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Sample records for neonatal immunotherapy study

  1. The INIS Study. International Neonatal Immunotherapy Study: non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis: an international, placebo controlled, multicentre randomised trial

    PubMed Central

    2008-01-01

    Background Sepsis is an important cause of neonatal death and perinatal brain damage, particularly in preterm infants. While effective antibiotic treatment is essential treatment for sepsis, resistance to antibiotics is increasing. Adjuvant therapies, such as intravenous immunoglobulin, therefore offer an important additional strategy. Three Cochrane systematic reviews of randomised controlled trials in nearly 6,000 patients suggest that non-specific, polyclonal intravenous immunoglobulin is safe and reduces sepsis by about 15% when used as prophylaxis but does not reduce mortality in this situation. When intravenous immunoglobulin is used in the acute treatment of neonatal sepsis, however, there is a suggestion that it may reduce mortality by 45%. However, the existing trials of treatment were small and lacked long-term follow-up data. This study will assess reliably whether treatment of neonatal sepsis with intravenous immunoglobulin reduces mortality and adverse neuro-developmental outcome. Methods and design A randomised, placebo controlled, double blind trial. Babies with suspected or proven neonatal sepsis will be randomised to receive intravenous immunoglobulin therapy or placebo. Eligibility criteria Babies must be receiving antibiotics and have proven or suspected serious infection AND have at least one of the following: birthweight less than 1500 g OR evidence of infection in blood culture, cerebrospinal fluid or usually sterile body fluid OR be receiving respiratory support via an endotracheal tube AND there is substantial uncertainty that intravenous immunoglobulin is indicated. Exclusion criteria Babies are excluded if intravenous immunoglobulin has already been given OR intravenous immunoglobulin is thought to be needed OR contra-indicated. Trial treatment Babies will be given either 10 ml/kg of intravenous immunoglobulin or identical placebo solution over 4–6 hours, repeated 48 hours later. Primary outcome Mortality or major disability at two years

  2. Canine cancer immunotherapy studies: linking mouse and human.

    PubMed

    Park, Jiwon S; Withers, Sita S; Modiano, Jaime F; Kent, Michael S; Chen, Mingyi; Luna, Jesus I; Culp, William T N; Sparger, Ellen E; Rebhun, Robert B; Monjazeb, Arta M; Murphy, William J; Canter, Robert J

    2016-01-01

    Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers. Additionally, laboratory mice uncommonly develop spontaneous tumors, are housed under specific-pathogen free conditions which markedly impacts immune development, and incompletely model key aspects of the tumor/immune microenvironment. The canine model represents a powerful tool in cancer immunotherapy research as an important link between murine models and human clinical studies. Dogs represent an attractive outbred combination of companion animals that experience spontaneous cancer development in the setting of an intact immune system. This allows for study of complex immune interactions during the course of treatment while also directly addressing long-term efficacy and toxicity of cancer immunotherapies. However, immune dissection requires access to robust and validated immune assays and reagents as well as appropriate numbers for statistical evaluation. Canine studies will need further optimization of these important mechanistic tools for this model to fulfill its promise as a model for immunotherapy. This review aims to discuss the canine model in the context of existing preclinical cancer immunotherapy models to evaluate both its advantages and limitations, as well as highlighting its growth as a powerful tool in the burgeoning field of both human and veterinary immunotherapy.

  3. The GILL study: glycerin-induced local reactions in immunotherapy.

    PubMed

    Calabria, Christopher W; Coop, Christopher A; Tankersley, Michael S

    2008-01-01

    The mechanism of local reactions is not well defined. Glycerin, an excellent preservative used commonly in immunotherapy extracts, is a recognized irritant. This study was undertaken to examine whether higher glycerin concentration in immunotherapy extracts is associated with an increase in local reaction rates during immunotherapy. A retrospective analysis of electronic immunotherapy records over a 12-month period was performed from a single site. A small local reaction was defined as induration and/or erythema at the injection site smaller than or equal to the size of the patient's palm. A large local reaction was defined as a reaction larger than the patient's palm. Over the 12-month period, 360 patients received a total of 9678 immunotherapy injections. For all injections, the total local reaction rate was 16.3% (1574/9678), the small local reaction rate was 15.9% (1536/9678), and the large local reaction rate was 0.4% (38/9678). For aeroallergens, small local reaction rates increased significantly with increasing allergen concentrations, from 7.3% (1:1000 vol/vol) to 23.0% (1:1 vol/vol; P < .001). The small local reaction rate was higher with increasing allergen content but not higher glycerin concentration. Large local reactions were infrequent and did not significantly increase with allergen or glycerin concentration. Small local, but not large local, reaction rates increase with higher allergen concentration, number, and volume. Higher glycerin concentrations (even 50%) are not associated with significantly higher small or large local reaction rates.

  4. Stability of Tumor Growth Under Immunotherapy: A Computational Study

    NASA Astrophysics Data System (ADS)

    Singh, Sandeep; Sharma, Prabha; Singh, Phool

    We present a mathematical model to study the growth of a solid tumor in the presence of regular doses of lymphocytes. We further extend it to take care of the periodic behavior of the lymphocytes, which are used for stimulating the immune system. Cell carrying capacity has been specified and a cell kill rate under immunotherapy is used to take care of how different metabolisms will react to the treatment. We analyze our model with respect to its stability and its sensitivity to the various parameters used.

  5. 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.

  6. Profiling families enrolled in food allergy immunotherapy studies.

    PubMed

    DunnGalvin, Audrey; Chang, Wen Chin; Laubach, Susan; Steele, Pamela H; Dubois, Anthony E J; Burks, A Wesley; Hourihane, Jonathan O'B

    2009-09-01

    Little is known about specific psychological factors that affect parents' decisions to take part in clinical studies. We examined factors, related to health-related quality of life (HRQoL), that may influence parents' decision to allow their children to participate in research on clinical food allergy. Parents of children with food allergies were offered investigational oral immunotherapy (OIT) in a regular outpatient clinic. Forty parents (group A) declined, and 25 parents (group B) agreed to take part. Both groups agreed to complete the Food Allergy Quality of Life-Parent Form and the Food Allergy Independent Measure. Children were aged between 1 and 12 years (mean: 6.5 years). Groups A and B displayed a similar and typical distribution for gender, age, number of foods, severity and number of symptoms, and socioeconomic variables. Parents who chose to enroll their children in the OIT trial reported a similar impact of food allergy on the HRQoL of their children as parents of children who did not volunteer for the study. Participating parents perceived a significantly higher likelihood (odds ratio: 6.753) of their child having a severe reaction and dying if food is ingested. By using this model, the likelihood of taking part in immunotherapy could be predicted accurately in 90% of cases. Parents who had higher anxiety about negative outcomes from accidental ingestion were more likely to consent to experimental therapy for their child. This finding has ethical implications for investigators and supports the need to create mechanisms to avoid unintended coercion in vulnerable groups.

  7. 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

  8. 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.

  9. Optical topographic studies of adults and neonates

    NASA Astrophysics Data System (ADS)

    Nissila, Ilkka T.; Kotilahti, Kalle; Noponen, Tommi E.; Huotilainen, Minna; Naatanen, Risto; Katila, Toivo E.

    2003-07-01

    We used a four-channel intensity-modulated near-infrared spectroscopy device to study the hemodynamic responses due to brain activation in adults and neonates. The stimuli included finger tapping, tickling of the heel, and auditory stimuli. The subjects included two adults and ten neonates of age between 0.5 and 4 days. A block paradigm was used in the studies, and responses were successfully obtained from both subject groups.

  10. Oral immunotherapy for food allergy: clinical and preclinical studies.

    PubMed

    Kulis, Mike; Wesley Burks, A

    2013-06-15

    Food allergies affect approximately 5% of the U.S. population and have increased in the last decade. In recent years, oral immunotherapy (OIT) has been tested in clinical trials for peanut, milk, and egg allergies in young children. OIT appears to be fairly well tolerated by most subjects and leads to desensitization with a greatly increased threshold of allergen required to induce reactions. Further approaches being investigated in preclinical studies in mouse models indicate the potential for using adjuvants, such as TLR9 agonists in combination with OIT; peptide OIT; and non-allergen specific applications such as herbal formulations. Further questions about OIT remain, including the optimal dosing and length of treatment; whether tolerance can be developed; and the exact cellular mechanisms resulting in protection following OIT. With many clinical trials underway across the United States and other countries, and a growing pipeline of preclinical research with translational potential, there is great hope for a widely applicable food allergy treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. 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.

  12. 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

  13. Accelerated immunotherapy schedules.

    PubMed

    Calabria, Christopher W

    2013-08-01

    Rush and cluster immunotherapy schedules are accelerated immunotherapy build-up schedules. A cluster immunotherapy schedule involves the patient receiving several allergen injections (generally 2-4) sequentially in a single day of treatment on nonconsecutive days. The maintenance dose is generally reached in 4-8 weeks. In rush immunotherapy protocols, higher doses are administered at 15- to 60-min intervals over a 1- to 3-day period until the maintenance dose is achieved. This review will serve as an update for accelerated immunotherapy schedules. The review will include recent investigations demonstrating the safety of cluster schedules in atopic dermatitis, pediatric patients, and inhalant allergen mixtures and an accelerated protocol utilizing an infusion pump for allergen delivery. There has also been further elucidation on the immunological changes which occur during accelerated immunotherapy. Finally, new studies analyzing systemic reaction risk factors are discussed.

  14. [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.

  15. 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.

  16. Immunotherapies in dermatologic disorders.

    PubMed

    Fallen, Robyn S; Terpstra, Collin R; Lima, Hermenio C

    2012-05-01

    Treatment modalities and therapeutic response experience support the use of immunotherapy in the treatment of many diseases in all fields of medicine. The aim of this article is to conduct and present a review of literature on the use of immunotherapy in the treatment of skin diseases analyzing scientific literature available up to January 2012. Studies that presented evidence-based data were selected. The article discusses how blocking or reverting the effect of a specific immunologic disequilibrium can treat dermatoses and intends to transfer a large amount of immunotherapy knowledge into a historical perspective for physicians naive to immunotherapy practices. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. 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. ...

  18. Allergen-specific sublingual immunotherapy in the treatment of migraines: a prospective study.

    PubMed

    Theodoropoulos, D S; Katzenberger, D R; Jones, W M; Morris, D L; Her, C; Cullen, N A M; Morrisa, D L

    2011-10-01

    Inflammation is a cardinal feature of migraines. A number of observations point to the possibility that an allergic component of a type I (IgE-mediated) nature may be involved in at least some migraineurs. Not only are migraines frequent among patients with allergic rhinitis but quite frequently the same medical approaches are beneficial in both diseases: anti-inflammatories, adrenergic tone modifiers, immune suppressants. The effect that immunotherapy for allergic rhinitis has upon migraines is studied. Patients were recruited who suffered from typical migraines but were not treated with regular migraine controllers (beta blockers, antiepileptics, tricyclics, etc.). They underwent allergen-specific, sublingual immunotherapy with physician-formulated, individually-prepared airborne allergen extracts. Response to treatment was assessed with serum C-reactive protein level changes and symptom scores. Serum C-reactive protein (CRP), an acute phase reactant, was chosen as a marker because its usefulness has already been assessed in interictal migraine activity. Interictal serum CRP levels decline was observed in the course of sublingual immunotherapy. Concurrent improvement in symptom scores for both rhinitis and migraines was also observed. In patients with allergic rhinitis, migraine development and course may have a significant allergic component. Assessment of migraineurs for the possibility of coexisting allergic rhinitis is justified. Treatment of allergic rhinitis by immune response modifiers, such as immunotherapy, may have a place in the management of migraines for these patients.

  19. 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.

  20. 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

  1. Severe neonatal hypernatraemia: a population based study.

    PubMed

    Oddie, Sam Joseph; Craven, Vanessa; Deakin, Kathryn; Westman, Janette; Scally, Andrew

    2013-09-01

    To describe incidence, presentation, treatment and short term outcomes of severe neonatal hypernatraemia (SNH, sodium ≥160 mmol/l). Prospective, population based surveillance study over 13 months using the British Paediatric Surveillance Unit. Cases were >33 weeks gestation at birth, fed breast or formula milk and <28 days of age at presentation. Of 62 cases of SNH reported (7, 95% CI 5.4 to 9.0 per 1 00 000 live births), 61 mothers had intended to achieve exclusive breast feeding. Infants presented at median day 6 (range 2-17) with median weight loss of 19.5% (range 8.9-30.9). 12 had jaundice and 57 weight loss as a presenting feature. 58 presented with weight loss ≥15%. 25 babies had not stooled in the 24 h prior to admission. Serum sodium fell by median 12.9 mmol/l per 24 h (range 0-30). No baby died, had seizures or coma or was treated with dialysis or a central line. At discharge, babies had regained 11% of initial birth weight after a median admission of 5 (range 2-14) days. 10 were exclusively breast fed on discharge from hospital. Neonatal hypernatraemia at this level, in this population, is strongly associated with weight loss. It occurs almost exclusively after attempts to initiate breast feeding, occurs uncommonly and does not appear to be associated with serious short term morbidities, beyond admission to hospital.

  2. 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.

  3. Seizures in Preterm Neonates: A Multicenter Observational Cohort Study.

    PubMed

    Glass, Hannah C; Shellhaas, Renée A; Tsuchida, Tammy N; Chang, Taeun; Wusthoff, Courtney J; Chu, Catherine J; Cilio, M Roberta; Bonifacio, Sonia L; Massey, Shavonne L; Abend, Nicholas S; Soul, Janet S

    2017-07-01

    The purpose of this study was to characterize seizures among preterm neonates enrolled in the Neonatal Seizure Registry, a prospective cohort of consecutive neonates with seizures at seven pediatric centers that follow the American Clinical Neurophysiology Society's neonatal electroencephalography monitoring guideline. Of 611 enrolled neonates with seizures, 92 (15%) were born preterm. Seizure characteristics were evaluated by gestational age at birth for extremely preterm (<28 weeks, N = 18), very preterm (28 to <32 weeks, N = 18), and moderate to late preterm (32 to <37 weeks, N = 56) and compared with term neonates. Hypoxic-ischemic encephalopathy (33%) and intracranial hemorrhage (27%) accounted for the etiology in more than half of preterm neonates. Hypothermia therapy was utilized in 15 moderate to late preterm subjects with encephalopathy. The presence of subclinical seizures, monotherapy treatment failure, and distribution of seizure burden (including status epilepticus) was similar in preterm and term neonates. However, exclusively subclinical seizures occurred more often in preterm than term neonates (24% vs 14%). Phenobarbital was the most common initial medication for all gestational age groups, and failure to respond to an initial loading dose was 63% in both preterm and term neonates. Mortality was similar among the three preterm gestational age groups; however, preterm mortality was more than twice that of term infants (35% vs 15%). Subclinical seizures were more common and mortality was higher for preterm than term neonates. These data underscore the importance of electroencephalographic monitoring and the potential for improved management in preterm neonates. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 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

  5. 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

  6. Immunotherapy with intralesional Candida albicans antigen in resistant or recurrent warts: a study.

    PubMed

    Majid, Imran; Imran, Saher

    2013-09-01

    Warts are sometimes resistant or they tend to recur after every possible destructive therapy. Immunotherapy with skin-test antigens has been used as a viable therapeutic option in such recalcitrant cases. The aim of the study was to evaluate the response of resistant or recurrent warts to intralesional Candida albicans antigen immunotherapy. A total of 40 patients with resistant or recurrent warts who showed a positive test reaction to C. albicans antigen were given intralesional injections of purified C. albicans antigen solution in a single wart at 3-weekly intervals for a total of three doses. The patients were monitored for resolution of the injected wart as well as other untreated warts. The patients who responded positively were then followed up for any relapses over the next 6 months. Adverse events, if any, were also documented. Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56%) showed a complete resolution of warts at all places on the body. In addition, two patients (6%) showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38%) failed to show any response to the treatment regimen. In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. The most common adverse effect seen was pain during the intralesional injection. Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences. The small sample size and lack of control group are the main limitations of the study.

  7. Immunotherapy with Intralesional Candida Albicans Antigen in Resistant or Recurrent Warts: A Study

    PubMed Central

    Majid, Imran; Imran, Saher

    2013-01-01

    Background: Warts are sometimes resistant or they tend to recur after every possible destructive therapy. Immunotherapy with skin-test antigens has been used as a viable therapeutic option in such recalcitrant cases. Aim: The aim of the study was to evaluate the response of resistant or recurrent warts to intralesional Candida albicans antigen immunotherapy. Materials and Methods: A total of 40 patients with resistant or recurrent warts who showed a positive test reaction to C. albicans antigen were given intralesional injections of purified C. albicans antigen solution in a single wart at 3-weekly intervals for a total of three doses. The patients were monitored for resolution of the injected wart as well as other untreated warts. The patients who responded positively were then followed up for any relapses over the next 6 months. Adverse events, if any, were also documented. Results: Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56%) showed a complete resolution of warts at all places on the body. In addition, two patients (6%) showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38%) failed to show any response to the treatment regimen. In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. The most common adverse effect seen was pain during the intralesional injection. Conclusions: Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences. Limitations: The small sample size and lack of control group are the main limitations of the study. PMID:24082180

  8. 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.

  9. Clinical studies in oral allergen-specific immunotherapy: differences among allergens.

    PubMed

    Sato, Sakura; Yanagida, Noriyuki; Ogura, Kiyotake; Imai, Takanori; Utsunomiya, Tomohiro; Iikura, Katsuhito; Goto, Makiko; Asaumi, Tomoyuki; Okada, Yu; Koike, Yumi; Syukuya, Akinori; Ebisawa, Motohiro

    2014-01-01

    Oral immunotherapy (OIT) is a significant focus of treatment of food allergy. OIT appears to be effective in inducing desensitization, however, patients receiving OIT frequently developmild/moderate symptoms during the therapy. It has not been clearly established whether the clinical tolerance induced by OIT resembles natural tolerance. According to our data, the efficacy of OIT is different among food antigens, and it is comparatively difficult to achieve the clinical tolerance in milk OIT. Moreover, the definitive evidence of efficacy and safety with long-term therapy is limited. Further studies need to be offered to patients in clinical practice. Recently, novel treatments for food allergy, sublingual and epicutaneous immunotherapy, and combination treatment with an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. OIT combined with omalizumab increased the threshold doses of food without adverse reactions and may be of benefit in food allergy treatment. More studies are needed to demonstrate long-term safety and treatment benefits in a larger patient cohort. © 2014 S. Karger AG, Basel

  10. Using neonatal skin to study the developmental programming of aging.

    PubMed

    Reynolds, Leryn J; Dickens, Brett J; Green, Benjamin B; Marsit, Carmen J; Pearson, Kevin J

    2017-08-01

    Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes. Neonatal foreskin was collected following circumcision and primary dermal fibroblasts were isolated to perform adipocyte differentiation and insulin stimulation experiments. Human neonatal foreskin primary fibroblasts take up lipid when stimulated with a differentiation cocktail and demonstrate insulin signaling when stimulated with insulin. Thus, we propose that foreskin tissue can be used to study developmental exposures and programming that occur in the neonate as it relates to age-associated diseases such as obesity and diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Efficacy of Sublingual Immunotherapy with Dermatophagoides Pteronyssinus: A Real-life Study.

    PubMed

    Vesna, Tomic-Spiric; Denisa, Dizdarevic; Slavenka, Jankovic; Lidija, Burazer; Aleksandra, Barac; Jasna, Bolpacic; Vojislav, Djuric; Aleksandra, Peric-Popadic; Aleksandra, Aleksic; Mirjana, Bogic

    2016-04-01

    Sublingual allergen immunotherapy (SLIT) is considered to be safer and more convenient than subcutaneus immunotherapy. SLIT trials with house dust mites involving patients with allergic rhinitis (AR) and asthma reported discordant results. The aim of the study was to investigate the clinical efficacy and safety of SLIT with Dermatophagoides pteronyssinus (D.pt) extract produced in Serbia and patient's satisfaction through open-label trial. Adult patients with allergic rhinitis were randomized into two groups: one received drugs and SLIT, while other received only drugs. Symptom score (SS), medication score (MS) and cumulative score (CS), skin prick tests (SPT) and serum level of D. pt specific IgE were assessed. One year after, the patients were re-evaluated. In total, 61 patients were enrolled in the study, but 52 of them were analyzed at the end of the year. CS (29.3%, p<0.001) and MS (54.3%, p<0.05) reduced significantly in the SLIT group. There was a significant improvement of MS and CS in the SLIT compared to control group (p<0.001 and p<0.05 respectively). There was no significant improvement of SS as well as specific slgE. Patients in the SLIT group were more satisfied with treatment (p<0.001). The incidence of mild adverse reaction was 38.4%. Specific lgG was not done. One year SLIT with D.pt extract was clinically efficient treatment in AR patients.

