious renal toxicity. Newer T-cell (sirolimus and alefacept) and B-cell (rituximab)-targeted therapies have provided some encouraging results in small pilot studies. Hematopoietic stem cell transplantation can be effective for severe fibrotic skin disease, but toxicity remains a concern. Clinical efficacy and safety of antifibrotic treatments (e.g., imatinib) await confirmation. Newer biological agents targeting key molecular or cellular effectors in scleroderma pathogenesis are now available for clinical testing. PMID:21091117

  16. Immunotherapy in antiphospholipid syndrome.

    PubMed

    Lopez-Pedrera, Ch; Aguirre, M A; Ruiz-Limon, P; Pérez-Sánchez, C; Jimenez-Gomez, Y; Barbarroja, N; Cuadrado, M J

    2015-08-01

    Antiphospholipid syndrome (APS) is a disorder characterized by the association of arterial or venous thrombosis and/or pregnancy morbidity with the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant antibodies, and/or anti-β2-glycoprotein I antibodies). Thrombosis is the major manifestation in patients with aPLs, but the spectrum of symptoms and signs associated with aPLs has broadened considerably, and other manifestations, such as thrombocytopenia, non-thrombotic neurological syndromes, psychiatric manifestations, livedo reticularis, skin ulcers, hemolytic anemia, pulmonary hypertension, cardiac valve abnormality, and atherosclerosis, have also been related to the presence of those antibodies. Several studies have contributed to uncovering the basis of antiphospholipid antibody pathogenicity, including the targeted cellular components, affected systems, involved receptors, intracellular pathways used, and the effector molecules that are altered in the process. Therapy for thrombosis traditionally has been based on long-term oral anticoagulation; however, bleeding complications and recurrence despite high-intensity anticoagulation can occur. The currently accepted first-line treatment for obstetric APS (OAPS) is low-dose aspirin plus prophylactic unfractionated or low-molecular-weight heparin (LMWH). However, in approximately 20% of OAPS cases, the final endpoint, i.e. a live birth, cannot be achieved. Based on all the data obtained in different research studies, new potential therapeutic approaches have been proposed, including the use of new oral anticoagulants, statins, hydroxychloroquine, coenzyme Q10, B-cell depletion, platelet and TF inhibitors, peptide therapy or complement inhibition among others. Current best practice in use of these treatments is discussed.

  17. 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.

  18. Immunotherapy against cancer-related viruses.

    PubMed

    Tashiro, Haruko; Brenner, Malcolm K

    2017-01-01

    Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects.

  19. Allergy immunotherapy: the future of allergy treatment.

    PubMed

    Larsen, Jørgen Nedergaard; Broge, Louise; Jacobi, Henrik

    2016-01-01

    Allergic respiratory disease represents a significant and expanding health problem worldwide. Allergic symptoms, such as asthma and hay fever, cause sleep impairment and reduce school and work performance. The cost to society is substantial. Allergen avoidance and pharmacotherapy cannot control the disease. Only allergy immunotherapy has disease-modifying potential and should be included in optimal treatment strategies. Allergy immunotherapy was first administered as subcutaneous injections and has been practiced for the past 100 years or so. Recently, tablet-based sublingual allergy immunotherapy (SLIT) was introduced with comprehensive clinical documentation. SLIT tablets represent a more patient-friendly concept because they can be used for self-treatment at home.

  20. New Immunotherapy Strategies in Breast Cancer

    PubMed Central

    Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

    2017-01-01

    Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies. PMID:28085094

  1. 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.

  2. New Immunotherapy Strategies in Breast Cancer.

    PubMed

    Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

    2017-01-12

    Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.