  12. 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

  13. 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

  14. Three-dimensional ultrasonographic imaging of the neonatal brain in high-risk neonates: preliminary study.

    PubMed

    Salerno, C C; Pretorius, D H; Hilton, S W; O'Boyle, M K; Hull, A D; James, G M; Riccabona, M; Mannino, F; Craft, A; Nelson, T R

    2000-08-01

    The aim of this investigation was to compare the utility of three-dimensional ultrasonography versus two-dimensional ultrasonography in imaging the neonatal brain. Thirty patients in the neonatal intensive care unit underwent two-dimensional and three-dimensional ultrasonography. The resultant two- and three-dimensional images recorded on film and three-dimensional volumes (reviewed on a workstation) were evaluated independently. Comparable numbers of normal and abnormal studies were diagnosed by each modality. Axial images were considered useful in approximately 50% of three-dimensional cases. Image quality, overall and in the far-field, was rated higher on two-dimensional images. Three-dimensional sonographic acquisition time in the neonatal intensive care unit (1.7 min+/-0.7 standard deviation) was significantly shorter than that for two-dimensional sonography (9.0+/-4.5 min). The total time for evaluation on the three-dimensional workstation (4.4+/-1.1 min) was significantly less than that for two-dimensional images on film (10.6+/-4.7 min). In conclusion, three-dimensional ultrasonography is a promising, diagnostically accurate, and efficient imaging tool for evaluation of the neonatal brain; however, visualization must improve before it can replace two-dimensional ultrasonography.

  15. The large contribution of twins to neonatal and post-neonatal mortality in The Gambia, a 5-year prospective study.

    PubMed

    Miyahara, Reiko; Jasseh, Momodou; Mackenzie, Grant Austin; Bottomley, Christian; Hossain, M Jahangir; Greenwood, Brian M; D'Alessandro, Umberto; Roca, Anna

    2016-03-15

    A high twinning rate and an increased risk of mortality among twins contribute to the high burden of infant mortality in Africa. This study examined the contribution of twins to neonatal and post-neonatal mortality in The Gambia, and evaluated factors that contribute to the excess mortality among twins. We analysed data from the Basse Health and Demographic Surveillance System (BHDSS) collected from January 2009 to December 2013. Demographic and epidemiological variables were assessed for their association with mortality in different age groups. We included 32,436 singletons and 1083 twins in the analysis (twining rate 16.7/1000 deliveries). Twins represented 11.8 % of all neonatal deaths and 7.8 % of post-neonatal deaths. Mortality among twins was higher than in singletons [adjusted odds ratio (AOR) 4.33 (95 % CI: 3.09, 6.06) in the neonatal period and 2.61 (95 % CI: 1.85, 3.68) in the post-neonatal period]. Post-neonatal mortality among twins increased in girls (P for interaction = 0.064), being born during the dry season (P for interaction = 0.030) and lacking access to clean water (P for interaction = 0.042). Mortality among twins makes a significant contribution to the high burden of neonatal and post-neonatal mortality in The Gambia and preventive interventions targeting twins should be prioritized.

  16. 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

  17. 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.

  18. 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.

  19. Propagating Humanized BLT Mice for the Study of Human Immunology and Immunotherapy.

    PubMed

    Smith, Drake J; Lin, Levina J; Moon, Heesung; Pham, Alexander T; Wang, Xi; Liu, Siyuan; Ji, Sunjong; Rezek, Valerie; Shimizu, Saki; Ruiz, Marlene; Lam, Jennifer; Janzen, Deanna M; Memarzadeh, Sanaz; Kohn, Donald B; Zack, Jerome A; Kitchen, Scott G; An, Dong Sung; Yang, Lili

    2016-12-15

    The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete human immune system, therefore providing a powerful tool to study human immunology and immunotherapy. However, its application is greatly limited by the restricted supply of human CD34(+) hematopoietic stem cells and fetal thymus tissues that are needed to generate these mice. The restriction is especially significant for the study of human immune systems with special genetic traits, such as certain human leukocyte antigen (HLA) haplotypes or monogene deficiencies. To circumvent this critical limitation, we have developed a method to quickly propagate established BLT mice. Through secondary transfer of bone marrow cells and human thymus implants from BLT mice into NSG (NOD/SCID/IL-2Rγ(-/-)) recipient mice, we were able to expand one primary BLT mouse into a colony of 4-5 proBLT (propagated BLT) mice in 6-8 weeks. These proBLT mice reconstituted human immune cells, including T cells, at levels comparable to those of their primary BLT donor mouse. They also faithfully inherited the human immune cell genetic traits from their donor BLT mouse, such as the HLA-A2 haplotype that is of special interest for studying HLA-A2-restricted human T cell immunotherapies. Moreover, an EGFP reporter gene engineered into the human immune system was stably passed from BLT to proBLT mice, making proBLT mice suitable for studying human immune cell gene therapy. This method provides an opportunity to overcome a critical hurdle to utilizing the BLT humanized mouse model and enables its more widespread use as a valuable preclinical research tool.

  20. Parents' experiences with neonatal home care following initial care in the neonatal intensive care unit: a phenomenological hermeneutical interview study.

    PubMed

    Dellenmark-Blom, Michaela; Wigert, Helena

    2014-03-01

    A descriptive study of parents' experiences with neonatal home care following initial care in the neonatal intensive care unit. As survival rates improve among premature and critically ill infants with an increased risk of morbidity, parents' responsibilities for neonatal care grow in scope and degree under the banner of family-centred care. Concurrent with medical advances, new questions arise about the role of parents and the experience of being provided neonatal care at home. An interview study with a phenomenological hermeneutic approach. Parents from a Swedish neonatal (n = 22) home care setting were extensively interviewed within one year of discharge. Data were collected during 2011-2012. The main theme of the findings is that parents experience neonatal home care as an inner emotional journey, from having a child to being a parent. This finding derives from three themes: the parents' experience of leaving the hospital milieu in favour of establishing independent parenthood, maturing as a parent and processing experiences during the period of neonatal intensive care. This study suggests that neonatal home care is experienced as a care structure adjusted to incorporate parents' needs following discharge from a neonatal intensive care unit. Neonatal home care appears to bridge the gap between hospital and home, supporting the family's adaptation to life in the home setting. Parents become empowered to be primary caregivers, having nurse consultants serving the needs of the whole family. Neonatal home care may therefore be understood as the implementation of family-centred care during the transition from NICU to home. © 2013 John Wiley & Sons Ltd.

  1. Effect of Pollen-Specific Sublingual Immunotherapy on Oral Allergy Syndrome: An Observational Study

    PubMed Central

    2008-01-01

    Background Oral allergy syndrome (OAS) triggered by fruit and vegetables often occurs in patients with pollen-induced rhinoconjunctivitis because of cross-reactive epitopes in pollen and associated foods. This open observational study examined the effect of pollen-specific sublingual immunotherapy ([SLIT] B. U. Pangramin or SLITone involving birch/alder/hazel, grasses/rye, and/or mugwort) on OAS triggered by several foods in patients treated in standard practice. Very few studies have examined SLIT use in this situation. Methods Patients (n = 102) had pollen-induced rhinoconjunctivitis and OAS and were followed for up to 12 months. Baseline OAS (triggers, symptoms, and symptom severity) was assessed by questionnaire and patient history. Change in OAS was assessed using oral challenge test with 1 or 2 dominant food triggers (and compared with the sum score calculated from the OAS questionnaire at baseline) and clinician ratings of change. Pollen-induced rhinoconjunctivitis symptoms and medication use were also measured. Results In the oral challenge test, 77.0% of patients were considered responders (decrease in sum score of ≥ 50%; no difference in patients receiving B. U. Pangramin or SLITone). At baseline, investigators rated OAS severity as at least moderate in 94.9% of patients compared with 36.9% after 12 months of treatment. After 12 months, OAS was rated as much or very much improved in 72.9% of patients. Sublingual immunotherapy significantly reduced rhinoconjunctivitis symptoms and medication use. Only 10% of patients experienced adverse drug reactions. Conclusion This study supplements the sparse literature on this topic and suggests that pollen-specific SLIT can reduce OAS triggered by pollen-associated foods in patients with pollen-induced rhinoconjunctivitis. PMID:23282323

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

    PubMed Central

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

    2011-01-01

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

  3. Natal and neonatal teeth: a retrospective study of 15 cases.

    PubMed

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

    2011-04-01

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

  4. 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

  5. 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.

  6. Analysis of neonatal resuscitation using eye tracking: a pilot study.

    PubMed

    Law, Brenda Hiu Yan; Cheung, Po-Yin; Wagner, Michael; van Os, Sylvia; Zheng, Bin; Schmölzer, Georg

    2017-08-19

    Visual attention (VA) is important for situation awareness and decision-making. Eye tracking can be used to analyse the VA of healthcare providers. No study has examined eye tracking during neonatal resuscitation. To test the use of eye tracking to examine VA during neonatal resuscitation. Six video recordings were obtained using eye tracking glasses worn by resuscitators during the first 5 min of neonatal resuscitation. Videos were analysed to obtain (i) areas of interest (AOIs), (ii) time spent on each AOI and (iii) frequency of saccades between AOIs. Five videos were of acceptable quality and analysed. Only 35% of VA was directed at the infant, with 33% at patient monitors and gauges. There were frequent saccades (0.45/s) and most involved patient monitors. During neonatal resuscitation, VA is often directed away from the infant towards patient monitors. Eye tracking can be used to analyse human performance during neonatal resuscitation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. 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.

  8. Oral Immunotherapy With Partially Hydrolyzed Wheat-Based Cereals: A Pilot Study.

    PubMed

    Lauener, Roger; Eigenmann, Philippe A; Wassenberg, Jacqueline; Jung, Andreas; Denery-Papini, Sandra; Sjölander, Sigrid; Pecquet, Sophie; Fritsché, Rodolphe; Zuercher, Adrian; Wermeille, Antoine; Fontanesi, Massimo; Mercenier, Annick; Vissers, Yvonne M; Nutten, Sophie

    2017-01-01

    To date, only few studies have assessed oral immunotherapy (OIT) for wheat allergy and often describe severe adverse reactions during therapy. We developed partially hydrolyzed wheat-based cereals (pHC), which were used in a multicenter, open-label, OIT pilot study, in immunoglobulin E-mediated wheat allergy children (NCT01332084). The primary objective of the study was to test whether wheat allergic patients tolerate pHC and primary end point was the presence or not of immediate adverse reactions to pHC during the 1-day initial escalation phase (stepwise increased doses of pHC), with evaluation of the maximum dose tolerated. Of the 9 patients enrolled in the trial, 4 discontinued OIT because of mild to severe reactions at the initial escalation phase. The 5 patients who passed the escalation phase consumed pHC daily for 1 to 6 months. One of these patients withdrew due to noncompliance, whereas the 4 others completed the study and successfully passed the wheat challenge test at the end of the study. About 60% of the adverse events were unrelated to the study product. Our study provides preliminary evidence that pHC is tolerated by a subset of wheat allergic patients. Further studies are warranted to test its efficacy as a potential therapeutic option for wheat allergic patients.

  9. Oral Immunotherapy With Partially Hydrolyzed Wheat-Based Cereals: A Pilot Study

    PubMed Central

    Lauener, Roger; Eigenmann, Philippe A; Wassenberg, Jacqueline; Jung, Andreas; Denery-Papini, Sandra; Sjölander, Sigrid; Pecquet, Sophie; Fritsché, Rodolphe; Zuercher, Adrian; Wermeille, Antoine; Fontanesi, Massimo; Mercenier, Annick; Vissers, Yvonne M; Nutten, Sophie

    2017-01-01

    To date, only few studies have assessed oral immunotherapy (OIT) for wheat allergy and often describe severe adverse reactions during therapy. We developed partially hydrolyzed wheat-based cereals (pHC), which were used in a multicenter, open-label, OIT pilot study, in immunoglobulin E–mediated wheat allergy children (NCT01332084). The primary objective of the study was to test whether wheat allergic patients tolerate pHC and primary end point was the presence or not of immediate adverse reactions to pHC during the 1-day initial escalation phase (stepwise increased doses of pHC), with evaluation of the maximum dose tolerated. Of the 9 patients enrolled in the trial, 4 discontinued OIT because of mild to severe reactions at the initial escalation phase. The 5 patients who passed the escalation phase consumed pHC daily for 1 to 6 months. One of these patients withdrew due to noncompliance, whereas the 4 others completed the study and successfully passed the wheat challenge test at the end of the study. About 60% of the adverse events were unrelated to the study product. Our study provides preliminary evidence that pHC is tolerated by a subset of wheat allergic patients. Further studies are warranted to test its efficacy as a potential therapeutic option for wheat allergic patients. PMID:28959122

  10. 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.

  11. 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

  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. 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

  14. 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.

  15. [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.

  16. 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.

  17. Emerging immunotherapies for glioblastoma

    PubMed Central

    Desai, Rupen; Suryadevara, Carter M.; Batich, Kristen A.; Harrison Farber, S.; Sanchez-Perez, Luis; Sampson, John H.

    2016-01-01

    Immunotherapy for brain cancer has evolved dramatically over the past decade, owed in part to our improved understanding of how the immune system interacts with tumors residing within the central nervous system (CNS). Glioblastoma (GBM), the most common brain tumor in adults, carries a poor prognosis (<15 months) and only few advances have been made since the FDA’s approval of temozolomide (TMZ) in 2005. Importantly, several immunotherapies have now entered patient trials based on promising preclinical data, and recent studies have shed light on how GBM employs a slew of immunosuppressive mechanisms which may be targeted for therapeutic gain. Altogether, accumulating evidence suggests immunotherapy may soon earn its keep as a mainstay of clinical management for GBM. Areas Covered Here, we review cancer vaccines, checkpoint inhibitors, T-cell immunotherapy, and oncolytic virotherapy. Expert Opinion Checkpoint blockade induces antitumor activity by preventing negative regulation of T-cell activation. This platform, however, depends on an existing frequency of tumor-reactive T cells, and GBM is weakly immunogenic and GBM patients are typically immunocompromised. Therefore, checkpoint blockade may be most effective when used in combination with a DC vaccine or adoptively transferred tumor-specific T cells generated ex vivo. Both approaches have been shown to induce endogenous immune responses against tumor antigens, providing a rationale for use with checkpoint blockade where both primary and secondary responses may be potentiated. PMID:27223671

  18. Neonatal invasive candidiasis: a prospective multicenter study of 118 cases.

    PubMed

    López Sastre, José B; Coto Cotallo, Gil D; Fernández Colomer, Belén

    2003-04-01

    A prospective multicenter study was conducted to assess the epidemiology of neonatal invasive candidiasis in Spain. In a total of 20,565 admissions to the 27 participating neonatal units over an 18-month period, systemic candidiasis was diagnosed in 118 (0.57%) neonates. Candida species were isolated from the blood in 79 infants, from the urine in 33, and from the cerebrospinal fluid in 4; in 2 cases, histologic evidence of deep tissue candidiasis was found at autopsy. Very-low-birth-weight (VLBW) infants (< or = 1500 g) showed a significantly higher incidence of systemic candidiasis (4.8%) than infants weighing > 1500 g (0.2%) ( p < 0.001). Candida albicans was the most frequent species (52.5%) followed by C. parapsilosis (23.7%), and C. tropicalis (7.6%). Only seven infants were treated with amphotericin B (initial dose 0.18 +/- 0.3 mg/kg, maximal daily dose 1.7 +/- 0.9 mg/kg) but treatment was stopped in three of them (43%) due to nephrotoxicity. Liposomal amphotericin B was given to 81 neonates and amphotericin B lipid complex to 29. There were no differences in mortality rate and in the incidence of adverse effects in relation to treatment with liposomal amphotericin B or amphotericin B lipid complex. The mortality rate was 10.2% and all deaths occurred in the VLBW cohort with candidemia.

  19. Analgesia and anesthesia for neonates: study design and ethical issues.

    PubMed

    Anand, K J S; Aranda, Jacob V; Berde, Charles B; Buckman, Shaavhrée; Capparelli, Edmund V; Carlo, Waldemar A; Hummel, Patricia; Lantos, John; Johnston, C Celeste; Lehr, Victoria Tutag; Lynn, Anne M; Maxwell, Lynne G; Oberlander, Tim F; Raju, Tonse N K; Soriano, Sulpicio G; Taddio, Anna; Walco, Gary A

    2005-06-01

    The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response.

    PubMed

    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

    2011-03-01

    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. To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study. In this multicenter study, children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge (OFC) at approximately 1 year. Titrated skin prick tests (SPTs) and laboratory studies were performed at regular intervals. Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study because of 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), whereas placebo subjects (n = 9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg; P < .001). In contrast with the placebo group, the peanut OIT group showed reductions in SPT size (P < .001), IL-5 (P = .01), and IL-13 (P = .02) and increases in peanut-specific IgG(4) (P < .001). Peanut OIT subjects had initial increases in peanut-specific IgE (P < .01) but did not show significant change from baseline by the time of OFC. The ratio of forkhead box protein 3 (FoxP3)(hi): FoxP3(intermediate) CD4+ CD25+ T cells increased at the time of OFC (P = .04) in peanut OIT subjects. These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. 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.

  6. 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.

  7. Clinical and ultrastructural study of natal and neonatal teeth.

    PubMed

    Uzamis, M; Olmez, S; Ozturk, H; Celik, H

    1999-01-01

    The present study was undertaken to evaluate the surface topography of mandibular natal and neonatal incisors at the ultrastructural level using the scanning electron microscope (SEM). The enamel of the teeth exhibited hypoplastic, depressed areas and the incisal edge of natal tooth lacked enamel. In addition, root formation of the teeth was not completed, which correlated with findings that teeth may erupt without root formation.

  8. Effects of maternal hypertension on the neonatal haemogram in southern Nigeria: A case-control study.

    PubMed

    Okoye, Helen C; Eweputanna, Lisa I; Korubo, Kaladada I; Ejele, Oseikhuemen A

    2016-12-01

    Hypertension in pregnancy is a leading cause of maternal and neonatal morbidity and mortality. This study aimed to compare the hematological parameters in neonates of hypertensive mothers with those of normotensive mothers, and also to compare the incidence of polycythaemia, neutropenia and thrombocytopenia in both groups. This was a hospital-based case control study. Three milliliters of cord blood from neonates of women with hypertension in pregnancy and those of normotensive pregnant women were sampled for haemogram parameters using a 3-part autoanalyser. Haematocrit and white blood cell differentials were done manually. Data were analysed using SPSS version 16. A total of 200 neonates were recruited, comprising 100 neonates of mothers with hypertensive disorders of pregnancy and 100 neonates of normotensive mothers. The mean haematocrit was significantly higher in neonates of hypertensive mothers than those of normotensive mothers. The neutrophil and platelet counts of neonates of hypertensive mothers were significantly lower than those of normotensive mothers. The incidences of polycythaemia, neutropenia, and thrombocytopenia were found to be 8%, 15%, and 38% among neonates of hypertensive mothers and 0%, 2%, and 8% among neonates of normotensive mothers, respectively. These incidences were significantly different between the groups. There was a positive association between hypertension in pregnancy and neonatal polycythaemia, neutropenia, and thrombocytopenia. Haematological parameters of neonates of mothers with hypertension in pregnancy should be properly evaluated and monitored to reduce the chances of developing complications associated with these abnormalities.

  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. Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study.

    PubMed

    Savi, Eleonora; Incorvaia, Cristoforo; Boni, Elisa; Mauro, Marina; Peveri, Silvia; Pravettoni, Valerio; Quercia, Oliviero; Reccardini, Federico; Montagni, Marcello; Pessina, Laura; Ridolo, Erminia

    2017-01-01

    Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal. We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP). The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom. The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

  11. Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study

    PubMed Central

    Savi, Eleonora; Incorvaia, Cristoforo; Boni, Elisa; Mauro, Marina; Peveri, Silvia; Pravettoni, Valerio; Quercia, Oliviero; Reccardini, Federico; Montagni, Marcello; Pessina, Laura

    2017-01-01

    Background Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal. Methods We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP). Results The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom. Conclusion The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom. PMID:28686638

  12. 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.

  13. Allergen-specific immunotherapy prescription patterns in veterinary practice: a US population-based cohort study.

    PubMed

    Tater, Kathy Chu; Cole, William Elliott; Pion, Paul David

    2017-08-01

    Poor adherence to continuing allergen-specific immunotherapy treatment (ASIT) may be an issue in veterinary medicine. No studies describe how allergen tests are used in general veterinary practice, including the percentage of patients that receive ASIT after allergen testing. Assess veterinary ASIT patterns in United States general practices. Dogs (n = 2,557) and 121 cats allergen-tested at 177 hospitals (173 general practice and four specialty practices) in 44 states. Invoiced service descriptions of allergen tests and ASIT orders were retrieved from an aggregated database of veterinary practices. In general practice, 42% (992 of 2,360) of patients did not begin ASIT after allergen testing. ASIT was not refilled for 29% (398 of 1,368) of patients after the initial order. ASIT was initiated and refilled more often in dogs (56.6%, 71.4%, respectively) than cats (38%, 67.4%). Specialty practice patients had the highest ASIT initiation (94.4%) and refill (92.7%) percentages in comparison to general practices (P < 0.001). Size, age, geographical region and type of practice were associated with whether dogs were started on ASIT. Geographical region was also associated with refilling a prescription for ASIT, which was considered to be evidence of adherence to continuing treatment. Almost one third of clients failed to continue ASIT beyond the initial order, which is a much shorter duration of therapy than the 12 months recommended for determining ASIT efficacy. A large number of general practice patients did not begin ASIT after allergen testing, likely due to differences in how clinicians in general and dermatology practices use allergen tests. © 2017 ESVD and ACVD.

  14. 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.

  15. To study the incidence, etiology and EEG profile of neonatal seizures: a prospective observational study from India.

    PubMed

    Ghanshyambhai, Padmani; Sharma, Deepak; Patel, Ankur; Shastri, Sweta

    2016-01-01

    To study the incidence, etiology and electroencephalography (EEG) profile of neonatal seizures and also to study the correlation between clinical picture and EEG appearance. Prospective observational cohort study. Study duration: September 2011 to April 2013. Inclusion and exclusion: Seizures within first 28 d of life and seizures documented by doctors. Neonates admitted in intensive care unit: intramural (4412) and extramural (1900) admissions (all together 6312). One hundred and seventy-two neonates with seizures were enrolled. All the neonates were evaluated with necessary investigation, ultrasound head and CT scan. All the neonates underwent EEG as early as possible with neonatal stabilization. The etiology of neonatal seizures, CT scan and ultrasound head, characteristic of the EEG and neonatal mortality were noted. The incidence of neonatal seizure was 0.77% in the intramural and 7.3% among the extramural neonates. The incidence of seizures in term newborn was 0.7% and in preterm was 1.1%. The most common cause of neonatal seizure was hypoxic ischemic encephalopathy (HIE) followed by hypocalcemia. The predominant seizure type was multifocal (51%) followed by subtle seizure (43%). There was an EEG abnormality in 72% of the total EEG with varied patterns. The mortality rate in the cohort was 15% with HIE being the most common cause. Most common cases of neonatal seizure were HIE and with the most common type being multifocal. EEG was abnormal in the majority of the neonates with various pattern of abnormality.

  16. Neonatal Safety Information Reported to the FDA During Drug Development Studies

    PubMed Central

    Avant, Debbie; Baer, Gerri; Moore, Jason; Zheng, Panli; Sorbello, Alfred; Ariagno, Ron; Yao, Lynne; Burckart, Gilbert J.; Wang, Jian

    2017-01-01

    Background Relatively few neonatal drug development studies have been conducted, but an increase is expected with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA). Understanding the safety of drugs studied in neonates is complicated by the unique nature of the population and the level of illness. The objective of this study was to examine neonatal safety data submitted to the FDA in studies pursuant to the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) between 1998 and 2015. Methods FDA databases were searched for BPCA and/or PREA studies that enrolled neonates. Studies that enrolled a minimum of 3 neonates were analyzed for the presence and content of neonatal safety data. Results The analysis identified 40 drugs that were studied in 3 or more neonates. Of the 40 drugs, 36 drugs received a pediatric labeling change as a result of studies between 1998 and 2015, that included information from studies including neonates. Fourteen drugs were approved for use in neonates. Clinical trials for 20 of the drugs reported serious adverse events (SAEs) in neonates. The SAEs primarily involved cardiovascular events such as bradycardia and/or hypotension or laboratory abnormalities such as anemia, neutropenia, and electrolyte disturbances. Deaths were reported during studies of 9 drugs. Conclusions Our analysis revealed that SAEs were reported in studies involving 20 of the 40 drugs evaluated in neonates, with deaths identified in 9 of those studies. Patients enrolled in studies were often critically ill, which complicated determination of whether an adverse event was drug-related. We conclude that the traditional means for collecting safety information in drug development trials needs to be adjusted for neonates and will require the collaboration of regulators, industry, and the clinical and research communities to establish appropriate definitions and reporting strategies for the neonatal

  17. Immunotherapy in Peripheral Neuropathies.

    PubMed

    Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina

    2016-01-01

    Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms.

  18. Changes in the Expression of MicroRNA in the Buildup Phase of Wasp Venom Immunotherapy: A Pilot Study.

    PubMed

    Specjalski, Krzysztof; Maciejewska, Agnieszka; Pawłowski, Ryszard; Chełmińska, Marta; Jassem, Ewa

    2016-01-01

    Allergen-specific immunotherapy is the most effective method of treatment in allergy to wasp venom. However, its mechanism of action is still not fully understood. The aim of this study is to describe changes in microRNA (miRNA) expression in patients undergoing the buildup phase of venom immunotherapy. The study group comprised 7 adult patients with a history of severe systemic reactions after stinging by a wasp. In all patients, sensitization to wasp venom had been confirmed by skin tests and serum IgE. The buildup phase of wasp venom immunotherapy (VIT) was conducted according to an ultrarush protocol. In blood samples collected before and 24 h after completing the VIT buildup phase, 740 miRNAs were assessed. Of the 740 miRNAs, 440 were detected in the study group, and in 5 expression was significantly changed after the buildup phase of VIT: miR-370, miR-539, miR-502-3p, miR-299, and miR-29c. Another 62 miRNAs changed 2-fold in some patients (nonsignificant), including increases in miR-143 (stimulating FOXp3 expression) and let-7d (reducing expression of IL-13, IL-6, and TLR4), and decreases in proinflammatory miR-301, miR-146b, miR-106, and miR-485. Several changes in miRNA expression have been found as a result of the buildup phase of wasp VIT, with lower expression of some miRNAs involved in allergic inflammation and higher expression of those possibly involved in tolerance induction. However, the role of the most significant changes is uncertain. © 2016 S. Karger AG, Basel.

  19. Discontinuing venom immunotherapy: extended observations.

    PubMed

    Golden, D B; Kwiterovich, K A; Kagey-Sobotka, A; Lichtenstein, L M

    1998-03-01

    Our studies of discontinuing venom immunotherapy after at least 5 years have led to the conclusion that the residual risk of a systemic reaction to a sting was in the range of 5% to 10% in adults, and no severe or life-threatening reaction occurred with 270 challenge stings in 74 patients after 1 to 5 years without venom immunotherapy. The objective of this study was to extend our observation of patients who discontinue venom immunotherapy over 5 to 10 years and to determine which patients are at higher risk for a reaction. Patients who discontinued venom immunotherapy were surveyed for 3 consecutive years to determine the frequency of systemic reactions to field stings and the fate of venom sensitivity. The evaluation included the 74 patients previously studied (group 1) and 51 additional patients followed after stopping therapy in our clinical center (group 2). Of the original 74 patients, 11 had field stings again after 3 to 7 years without venom immunotherapy, with one systemic reaction (dyspnea). Of the 51 patients in the other group, 15 were stung, of whom four (26%) had systemic reactions, including respiratory symptoms requiring epinephrine. Review of group 1 and group 2 revealed that half of the patients who had systemic reactions to a sting after stopping venom immunotherapy had a history of a systemic reaction occurring during venom immunotherapy (to an injection or a sting). Systemic reactions occurred in three patients who had negative skin test reactions; all three had very low but detectable venom-specific serum IgE antibody levels as determined by RAST and had a history of systemic reactions during venom immunotherapy. Greater severity of the pretreatment reaction was not associated with higher frequency of reaction to stings after stopping therapy but was associated with greater severity if a reaction did occur. Venom immunotherapy (yellow jacket/mixed vespid) in adults can be discontinued after 5 to 6 years with a 5% to 10% residual risk of a

  20. 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

  1. 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

  2. [Neonatal meningitis. Epidemiological study of the Grupo de Hospitales Castrillo].

    PubMed

    2002-06-01

    A prospective multicenter study was designed to assess the incidence, etiology, risk factors and outcomes of vertically transmitted and nosocomial meningitis in neonates over a two-year period. Cases of neonatal meningitis diagnosed between January 1, 1997 and December 31, 1998 in the neonatology departments of 28 acute-care hospitals in Spain ("Grupo de Hospitales Castrillo") were prospectively studied. Bacteriological meningitis was considered confirmed when cerebrospinal fluid culture (CSF) was positive for bacteria, virus or fungi, probable when CSF culture was negative but blood culture was positive, and unconfirmed when both cultures were negative. During the study period, 151 cases of meningitis were diagnosed. Transmission was vertical in 84 cases and nosocomial in 67. The incidence of vertically transmitted meningitis was 0.51 of live births, and was significantly higher in very low birth weight (VLBW) infants. Confirmed bacteriological meningitis was diagnosed in 66 patients (78.6 %). No risk factors were identified in 46.4 % of the patients. Group B Streptococcus (agalactiae) was isolated in 48.5 % of cases of confirmed meningitis and Escherichia coli was isolated in 18.2 %. In 69.7 % of cases the results of blood culture were in agreement with those of CSF culture. The overall mortality rate was 8.3 %; mortality was significantly higher in VLBW infants (33.3 % vs 4.2 % in infants weighing 1,500 g). Thirteen percent of survivors had sequelae. The incidence of meningitis of nosocomial transmission was 0.2 % of admissions and was more frequent in VLBW infants. Confirmed bacteriological meningitis was diagnosed in 49 patients (73.1 %). Two or more risk factors were present in 62.7 % of patients. E. coli was isolated in 26.5 % of cases of nosocomial meningitis and Staphylococcus epidermidis was isolated in 24.5 %. In 55 % of patients the results of blood culture agreed with those of CSF culture. The overall mortality rate was 19.4 %. Mortality was

  3. 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

  4. Factors influencing timing of neonatal discharge in Japan: retrospective study.

    PubMed

    Ishida, Yasushi; Nagaoki, Yuko; Nakagawa, Machiko; Hirata, Michio; Shimabukuro, Rinshu; Kusakawa, Isao; Hosoya, Ryota; Fukui, Tsuguya

    2014-06-01

    The aim of this study was to evaluate the birth and discharge dates of neonates and analyze their distribution over days of the week and the old lunar calendar. A retrospective study of the neonates discharged in the years 1990, 2000, 2005, and 2010 was conducted in a general hospital in Tokyo, Japan. Data are represented as odds ratios (OR) of the total number of discharges per day divided by the expected number of days per year, for each day of the week as well as each 6 day cycle of the lunar calendar. The timing of discharge has an uneven distribution across the days of the week, with weekday discharge rates significantly lower than weekend discharge rates. This uneven distribution is particularly significant in the preterm subgroup. In contrast, there is a minor uneven distribution of births across the days of the week and that of discharges across the 6 day cycle of the lunar calendar. Logistic regression analysis for 2005 and 2010 identified admission fee paid by insurance and prematurity as significant factors associated with weekend/holiday discharge (OR, 1.84; 95% confidence interval [CI]: 1.23-2.75; OR, 1.71; 95% CI: 1.15-2.55, respectively). The average length of stay of neonates discharged on the weekend was longer than that for those discharged on a weekday, in both term and preterm infants. Japanese parents prefer the convenience of weekends over old superstitions about using the lunar calendar to determine the discharge date. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  5. 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

  6. 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.

  7. 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.

  8. High Incidence of Neonatal Danger Signs and Its Implications for Postnatal Care in Ghana: A Cross-Sectional Study

    PubMed Central

    Okawa, Sumiyo; Ansah, Evelyn Korkor; Nanishi, Keiko; Enuameh, Yeetey; Shibanuma, Akira; Kikuchi, Kimiyo; Yasuoka, Junko; Gyapong, Margaret; Owusu-Agyei, Seth; Oduro, Abraham Rexford; Asare, Gloria Quansah; Hodgson, Abraham; Jimba, Masamine

    2015-01-01

    Background Reducing neonatal mortality is a major public health priority in sub-Saharan Africa. Numerous studies have examined the determinants of neonatal mortality, but few have explored neonatal danger signs which potentially cause morbidity. This study assessed danger signs observed in neonates at birth, determined the correlations of multiple danger signs and complications between neonates and their mothers, and identified factors associated with neonatal danger signs. Methods A cross-sectional study was conducted in three sites across Ghana between July and September in 2013. Using two-stage random sampling, we recruited 1,500 pairs of neonates and their mothers who had given birth within the preceding two years. We collected data on their socio-demographic characteristics, utilization of maternal and neonatal health services, and experiences with neonatal danger signs and maternal complications. We calculated the correlations of multiple danger signs and complications between neonates and their mothers, and performed multiple logistic regression analysis to identify factors associated with neonatal danger signs. Results More than 25% of the neonates were born with danger signs. At-birth danger signs in neonates were correlated with maternal delivery complications (r = 0.20, p < 0.001), and neonatal complications within the first six weeks of life (r = 0.19, p < 0.001). However, only 29.1% of neonates with danger signs received postnatal care in the first two days, and 52.4% at two weeks of life. In addition to maternal complications during delivery, maternal age less than 20 years, maternal education level lower than secondary school, and fewer than four antenatal care visits significantly predicted neonatal danger signs. Conclusions Over a quarter of neonates are born with danger signs. Maternal factors can be used to predict neonatal health condition at birth. Management of maternal health and close medical attention to high-risk neonates are crucial to

  9. Life quality of patients with metastatic renal cell carcinoma and chemo-immunotherapy--a pilot study.

    PubMed

    Kröger, M J; Menzel, T; Gschwend, J E; Bergmann, L

    1999-01-01

    Renal cell cancer (RCC) accounts for 2-3% of all malignant tumors in adults. Due to the indolent course of disease and the few signs and symptoms in early stages the majority of patients presents with metastatic disease when diagnosed. The aims of systemic therapy of RCC are therefore palliative. Recent research shows the key role of immune mechanisms in the course of RCC. The therapeutic use of cytokines, mainly interleukin-2 (IL-2) and interferon-alpha (IFN) results in improvement of remission rates. To date it is unknown to what extent multiple cycles of chemo-immunotherapy alter the life quality (LQ) of patients with metastatic RCC. We monitored life quality during therapy in a three-armed protocol with interferon-alpha 2a, interleukin-2, 5-fluorouracil (5-FU), isotretinoin (ISO) and vinblastin (VBL). Life quality was impaired by two factors: response to chemo-immunotherapy and therapy side effects. A steep decrease of LQ-scores was seen in week 1 of therapy, LQ improved then for patients with stable disease (SD) and partial remission (PR) but not for those with progressive disease (PD).

  10. [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%).

  11. 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

  12. Risk factors associated with neonatal deaths: a matched case-control study in Indonesia.

    PubMed

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

    2016-01-01

    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. 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. 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. 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. The study identified a number of factors amenable to health service intervention associated with neonatal deaths in normal and low

  13. Determinants of neonatal mortality in rural Northern Ethiopia: A population based nested case control study.

    PubMed

    Yirgu, Robel; Molla, Mitike; Sibley, Lynn

    2017-01-01

    In low income and middle income countries, neonatal mortality remains high despite the gradual reduction in under five mortality. Newborn death contributes for about 38% of all under five deaths. This study has identified the magnitude and independent predictors of neonatal mortality in rural Ethiopia. This population based nested case control study was conducted in rural West Gojam zone, Northern Ethiopia, among a cohort of pregnant women who gave birth between March 2011 and Feb 2012. The cohort was established by Maternal and Newborn Health in Ethiopia Partnership (MaNHEP) project in 2010 by recruiting mothers in their third trimester, as identified by trained community volunteers. Once identified, women stayed in the cohort throughout their pregnancy period receiving Community Maternal and Newborn Health (CMNH) training by health extension workers and community volunteers till the end of the first 48 hours postpartum. Cases were 75 mothers who lost their newborns to neonatal death and controls were 150 randomly selected mothers with neonates who survived the neonatal period. Data to identify cause of death were collected using the WHO standard verbal autopsy questionnaire after the culturally appropriate 40 days of bereavement period. Binomial logistic regression model was used to identify independent contributors to neonatal mortality. The neonatal mortality rate was AOR(95%CI) = 18.6 (14.8, 23.2) per 1000 live births. Neonatal mortality declined with an increase in family size, neonates who were born among a family of more than two had lesser odds of death in the neonatal period than those who were born in a family of two AOR (95% CI) = 0.13 (0.02, 0.71). Mothers who gave birth to 2-4 AOR(95%CI) = 0.15 (0.05, 0.48) and 5+ children AOR(95%CI) = 0.08 (0.02, 0.26) had lesser odds of losing their newborns to neonatal mortality. Previous history of losing a newborn to neonatal death also increased the odds of neonatal mortality during the last birth AOR (95%CI

  14. [Study on antibiotic resistance of Escherichia coli and Enterococcus colonized in intestine of neonates from neonatal intensive care unit].

    PubMed

    Li, X F; Liu, Z J; Chen, X; Li, J; Cui, Z G; Kan, B; Ma, J R; Cui, J H

    2017-09-10

    Objective: To understand the antibiotic resistance of bacteria colonized in intestine of the neonates from neonatal intensive care unit (NICU) and provide evidence to guide clinical antibiotic treatment. Methods: From May, 2014 to May, 2015, a total of 572 stool samples were collected from the neonates of NICU in our hospital. Escherichia coli and Enterococcus were detected with VITEK-2 system. Results: A total of 328 strains of E. coli and 243 strains of Enterococcus were isolated respectively in this study. The 199 strains of E. coli selected for drug susceptibility test showed lower resistant rate to imipenem, ertapenem, amikacin, nitrofurantoin, ranging from 0.50% to 3.52% and showed higher resistant rate to ampicillin, tetracycline, trimethoprim/sulfamethoxazole and cefazolin, ranging from 54.27% to 84.92%. No meropenem resistant strainsere were found. The percentage of ESBLs production strains was 45%. The multi drug resistance test showed that 34.6% of the strains were resistant to four antibiotics. Three strains were resistant to seven antibiotics. The 243 strains of Enterococcus showed lower resistant rate to quinupristin/dalfopristin, nitrofurantoin, streptomycin, ranging from 0.41% to 4.53% and showed higher resistant rate to ampicillin, benzylpenicillin, ciprofloxacin, tetracycline, gentamicin and erythromycin, ranging from 70.78% to 91.77%. No strains which were resistant to tigecycline, vancomycin, rina thiazole amine/ketone were found. The multi drug-resistance test showed that 86.5% of the strains were resistant to five antibiotics. Conclusions: According to the analysis of the 199 strains of E. coli and 243 strains of Enterococcus isolated from the neonates, we found that the resistance of intestinal bacteria in the neonates was very serious, showing multi drug resistance. It is necessary to use antibiotics according to the drug susceptibility test results in clinical treatment.

  15. 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

  16. 1:4 matched case-control study on influential factor of early onset neonatal sepsis.

    PubMed

    Jiang, Z; Ye, G-Y

    2013-09-01

    Bacteria, funghi, viruses and protozoa can lead to neonatal sepsis. Neonatal sepsis is the leading cause of infectious disease onset and death in many neonates. To explore the major risk factors of early-onset neonatal sepsis and provide a scientific basis for strategies of early-onset neonatal sepsis prevention. A 1:4 matched case-control study was adopted and 147 cases of early-onset neonatal sepsis were enrolled. Conditional logistic regression model was used to analyze the univariate and multivariate data to estimate the odds ratio (OR) and the 95% confidence interval (95% CI). Univariate analysis shows that the impact factors on the occurrence of early-onset neonatal sepsis include the following: Maternal age > 35, mother having fixed occupation, mother of urban residence, abnormal fetal position, fetal times, parity, caesarean section, premature rupture of membranes, amniotic fluid volume abnormalities, pregnancy-induced hypertension, placental abnormalities, fetal distress, newborn gender, low birth weight infants, neonatal Apgar scoring at one and five minutes, neonatal jaundice, wet lung, anemia, IVH, and premature infant. Multivariate logistic regression analysis showed that maternal age > 35 (OR = 4.835, OR 95% CI = 1.170-19.981), cesarean section (OR = 0.103, OR 95% CI = 0.041-0.258), premature rupture of membranes (OR = 0.207, OR 95% CI = 0.078-0.547), premature infants (OR = 0.059, OR 95% CI = 0.010-0.329) and newborn jaundice (OR = 0.092, OR 95% CI = 0.021-0.404) were the factors of early-onset neonatal sepsis. Early-onset neonatal sepsis could be affected by multi-factors, and targeted prevention may reduce the incidence of early-onset neonatal sepsis rates.

  17. 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

  18. 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.

  19. Institution Based Prospective Cross-Sectional Study on Patterns of Neonatal Morbidity at Gondar University Hospital Neonatal Unit, North-West Ethiopia.