  3. Immunotherapy for B-Cell Lymphoma: Current Status and Prospective Advances

    PubMed Central

    Hollander, Nurit

    2011-01-01

    Therapy for non-Hodgkin’s lymphoma has progressed significantly over the last decades. However, the majority of patients remain incurable, and novel therapies are needed. Because immunotherapy ideally offers target selectivity, an ever increasing number of immunotherapies, both passive and active, are undergoing development. The champion of passive immunotherapy to date is the anti-CD20 monoclonal antibody rituximab that revolutionized the standard of care for lymphoma. The great success of rituximab catalyzed the development of new passive immunotherapy strategies that are currently undergoing clinical evaluation. These include improvement of rituximab efficacy, newer generation anti-CD20 antibodies, drug-conjugated and radio labeled anti-CD20 antibodies, monoclonal antibodies targeting non-CD20 lymphoma antigens, and bispecific antibodies. Active immunotherapy aims at inducing long-lasting antitumor immunity, thereby limiting the likelihood of relapse. Current clinical studies of active immunotherapy for lymphoma consist largely of vaccination and immune checkpoint blockade. A variety of protein- and cell-based vaccines are being tested in ongoing clinical studies. Recently completed phase III clinical trials of an idiotype protein vaccine suggest that the vaccine may have clinical activity in a subset of patients. Efforts to enhance the efficacy of active immunotherapy are ongoing with an emphasis on optimization of antigen delivery and presentation of vaccines and modulation of the immune system toward counteracting immunosuppression, using antibodies against immune regulatory checkpoints. This article discusses results of the various immunotherapy approaches applied to date for B-cell lymphoma and the ongoing trials to improve their effect. PMID:22566889

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Autonomy gone awry: a cross-cultural study of parents' experiences in neonatal intensive care units.

    PubMed

    Orfali, Kristina; Gordon, Elisa J

    2004-01-01

    This paper examines parents' experiences of medical decision-making and coping with having a critically ill baby in the Neonatal Intensive Care Unit (NICU) from a cross-cultural perspective (France vs. U.S.A.). Though parents' experiences in the NICU were very similar despite cultural and institutional differences, each system addresses their needs in a different way. Interviews with parents show that French parents expressed overall higher satisfaction with the care of their babies and were better able to cope with the loss of their child than American parents. Central to the French parents' perception of autonomy and their sense of satisfaction were the strong doctor-patient relationship, the emphasis on medical certainty in prognosis versus uncertainty in the American context, and the "sentimental work" provided by the team. The American setting, characterized by respect for parental autonomy, did not necessarily translate into full parental involvement in decision-making, and it limited the rapport between doctors and parents to the extent of parental isolation. This empirical comparative approach fosters a much-needed critique of philosophical principles by underscoring, from the parents' perspective, the lack of "emotional work" involved in the practice of autonomy in the American unit compared to the paternalistic European context. Beyond theoretical and ethical arguments, we must reconsider the practice of autonomy in particularly stressful situations by providing more specific means to cope, translating the impersonal language of "rights" and decision-making into trusting, caring relationships, and sharing the responsibility for making tragic choices.

  9. Effect of timing of first postnatal care home visit on neonatal mortality in Bangladesh: a observational cohort study

    PubMed Central

    Ahmed, Saifuddin; Arifeen, Shams El; Darmstadt, Gary L; Rosecrans, Amanda M; Mannan, Ishtiaq; Rahman, Syed M; Begum, Nazma; Mahmud, Arif B A; Seraji, Habibur R; Williams, Emma K; Winch, Peter J; Santosham, Mathuram; Black, Robert E

    2009-01-01

    Objective To assess the effect of the timing of first postnatal home visit by community health workers on neonatal mortality. Design Analysis of prospectively collected data using time varying discrete hazard models to estimate hazard ratios for neonatal mortality according to day of first postnatal home visit. Data source Data from a community based trial of neonatal care interventions conducted in Bangladesh during 2004-5. Main outcome measure Neonatal mortality. Results 9211 live births were included. Among infants who survived the first day of life, neonatal mortality was 67% lower in those who received a visit on day one than in those who received no visit (adjusted hazard ratio 0.33, 95% confidence interval 0.23 to 0.46; P<0.001). For those infants who survived the first two days of life, receiving the first visit on the second day was associated with a 64% lower neonatal mortality than in those who did not receive a visit (adjusted hazard ratio 0.36, 0.23 to 0.55; P<0.001). First visits on any day after the second day of life were not associated with reduced mortality. Conclusions In developing countries, especially where home delivery with unskilled attendants is common, postnatal home visits within the first two days of life by trained community health workers can significantly reduce neonatal mortality. PMID:19684100

  10. Immunoediting and Antigen Loss: Overcoming the Achilles Heel of Immunotherapy with Antigen Non-Specific Therapies

    PubMed Central

    Monjazeb, Arta Monir; Zamora, Anthony E.; Grossenbacher, Steven K.; Mirsoian, Annie; Sckisel, Gail D.; Murphy, William J.