    PubMed

    Kokeb, Mehretie; Desta, Teshome

    2016-01-01

    Every year, millions of babies are born and a large proportion of them are being admitted to hospital for various indications. This study was conducted to identify the general characteristics, disease spectrum and common causes of Neonatal morbidity and mortality at Gondar University Hospital, Neonatal Unit. Institution based prospective cross-sectional study was conducted at Gondar University Hospital (GUH), Neonatal Unit, from January 1(st) to March 31(st), 2014. The study included 325 newborns who were admitted to the unit during the study period. The neonates were followed up using structured checklist and neonatal parameters like Neonatal sex, place of delivery, address, length of stay, gestational age, diagnosis and discharge conditions were transcribed into an electronic database for all observations. The primary outcome measures were death and cause of death. A total of 325 neonates were admitted during the study period. Of these, 75.1%, 23.1%, 1.2% and 0.6% were discharged improved, died, discharged with same condition and disappeared, respectively. Ten variables were found to have significant statistical associations with neonatal mortality after adjusting for demographic covariates: Prematurity (p < 0.001), Meningitis (p <0.001), Hemorrhagic Diseases (P <0.001), Hyaline Membrane Disease (P<0.001), Neonatal Sepsis (p <0.05), Meningitis (<0.05), Perinatal Asphyxia (p <0.05), Neonatal Seizure (p <0.05), Home delivery (p <0.05) and Meconium Aspiration (p <0.05). Our study showed that the common causes of neonatal mortality are almost similar with the previous evidences (problems of prematurity, Asphyxia and Sepsis).

  20. Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study.

    PubMed

    Schmitt, Jochen; Schwarz, Kristin; Stadler, Erich; Wüstenberg, Eike Gunther

    2015-12-01

    Allergic rhinitis (AR) is a main risk factor for the development of asthma. Two randomized open-label trials indicated that allergy immunotherapy (AIT) prevents the onset of asthma in patients with AR. However, these trials have methodological limitations, and it is unclear to what extent this experimental efficacy translates into clinical effectiveness. We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR. Using routine health care data from German National Health Insurance beneficiaries, we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005. These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006. Both groups were observed regarding the risk of incident asthma in 2007 to 2012. Risk ratios (RRs) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age, sex, health care use because of AR, and use of antihistamines. In a total of 2431 (2.0%) patients, AIT was started in 2006. Asthma was newly diagnosed from 2007-2012 in 1646 (1.4%) patients. The risk of incident asthma was significantly lower in patients exposed to AIT (RR, 0.60; 95% CI, 0.42-0.84) compared with patients receiving no AIT in 2006. Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy (RR, 0.54; 95% CI, 0.38-0.84) and AIT including native (nonallergoid) allergens (RR, 0.22; 95% CI, 0.02-0.68). AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years. AIT effectively prevents asthma in patients with AR in a real-world setting. Confounding by indication cannot be excluded but would lead to an underestimation of the true preventive effects of AIT. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Patient education programme on immunotherapy in multiple sclerosis (PEPIMS): a controlled rater-blinded study.

    PubMed

    Köpke, S; Kasper, J; Flachenecker, P; Meißner, H; Brandt, A; Hauptmann, B; Bender, G; Backhus, I; Rahn, A C; Pöttgen, J; Vettorazzi, E; Heesen, C

    2017-02-01

    To investigate the effectiveness of a multi-component evidence-based education programme on disease modifying therapies in multiple sclerosis. Controlled trial with two consecutive patient cohorts and a gap of two months between cohorts. Three neurological rehabilitation centres. Patients with multiple sclerosis within rehabilitation. Control group (CG) participants were recruited and received standard information. Two months later, intervention group (IG) participants were recruited and received a six-hour nurse-led interactive group education programme consisting of two parts and a comprehensive information brochure. Primary endpoint was "informed choice", comprising of adequate risk knowledge in combination with congruency between attitude towards immunotherapy and actual immunotherapy uptake. Further outcomes comprised risk knowledge, decision autonomy, anxiety and depression, self-efficacy, and fatigue. A total of 156 patients were included (IG=75, CG=81). The intervention led to significantly more participants with informed choice (IG: 47% vs. CG: 23%, P=0.004). The rate of persons with adequate risk knowledge was significantly higher in the IG two weeks after the intervention (IG: 54% vs. CG: 31%, P=0.007), but not after six months (IG: 48% vs. CG: 31%, P=0.058). No significant differences were shown for positive attitude towards disease modifying therapy (IG: 62% vs. CG: 71%, P=0.29) and for disease modifying therapy status after six months (IG: 61.5% vs CG: 68.6%, P=0.39). Also no differences were found for autonomy preferences and decisional conflict after six months. Delivering evidence-based information on multiple sclerosis disease modifying therapies within a rehabilitation setting led to a marked increase of informed choices.

  2. 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

  3. 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

  4. Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study.

    PubMed

    Maple-Brown, Louise J; Brown, Alex; Lee, I-Lynn; Connors, Christine; Oats, Jeremy; McIntyre, Harold D; Whitbread, Cherie; Moore, Elizabeth; Longmore, Danielle; Dent, Glynis; Corpus, Sumaria; Kirkwood, Marie; Svenson, Stacey; van Dokkum, Paula; Chitturi, Sridhar; Thomas, Sujatha; Eades, Sandra; Stone, Monique; Harris, Mark; Inglis, Chrissie; Dempsey, Karen; Dowden, Michelle; Lynch, Michael; Boyle, Jacqueline; Sayers, Sue; Shaw, Jonathan; Zimmet, Paul; O'Dea, Kerin

    2013-12-01

    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. 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. 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.

  5. Grass pollen sublingual immunotherapy: a double-blind, placebo-controlled study in elderly patients with seasonal allergic rhinitis.

    PubMed

    Bozek, Andrzej; Kolodziejczyk, Krzysztof; Warkocka-Szoltysek, Barbara; Jarzab, Jerzy

    2014-01-01

    This study evaluates the safety and efficacy of specific sublingual immunotherapy (SLIT) against grass pollen allergens in patients >60 years of age with seasonal allergic rhinitis (SAR) and/or asthma. This study sought to assess nasal symptoms during the grass pollen season, reduce medication use, and monitor adverse reactions during immunotherapy. Seventy-eight 60- to 70-year-old patients with SAR and a confirmed grass pollen allergy according to skin-prick tests, nasal provocation, and measurement of serum IgE were included in the study. The patients were individually randomized to the active or placebo groups using a double-blind method. A total of 41 subjects in the SLIT group (5 grass pollen mixture) and 37 subjects in the placebo group were monitored for 3 years. The patients were required to record each use of an antiallergy medication on a diary card. Thirty-eight patients completed 3 years (preseasonal) of SLIT, and 34 subjects finished the placebo treatment in the same time period. The total nasal symptom score decreased by 64% in the active group and 7% in the placebo group after SLIT. This difference was only significant in the active group (p < 0.05). At the end of therapy, the total medication score of the active group decreased significantly by a maximum of 51% (p < 0.05), whereas the total medication score of the placebo group had an insignificant decrease. None of the study participants had systemic adverse reactions during the study period. SLIT in elderly patients with a grass pollen allergy generated a significant clinical improvement in the active group compared with the placebo group for grass pollen season. This therapy was well tolerated.

  6. 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…

  7. Methodological issues in the design and analyses of neonatal research studies: Experience of the NICHD Neonatal Research Network.

    PubMed

    Das, Abhik; Tyson, Jon; Pedroza, Claudia; Schmidt, Barbara; Gantz, Marie; Wallace, Dennis; Truog, William E; Higgins, Rosemary D

    2016-10-01

    Impressive advances in neonatology have occurred over the 30 years of life of The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN). However, substantial room for improvement remains in investigating and further developing the evidence base for improving outcomes among the extremely premature. We discuss some of the specific methodological challenges in the statistical design and analysis of randomized trials and observational studies in this population. Challenges faced by the NRN include designing trials for unusual or rare outcomes, accounting for and explaining center variations, identifying other subgroup differences, and balancing safety and efficacy concerns between short-term hospital outcomes and longer-term neurodevelopmental outcomes. In conclusion, the constellation of unique patient characteristics in neonates calls for broad understanding and careful consideration of the issues identified in this article for conducting rigorous studies in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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.

  9. 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.

  10. Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study.

    PubMed

    Carbajal, Ricardo; Eriksson, Mats; Courtois, Emilie; Boyle, Elaine; Avila-Alvarez, Alejandro; Andersen, Randi Dovland; Sarafidis, Kosmas; Polkki, Tarja; Matos, Cristina; Lago, Paola; Papadouri, Thalia; Montalto, Simon Attard; Ilmoja, Mari-Liis; Simons, Sinno; Tameliene, Rasa; van Overmeire, Bart; Berger, Angelika; Dobrzanska, Anna; Schroth, Michael; Bergqvist, Lena; Lagercrantz, Hugo; Anand, Kanwaljeet J S

    2015-10-01

    Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries. EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective cohort study of the management of sedation and analgesia in patients in NICUs. All neonates admitted to NICUs during 1 month were included in this study. Data on demographics, methods of respiration, use of continuous or intermittent sedation, analgesia, or neuromuscular blockers, pain assessments, and drug withdrawal syndromes were gathered during the first 28 days of admission to NICUs. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (TV) and exposure to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA). This study is registered with ClinicalTrials.gov, number NCT01694745. From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in 18 European countries. Mean gestational age of these neonates was 35.0 weeks (SD 4.6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496 (22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV, and SV groups, respectively, were given sedation or analgesia as a continuous infusion, intermittent doses, or both (p<0.0001). In the participating NICUs, the median use of sedation or analgesia was 89.3% (70.0-100) for neonates in the TV group. Opioids were given to 1764 (26%) of 6680 neonates and to 1589 (74%) of 2142 neonates in the TV group. Midazolam was given to 576 (9%) of 6680 neonates and 536 (25%) neonates of 2142 neonates in the TV group. 542 (25%) neonates in the TV group were given neuromuscular blockers, which were administered as continuous infusions to 146 (7%) of these neonates. Pain

  11. Dutch pediatricians' views on the use of neuromuscular blockers for dying neonates: a qualitative study.

    PubMed

    ten Cate, K; van de Vathorst, S

    2015-07-01

    To assess Dutch pediatricians' views on neuromuscular blockers for dying neonates. Qualitative study involving in-depth interviews with 10 Dutch pediatricians working with severely ill neonates. Data were analyzed using appropriate qualitative research techniques. Participants explained their view on neuromuscular blockers for neonates with a protracted dying process. Major themes were the interpretation of gasping, the role of (the suffering of) the parents, the need for judicial review and legislation's impact on the care participants provide for dying neonates. The interviews show no consensus between pediatricians and provide insights into the points of disagreement. Interviews also suggest friction between the convictions of pediatricians and legislation, which seems to have an undesirable impact on Dutch care for dying neonates and their parents. This study raises important questions for pediatricians worldwide to reflect upon, such as: 'what constitutes 'dying well'?' and 'what role should the parents' perspective play?'.

  12. 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

  13. 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

  14. Phase I/II study of oral immunotherapy with Cry j1-galactomannan conjugate for Japanese cedar pollinosis.

    PubMed

    Murakami, Daisuke; Kubo, Kazuhiko; Sawatsubashi, Motohiro; Kikkawa, Sayaka; Ejima, Masayoshi; Saito, Akira; Kato, Akio; Komune, Shizuo

    2014-08-01

    Among many immunotherapeutic approaches, oral immunotherapy (OIT) is thought to be an effective route for desensitization against a variety of allergens. However, there is little evidence that OIT is effective for airway allergic diseases such as pollen allergy. Thus, in the present study, we assessed the safety, efficacy and immune response of OIT using the Cry j1-galactomannan conjugate for Japanese cedar pollen allergy. An open trial was conducted over a period of 4 months. The OIT group comprised of 23 subjects. Treatment was initiated 1 month before the estimated pollen season and continued for 1 month. The control group (the pharmacological treatment group without OIT) comprised of 11 subjects. The symptoms and medication score, levels of allergen-specific serum antibodies, cellular components of lymphocytes and cytokine production from peripheral blood mononuclear cells (PBMCs) were evaluated throughout the pollen season. The participants receiving OIT treatment showed significant improvements in total symptom scores and symptom-medication scores during the pollen season compared with the control group. The levels of allergen-specific serum IgG4 and IL-10 production in PBMCs were significantly increased in the OIT group compared with that in the control group. Importantly, no severe adverse effects were observed in the participants receiving OIT treatment. Short-term OIT using the Cry j1-galactomannan conjugate is effective, relatively safe and induces tolerant immune responses such as increased allergen-specific serum IgG4 and IL-10 production in PBMCs. These results suggest that OIT using allergen-galactomannan conjugates may provide a rapid, effective, and safe immunotherapy regimen for cedar pollen allergy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Sublingual immunotherapy with a latex extract in paediatric patients: a double-blind, placebo-controlled study.

    PubMed

    Bernardini, Roberto; Campodonico, Patrizia; Burastero, Samuele; Azzari, Chiara; Novembre, Elio; Pucci, Neri; Massai, Cristina; De Martino, Maurizio; Vierucci, Alberto

    2006-08-01

    Natural rubber latex (NRL) allergy remains an important allergic disease triggering urticaria, asthma, angioedema and anaphylaxis. Specific immunotherapy can help to solve problems related to NRL allergy. So far, no controlled clinical trials have been performed in children suffering from NRL allergy. To evaluate the safety and efficacy of sublingual immunotherapy (SLIT) with a commercial NRL extract in children with NRL allergy. Randomized, double-blind, placebo-controlled, 12-month trial. Twenty-six children (aged 4-15 years) with NRL allergy, who had cutaneous and/or respiratory symptoms, including oral allergy syndrome to fruits containing cross-reactive allergens, were recruited. Twelve children were randomized to SLIT with a commercial NRL extract and eight to placebo (3:2). An additional six children with NRL allergy served as untreated controls. A glove use test was utilized to monitor skin and systemic symptoms triggered by NRL exposure at baseline and 3, 6, 9 and 12 months later. Oral allergy symptoms were also monitored. No side effects related to treatments were observed in any patient. A significant improvement of symptom score in treated patients in comparison with baseline values was observed at 3 months (p = 0.01) and consolidated after 1 year of treatment (p = 0.0005). In comparison with placebo, significant improvements were observed starting at 9 months from study start (p = 0.015) and at 12 months (p = 0.005). The number of foods triggering oral allergy symptoms increased in placebo and control subjects, but not in active treated patients (p = 0.05). Latex SLIT was safe and efficacious in paediatric patients with NRL allergy.

  16. Cellular immunotherapies for cancer.

    PubMed

    Berraondo, Pedro; Labiano, Sara; Minute, Luna; Etxeberria, Iñaki; Vasquez, Marcos; Sanchez-Arraez, Alvaro; Teijeira, Alvaro; Melero, Ignacio

    2017-01-01

    Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells. In this meeting report, we summarize the main topics covered and provide an overview of the field of cellular immunotherapy.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. A 2-year study of neonatal mortality in a large Malaysian hospital.

    PubMed

    Boo, N Y; Nasri, N M; Cheong, S K; Sivamohan, N

    1991-04-01

    A 2-year study was carried out in the Maternity Hospital, Kuala Lumpur to determine the neonatal mortality rates. This Hospital functions both as the local service centre as well as the national referral centre in Malaysia. Its neonatal services, however, were equipped and manned at those below Level III perinatal centre. During the study period 52, 877 livebirths took place in the Hospital. In 1987 and 1988 respectively, the low birthweight (less than 2500 gm) rates were: 112.8 and 101.9 per 1000 livebirths, very low birthweight (less than 1500 gm) rates: 11.1 and 8.8 per 1000 livebirths, neonatal mortality rates: 12.5 and 10.7 per 1000 livebirths and neonatal mortality risk ratio: 1.15 and 1.27. There was significant difference in mortality rates among the Malay, Chinese and Indian babies born in this hospital: the Indians had the highest and the Chinese the lowest rates. Babies delivered by breech or lower segment Caesarean section (LSCS) also had significantly higher mortality than those delivered by other modes of delivery. Low birthweight neonates constituted less than 45% of the total special care nursery admission but contributed to more than 70% of the total neonatal deaths. The common causes of neonatal deaths were problems of prematurity, infection, asphyxia and congenital malformations. Preterm and low birthweight neonates died primarily from problems of prematurity or infection. Term and larger neonates died mainly from asphyxia. More than 75% of the neonatal deaths occurred before 7 days of life. Improvement of antenatal care in the community and upgrading of perinatal services in this Hospital could help to lower the morbidity and mortality due to preventable causes.

  2. Ventilator-Associated Pneumonia in Low Birth Weight Neonates at a Neonatal Intensive Care Unit: A Retrospective Observational Study.

    PubMed

    Lee, Pei-Lun; Lee, Wei-Te; Chen, Hsiu-Lin

    2017-02-01

    Ventilator-associated pneumonia (VAP) is one of the most common healthcare-associated infections among ventilated patients. The aim of this study was to determine the clinical characteristics and risk factors for the development of VAP in intubated low birth weight (LBW) neonates in a neonatal intensive care unit. LBW infants (<2.5 kg) admitted to the neonatal intensive care unit of Kaohsiung Medical University Hospital from January 2005 to December 2009 were enrolled. We retrospectively analyzed perinatal and neonatal data of the enrolled intubated LBW infants by chart review. Six hundred and five LBW infants were analyzed. One hundred and fourteen of the infants were intubated for >48 hours, 15 (13.2%) of whom had VAP. Of these 15 patients, the average age at onset of VAP was 24.0 ± 11.2 days, the average postmenstrual age was 30.6 ± 1.8 weeks, and the mean gestational age was 27.1 ± 2.3 weeks, which was significantly lower than the mean gestational age in the group without VAP (30.2 ± 3.5 weeks). The mean birth body weight was 944.4 ± 268.4 g in the VAP group and 1340.1 ± 455.4 g in the group without VAP (p < 0.001). Longer duration of intubation (odds ratio: 1.35, 95% confidence interval: 1.12-1.62) and parenteral nutrition (odds ratio: 1.32, 95% confidence interval: 1.14-1.51) were found in the VAP group after adjusting for gestational age and birth weight. VAP was a problem for the LBW infants with intubation for >48 hours in our neonatal intensive care unit. VAP most frequently occurred at a postmenstrual age of 30-32 weeks in this study. Longer duration of tube placement and parenteral nutrition were found in the VAP group. Early removal of the endotracheal tube and adequate enteral nutrition may decrease the occurrence of VAP in LBW infants. Copyright © 2016. Published by Elsevier B.V.

  3. Care seeking for fatal illness episodes in Neonates: a population-based study in rural Bangladesh

    PubMed Central

    2011-01-01

    Background Poor neonatal health is a major contributor to under-five mortality in developing countries. A major constraint to effective neonatal survival programme has been the lack of population level data in developing countries. This study investigated the consultation patterns of caregivers during neonatal fatal illness episodes in the rural Matlab sub-district of eastern Bangladesh. Methods Neonatal deaths were identified through a population-based demographic surveillance system in Matlab ICDDR,B maternal and child health (MCH) project area and an adjoining government service area. Trained project staff administered a structured questionnaire on care seeking to mothers at home who had experienced a neonatal death. Univariate, bivariate and binary multivariate logistic regressions were performed to describe care seeking during the fatal illness episode. Results Of the 365 deaths recorded during 2003 and 2004, 84% died in the early (0-7 days) neonatal period, with the remaining deaths occurring over the subsequent 8 to 28 days. The first resort of care by parents was a qualified doctor or paramedic in 37% of cases, followed by traditional and unqualified health care providers in 25%, while 38% sought no care. Thus, almost two thirds (63%) of neonates who died received only traditional and unqualified care or no care at all during their final illness episode. About 22% sought care from more than one provider, including 6% from 3 or more providers. Such plurality in care seeking was more likely among male infants, in the late neonatal period, and in the MCH project area. Conclusions The high proportion of neonatal deaths that had received traditional care or no medical care in a rural area of Bangladesh highlights the need to develop community awareness about prompt medical care seeking for neonatal illnesses and to improve access to effective health care. Integration of traditional care providers into mainstream health programs should also be considered. PMID

  4. 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

  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. [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.

  7. Anatomical study of minor alterations in neonate vocal folds.

    PubMed

    Silva, Adriano Rezende; Machado Jr, Almiro José; Crespo, Agrício Nubiato

    2014-01-01

    Minor structural alterations of the vocal fold cover are frequent causes of voice abnormalities. They may be difficult to diagnose, and are expressed in different manners. Cases of intracordal cysts, sulcus vocalis, mucosal bridge, and laryngeal micro-diaphragm form the group of minor structural alterations of the vocal fold cover investigated in the present study. The etiopathogenesis and epidemiology of these alterations are poorly known. To evaluate the existence and anatomical characterization of minor structural alterations in the vocal folds of newborns. 56 larynxes excised from neonates of both genders were studied. They were examined fresh, or defrosted after conservation via freezing, under a microscope at magnifications of 25× and 40×. The vocal folds were inspected and palpated by two examiners, with the aim of finding minor structural alterations similar to those described classically, and other undetermined minor structural alterations. Larynges presenting abnormalities were submitted to histological examination. Six cases of abnormalities were found in different larynges: one (1.79%) compatible with a sulcus vocalis and five (8.93%) compatible with a laryngeal micro-diaphragm. No cases of cysts or mucosal bridges were found. The observed abnormalities had characteristics similar to those described in other age groups. Abnormalities similar to sulcus vocalis or micro-diaphragm may be present at birth. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  9. [Time of cord clamping and neonatal complications, a prospective study].