    2013-01-01

    Cancer immunotherapy has emerged as a mainstream therapy option in the battle against cancer. Pre-clinical data demonstrates the ability of immunotherapy to harness the immune system to fight disseminated malignancy. Clinical translation has failed to recapitulate the promising results of pre-clinical studies although there have been some successes. In this review we explore some of the short-comings of cancer immunotherapy that have limited successful clinical translation. We will give special consideration to what we consider the most formidable hurdle to successful cancer immunotherapy: tumor-induced immune suppression and immune escape. We will discuss the need for antigen-specific immune responses for successful immunotherapy but also consider the need for antigen specificity as an Achilles heel of immunotherapy given tumor heterogeneity, immune editing, and antigen loss. Finally, we will discuss how combinatorial strategies may overcome some of the pitfalls of antigen specificity and highlight recent studies from our lab which suggest that the induction of antigen non-specific immune responses may also produce robust anti-tumor effects and bypass the need for antigen specificity. PMID:23898464

  11. Immunotherapy

    MedlinePlus

    ... CSF) Interleukin-2 (IL-2) Interferon Donor lymphocyte infusion Some blood cancer patients, especially those with chronic ... from an immune cell treatment called donor lymphocyte infusion. During this procedure, doctors transfer lymphocytes (a type ...

  12. 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

  13. Comparative analysis of cluster versus conventional immunotherapy in patients with allergic rhinitis

    PubMed Central

    Fan, Qijun; Liu, Xuejun; Gao, Jinjian; Huang, Saiyu; Ni, Liyan

    2017-01-01

    The present study aimed to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract administered in conventional and cluster immunotherapy regiments for patients with persistent allergic rhinitis. A total of 60 patients with moderate to severe allergic rhinitis caused by dust mites were treated for 1 year with either conventional immunotherapy (n=30) or cluster immunotherapy (n=30). Nasal conjunctival symptoms and signs were assessed to evaluate the clinical efficacy of the two regimens, and the incidence of local and systemic adverse reactions were also evaluated. The findings demonstrated that the cluster regimen reduced the duration between the initial and maintenance dose by >60%, and resulted in a significant improvement, as compared with the conventional regimen, after 6 weeks of observation (P<0.05). However, the incidence of local and systemic adverse reactions in the cluster regimen during the dose accumulation phase and the dose maintenance phase was not significantly different, as compared with the conventional immunotherapy regimen. These results suggest that cluster immunotherapy is efficacious and safe to treat patients who are clinically sensitive to dust mites. PMID:28352357

  14. Long-term consequences of the early treatment of children with congenital hypothyroidism detected by neonatal screening in Nanjing, China: a 12-year follow-up study.

    PubMed

    Sun, Qing; Chen, Yu-Lin; Yu, Zhang-Bin; Han, Shu-Ping; Dong, Xiao-Yue; Qiu, Yu-Fang; Sha, Li; Guo, Xi-Rong

    2012-02-01

    This study was performed to investigate the prevalence of congenital hypothyroidism (CH) in neonates in Nanjing, China and the long-term consequences of early treatment. A total of 442 454 neonates were screened for CH and 183 neonates were confirmed, with a prevalence of 1 in 2418. Of these, 163 neonates completed the follow-up process and 163 healthy children were recruited as the control group. The height, weight and body mass index (BMI) of the children with CH from 0.5 to 6 years were not significantly different from the control group (p > 0.05). The children with CH had a significantly increased risk for being overweight or obese between 0.5 and 6 years (p < 0.05). The children with CH showed a significantly lower developmental quotient (DQ) than the control group in all four areas of the Gesell test (p < 0.05). The results suggest that children with CH that has been identified by newborn screening and early treatment have normal growth and neuromotor development.

  15. Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study.

    PubMed

    Stammers, A H; Rauch, E D; Willett, L D; Newberry, J W; Duncan, K F

    2000-03-01

    Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital

  16. Allergen immunotherapy for allergic respiratory diseases.

    PubMed

    Cappella, Antonio; Durham, Stephen R

    2012-10-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy.

  17. Grass pollen immunotherapy: where are we now.

    PubMed

    Würtzen, Peter A; Gupta, Shashank; Brand, Stephanie; Andersen, Peter S

    2016-01-01

    During allergen immunotherapy (AIT), the allergic patient is exposed to the disease-inducing antigens (allergens) in order to induce clinical and immunological tolerance and obtain disease modification. Large trials of grass AIT with highly standardized subcutaneous and sublingual tablet vaccines have been conducted to document the clinical effect. Induction of blocking antibodies as well as changes in the balance between T-cell phenotypes, including induction of regulatory T-cell subtypes, have been demonstrated for both treatment types. These observations increase the understanding of the immunological mechanism behind the clinical effect and may make it possible to use the immunological changes as biomarkers of clinical effect. The current review describes the recent mechanistic findings for subcutaneous immunotherapy and sublingual immunotherapy/tablet treatment and discusses how the observed immunological changes translate into a scientific foundation for the observed clinical effects of grass pollen immunotherapy and lead to new treatment strategies for grass AIT.

  18. 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.

  19. Allergen immunotherapy for allergic respiratory diseases

    PubMed Central

    Cappella, Antonio; Durham, Stephen R.

    2012-01-01

    Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy. PMID:23095870

  20. 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.

  1. [Neonatal resuscitation].

    PubMed

    Burón Martínez, E; Aguayo Maldonado, J

    2006-11-01

    At birth approximately 10 % of term or near-term neonates require initial stabilization maneuvers to establish a cry or regular breathing, maintain a heart rate greater than 100 beats per minute (bpm), and good color and muscular tone. About 1 % requires ventilation and very few infants receive chest compressions or medication. However, birth asphyxia is a worldwide problem and can lead to death or serious sequelae. Recently, the European Resuscitation Council (ERC) and the International Liaison Committee on Resuscitation (ILCOR) published new guidelines on resuscitation at birth. These guidelines review specific questions such as the use of air or 100 % oxygen in the delivery room, dose and routes of adrenaline delivery, the peripartum management of meconium-stained amniotic fluid, and temperature control. Assisted ventilation in preterm infants is briefly described. New devices to improve the care of newborn infants, such as the laryngeal mask airway or CO2 detectors to confirm tracheal tube placement, are also discussed. Significant changes have occurred in some practices and are included in this document.

  2. 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.

  3. Human Umbilical Cord Blood CD34-Positive Cells as Predictors of the Incidence and Short-Term Outcome of Neonatal Hypoxic-Ischemic Encephalopathy: A Pilot Study

    PubMed Central

    Nasr Eldin, Mohamed Hassan; Amer, Hanaa A.; Abdelhamid, Adel E.; El Houssinie, Moustafa; Ibrahim, Abir