    PubMed

    Rincón, D; Foguet, A; Rojas, M; Segarra, E; Sacristán, E; Teixidor, R; Ortega, A

    2014-09-01

    To assess the effects of early or late clamping of the umbilical cord in term newborns, assessing the levels of hemoglobin, hematocrit, and ferritin, and their correlation with some of the complications. A prospective study of healthy newborns at term or born by dystotic or eutocic delivery in our hospital between May 2009 until May 2010. Patients were assigned according to the time of clamping, group 1 (<60 seconds), group 2 (1 to<2 minutes), and group 3 (2 to 3 minutes). Laboratory tests were performed at birth and at 48 hours of life, assessing the levels of hemoglobin, hematocrit, ferritin, and bilirubin. The risk of polycythemia, respiratory distress syndrome, neonatal phototherapy or admission to the Intensive Care Unit and the hospital stay, were evaluated. A total of 242 patients were included: group 1 (g1=80), group 2 (g2=31) y group 3 (g3=131). The background maternal and neonatal characteristics were similar in all sets. The first test showed significant differences in ferritin levels in those infants with delayed clamping (g1: 111 mg/dl, g2: 125 mg/dl, g3: 173 mg/dl; p<0.01). In the second analysis the values of hemoglobin (g1: 17.3 g/dl, g2: 18.9 g/dl, g3: 19.2 g/dl; p<0.01), hematocrit (g1: 53.4%, g2: 58%, g3: 59%; p<0.01) and ferritin (g1: 254 mg/dl, g2: 254.7 mg/dl, g3: 313 mg/dl; p = 0.008) were statistically higher in this group. As regards complications, a significant increase was observed in the number of cases of polycythemia symptoms in group 3. The late cord clamping is associated with an increase in hematocrit, hemoglobin and ferritin at 48 hours of life, as well as an increased risk of polycythemia present with symptoms. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  10. Particulate Study on NeoProfen, a Neonatal Injectable Product.

    PubMed

    Krishna, Aravind; Rice, Michael; Kester, Tom; Waters, Michael; Wilson, Terry

    2016-01-01

    NeoProfen or sterile ibuprofen L-lysine at 10 mg/mL ibuprofen, in 2 mL single-use Type I glass vials is often a first choice medication used to close a patent ductus arteriosus in neonatal patients from 500 to 1500 g body weight. Visible particulate matter was found in vials that were placed on a commercial stability program prior to the approved expiration date of 2 years. A combination of instrumental techniques including inductively coupled plasma-mass spectrometry, x-ray photoelectron spectroscopy, scanning electron microscopy energy dispersive x-ray spectrometry, and Raman and Fourier transform infrared microspectroscopy was used to evaluate stability, pilot batch and packaging samples in a root cause investigation. The particulate matter was shown to consist largely of ibuprofen aluminum salts of various stoichiometries. It developed over time by a substitution mechanism, in which the ibuprofen anion in solution reacts with the aluminum oxide network of the borosilicate glass giving the ibuprofen aluminum salt with =Al-OH remaining in the network. For corrective action an alternate Type I borosilicate glass vial with interior coating, not found in the original vial, was chosen for the product to prevent this occurrence. NeoProfen (sterile preservative-free ibuprofin L-lysine at 17 mg/mL in a single-use glass vial) is used to close a clinically significant patent ductus arteriosus in premature infants no more than 32 weeks gestational age. The neonatal population is especially sensitive to outside chemical, physical and environmental conditions because of incompletely developed organ systems, low birth weight and other underlying conditions. Two batches of this product were voluntarily recalled by the manufacturer, Lundbeck, and investigated for the source of particulate matter observed during a commercial stability testing program. This was found to result from an interaction between the product and the Type I borosilicate glass vial where ibuprofen

  11. Platelets for neonatal transfusion - study 2: a randomised controlled trial to compare two different platelet count thresholds for prophylactic platelet transfusion to preterm neonates.

    PubMed

    Curley, Anna; Venkatesh, Vidheya; Stanworth, Simon; Clarke, Paul; Watts, Timothy; New, Helen; Willoughby, Karen; Khan, Rizwan; Muthukumar, Priya; Deary, Alison

    2014-01-01

    Neonatal thrombocytopenia is a common and important clinical problem in preterm neonates. A trial assessing clinically relevant outcomes in relation to the different platelet count thresholds used to trigger transfusion has never been undertaken in preterm neonates with severe thrombocytopenia. Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in current standard practice in reducing the proportion of patients who have a major bleed or die up to study day 28. PlaNeT-2 is a two-stage, randomised, parallel-group, superiority trial. PlaNet-2 compares clinical outcomes in preterm neonates (<34 weeks' gestation at birth) randomised to receive prophylactic platelet transfusions to maintain platelet counts at or above either 25 × 10(9)/l or 50 × 10(9)/l. The primary outcome measure is the proportion of patients who either die or experience a major bleed up to and including study day 28. A total of 660 infants will be randomised. This trial will help define optimal platelet transfusion support for severely thrombocytopenic preterm neonates by evaluating the risks and benefits of two different prophylactic neonatal platelet transfusion thresholds. © 2014 S. Karger AG, Basel.

  12. 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.

  13. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment

    PubMed Central

    de Bot, Cindy MA; Moed, Heleen; Berger, Marjolein Y; Röder, Esther; de Groot, Hans; de Jongste, Johan C; van Wijk, Roy Gerth; Wouden, Johannes C van der

    2008-01-01

    Background For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the efficacy of sublingual immunotherapy with house dust mite allergen compared to placebo treatment in 6 to18-year-old children with allergic rhinitis and a proven house dust mite allergy in primary care. Described here are the methodology, recruitment phases, and main characteristics of the recruited children. Methods Recruitment took place in September to December of 2005 and 2006. General practitioners (in south-west Netherlands) selected children who had ever been diagnosed with allergic rhinitis. Children and parents could respond to a postal invitation. Children who responded positively were screened by telephone using a nasal symptom score. After this screening, an inclusion visit took place during which a blood sample was taken for the RAST test. Results A total of 226 general practitioners invited almost 6000 children: of these, 51% was male and 40% <12 years of age. The target sample size was 256 children; 251 patients were finally included. The most frequent reasons given for not participating were: absence or mildness of symptoms, absence of house dust mite allergy, and being allergic to grass pollen or tree pollen only. Asthma symptoms were reported by 37% of the children. Of the enrolled children, 71% was sensitized to both house dust mite and grass pollen. Roughly similar proportions of children were diagnosed as being sensitized to one, two, three or four common inhalant allergens. Conclusion Our study was designed in accordance with recent recommendations for research on establishing the efficacy of sublingual immunotherapy; 98% of the target sample size was achieved. This study is expected to

  14. 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

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

    PubMed

    Bhagwani, Dalip Kumar; Sharma, Manisha; Dolker, Stanzin; Kothapalli, Sharada

    2016-11-01

    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. 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. 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). 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. 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 seizure was subtle seizure in 25 (40.3%) followed by multifocal in 21 (33

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

    PubMed Central

    2011-01-01

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

  17. A microbiological study of neonatal conjunctivitis in two hospitals in Tehran, Iran

    PubMed Central

    Afjeiee, Seyed Abolfazl; Tabatabaei, Sedigheh Rafiei; Fallah, Fatemeh; Shiva, Farideh; Zanjani, Nafiseh Tahami; Fard, Arezou Tavakkoly; Adabian, Saadat; Rahbar, Mohammad; Nourinia, Ramin; Karimi, Abdollah

    2013-01-01

    Objective To determine the prevalence of neonatal conjunctivitis and to identify the causative agents of ophthalmia neonatorum in two university affiliated hospitals from 2008 to 2009. Methods All neonates admitted in the neonatal department during the study period were examined for the presence of conjunctivitis. Two swab specimens containing epithelial cells of the conjunctiva were collected from newborns presenting with conjuntival inflammation. Laboratory diagnosis was based on direct smear for Gramstaining and bacterial culture. The isolated bacteria were identified using standard procedures. PCR and cell culture were used for identification. Results Of the 2 253 neonates, (age ranged 1–30 days), clinical findings of conjunctivitis were found in 241 cases (10.7%). The most commonly isolated bacteria were Coagulase negative staphylococci, (n=130, 53.9%); Chlamydia trachomatis was the second most common cause of acute neonatal conjunctivitis (n=40, 16.6%). Bacterial cultures were negative in 47 neonates (19.5%) despite clinical signs of conjunctivitis. The median age at presentation for bacterial culture positive was day 8 of life. Conclusions Neonatal conjunctivitis is prevalent in newborns; Gram positive cocci and Chlamydia trachomatis are the most common causative organisms.

  18. 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.

  19. 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.

  20. 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

  1. Immunotherapy in Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-01-01

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

  2. 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.

  3. 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.

  4. 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

  5. A randomized trial of immunotherapy for persistent genital warts

    PubMed Central

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

    2012-01-01

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

  6. 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

  7. 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.

  8. Neonatal mortality and perinatal risk factors in rural southwestern Nigeria: a community-based prospective study.

    PubMed

    Lawoyin, T O; Onadeko, M O; Asekun-Olarimoye, E O

    2010-01-01

    Reliable data on births and deaths particularly at the community level are scarce yet they are urgently needed to inform policy and assess the improvements which may have occurred with recent interventions. To determine neonatal mortality rate and identify perinatal risk factors associated with neonatal deaths. In a community based prospective study, baseline data on births and deaths were collected as they occurred in a rural community of Southwest Nigeria from 1993 to 1998. Data on births and deaths were collected for the period. There were 972 live births and 64 infant deaths giving an infant mortality rate of 65.8 per 1000. Neonatal deaths accounted for a half of all infant deaths (32) giving a neonatal mortality rate of 32.9 per 1000. Twelve (37.5%) of neonatal deaths occurred on the first day of life; half of all neonatal deaths occurred within two days of birth, 21(65.6%) occurred during the first seven days of life and only 11 (34.4%) occurred over the last three weeks of the first month. The commonest known cause of death was associated with low birth weight (LBW) which was responsible for eight (25%) of deaths, while sepsis and fever and maternal deaths and failure to thrive were responsible for four (12.5%) and three (9.4%) deaths respectively. Asphyxia accounted for 3(9.4%) deaths; neonatal tetanus, congenital abnormality and diarrhoea were responsible for one (3.1%) death each. Cause of death was unclassified in many early neonatal deaths particularly those which occurred at home. Predictors of neonatal death included LBW, RR of 4.7; delivery outside a health facility, RR of 3.6; lack of attendant at delivery, RR of 5.01; and Traditional Birth Attendant (TBA) delivering the baby, RR of 2.7. Effect of sex of the neonate, mother and fathers ages were not significant at the 5% level in the model. Neonatal deaths contribute significantly to the high infant mortality in this rural community. Services provided by TBAs are not optimal but appear to be better

  9. Specific immunotherapy using Hymenoptera venom: systematic review.

    PubMed

    Watanabe, Alexandra Sayuri; Fonseca, Luiz Augusto Marcondes; Galvão, Clóvis Eduardo Santos; Kalil, Jorge; Castro, Fabio Fernandes Morato

    2010-01-01

    The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95% confidence intervals. 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.

  10. Side-effects of insect venom immunotherapy: results from an EAACI multicenter study. European Academy of Allergology and Clinical Immunology.

    PubMed

    Mosbech, H; Müller, U

    2000-11-01

    The effect of venom immunotherapy (VIT) is well documented, but fear of systemic side-effects (SE) may prevent its use. The study aimed to analyze the character and frequency of SE and risk factors. In a prospective study, 19 European centers included patients starting on VIT for systemic reactions to insect stings. Various dose regimens were applied. Data from 840 patients with a total of 26 601 injections were obtained. Seventy-one percent were treated with Vespula-venom extract and 27% with honeybee-venom extract. Twenty percent of patients had SE corresponding to 1.9% of injections during dose increase and 0.5% during the maintenance phase. The vast majority of the 280 reactions were mild: only one-third required medical treatment. Injected or inhaled adrenaline was applied in six patients, of whom only one had a drop in blood pressure and collapse. Female sex, bee-venom extract, and rapid dose increase, but not severity of insect sting reactions, increased the risk of SE. The severity of SE was less in males but was not related to age, treatment phase, species of insect, or severity of insect sting reactions. The frequency of SE was low, and the majority of these could be managed without treatment. Risk was increased in females, in bee-venom-treated patients, and in those with rapid dose increase.

  11. 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.

  12. 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.

  13. [Neonatal meningitis. Study of 26 cases and a review of its sequelae after 5 years].

    PubMed

    Cervantes Pardo, A; Tauler Girona, M C; López Soler, C; Puche Mira, A; Casas Fernández, C; Rodríguez Costa, T

    1988-06-01

    Twenty-six cases of neonatal meningitis in term newborns are studied. Incidence, etiological features, treatment, clinical and biochemical evolution and mortality are analysed. Lief motif of this paper is the search for deficits in psychomotor growth in propositi of four and six years old, finding an important relation between neonatal bacterial meningitis and neuropsychological deficits (hyperkinesia, perceptive area impairment, reading-writing disorders, etc.) in contrast to the good evolution of lymphocytic meningitis.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Neonatal magnetocardiography.

    PubMed

    Anastasiadis, P G; Anninos, P; Kotini, A; Koutlaki, N; Garas, A; Galazios, G

    2001-01-01

    The aim of the present study was to test the validity of magnetocardiography (MCG) in the estimation of neonatal cardiac rhythm using a single channel superconductive quantum interference device (SQUID). Our study population consisted of 50 neonates who were delivered normally between 37-41 weeks of gestation from clinically uncomplicated pregnancies. There was also a neonate included in the study in which the diagnosis of "hypoplastic left heart syndrome" was demonstrated by U/S Doppler examination. Maternal age ranged from 18 to 39 years (mean=29.15, SD=6.13). Our study results revealed 44 neonates with normal cardiac rhythm, four with ventricular tachycardia (VT), one with ventricular tachycardia (VT) and extrasystolic beats and one with bradycardia. The neonate with the hypoplastic left heart syndrome presented frequent episodes of ventricular bigeminy in the magnetocardiographic trace. M-mode echocardiography confirmed the diagnosis of the seven cases of arrhythmia in our study group. Results gained from the study lead us to believe that MCG could provide clinical practice with a non-invasive, rapid and easy to perform method, which could be used as an adjunct to conventional methods for the evaluation of neonatal cardiac rhythm.

  1. New architectural design of delivery room reduces morbidity in preterm neonates: a prospective cohort study.

    PubMed

    Terrin, Gianluca; Conte, Francesca; Scipione, Antonella; Aleandri, Vincenzo; Di Chiara, Maria; Bacchio, Erica; Messina, Francesco; De Curtis, Mario

    2016-03-23

    A multidisciplinary committee composed of a panel of experts, including a member of the American Academy of Pediatrics and American Institute of Architects, has suggested that the delivery room (DR) and the neonatal intensive care units (NICU) room should be directly interconnected. We aimed to investigate the impact of the architectural design of the DR and the NICU on neonatal outcome. Two cohorts of preterm neonates born at < 32 weeks of gestational age, consecutively observed during 2 years, were compared prospectively before (Cohort 1: "conventional DR") and after architectural renovation of the DR realized in accordance with specific standards (Cohort 2: "new concept of DR"). In Cohort 1, neonates were initially cared for a conventional resuscitation area, situated in the DR, and then transferred to the NICU, located on a separate floor of the same hospital. In Cohort 2 neonates were assisted at birth directly in the NICU room, which was directly connected to the DR via a pass-through door. The primary outcome of the study was morbidity, defined by the proportion of neonates with at least one complication of prematurity (i.e., late-onset sepsis, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis). Secondary outcomes were mortality and duration of hospitalization. Statistical analysis was performed using standard methods by SPSS software. We enrolled 106 neonates (56 in Cohort 1 and 50 in Cohort 2). The main clinical and demographic characteristics of the 2 cohorts were similar. Moderate hypothermia (body temperature ≤ 35.9 °C) was more frequent in Cohort 1 (57%) compared with Cohort 2 (24%, p = 0.001). Morbidity was increased in Cohort 1 (73%) compared with Cohort 2 (44%, p = 0.002). No statistically significant differences in mortality and median duration of hospitalization were observed between the 2 cohorts of the study. If realized

  2. Nanoparticle Design Strategies for Effective Cancer Immunotherapy

    PubMed Central

    Velpurisiva, Praveena; Gad, Aniket; Piel, Brandon; Jadia, Rahul; Rai, Prakash

    2017-01-01

    Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients. Early clinical substantiation lends weight to the claim that cancer immunotherapies, which are adaptive and enduring treatment methods, generate much more sustained and robust anticancer effects when they are effectively formulated in nanoparticles or scaffolds than when they are administered as free drugs. Engineering cancer immunotherapies using nanomaterials is, therefore, a very promising area worthy of further consideration and investigation. This review focuses on the recent advances in cancer immunoengineering using nanoparticles for enhancing the therapeutic efficacy of a diverse range of immunotherapies. The delivery of immunostimulatory agents to antitumor immune cells, such as dendritic or antigen presenting cells, may be a far more efficient tactic to eradicate tumors than delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In addition to its immense therapeutic potential, immunoengineering using nanoparticles also provides a valuable tool for unearthing and understanding the basics of tumor biology. Recent research using nanoparticles for cancer immunotherapy has demonstrated the advantage of physicochemical manipulation in improving the delivery of immunostimulatory agents. In vivo studies have tested a range of particle sizes, mostly less than 300 nm, and particles with both positive and negative zeta potentials for various applications. Material composition and surface modifications have been shown to

  3. Nanoparticle Design Strategies for Effective Cancer Immunotherapy.

    PubMed

    Velpurisiva, Praveena; Gad, Aniket; Piel, Brandon; Jadia, Rahul; Rai, Prakash

    2017-01-01

    Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients. Early clinical substantiation lends weight to the claim that cancer immunotherapies, which are adaptive and enduring treatment methods, generate much more sustained and robust anticancer effects when they are effectively formulated in nanoparticles or scaffolds than when they are administered as free drugs. Engineering cancer immunotherapies using nanomaterials is, therefore, a very promising area worthy of further consideration and investigation. This review focuses on the recent advances in cancer immunoengineering using nanoparticles for enhancing the therapeutic efficacy of a diverse range of immunotherapies. The delivery of immunostimulatory agents to antitumor immune cells, such as dendritic or antigen presenting cells, may be a far more efficient tactic to eradicate tumors than delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In addition to its immense therapeutic potential, immunoengineering using nanoparticles also provides a valuable tool for unearthing and understanding the basics of tumor biology. Recent research using nanoparticles for cancer immunotherapy has demonstrated the advantage of physicochemical manipulation in improving the delivery of immunostimulatory agents. In vivo studies have tested a range of particle sizes, mostly less than 300 nm, and particles with both positive and negative zeta potentials for various applications. Material composition and surface modifications have been shown to

  4. 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

  5. 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

  6. 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.

  7. 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

  8. An observational study of blood concentrations and kinetics of methyl- and propyl-parabens in neonates.

    PubMed

    Mulla, H; Yakkundi, S; McElnay, J; Lutsar, I; Metsvaht, T; Varendi, H; Nellis, G; Nunn, A; Duncan, J; Pandya, H; Turner, M

    2015-03-01

    Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients. A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. 'Dried Blood Spot' samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach. A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CL PNA<21 days 0.57 versus CL PNA>21 days 0.88 L/h. Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

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

    PubMed Central

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

    2010-01-01

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

  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. 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

  12. 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.

  13. 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

  14. [Sepsis in neonate, A 291 cases study (author's transl)].

    PubMed

    Lozano Giménez, C; Gómez-Taylor, J C; Otero, M C; Fernández-Gilino, C; Mascarós, E

    1979-02-01

    A four-year experience with sepsis in the neonate is described. Clinical picture, laboratory data and mortality of 291 newborn, aged 0-28 days, are analyzed. The rise in the incidence of septicemia in the group of newborn with clinical onset within the first 24 hours of life and the preterm 5. degrees to 9. degrees day of life, was commented. The need to develop a more effective profilaxis toward the reduction of morbidity and mortality is emphasized.

  15. 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

  16. 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

  17. 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

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

    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.