    2017-01-01

    Background and Purpose Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neurological handicap in developing countries. Human umbilical cord blood (hUCB) CD34-positive (CD34+) stem cells exhibit the potential for neural repair. We tested the hypothesis that hUCB CD34+ stem cells and other cell types [leukocytes and nucleated red blood cells (NRBCs)] that are up-regulated during the acute stage of perinatal asphyxia (PA) could play a role in the early prediction of the occurrence, severity, and mortality of HIE. Methods This case-control pilot study investigated consecutive neonates exposed to PA. The hUCB CD34+ cell count in mononuclear layers was assayed using a flow cytometer. Twenty full-term neonates with PA and 25 healthy neonates were enrolled in the study. Results The absolute CD34+ cell count (p=0.02) and the relative CD34+ cell count (CD34+%) (p<0.001) in hUCB were higher in the HIE patients (n=20) than the healthy controls. The hUCB absolute CD34+ cell count (p=0.04), CD34+% (p<0.01), and Hobel risk scores (p=0.04) were higher in patients with moderate-to-severe HIE (n=9) than in those with mild HIE (n=11). The absolute CD34+ cell count was strongly correlated with CD34+% (p<0.001), Hobel risk score (p=0.04), total leukocyte count (TLC) (p<0.001), and NRBC count (p=0.01). CD34+% was correlated with TLC (p=0.02). Conclusions hUCB CD34+ cells can be used to predict the occurrence, severity, and mortality of neonatal HIE after PA. PMID:28079317

  4. 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.

  5. Reiter's syndrome following intravesical BCG immunotherapy

    PubMed Central

    Hogarth, M; Thomas, S; Seifert, M; Tariq, S

    2000-01-01

    A 71 year old woman developed conjunctivitis, asymmetrical oligoarthritis, and cystitis (Reiter's syndrome) secondary to intravesical BCG treatment for transitional cell carcinoma of the bladder. She received oral prednisolone, izoniazid, and pyridoxine and made a full recovery. Increasing use of BCG as immunotherapy will lead to an increase in the incidence of BCG associated reactive arthritis. Prompt recognition and early diagnosis will facilitate treatment and recovery.


Keywords: arthritis; BCG immunotherapy; Reiter's syndrome PMID:11085772

  6. Immunotherapy: Exploring the State of the Science
.

    PubMed

    Ginex, Pamela K; Brassil, Kelly; Ely, Beth

    2017-04-01

    Immunotherapy research provides opportunities for nurse scientists and researchers to be at the forefront of the changing landscape of cancer treatment. As these therapies continue to develop, current initiatives will seek to support nurses in clinical practice who must provide safe, evidence-based care and education to patients and their families. This article explores the current state of immunotherapy research and the ways in which continued research can help to advance nursing education and practice.

  7. Advances in upper airway diseases and allergen immunotherapy.

    PubMed

    Nelson, Harold S

    2004-04-01

    Evidence for one airway continues to accumulate. Nasal allergen challenges increase lower airway inflammation, and nasal corticosteroid treatment reduces lower airway inflammation. Allergic respiratory inflammation might even spread systemically to involve nonrespiratory organs. Eosinophilic enteritis and eosinophilic esophagitis are reported during pollen seasons in patients with seasonal allergic rhinitis. Chronic hypertrophic sinusitis (CHS) is found in the majority of patients with asthma. Like asthma, the histology of CHS is characterized by epithelial damage, basement membrane thickening, and eosinophilic inflammation. The damaged epithelium might explain the acute bacterial exacerbations seen in patients with CHS. Studies have extended evidence of the safety and efficacy of the second- and third-generation antihistamines to younger children and to patients with perennial rhinitis but continue to show improvement of symptom scores over that seen with placebo of less than 20%. Studies on antihistamine use in the first trimester in nearly 500 women (65% taking loratadine) revealed no increase in the complications of pregnancy or congenital anomalies. Positive skin prick test responses to birch in asymptomatic young adults predicted later development of clinical allergic rhinitis. A dose response was demonstrated for immunotherapy with cat dander extract. The best results were in subjects receiving a dose containing 15 microg of the major cat allergen Fel d 1 (equivalent to approximately 2500 bioequivalent allergen units). Both topical intranasal immunotherapy and high-dose sublingual immunotherapy have been repeatedly proved to be safe and effective in double-blind, placebo-controlled studies. CD4+CD25+ regulatory T cells secreting IL-10, TGF-beta, or both appear important in normal individuals and in patients treated with allergen immunotherapy in maintaining or restoring normal T(H)1/T(H)2 balance and overall suppression of both phenotypes.

  8. 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.