  19. 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

  20. Oral cyclosporine A in neonatal swines for transplantation studies.

    PubMed

    Pan, Hua; Gazarian, Aram; Buff, Samuel; Solla, Federico; Gagnieu, Marie-Claude; Leveneur, Olivia; Watrelot-Virieux, Dorothée; Morisset, Stéphane; Sobh, Mohamad; Michallet, Marie-Cécile; Roger, Thierry; Dubernard, Jean-Michel; Michallet, Mauricette

    2015-02-01

    The purpose of this study is to define the optimal dose of oral cyclosporine A (CsA) microemulsion in newborn swine for transplantation studies and to describe its pharmacokinetics and acute renal effects in short-term administration. Thirteen neonatal pigs were randomized into four groups: one control and three groups with CsA administration at 4, 8 and 12 mg/kg/d for 15 days (D). Blood samples were collected on D 0, 2, 4, 9 and 14 to determine the changes of the CsA trough concentrations, the creatinine (Cr) and blood urea nitrogen (BUN) serum concentrations. On D 14, blood samples were collected every hour from 1 h to 10 h after CsA administration to determine the area under the curve (AUC). On D 15, kidneys were removed for histological analysis. We observed a stabilization of CsA trough concentrations from D 4 to D 14. On D 14, in the three treated groups, CsA trough concentrations were 687 ± 7, 1200 ± 77 and 2211 ± 1030 ng/ml, respectively; AUC (0-10 h) were 6721 ± 51 ng·h/ml in group 4 mg/kg/d, 13431 ± 988 ng·h/ml in group 8 mg/kg/d and 28264 ± 9430 ng·h/ml in group 12 mg/kg/d. Cr concentrations were not significantly different among the four groups; but compared to control group, BUN concentrations of the three treated groups increased significantly. CsA was well tolerated; neither acute, severe adverse event nor renal histological abnormality was observed. In conclusion, a 15-d course of oral CsA treatment ranged from 4 to 12 mg/kg/d is safe for newborn pigs, which need much lower CsA dose than adult pigs to reach comparable trough level and AUC. As immunosuppressive therapy in newborn pigs, we recommend a CsA dose of 4 mg/kg/d to achieve a trough blood concentration between 400 and 800 ng/ml.

  1. 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.

  2. Systematic review of qualitative studies exploring parental experiences in the Neonatal Intensive Care Unit.

    PubMed

    Al Maghaireh, Dua'a Fayiz; Abdullah, Khatijah Lim; Chan, Chong Mei; Piaw, Chua Yan; Al Kawafha, Mariam Mofleh

    2016-10-01

    To determine the feasibility and utility of a thematic analysis approach to synthesising qualitative evidence about parental experiences in the neonatal intensive care unit. Admission of infants to the neonatal intensive care unit is usually an unexpected event for parents who can cause them to experience psychosocial difficulties. A qualitative systematic review is the best method for exploring these parents' experiences regarding this type of admission. Systematic review. Qualitative studies in peer-reviewed journals aimed at understanding parental experiences regarding infant neonatal intensive care unit admission were identified in six electronic databases. Three reviewers selected relevant articles and assessed the quality of the methodological studies using the Critical Appraisal Skills Programme. A thematic analysis approach was used to identify the most common themes in the studies describing parental experiences in the neonatal intensive care unit. A total of eighty articles were identified; nine studies were included in this review. Four studies used semistructured interviews, three used interviews, one used self-reporting and one used both focus group and interview methodologies. Common themes across parents' experiences were the stress of hospitalisation, alteration in parenting roles and the impact of infant hospitalisation on psychological health. Having an infant hospitalised in the neonatal intensive care unit is a stressful experience for parents. This experience is the result of exposure to different stressors related to the infant's condition, an alteration in parenting roles or the neonatal intensive care unit environment and staffing. These parents suffered negative psychological effects, experienced an interrupted development of a healthy parent-infant attachment and/or felt parental role alteration. The study's findings are crucial for neonatal intensive care unit nurses to develop intervention strategies and programmes that help parents to

  3. Oral immunotherapy and potential treatment.

    PubMed

    Sato, Sakura; Yanagida, Noriyuki; Ebisawa, Motohiro

    2015-01-01

    The standardized therapeutic approach for food allergy is based on avoidance of allergens in foods. Oral immunotherapy (OIT) is a significant focus of food allergy research and appears to be effective in inducing desensitization. However, most patients receiving OIT have mild to moderate symptoms during the therapy, and it has not been clearly established whether OIT is effective in inducing permanent tolerance. Recently, novel therapeutic approaches for food allergy, or sublingual immunotherapy and epicutaneous immunotherapy using an anti-IgE monoclonal antibody (omalizumab), have been examined in some studies. These studies showed that the frequency of adverse reactions is lower than with OIT and that patients can increase their food tolerance. Other novel approaches, including the use of omalizumab in combination with OIT, may be useful in food allergy treatment. There is some evidence that a combination of OIT with omalizumab increases threshold doses of food without causing symptoms. OIT offers a new approach for treating food allergy, although further study is needed to demonstrate long-term safety and benefits in larger numbers of patients. © 2015 S. Karger AG, Basel.

  4. Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases.

    PubMed

    Moreno, C; Cuesta-Herranz, J; Fernández-Távora, L; Alvarez-Cuesta, E

    2004-04-01

    The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17,526 administered doses, 17,368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.

  5. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers.

    PubMed

    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.

  6. Current Status and Perspective of Immunotherapy in Gastrointestinal Cancers

    PubMed Central

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

    2016-01-01

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

  7. 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

  8. Oral Immunotherapy for Egg Allergy: A Double-Blind Placebo-Controlled Study, with Postdesensitization Follow-Up.

    PubMed

    Caminiti, Lucia; Pajno, Giovanni B; Crisafulli, Giuseppe; Chiera, Fernanda; Collura, Mirella; Panasci, Girolamo; Ruggeri, Paolo; Guglielmo, Francesco; Passalacqua, Giovanni

    2015-01-01

    Oral immunotherapy (OIT) may be an effective treatment for food allergy in children. It is not clear if the OIT-induced effect is achieved by desensitization (transient state dependent on regular antigen exposure), or by tolerance (persistent condition where the ability to consume the food is retained even after a period of withdrawal). The aim of this study was to investigate the efficacy of OIT-egg desensitization in a double-blind placebo-controlled study, and to evaluate if, after desensitization, tolerance can be maintained. Children with egg allergy were randomized to OIT or placebo for 4 months. At the end of the controlled phase, a double-blind food challenge was repeated to confirm the achieved desensitization. Those subjects found to be desensitized were placed on an egg-containing diet for 6 months, followed by an egg avoidance phase for 3 months, when the food challenge was repeated to determine the maintained tolerance. A total of 31 children were randomized to OIT with dehydrated egg white (n = 17) or placebo (n = 14). Of the 17 active patients (1 dropout), 16 achieved desensitization and started the 6-month egg-containing diet. After 3-month of egg avoidance, 31% remained tolerant. In the control group, only 1 passed the final food challenge. Egg-specific IgG4 increased only in the active group. Five active OIT patients had side effects. Egg OIT results in desensitization in almost all subjects, although tolerance was maintained in only 1/3 of them after a 3-month period of withdrawal. Side effects were encountered, but the procedure appeared safe. In hen egg allergy, OIT is effective for desensitization. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. A Single-Center, Case-Control Study of Low-Dose-Induction Oral Immunotherapy with Cow's Milk.

    PubMed

    Yanagida, Noriyuki; Sato, Sakura; Asaumi, Tomoyuki; Okada, Yu; Ogura, Kiyotake; Ebisawa, Motohiro

    2015-01-01

    This study aimed to investigate the efficacy and safety of low-dose-induction oral immunotherapy (OIT) with 3 ml of milk, which is a lower target volume than is conventionally used. Children aged ≥5 years with milk allergies [confirmed by oral food challenge (OFC) against 3 ml of milk] were enrolled. The OIT group was admitted to the hospital for 5 days for build-up. Subsequently, at home, the volume was gradually increased by up to a maximum of 3 ml every 5 days. While the OIT group ingested a small amount of milk every day, the control group completely eliminated their milk intake. Both groups underwent OFCs approximately 1 year later in order to assess their responsiveness to 3 ml and 25 ml of cow's milk. The OIT and control groups had no background differences; the proportion of patients unresponsive to 3 ml of milk after 1 year was 58.3% (7/12) and 13.8% (4/25), respectively (p = 0.018), while the proportion unresponsive to 25 ml of milk was 33.3% (4/12) and 0.0% (0/25), respectively (p = 0.007). Furthermore, a significant decrease in the casein-specific immunoglobulin E levels was seen after 12 months when compared to baseline in the OIT group (p = 0.033). Adverse allergic reactions were rare and most symptoms were mild. This study of a high-risk population reacting to very low amounts of milk showed that low-dose-induction OIT appeared effective for acquiring unresponsiveness to 3 ml and 25 ml of milk, with severe symptoms being rare, indicating that for improvement of food allergies, continuous intake of small amounts may be as effective as intake of larger amounts. © 2015 S. Karger AG, Basel.

  10. Recombinant allergens for specific immunotherapy.

    PubMed

    Cromwell, Oliver; Häfner, Dietrich; Nandy, Andreas

    2011-04-01

    Recombinant DNA technology provides the means for producing allergens that are equivalent to their natural counterparts and also genetically engineered variants with reduced IgE-binding activity. The proteins are produced as chemically defined molecules with consistent structural and immunologic properties. Several hundred allergens have been cloned and expressed as recombinant proteins, and these provide the means for making a very detailed diagnosis of a patient's sensitization profile. Clinical development programs are now in progress to assess the suitability of recombinant allergens for both subcutaneous and sublingual immunotherapy. Recombinant hypoallergenic variants, which are developed with the aim of increasing the doses that can be administered while at the same time reducing the risks for therapy-associated side effects, are also in clinical trials for subcutaneous immunotherapy. Grass and birch pollen preparations have been shown to be clinically effective, and studies with various other allergens are in progress. Personalized or patient-tailored immunotherapy is still a very distant prospect, but the first recombinant products based on single allergens or defined mixtures could reach the market within the next 5 years. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  11. 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.

  12. Effect of obesity on neonatal hypoglycaemia in mothers with gestational diabetes: A comparative study.

    PubMed

    Collins, Katherine; Oehmen, Raoul; Mehta, Shailender

    2017-09-13

    Rates of pre-gestational obesity and gestational diabetes mellitus (GDM) are increasing in Australia. While both are established risk factors for neonatal hypoglycaemia, the additive effect of both risks on neonatal hypoglycaemia is not well understood. To determine the influence of obesity on neonatal hypoglycaemia among infants born to GDM mothers. The authors hypothesise the presence of a greater frequency and severity of neonatal hypoglycaemia in infants born to obese GDM women. A cohort of 471 singleton GDM pregnancies was retrospectively studied. Women were divided into obese (body mass index (BMI) ≥ 30 kg/m(2) ) and not-obese (BMI < 30 kg/m(2) ) groups according to self-reported pre-pregnancy weight. Perinatal outcomes and details of hypoglycaemic episodes were obtained by reviewing medical records. Twenty-five percent (104/410) of the GDM mothers were obese, while 36% (146/410) exceeded pregnancy weight gain recommendations. GDM and obesity resulted in a greater frequency of neonatal hypoglycaemia as compared to women with GDM alone (obese 44%, not obese 34%, P = 0.046). Obesity increased the likelihood of having multiple hypoglycaemic episodes (P = 0.022). Excess weight gain increased the likelihood of the neonate requiring intravenous dextrose (P = 0.0012). No differences were found in the likelihood of nursery admissions or lowest plasma glucose levels. Pre-pregnancy obesity and weight gain during pregnancy above the recommended limits increased the likelihood of neonatal hypoglycaemia among infants of GDM mothers. Further studies with larger cohorts are warranted to confirm our findings. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  13. A chronological study of the bacterial pathogen changes in acute neonatal bacterial conjunctivitis in southern China.

    PubMed

    Tang, Song; Li, Ming; Chen, Hongbo; Ping, Guo; Zhang, Chun; Wang, Shusheng

    2017-09-26

    The aim of the project is to retrospectively study the changes in bacterial pathogens in acute neonatal bacterial conjunctivitis from 2002 to 2016 in Southern China. The results may provide the guidance for drug choice for acute neonatal bacterial conjunctivitis. Secretion specimens for bacterial culture were taken from 485 cases with clinically diagnosed acute bacterial neonatal conjunctivitis. Bacterial pathogens were detected by Gram staining and subsequent bacterial culture. From the analysis of the bacterial pathogens in 485 cases of acute neonatal conjunctivitis patients from 2002 to 2016 in Southern China, there is an overall trend of decreasing detection of Gram-positive bacteria and increasing detection of Gram-negative bacteria from the conjunctival sac secretions. Gram-positive bacteria in the bacteria-positive samples dropped year by year from 82.6% in 2002 to 72.4% in 2016. Accordingly, the ratio of Gram-negative bacteria increased from 17.4% in 2002 to 27.6% in 2016. Of note, despite the overall trend, there was a significant increase in detection of Gram-positive bacteria and decrease in detection of Gram-negative bacteria from 2011 to 2012. Among the Gram-positive bacteria, there is a trend of increasing percentage of the opportunistic pathogens (an ~60% increase in Staphylococcus epidermidis and Staphylococcus saprophytic) and decreasing percentage of Staphylococcus aureus (~30% decrease) and hemolytic streptococcus (~20% decrease) in the last 15 years. The main Gram-negative bacterium is Neisseria gonorrhoeae. Overall, there is a change in the pattern of bacterial species in acute neonatal bacterial conjunctivitis in Southern China in the last 15 years. Our study provides a trend analysis of the bacterial pathogens in the conjunctival sac secretions of the acute neonatal bacterial conjunctivitis patients in Southern China in recent years. This data could provide useful information regarding the treatment options for neonatal bacterial

  14. Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

    PubMed

    Palacio, Montse; Bonet-Carne, Elisenda; Cobo, Teresa; Perez-Moreno, Alvaro; Sabrià, Joan; Richter, Jute; Kacerovsky, Marian; Jacobsson, Bo; García-Posada, Raúl A; Bugatto, Fernando; Santisteve, Ramon; Vives, Àngels; Parra-Cordero, Mauro; Hernandez-Andrade, Edgar; Bartha, José Luis; Carretero-Lucena, Pilar; Tan, Kai Lit; Cruz-Martínez, Rogelio; Burke, Minke; Vavilala, Suseela; Iruretagoyena, Igor; Delgado, Juan Luis; Schenone, Mauro; Vilanova, Josep; Botet, Francesc; Yeo, George S H; Hyett, Jon; Deprest, Jan; Romero, Roberto; Gratacos, Eduard

    2017-08-01

    Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique. Copyright © 2017. Published by Elsevier Inc.

  15. Dendritic cell immunotherapy for urological cancers using cryopreserved allogeneic tumour lysate-pulsed cells: a phase I/II study.

    PubMed

    Pandha, Hardev S; John, Robert J; Hutchinson, James; James, Nick; Whelan, Mike; Corbishley, Catherine; Dalgleish, Angus G

    2004-08-01

    To assess the feasibility, toxicity and immunogenicity of dendritic cell (DC)-based immunotherapy in patients with advanced urological cancers. Patients with hormone-refractory prostate cancer (11) and metastatic renal cell carcinoma (five) received 1-3 x 10(6) intradermal allogeneic tumour lystate-pulsed DCs fortnightly for six vaccinations then monthly until disease progression. Intradermal keyhole limpet haemocyanin was injected near the DCs as the adjuvant. DC vaccine was prepared from buffy coats, then lysate-pulsed, cryopreserved in aliquots, and tested for phenotypic expression and activity in an allogeneic mixed lymphocyte reaction before clinical use. There was no evidence of significant toxicity from vaccine or adjuvant. Delayed-type hypersensitivity skin testing and biopsy revealed a cellular infiltrate to intradermal re-challenge to tumour lysate and adjuvant in almost all patients. In addition, there was increased expression of T helper type 1 cytokines, interferon-gamma-expressing T cell by ELISPOT analysis, but also interleukin-10 in a few patients. Vaccination resulted in a reduction in the level of prostate-specific antigen (PSA) in one patient, a reduction in PSA velocity in a further man and an increased PSA doubling time in six. Two of five patients with renal cell carcinoma had stabilization of disease. The cryopreservation and repeated administration of DC vaccine was feasible and not toxic. There was evidence of induction of both humoral and cellular immunity to vaccine and adjuvant in most patients. The use of sequential aliquots of identical cryopreserved vaccine will ensure quality control and greatly facilitate future clinical studies in terms of consistency of vaccine administered and the provision of primed DCs for in vitro assessment of response.

  16. 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.

  17. Comparing apples with apples: it is time for standardized reporting of neonatal nutrition and growth studies.

    PubMed

    Cormack, Barbara E; Embleton, Nicholas D; van Goudoever, Johannes B; Hay, William W; Bloomfield, Frank H

    2016-06-01

    The ultimate goal of neonatal nutrition care is optimal growth, neurodevelopment, and long-term health for preterm babies. International consensus is that increased energy and protein intakes in the neonatal period improve growth and neurodevelopment, but after more than 100 y of research the optimum intakes of energy and protein remain unknown. We suggest an important factor contributing to the lack of progress is the lack of a standardized approach to reporting nutritional intake data and growth in the neonatal literature. We reviewed randomized controlled trials and observational studies documented in MEDLINE and the Web of Science from 2008 to 2015 that compared approximately 3 vs. 4 g.kg(-1).d(-1) protein for preterm babies in the first month after birth. Consistency might be expected in the calculation of nutritional intake and assessment of growth outcomes in this relatively narrow scope of neonatal nutrition research. Twenty-two studies were reviewed. There was substantial variation in methods used to estimate and calculate nutritional intakes and in the approaches used in reporting these intakes and measures of infant growth. Such variability makes comparisons amongst studies difficult and meta-analysis unreliable. We propose the StRONNG Checklist-Standardized Reporting Of Neonatal Nutrition and Growth to address these issues.

  18. Developing Precision Immunotherapies - Annual Plan

    Cancer.gov

    Despite remarkable progress, cancer immunotherapies can be toxic to some patients. Learn how NCI-funded research will extend the benefits of immunotherapy to more patients through biomarker research and collaboration.

  19. A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries

    PubMed Central

    Saleem, Sarah; Goudar, Shivaprasad S; Patel, Archana; Esamai, Fabian; Garces, Ana; Chomba, Elwyn; Althabe, Fernando; Moore, Janet; Kodkany, Bhalachandra; Pasha, Omrana; Belizan, Jose; Mayansyan, Albert; Derman, Richard J; Hibberd, Patricia L; Liechty, Edward A; Krebs, Nancy F; Hambidge, K Michael; Buekens, Pierre; Carlo, Waldemar A; Wright, Linda L; Koso-Thomas, Marion; Jobe, Alan H; Goldenberg, Robert L

    2014-01-01

    Abstract Objective To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths. Methods A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum. Findings Between 2010 and 2012, 214 070 of 220 235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100 000 live births, ranging from 69 per 100 000 in Argentina to 316 per 100 000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97–11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26–5.67) and 7-day (RR: 3.94; 95% CI: 2.74–5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54–9.77). Conclusion Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality. PMID:25177075

  20. A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries.

    PubMed

    Saleem, Sarah; McClure, Elizabeth M; Goudar, Shivaprasad S; Patel, Archana; Esamai, Fabian; Garces, Ana; Chomba, Elwyn; Althabe, Fernando; Moore, Janet; Kodkany, Bhalachandra; Pasha, Omrana; Belizan, Jose; Mayansyan, Albert; Derman, Richard J; Hibberd, Patricia L; Liechty, Edward A; Krebs, Nancy F; Hambidge, K Michael; Buekens, Pierre; Carlo, Waldemar A; Wright, Linda L; Koso-Thomas, Marion; Jobe, Alan H; Goldenberg, Robert L

    2014-08-01

    To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths. A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum. Between 2010 and 2012, 214,070 of 220,235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100,000 live births, ranging from 69 per 100,000 in Argentina to 316 per 100,000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97-11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26-5.67) and 7-day (RR: 3.94; 95% CI: 2.74-5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54-9.77). Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality.

  1. 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

  2. Maternal Overt Hypothyroidism and Neurobehavioral Outcome of Neonates: A Cohort Study from an Iodine-deficient Area of Northern India.

    PubMed

    Ganaie, Mohammad Ashraf; Charoo, Bashir A; Sofi, Riyaz Ahmad; Ahmed, Asif; Bhat, Javeed Iqbal

    2015-10-01

    To study the relation between maternal overt hypothyroidism and neurodevelopmental outcome of neonates in iodine-deficient region of Northern India (Kashmir Valley). Prospective cohort study. Endocrinology department of a tertiary-care hospital. 82 hypothyroid pregnant women were enrolled and followed up till delivery. The neonates born to this group represented the case neonates. 51 euthyroid healthy pregnant women were selected as control group. The neonates born to these mothers served as controls. Early neonatal behavioral assessment at 3-4 weeks of age. The mean TSH and free T4 in neonates of mothers with well controlled hypothyroidism was significantly different from those born to mothers with poorly controlled hypothyroidism and controls in 1st trimester, but the difference was statistically insignificant for 2nd and 3rd trimester values. Overt maternal hypothyroidism in iodine-deficient area constitutes a risk factor for an abnormal neurobehavioral development of affected child.