  9. Immunotherapy and targeted therapy for cervical cancer: an update.

    PubMed

    Menderes, Gulden; Black, Jonathan; Schwab, Carlton L; Santin, Alessandro D

    2016-01-01

    The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. In the last few years, a better understanding of Human papillomavirus tumor-host immune system interactions and the development of new therapeutics targeting immune check points have renewed interest in the use of immunotherapy in cervical cancer patients. Moreover, next generation sequencing has emerged as an attractive option for the identification of actionable driver mutations and other markers. In this review, we provide background information on the molecular biology of cervical cancer and summarize immunotherapy studies, targeted therapies, including those with angiogenesis inhibitors and tyrosine kinase inhibitors recently completed or currently on-going in cervical cancer patients.

  10. 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.

  11. 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.

  12. 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.

  13. Evidence-Based Neonatal Unit Practices and Determinants of Postnatal Corticosteroid-Use in Preterm Births below 30 Weeks GA in Europe. A Population-Based Cohort Study

    PubMed Central

    Nuytten, Alexandra; Behal, Hélène; Duhamel, Alain; Jarreau, Pierre-Henri; Mazela, Jan; Milligan, David; Gortner, Ludwig; Piedvache, Aurélie; Zeitlin, Jennifer; Truffert, Patrick

    2017-01-01

    Background Postnatal corticosteroids (PNC) were widely used to treat and prevent bronchopulmonary dysplasia in preterm infants until studies showed increased risk of cerebral palsy and neurodevelopmental impairment. We aimed to describe PNC use in Europe and evaluate the determinants of their use, including neonatal characteristics and adherence to evidence-based practices in neonatal intensive care units (NICUs). Methods 3917/4096 (95,6%) infants born between 24 and 29 weeks gestational age in 19 regions of 11 European countries of the EPICE cohort we included. We examined neonatal characteristics associated with PNC use. The cohort was divided by tertiles of probability of PNC use determined by logistic regression analysis. We also evaluated the impact of the neonatal unit’s reported adherence to European recommendations for respiratory management and a stated policy of reduced PNC use. Results PNC were prescribed for 545/3917 (13.9%) infants (regional range 3.1–49.4%) and for 29.7% of infants in the highest risk tertile (regional range 5.4–72.4%). After adjustment, independent predictors of PNC use were a low gestational age, small for gestational age, male sex, mechanical ventilation, use of non-steroidal anti-inflammatory drugs to treat persistent ductus arteriosus and region. A stated NICU policy reduced PNC use (odds ratio 0.29 [95% CI 0.17; 0.50]). Conclusion PNC are frequently used in Europe, but with wide regional variation that was unexplained by neonatal characteristics. Even for infants at highest risk for PNC use, some regions only rarely prescribed PNC. A stated policy of reduced PNC use was associated with observed practice and is recommended. PMID:28114369

  14. [A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency].

    PubMed

    Song, Yuan-Zong; Hao, Hu; Ushikai, Miharu; Liu, Guo-Sheng; Xiao, Xin; Saheki, Takeyori; Kobayashi, Keiko; Wang, Zi-Neng

    2006-04-01

    Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial solute carrier protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6 months old) was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5 cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin (especially conjugated bilirubin), and decreased levels of total protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319,225.70 microg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and multiple vitamins (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared

  15. Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study.

    PubMed

    Bakshi, Mayur V; Barjaktarovic, Zarko; Azimzadeh, Omid; Kempf, Stefan J; Merl, Juliane; Hauck, Stefanie M; Eriksson, Per; Buratovic, Sonja; Atkinson, Michael J; Tapio, Soile

    2013-11-01

    Epidemiological studies establish that children and young adults are especially susceptible to radiation-induced cardiovascular disease (CVD). The biological mechanisms behind the elevated CVD risk following exposure at young age remain unknown. The present study aims to elucidate the long-term effects of ionizing radiation by studying the murine cardiac proteome after exposure to low and moderate radiation doses. NMRI mice received single doses of total body (60)Co gamma-irradiation on postnatal day 10 and were sacrificed 7 months later. Changes in cardiac protein expression were quantified using isotope-coded protein label and tandem mass spectrometry. We identified 32, 31, 66, and 34 significantly deregulated proteins after doses of 0.02, 0.1, 0.5, and 1.0 Gy, respectively. The four doses shared 9 deregulated proteins. Bioinformatics analysis showed that most of the deregulated proteins belonged to a limited set of biological categories, including metabolic processes, inflammatory response, and cytoskeletal structure. The transcription factor peroxisome proliferator-activated receptor alpha was predicted as a common upstream regulator of several deregulated proteins. This study indicates that both adaptive and maladaptive responses to the initial radiation damage persist well into adulthood. It will contribute to the understanding of the long-term consequences of radiation-induced injury and developmental alterations in the neonatal heart.

  16. 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

  17. IgE-based immunotherapy of cancer: challenges and chances

    PubMed Central

    Singer, J; Jensen-Jarolim, E

    2014-01-01

    Passive immunotherapy with monoclonal antibodies is an indispensable cornerstone of clinical oncology. Notably, all FDA-approved antibodies comprise the IgG class, although numerous research articles proposed monoclonal antibodies of the IgM, IgG, IgA and IgE classes directed specifically against tumor-associated antigens. In particular, for the IgE isotype class, several recent studies could demonstrate high tumoricidic efficacy. Therefore, this review specifically highlights the latest developments toward IgE-based immunotherapy of cancer. Possible mechanisms and safety aspects of IgE-mediated tumor cell death are discussed with special focus on the attracted immune cells. An outlook is given on how especially comparative oncology could contribute to further developments. Humans and dogs have a highly comparable IgE biology, suggesting that translational AllergoOncology studies in patients with canine cancer could have predictive value for the potential of IgE-based anticancer immunotherapy in human clinical oncology. PMID:24117861

  18. Update on antigen-specific immunotherapy of acute myeloid leukemia.

    PubMed

    Buckley, Sarah A; Walter, Roland B

    2015-06-01

    Among the few drugs that have shown a benefit for patients with acute myeloid leukemia (AML) in randomized clinical trials over the last several decades is the CD33 antibody-drug conjugate, gemtuzumab ozogamicin (GO). Undoubtedly, this experience has highlighted the value of antigen-specific immunotherapy in AML. A wide variety of therapeutics directed against several different antigens on AML cells are currently explored in preclinical and early clinical studies. On the one hand, these include passive strategies such as unconjugated antibodies targeting one or more antigens, antibodies armed with drugs, toxic proteins, or radionuclides, or adoptive immunotherapies, in particular utilizing T cells engineered to express chimeric antigen receptors (CARs) or modified T cell receptor (TCR) genes; on the other hand, these include active strategies such as vaccinations. With the documented benefit for GO and the emerging data with several classes of therapeutics in other leukemias, in particular small bispecific antibodies and CAR T cells, the future is bright. Nevertheless, a number of important questions related to the choice of target antigen(s), patient population, exact treatment modality, and supportive care needs remain open. Addressing such questions in upcoming studies will ultimately be required to optimize the clinical use of antigen-specific immunotherapies in AML and ensure that such treatments become an effective, versatile tool for this disease for which the outcomes have remained unsatisfactory in many patients.

  19. 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

  20. Can Alzheimer disease be prevented by amyloid-beta immunotherapy?

    PubMed

    Lemere, Cynthia A; Masliah, Eliezer

    2010-02-01

    Alzheimer disease (AD) is the most common form of dementia. The amyloid-beta (Abeta) 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 Abeta immunotherapies have been shown to lower cerebral Abeta levels and improve cognition in animal models of AD. In humans, dosing in the phase II clinical trial of the AN1792 Abeta vaccine was stopped when approximately 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 Abeta immunotherapies are now in clinical trials in patients with mild to moderate AD. Several second-generation active Abeta vaccines are also in early clinical trials. On the basis of preclinical studies and the limited data from clinical trials, Abeta 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 Abeta immunization.