  3. Egg oral immunotherapy.

    PubMed

    Vickery, Brian P

    2012-06-01

    Egg allergy is one of the most common food allergies of childhood and no interventional therapy is currently approved by the Food and Drug Administration. Much recent research has focused on the safety, efficacy, and mechanism of oral immunotherapy (OIT) as a disease-modifying treatment. Small pilot studies with varying protocol designs have shown egg OIT to be relatively well tolerated, and efficacy is suggested but not formally demonstrated. At this time, no placebo-controlled randomized trial has been published confirming desensitization and no published study has convincingly demonstrated the development of OIT-induced tolerance to egg. Egg OIT is a promising modality for providing temporary protection from reactions caused by accidental egg exposure. However, the overall strength of the evidence in favor of egg OIT is limited by small sample sizes and the lack of controls, both of which are important considerations given the spontaneous resolution expected in egg allergy. More high-quality studies are necessary before egg OIT can be recommended as a viable treatment option.

  4. Prenatal, perinatal, and neonatal risk factors for specific language impairment: a prospective pregnancy cohort study.

    PubMed

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

    2014-08-01

    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. Participants were members of the Raine Study, a prospective cohort investigation of pregnant women and their offspring. Parent report indicated that 26 children had received a clinical diagnosis of SLI. Data from antenatal and birth medical records were compared between the children with SLI and typically developing comparison children (N = 1,799). There were no statistically significant differences between the SLI and comparison groups in the individual prenatal, perinatal, and neonatal factors examined. Aggregate risk scores were calculated for each period on the basis of factors known to be associated with neurodevelopmental disorder. There were no group differences in aggregate risk scores in the prenatal and perinatal periods. However, significantly more children in the SLI group (50%) compared with the comparison group (27.6%) experienced 2 or more risk factors during the neonatal period. The vast majority of prenatal, perinatal, and neonatal complications do not play a clear causal role in childhood SLI. However, poor neonatal health may signify increased risk for SLI.

  5. 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.

  6. 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

  7. Anxiety and depression in parents of sick neonates: a hospital-based study.

    PubMed

    Kong, Li-Ping; Cui, Yan; Qiu, Yu-Fang; Han, Shu-Ping; Yu, Zhang-Bin; Guo, Xi-Rong

    2013-04-01

    To investigate the prevalence of anxiety and depression in parents of hospitalised neonates and to analyse their relationship with other factors such as stress and social support, to provide evidence for targeted clinical interventions. The perinatal period, a special susceptibility to negative emotions, is a period that women and their spouses have to face. In this time, the fact that the neonates have to be hospitalised is no doubt a huge psychological stress to their parents. Little understanding of the hospitalisation environment, lacking awareness of neonatal diseases as well as concerns about the neonates' safety, can easily lead to negative emotions in parents. Under the influence of negative mood, parents could become irritable and vulnerable, which may do harm to their physical and mental health, impact family harmony and even result in ineffective communication with doctors, affecting the care of neonates. This study applied a cross-sectional study design. The psychological status of 600 parents (400 fathers and 200 mothers) was assessed in the first week of the hospitalisation of neonates, using the Self-Rating Anxiety Scale, Self-Rating Depressive Scale, Social Support Rating Scale and Perceived Stress Scale. The results of the cross-sectional survey showed that 20% of fathers and 24% of mothers had symptoms of anxiety, while 30.8% of fathers and 35% of mothers had depressive symptoms. The total scores for anxiety and depression in these parents were significantly higher than the normal population (p<0.01). The level of social support and perceived stress were the most important factors relating to parental anxiety and depression. Parents of hospitalised neonates are more prone to suffer from negative emotions than normal population. Anxiety and depression are common emotions in these parents. However, the social support they receive is far from satisfactory, so timely and effective nursing interventions are essential. Health professionals should

  8. First-in-Human Study of Interleukin-15 as Immunotherapy for Metastatic Cancer | Center for Cancer Research

    Cancer.gov

    One of the hallmarks of cancer that is now more clearly recognized is tumors’ ability to avoid recognition and destruction by the immune system. A novel class of treatments, dubbed immunotherapy, attempts to overcome this aspect by stimulating the immune system to attack cancer cells. The cytokine interleukin-2 (IL-2), which is approved for the treatment of renal cancer and melanoma, is the prototypic immunotherapy. Treatment with IL-2 enhances the proliferation of effector immune cells, such as cytotoxic T lymphocytes and natural killer (NK) cells. Unfortunately, IL-2 also exerts immunosuppressive activity through maintenance of regulatory T cells and activation-induced cell death. The related cytokine, interleukin-15 (IL-15), displays similar immune cell stimulatory activity, but without the inhibitory effects of IL-2. These findings, suggest that IL-15 may have greater potential as an immunotherapeutic agent and is consistent with the results seen in melanoma and prostate and colon cancer mouse models.

  9. A single case study of the communication development of a high-risk neonate, from birth to discharge from a neonatal intensive care unit.

    PubMed

    McInroy, Alethea; Kritzinger, Alta

    2005-01-01

    Since preterm and low birth weight infants display a high-risk for communication disorders or delays, the Neonatal Intensive Care Unit (NICU) provides the earliest opportunity where family-centered early communication intervention (ECI) services can be initiated. Extensive knowledge about high-risk neonates exists, but there appears to be limited knowledge about the emergence of early communication skills in these neonates. The aim of the study was to provide a systematic description of the successive communication developmental steps of a high-risk neonate on a weekly basis, from birth to discharge from a NICU, in order to guide further research on a larger scale. An A-type single case study design was used to collect prospective data over 14 sessions during the participant's 51-day stay in the NICU. Using a comprehensive data-collection protocol, rich data sets were gleaned over time. The results are described as a chronology of events contributing to the participant's risk status and influencing his early communication development. The successive emergence of the different components of language skills in the participant provided new insights into the communication development of a preterm neonate and should be further investigated. An ECI programme and guidelines for implementation in the NICU are discussed as a treatment option.

  10. 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

  11. 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.

  12. Maternal and neonatal risk factors for childhood type 1 diabetes: a matched case-control study.

    PubMed

    Robertson, Lynn; Harrild, Kirsten

    2010-05-27

    An interaction between genetic susceptibility and environmental factors is thought to be involved in the aetiology of type 1 diabetes. The aim of this study was to investigate maternal and neonatal risk factors for type 1 diabetes in children under 15 years old in Grampian, Scotland. A matched case-control study was conducted by record linkage. Cases (n = 361) were children born in Aberdeen Maternity Hospital from 1972 to 2002, inclusive, who developed type 1 diabetes, identified from the Scottish Study Group for the Care of Diabetes in the Young Register. Controls (n = 1083) were randomly selected from the Aberdeen Maternity Neonatal Databank, matched by year of birth. Exposure data were obtained from the Aberdeen Maternity Neonatal Databank. Conditional logistic regression was used to evaluate the association between various maternal and neonatal factors and the risk of type 1 diabetes. There was no evidence of statistically significant associations between type 1 diabetes and maternal age, maternal body mass index, previous abortions, pre-eclampsia, amniocentesis, maternal deprivation, use of syntocinon, mode of delivery, antepartum haemorrhage, baby's sex, gestational age at birth, birth order, birth weight, jaundice, phototherapy, breast feeding, admission to neonatal unit and Apgar score (P > 0.05). A significantly decreased risk of type 1 diabetes was observed in children whose mothers smoked at the booking appointment compared to those whose mothers did not, with an adjusted OR of 0.67, 95% CI (0.46, 0.99). This case-control study found limited evidence of a reduced risk of the development of type 1 diabetes in children whose mothers smoked, compared to children whose mothers did not. No evidence was found of a significant association between other maternal and neonatal factors and childhood type 1 diabetes.

  13. 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.

  14. Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs: a blind, randomized, placebo-controlled study.

    PubMed

    Maina, E; Pelst, M; Hesta, M; Cox, E

    2017-01-18

    Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 μg of peanut extract daily for 7 to 14 days. All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions

  15. 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.

  16. 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).

  17. Oral morphine weaning for neonatal abstinence syndrome at home compared with in-hospital: an observational cohort study.

    PubMed

    Kelly, Lauren E; Knoppert, David; Roukema, Henry; Rieder, Michael J; Koren, Gideon

    2015-04-01

    The objective of this observational study was to evaluate the safety and effectiveness of discharging stabilized neonates to complete their oral morphine weaning at home. This retrospective cohort study evaluated neonates treated with oral morphine at two hospitals in London, Ontario, Canada. Neonates who completed their morphine wean in hospital were compared with neonates who completed their morphine wean following discharge from hospital (at home). There were 80 neonates treated with oral morphine at two hospitals from 2006 to 2010. The majority (65%, 52/80) of neonates completed their morphine weaning after hospital discharge and were significantly less likely to return to hospital for further withdrawal treatment (1/52 vs. 4/28, p < 0.05). Neonates who were treated at home remained on morphine for more days (32 vs. 19 days, p < 0.01). We present the first North American cohort of neonates weaned with morphine at home for neonatal abstinence syndrome (NAS). We found that more days on oral morphine resulted in fewer returns to hospital for continued withdrawal management. There was no evidence of increased effectiveness, measured by the number of returns to hospital for further NAS management with in-hospital weaning. The estimated cost savings of continued weaning upon discharge was approximately $11,000 per patient (Canadian dollars). While further prospective research is necessary, in some cases morphine weaning at home may present a safe and cost-effective strategy for NAS management.

  18. 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

  19. Pre-seasonal, subcutaneous immunotherapy: a double-blinded, placebo-controlled study in elderly patients with an allergy to grass.

    PubMed

    Bozek, Andrzej; Kolodziejczyk, Krzysztof; Krajewska-Wojtys, Anna; Jarzab, Jerzy

    2016-02-01

    There is limited evidence indicating that specific immunotherapy in elderly patients is safe and effective. To evaluate the safety and efficacy of pre-seasonal specific subcutaneous immunotherapy (SCIT) against grass pollen allergens in patients older than 65 years with seasonal allergic rhinitis and to measure the prime outcome of area under the curve for the combined symptoms and medication score during grass pollen season after 3 years of SCIT in a double-blinded, placebo-controlled trial. This study included 60 65- to 75-year-old patients with seasonal allergic rhinitis and grass pollen allergy. Patients were individually randomized to the active or placebo group. Thirty-three subjects in the SCIT group and 27 subjects in the placebo group were monitored for 3 years. Patients were required to record each use of anti-allergy medication. Thirty-one patients completed 3 years of pre-seasonal SCIT and 24 subjects finished placebo treatment. The median area under the curve for the combined symptoms and medication score after the third grass pollen season after SCIT was significantly decreased from 7.85 (range 3.67-8.98) to 4.63 (range 3.56-7.80) in the active group and did not significantly change in the placebo group. In the active group, the combined symptoms and medication score was decreased by 41%, the symptoms score was decreased by 55%, and the medication score was decreased by 64% after 3 years of immunotherapy. Pre-seasonal SCIT in the elderly is safe and efficacious and elicits an immune response comparable to what is found in studies of younger patients. Copyright © 2016. Published by Elsevier Inc.

  20. 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…

  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. 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…

  3. 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…

  4. Accelerated immunotherapy schedules and premedication.

    PubMed

    Calabria, Christopher W; Cox, Linda

    2011-05-01

    Subcutaneous immunotherapy is divided into a buildup and a maintenance phase. Accelerated immunotherapy has the advantage of a reduced number of office visits. Rush and cluster immunotherapy schedules are the most common accelerated schedules used in the United States. A cluster immunotherapy schedule involves the patient receiving several allergen injections sequentially in a single day of treatment on nonconsecutive days. The maintenance dose is reached in 4 to 8 weeks. In rush immunotherapy protocols, higher doses are administered at intervals of 15 to 60 minutes in a period of 1 to 3 days until the maintenance dose is achieved. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. A descriptive study of nurse-reported missed care in neonatal intensive care units.

    PubMed

    Tubbs-Cooley, Heather L; Pickler, Rita H; Younger, Janet B; Mark, Barbara A

    2015-04-01

    The aims of this study are to describe: (1) the frequency of nurse-reported missed care in neonatal intensive care units; and (2) nurses' reports of factors contributing to missed care on their last shift worked. Missed nursing care, or necessary care that is not delivered, is increasingly cited as a contributor to adverse patient outcomes. Previous studies highlight the frequency of missed nursing care in adult settings; the occurrence of missed nursing care in neonatal intensive care units is unknown. A descriptive analysis of neonatal nurses' self-reports of missed care using data collected through a cross-sectional web-based survey. A random sample of certified neonatal intensive care nurses in seven states was invited to participate in the survey in April 2012. Data were collected from nurses who provide direct patient care in a neonatal intensive care unit (n = 230). Descriptive statistics constituted the primary analytic approach. Nurses reported missing a range of patient care activities on their last shift worked. Nurses most frequently missed rounds, oral care for ventilated infants, educating and involving parents in care and oral feedings. Hand hygiene, safety and physical assessment and medication administration were missed least often. The most common reasons for missed care included frequent interruptions, urgent patient situations and an unexpected rise in patient volume and/or acuity on the unit. We find that basic nursing care in the neonatal intensive care unit is missed and that system factors may contribute to missed care in this setting. © 2014 John Wiley & Sons Ltd.

  6. A comparative study of neonatal outcomes in placenta previa versus cesarean for other indication at term.

    PubMed

    Schneiderman, Megan; Balayla, Jacques

    2013-07-01

    Currently, no ACOG guidelines address the issue of the optimal timing of delivery in placenta previa. Though there is an increased risk of neonatal morbidity and mortality when electively delivered preterm, it is unclear whether adverse neonatal outcomes exist when these pregnancies make it beyond term. By comparing neonatal outcomes amongst pregnancies with placenta previa versus those from cesarean for another indication at term, the objective of this study was to determine whether placenta previa is an independent risk factor for adverse neonatal outcomes at term. We conducted a population-based cohort-study using the CDC's Linked Birth-Infant Death data from the United States. The effect of placenta previa on the risk of adverse neonatal outcomes was estimated using unconditional logistic regression analysis, adjusting for relevant confounders. Our cohort consisted of 3,550,842 deliveries meeting inclusion criteria. The incidence of placenta previa at term was 1.3/1000 (n = 4,492), accounting for 40.6% of all previa cases. Relative to cesareans for other indications, pregnancies with placenta previa had an increased risk of IUGR 3.20 [2.50-4.10], SGA 2.70 [2.45-2.97], respiratory distress 3.82 [2.91-5.00], prolonged ventilation 3.41 [2.70-4.32] and neonatal anemia 6.87 [4.43-10.65]. Rates of meconium aspiration syndrome, seizures, birth injury and overall infant mortality do not appear to be affected by this condition. Relative to cesareans for other indications, placenta previa is associated with increased morbidity, but not mortality, at term. This information might be helpful in the development of future guidelines, which are currently needed to guide and standardize clinical practice regarding the optimal timing of delivery in placenta previa.

  7. 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

  8. Early sustained unresponsiveness after short-course egg oral immunotherapy: a randomized controlled study in egg-allergic children.

    PubMed

    Escudero, C; Rodríguez Del Río, P; Sánchez-García, S; Pérez-Rangel, I; Pérez-Farinós, N; García-Fernández, C; Ibáñez, M D

    2015-12-01

    No studies have evaluated the potential of egg oral immunotherapy (egg-OIT) to induce sustained unresponsiveness after discontinuing therapy following short-term treatments. We assessed the efficacy of short-course egg-OIT to induce sustained unresponsiveness. Sixty-one egg-allergic children, 5 to 17 years old, with positive double-blind placebo-controlled food challenge (DBPCFC) to dehydrated egg white (EW) were randomized to receive egg-OIT (OITG) for 3 months (maintenance dose one undercooked egg every 48 hours) or to continue egg avoidance diet (control group, CG) for 4 months. Children who completed egg-OIT avoided egg for 1 month. At 4 months, both groups underwent a DBPCFC. OITG participants who passed this challenge were instructed to add egg to their diet ad libitum. Immune markers were studied at different time points. Ninety-three percent (28/30) of OITG children were desensitized in a median of 32.5 days (IQR, 14 days). At 4 months, 1/31 (3%) in CG passed DBPCFC and 11/30 (37%) of OITG (95% CI, 14 to 51%; P = 0.003), all of them were consuming egg at 36 months. A decrease in EW, OVA and OVM skin test results and OVA-specific IgE (sIgE) levels was observed on OITG at 4 months (P = 0.001). EW-, OVA- and OVM-sIgE levels prior to the start of egg avoidance diet were lower in OITG children who passed DBPCFC at 4 months than in those who did not pass it. EW- and OVM-sIgE showed the best diagnostic performance in predicting DBPCFC result at 4 months. Levels above optimal EW-sIgE cut-off of 7.1 kU/L indicated 90% probability of failing DBPCFC. This is the first demonstration of sustained unresponsiveness with a three-month egg-OIT protocol. Almost all treated subjects were desensitized and 37% achieved sustained unresponsiveness. EW-sIgE levels at the end of treatment predicted sustained unresponsiveness. This protocol shows a new approach to OIT for egg-allergic children. © 2015 John Wiley & Sons Ltd.

  9. 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

  10. 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

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

    PubMed

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

    2016-10-01

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

  12. Immunotherapy in food allergy: towards new strategies.

    PubMed

    Sato, Sakura; Yanagida, Noriyuki; Ogura, Kiyotake; Asaumi, Tomoyuki; Okada, Yu; Koike, Yumi; Iikura, Katsuhito; Syukuya, Akinori; Ebisawa, Motohiro

    2014-09-01

    Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a significant focus for treating food allergies, and oral immunotherapy (OIT) appears to be particularly effective in inducing desensitization. The majority of patients who receive OIT show increased threshold doses of their food allergen. The efficacy of OIT is different among food antigen, and milk OIT is relatively difficult to achieve tolerance. OIT may induce mild to moderate symptoms during the therapy, widespread acceptance of OIT for long-term therapy is unclear. Recently, novel immunotherapies for food allergies, such as sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) and using an anti-IgE monoclonal antibody (omalizumab), have been assessed. In addition, a combination of OIT with omalizumab, which was found to increase the threshold doses of the offending foods without producing adverse reactions, may be effective and useful in the treatment of food allergies. These treatments have been used only in research settings; further studies in large numbers of patients are needed to demonstrate their long-term safety and benefits in clinical practice.

  13. 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.

  14. Up to 15-year clinical follow-up of a pilot Phase III immunotherapy study in stage II breast cancer patients using oxidized mannan-MUC1.

    PubMed

    Vassilaros, Stamatis; Tsibanis, Anastasios; Tsikkinis, Annivas; Pietersz, Geoffrey A; McKenzie, Ian F C; Apostolopoulos, Vasso

    2013-11-01

    Targeting antigens to dendritic cell receptors has recently become a popular approach to inducing effective immune responses against cancer antigens. Almost 20 years ago, however, we demonstrated that targeting the mannose receptor on macrophages and dendritic cells leads to strong cellular immune responses. We conducted numerous human clinical trials demonstrating the effectiveness of oxidized mannan-MUC1 (M-FP) in MUC1(+) adenocarcinoma patients. In one trial, the 5-8-year follow-up of breast cancer patients vaccinated with M-FP was published previously; we now report here the 12-15-year follow-up. Details regarding the preparation of the vaccine, inclusion and exclusion criteria, immunotherapy and follow-up schedule, were published previously. The follow-up at 12-15 years showed that the recurrence rate in patients receiving placebo was 60% (nine of 15). In those receiving immunotherapy (M-FP), the rate was 12.5% (two of 16). The time of recurrence in the placebo group ranged from 7 to 180 months (mean: 65.8 months) and in the two patients of the vaccine group, the recurrence appeared at 95 and 141 months (mean: 118 months) after surgery. These findings are statistically significant (p = 0.02 for survival and p = 0.009 for percentage of patients cancer-free). All patients injected with M-FP showed no evidence of toxic effects or signs of autoimmunity during the 12-15-year follow-up. The preliminary evidence indicates that M-FP is beneficial in the overall survival of early-stage breast cancer patients. This long-term clinical follow-up of patients strongly supports the necessity for a large Phase III study of direct M-FP injection in early-stage breast cancer patients, to evaluate immunotherapy as an adjuvant treatment for breast cancer.

  15. 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

  16. Clinical experience of integrative cancer immunotherapy with GcMAF.

    PubMed

    Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Mette, Martin; Uto, Yoshihiro; Hori, Hitoshi; Sakamoto, Norihiro

    2013-07-01

    Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

  17. [Study on relationship between mother's animal sourced food intake during pregnancy and neonate birth weight].

    PubMed

    Yan, H; Dang, S N; Mi, B B; Qu, P F; Zhang, L; Wang, H L; Bi, Y X; Zeng, L X; Li, Q; Yan, H

    2017-05-10

    Objective: To explore the effect of maternal animal sourced food intake during pregnancy on neonate birth weight and provide scientific basis for guiding the reasonable diet intake in pregnant women and increasing neonate birth weight. Methods: Data were derived from a cross-sectional project of"the prevalence and risk factors of birth defects in Shaanxi province" , which were conducted in 30 counties in Shaanxi province from July to November in 2013. A stratified multistage random sampling method was used to select women who were pregnant between January 2010 and December 2013 for a random semi-quantitative food frequency questionnaire survey to collect the data on the frequency and amount of food consumption on animal protein sources and the data of newborns. Children aged 0-1 years and their mothers were selected as the study subjects. The generalized linear model was used to analyze the relationship between the neonate birth weight and maternal animal sourced food intake during pregnancy, and by using neonate birth weight as dependent variable, food intake frequency as independent variable, three adjustment models were established for stratified analysis. Results: Totally 11 459 participants were involved in this study. The average birth weight of newborn was (3 279.9±454.6) g, the average weekly intake of animal sourced foods was4.00 times for egg, 1.50 times for meat, 3.00 times for dairy foods, 0.50 times for fish and 5.00 times for overall animal sourced foods in pregnant women. Without stratification, three models shown that meat and overall animal sourced food intake had effects on neonate birth weight. After adjustment for gestational weeks, maternal age, social and demographic factors and others, meat intake increased by 1 time a week, the increase of neonate birth weight was about 5.26 (95%CI: 1.32-9.20) g, and the overall animal food increased by 1 times a week, the average neonate birth weight increased by 3.24 (95%CI: 1.09-5.39) g. Stratified

  18. Neonatal and prospective follow-up study of infants delivered by vacuum extraction (VE).

    PubMed

    Blennow, G; Svenningsen, N W; Gustafson, B; Sundén, B; Cronquist, S

    1977-01-01

    Forty infants delivered by vacuum extraction have been studied in the neonatal period--neurological examination, neonatal CSF-examinations, skull X-ray examination, transillumination and sonoencephalography --and at 14 months of age--developmental and behavioural evaluation, neurological examination, skull X-ray examination, sonoencephalography and electroencephalography. Two infants died in the neonatal period but in both cases a life-threatening situation of the fetus required immediate delivery. CSF cytological signs of haemorrhage were observed in 42% of the 26 infants who had a successful lumbar tap, compared to 10% found in normal deliveries. The result of the neonatal neurological study did not differ from that in a control group. The result of the skull X-ray examination and sonoencephalography were also within normal limits. In the follow-up study behavioural problems were found in 25%, but otherwise very few abnormalities were found. The deviatiosn found do not for the present indicate any later signs of brain lesions. It is concluded that this prospective study has shown that VE-delivery in fullterm babies seem to imply no risk fo serious cerebral sequelae. Further follow-up studies at a later age in order to evaluate the incidence of so-called minimal brain damage in VE-delivered children are required.

  19. Treatment of neonatal jaundice with filtered sunlight in Nigerian neonates: study protocol of a non-inferiority, randomized controlled trial

    PubMed Central

    2013-01-01

    Background Severe neonatal jaundice and its progression to kernicterus is a leading cause of death and disability among newborns in poorly-resourced countries, particularly in sub-Saharan Africa. The standard treatment for jaundice using conventional phototherapy (CPT) with electric artificial blue light sources is often hampered by the lack of (functional) CPT devices due either to financial constraints or erratic electrical power. In an attempt to make phototherapy (PT) more readily available for the treatment of pathologic jaundice in underserved tropical regions, we set out to test the hypothesis that filtered sunlight phototherapy (FS-PT), in which potentially harmful ultraviolet and infrared rays are appropriately screened, will be as efficacious as CPT. Methods/design This prospective, non-blinded randomized controlled non-inferiority trial seeks to enroll infants with elevated total serum/plasma bilirubin (TSB, defined as 3 mg/dl below the level recommended by the American Academy of Pediatrics for high-risk infants requiring PT) who will be randomly and equally assigned to receive FS-PT or CPT for a total of 616 days at an inner-city maternity hospital in Lagos, Nigeria. Two FS-PT canopies with pre-tested films will be used. One canopy with a film that transmits roughly 33% blue light (wavelength range: 400 to 520 nm) will be used during sunny periods of a day. Another canopy with a film that transmits about 79% blue light will be used during overcast periods of the day. The infants will be moved from one canopy to the other as needed during the day with the goal of keeping the blue light irradiance level above 8 μW/cm2/nm. Primary outcome: FS-PT will be as efficacious as CPT in reducing the rate of rise in bilirubin levels. Secondary outcome: The number of infants requiring exchange transfusion under FS-PT will not be more than those under CPT. Conclusion This novel study offers the prospect of an effective treatment for infants at risk of severe

  20. Maintenance immunotherapy in recurrent ovarian cancer: long term follow-up of a phase II study.

    PubMed

    Recchia, Francesco; Di Orio, Ferdinando; Candeloro, Giampiero; Guerriero, Gabriele; Piazze, Juan; Rea, Silvio

    2010-02-01

    Vascular endothelial growth factor (VEGF), a mediator of tumor-associated immunodeficiency, plays a key role in angiogenesis and is a prognostic factor in advanced ovarian cancer (AOC). Previously, we showed that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) improved the tumor-associated immunodeficiency and decreased VEGF in patients with AOC. Here, we report long term follow-up of a group of patients with platinum-sensitive AOC who were treated with IL-2 and RA. Sixty-five patients with AOC who had a clinical benefit from second line chemotherapy and elevated serum levels of VEGF were entered into the study from 04/98 to 04/05. Therapy consisted of low-dose subcutaneous IL-2 and oral RA, administered on intermittent schedules for up to 5 years. A statistically significant improvement in lymphocyte and NK counts and a decrease in VEGF levels were observed with respect to baseline values among the 65 evaluable patients. Five-year progression-free survival and overall survival rate were 29% and 38%, respectively. These data show that patients treated with low-dose IL-2 and RA have a statistically significant improvement in their lymphocyte and NK counts, a decrease in VEGF, and seem to have an improved clinical outcome. Copyright 2009 Elsevier Inc. All rights reserved.

  1. A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent grade III/IV astrocytoma.

    PubMed

    Wood, G W; Holladay, F P; Turner, T; Wang, Y Y; Chiga, M

    2000-06-01

    The study objectives were to determine; (1) whether activated T cells could be generated from peripheral blood of patients immunized with their own cancer cells, (2) whether adoptive transfer of the activated T cells to patients had toxic effects and (3) whether the infused cells produced clinical responses. Study patients had recurrent, surgically accessible grade III/IV astrocytomas. The patients were tapered off steroids after total surgical resection and immunized with autologous cancer cells plus Bacillus, Calmette and Guerin (BCG). Peripheral blood mononuclear cells were activated with anti-CD3, expanded with interleukin-2 (IL-2) and reinfused to patients. The number of activated T cells that was given back to patients varied between 10(10) and 10(11). Side effects that were observed following immunization and adoptive cell transfer included mainly transient flu-like symptoms. One patient's tumor partially regressed, but there was no effect on survival. Two other patients' tumors regressed, and the patients are apparently disease-free more than 5 and 4 years later. The other six patients' tumors were apparently unaffected by the treatment. Patient age, tumor grade and CD4/CD8 composition of infused cells were positively correlated with clinical responses. Cellular immunotherapy is feasible and is associated with minimal toxicity. Additional appropriately controlled studies will be required to determine whether cellular immunotherapy could be used as a treatment for central nervous system malignancy. Additional studies also will be required to determine the underlying immunological mechanisms.

  2. Immunotherapy in Gastrointestinal Cancers

    PubMed Central

    Procaccio, Letizia; Schirripa, Marta; Fassan, Matteo; Vecchione, Loredana; Bergamo, Francesca; Prete, Alessandra Anna; Intini, Rossana; Manai, Chiara; Dadduzio, Vincenzo; Boscolo, Alice; Zagonel, Vittorina

    2017-01-01

    Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials. In the present review a general overview is firstly provided followed by a focus on major findings on gastric, colorectal, and hepatocellular carcinomas. Finally, pathological and molecular perspectives are provided since many efforts are ongoing in order to identify possible predictive biomarkers and to improve patients' selection. Many issues are still unsolved in this field; however, we strongly believe that immunotherapy might positively affect the natural history of a subgroup of GI cancer patients improving outcome and the overall quality of life. PMID:28758114

  3. 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.

  4. 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.

  5. Skin care product evaluation in a group of critically ill, premature neonates: a descriptive study.

    PubMed

    Young, Daniel L; Chakravarthy, Debashish; Drower, Edward; Reyna, Roxana

    2014-01-01

    Cleansing, moisturizing, and protecting neonatal skin is important, but literature evaluating specific product lines is limited. The purpose of this study was to measure the influence of a skin care product line on overall skin condition, perineal erythema, and pain when applied to neonates in a neonatal intensive care unit (NICU). This was an open label, descriptive study. Comparisons were made between measurements taken at the beginning of the study to those at the end, on the same subjects. The study was conducted in a 41-bed NICU at Driscoll Children's Hospital in Corpus Christi, Texas, that serves 31 counties in the region. This NICU treats children needing level 2 and 3 care, with a 1:1 or 2:1 nurse staffing ratio. This is not a birthing center; patients come from other community hospitals. Twenty-nine neonates participated in the study; their average body weight was 1.39 kg (3.06 lb) and their average gestation was 31.7 weeks. A skin care product line was introduced into a neonatal intensive care unit for 14 days. The products included 2 cleansers, 2 moisturizers, and a skin protectant with zinc oxide. Three outcome measures were tracked: Neonatal Skin Condition Score (NSCS), Skin Erythema Scale (SES), and pain. Nurses were also given a product evaluation survey. Descriptive statistics were used to report percentages and trends. Paired t tests were used to compare the mean NSCS, SES, and pain scores from the first 2 days a subject was in the study to the mean of the scores from the last 2 days they were in the study. Subjects experienced approximately 1774 exposures to individual products during data collection. No differences were found in pain scores (P = .132), SES score (P = .059), or NSCS (P = .603) when mean values were compared at the beginning and end of the study. Analysis of the product evaluation survey for questions on cleaning, moisturizing, and reducing discomfort found that more than 90% of nurses ranked the new products as better than or

  6. 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

  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. 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…

  9. Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: a retrospective cohort study.

    PubMed

    Juurlink, David N; Gomes, Tara; Guttmann, Astrid; Hellings, Chelsea; Sivilotti, Marco L A; Harvey, Marie-Andrée; Mamdani, Muhammad M

    2012-06-01

    To examine whether postpartum maternal prescription of codeine was associated with an increased risk of harm to newborns. Population-based retrospective cohort study. Ontario, Canada, from April 1, 1998 to March 1, 2008. A total of 7804 mothers with publically-funded prescription drug coverage. Women who received a prescription for a codeine-containing product within 7 days following hospital discharge and their neonates were matched to 7804 mothers who did not receive codeine following delivery. The primary outcome was readmission of the neonate to hospital for any reason within 30 days. Secondary outcomes included arrival to hospital by ambulance, hospitalization for dehydration, for injury, any hospitalization involving resuscitation or assisted ventilation, and all-cause mortality. We studied 7804 infants whose mothers filled a prescription for codeine shortly after delivery and 7804 whose mothers did not. In the primary analysis, infants whose mothers received codeine were no more likely to be readmitted to hospital in the subsequent 30 days than children whose mothers did not (hazard ratio 0.95, 95% confidence interval (CI) 0.81-1.11). Moreover, we found no association between maternal codeine use and the other adverse neonatal outcomes studied. A stratified analysis revealed no differential risk among infants born by Caesarean section (hazard ratio 0.86; 95% CI 0.69-1.08). In this large population-based study, maternal prescription of codeine following delivery was not associated with death or hospitalization in the early neonatal period.

  10. 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

  11. Neonatal Early Warning Tools for recognising and responding to clinical deterioration in neonates cared for in the maternity setting: A retrospective case-control study.

    PubMed

    Paliwoda, Michelle; New, Karen; Bogossian, Fiona

    2016-09-01

    All newborns are at risk of deterioration as a result of failing to make the transition to extra uterine life. Signs of deterioration can be subtle and easily missed. It has been postulated that the use of an Early Warning Tool may assist clinicians in recognising and responding to signs of deterioration earlier in neonates, thereby preventing a serious adverse event. To examine whether observations from a Standard Observation Tool, applied to three neonatal Early Warning Tools, would hypothetically trigger an escalation of care more frequently than actual escalation of care using the Standard Observation Tool. A retrospective case-control study. A maternity unit in a tertiary public hospital in Australia. Neonates born in 2013 of greater than or equal to 34(+0) weeks gestation, admitted directly to the maternity ward from their birthing location and whose subsequent deterioration required admission to the neonatal unit, were identified as cases from databases of the study hospital. Each case was matched with three controls, inborn during the same period and who did not experience deterioration and neonatal unit admission. Clinical and physiological data recorded on a Standard Observation Tool, from time of admission to the maternity ward, for cases and controls were charted onto each of three Early Warning Tools. The primary outcome was whether the tool 'triggered an escalation of care'. Descriptive statistics (n, %, Mean and SD) were employed. Cases (n=26) comprised late preterm, early term and post-term neonates and matched by gestational age group with 3 controls (n=78). Overall, the Standard Observation Tool triggered an escalation of care for 92.3% of cases compared to the Early Warning Tools; New South Wales Health 80.8%, United Kingdom Newborn Early Warning Chart 57.7% and The Australian Capital Territory Neonatal Early Warning Score 11.5%. Subgroup analysis by gestational age found differences between the tools in hypothetically triggering an escalation of

  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. 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

  14. [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.

  15. Specific immunotherapy with allergen mixes: what is the evidence?

    PubMed

    Nelson, Harold S

    2009-12-01

    The purpose is to review the published evidence for the use of multiallergen mixes in subcutaneous and sublingual immunotherapy. Data are drawn from published articles and reviews, including a recent complete search of the English and non-English literature for publications on multiallergen immunotherapy.The problems arising from dilution of extracts and degradation of extracts resulting from adding additional extracts to a mixture are confirmed. The published literature of the use of multiallergen extracts in subcutaneous and sublingual immunotherapy indicates that multiallergen extracts are effective when given by injection, but a similar efficacy has not been established for them when administered sublingually. Multiallergen extract mixes are probably effective for subcutaneous immunotherapy provided attention is paid to the concentration of each allergen in the mix and mixing of protease containing extracts with pollen and dander extracts is avoided. Further studies are needed to determine if multiallergen mixes are effective in sublingual immunotherapy.

  16. Fetal and maternal factors associated with neonatal adiposity as measured by air displacement plethysmography: a large cross-sectional study.

    PubMed

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

    2013-10-01

    There is evidence that the fetal and early postnatal environments play a role in determining the risk of lifetime obesity, diabetes and cardiovascular disease. Neonatal body composition, as a surrogate marker of the in-utero environment, can be reliably and accurately measured by air displacement plethysmography (ADP). Our primary objective was to identify preconception, fetal and maternal factors affecting neonatal body composition. This cross-sectional study included 599 term babies born between September and October 2010 at Royal Prince Alfred Hospital, Sydney, Australia. Neonatal body fat percentage (BF%) was measured within 48 h of birth using ADP. Maternal demographic, anthropometric and medical data as well as neonatal gestational age and sex were used to develop a regression model that predicted body composition and birthweight. The mean (SD) neonatal BF% in our whole population was 9.2(4.4)%. Significant variables in the model for neonatal BF% were neonatal sex, gestational age, maternal ethnicity, gestational weight gain (GWG), pre-pregnancy BMI, parity and maternal hypertension (p<0.05); together, these explained 19% of the variation in BF%. GDM status was not a significant variable. Neonatal female sex, maternal Caucasian ethnicity and increased gestational weight gain explained the most variation and were most strongly associated with increased BF%. This study highlights maternal obesity and increased gestational weight gain as two factors that are amenable to intervention as risk factors for newborn adiposity, which is important in the future study of the "developmental origins of health and disease" hypothesis. © 2013.

  17. 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.

  18. 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

  19. Mapping cortical haemodynamics during neonatal seizures using diffuse optical tomography: A case study

    PubMed Central

    Singh, Harsimrat; Cooper, Robert J.; Wai Lee, Chuen; Dempsey, Laura; Edwards, Andrea; Brigadoi, Sabrina; Airantzis, Dimitrios; Everdell, Nick; Michell, Andrew; Holder, David; Hebden, Jeremy C.; Austin, Topun

    2014-01-01

    Seizures in the newborn brain represent a major challenge to neonatal medicine. Neonatal seizures are poorly classified, under-diagnosed, difficult to treat and are associated with poor neurodevelopmental outcome. Video-EEG is the current gold-standard approach for seizure detection and monitoring. Interpreting neonatal EEG requires expertise and the impact of seizures on the developing brain remains poorly understood. In this case study we present the first ever images of the haemodynamic impact of seizures on the human infant brain, obtained using simultaneous diffuse optical tomography (DOT) and video-EEG with whole-scalp coverage. Seven discrete periods of ictal electrographic activity were observed during a 60 minute recording of an infant with hypoxic–ischaemic encephalopathy. The resulting DOT images show a remarkably consistent, high-amplitude, biphasic pattern of changes in cortical blood volume and oxygenation in response to each electrographic event. While there is spatial variation across the cortex, the dominant haemodynamic response to seizure activity consists of an initial increase in cortical blood volume prior to a large and extended decrease typically lasting several minutes. This case study demonstrates the wealth of physiologically and clinically relevant information that DOT–EEG techniques can yield. The consistency and scale of the haemodynamic responses observed here also suggest that DOT–EEG has the potential to provide improved detection of neonatal seizures. PMID:25161892

  20. Neonatal outcomes following elective caesarean delivery at term: a hospital-based cohort study.

    PubMed

    Finn, Daragh; O'Neill, Sinéad M; Collins, Aedin; Khashan, Ali S; O'Donoghue, Keelin; Dempsey, Eugene

    2016-03-01

    To assess neonatal outcomes following elective caesarean delivery (CD) at term (≥37 + 0 weeks gestation). A retrospective cohort study was conducted in a single Irish maternity hospital. Elective CDs at term between August 2008 and July 2012 were reviewed. Outcome measures were admission to the neonatal intensive care unit (NICU), length of stay, respiratory complications, hypoglycaemia, jaundice, newborn sepsis and medical interventions. A total of 4242 women had an elective CD at term, accounting for approximately 15% of all term deliveries. Admission rate to the NICU at 37 weeks gestation was 21.8% versus 10% at 39 weeks (p for trend <0.0001). Similar trends of decreasing risk with later gestational age were noted for the other outcomes. An increased odds of admission to the NICU at 37 weeks [adjusted odds ratio (OR) 2.48 (95% CI 1.28, 4.79)] and at 38 weeks [OR 1.34, 95% CI 1.02, 1.77] compared to the reference of 39 weeks gestation was found. This study supports evidence that, with regard to neonatal outcome, 39 weeks gestational age is the optimal delivery time. Heightened awareness of the increased risk of neonatal morbidity, when delivery is performed electively before 39 weeks, is warranted among healthcare workers.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. [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.

  7. 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.

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

    PubMed

    Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2016-09-01

    The number of cancer survivors continues to increase worldwide. Many of these survivors have had children of their own. It is less well-known whether radiation therapy or chemotherapy could affect the risk of stillbirth and neonatal death for these children. To explore this research questions, we identified all women diagnosed with cancer between 1958 and 2012 from the Swedish Cancer Register and they were further linked to the Swedish Medical Birth Register to identify their subsequent child birth between 1973 and 2012. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between stillbirth and neonatal death and maternal cancer diagnosis. As compared to the children without maternal cancer, the risk of stillbirth was significantly higher among children of female cancer survivors born within three years after cancer diagnosis with an OR of 1.92 (95% CI 1.03-3.57). The incidence of neonatal death did not show a significant change. For women with more than one pregnancy after cancer diagnosis, the risk of stillbirth and neonatal death was lower for the second child birth compared to the first child birth. Our study suggested that the risk of stillbirth was negatively associated with the time after cancer diagnosis, providing evidence that the adverse effect associated with cancer treatment may diminish with time. © 2016 UICC.

  9. Continuous Video EEG Monitoring for Electrographic Seizure Diagnosis in Neonates: A Single Center Study

    PubMed Central

    Wietstock, SO; Bonifacio, SL; Sullivan, JE; Nash, KB; Glass, HC

    2015-01-01

    The objective of this study was to determine the diagnostic yield of continuous video-electroencephalography (cEEG) monitoring in critically ill neonates in the setting of a novel, university-based Neonatal Neurocritical Care Service. Patient demographic characteristics, indication for seizure monitoring, and presence of electrographic seizures were obtained by chart review. Among 595 patients cared for by the Neonatal Neurocritical Care Service, 400 (67%) received cEEG. The median duration of cEEG monitoring was 49 (IQR: 22 to 87) hours. Electrographic seizures were captured in 105/400 (26% of monitored patients) and of those, 25/105 (24%) had no clinical correlate. In addition, 52/400 subjects (13