  1. Safety of Accelerated Schedules of Subcutaneous Allergen Immunotherapy with House Dust Mite Extract in Patients with Atopic Dermatitis

    PubMed Central

    Kim, Myoung-Eun; Kim, Jeong-Eun; Sung, Joon-Mo; Lee, Jin-Woo; Choi, Gil-Soon

    2011-01-01

    The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD. PMID:21935270

  2. Idiopathic Neonatal Colonic Perforation

    PubMed Central

    Tuncer, Oğuz; Melek, Mehmet; Kaba, Sultan; Bulan, Keziban; Peker, Erdal

    2014-01-01

    Though the perforation of the colon in neonates is rare, it is associated with more than 50% mortality in high-risk patients. We report a case of idiopathic neonatal perforation of the sigmoid colon in an 8-day-old, healthy, male neonate without any demonstrable cause. PMID:26023477

  3. Neonatal Acute Kidney Injury.

    PubMed

    Selewski, David T; Charlton, Jennifer R; Jetton, Jennifer G; Guillet, Ronnie; Mhanna, Maroun J; Askenazi, David J; Kent, Alison L

    2015-08-01

    In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.

  4. Nursing scripts and the organizational influences on critical thinking: report of a study of neonatal nurses' clinical reasoning.

    PubMed

    Greenwood, J; Sullivan, J; Spence, K; McDonald, M

    2000-05-01

    During 1995-1997 a study was undertaken to explore the extent to which theoretical knowledge acquired through a distance education programme in neonatal nursing was brought to bear in the real-world clinical reasoning of course participants. The study utilized a think aloud technique and included both concurrent (on-the-job) and retrospective verbal reports at 0, 6 and 12 months into the programme. Participants (n=4) were also interviewed individually on completion of the study. Results indicated that important inconsistencies existed between participants' theoretical knowledge and their practice; they also pointed to some organizational influences on these theory-practice inconsistencies. Script (or schema) theory provided a useful explanatory framework for these results. The paper includes a brief description of data collection and analysis techniques; its main emphasis, however, is on these theory-practice inconsistencies and their explanation in terms of the nature and acquisition of nursing practice scripts. The implications of nursing scripts for the promotion of critical thinking and evidence-based practice are discussed.

  5. Allergen immunotherapy and allergic rhinitis: false beliefs

    PubMed Central

    2013-01-01

    Background Over the last 100 years, several persistent misconceptions or ‘false beliefs’ have built up around allergen immunotherapy and its use in allergic rhinitis. This is perhaps because enthusiastic physicians administered complex allergen extracts to a diverse population of patients suffering from heterogeneous atopic conditions. Here, we review evidence that counters seven of these ‘false beliefs.’ Discussion 1. The symptoms of allergic rhinitis can be more heterogeneous, more severe and more troublesome in everyday life than many physicians believe. Large-scale epidemiological surveys show that the majority of allergic rhinitis patients have at least one symptom severe enough to interfere with sleep quality, productivity and/or well-being. 2. Allergen immunotherapy is not necessarily suitable for all allergic rhinitis patients (notably those with mild symptoms). Recent evidence from double-blind, placebo-controlled, randomized clinical trials suggests that the more severe the disease, the greater the treatment effect. 3. Allergen immunotherapy is often accused of lack of efficacy (relative to pharmacotherapy, for example). However, there are now many meta-analyses, systematic reviews and high-quality clinical trials that find overwhelmingly in favor of the efficacy of allergen immunotherapy (including sublingual formulations) in allergic rhinitis induced by pollen and, increasingly, other allergens. 4. Natural-exposure and challenge-chamber trials have shown that symptom relief may become apparent within months or even weeks of the initiation of allergen immunotherapy. 5. In pollen-induced allergic rhinitis, several years of subcutaneous or sublingual allergen immunotherapy are associated with sustained clinical efficacy after subsequent treatment cessation – confirming the disease-modifying nature of this therapy. 6. Most patients seeking treatment for allergic rhinitis are polysensitized, and allergen immunotherapy has proven efficacy in large

  6. Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30 year prospective follow-up study.

    PubMed

    Hokkanen, Laura; Launes, Jyrki; Michelsson, Katarina

    2014-01-01

    Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood. Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrat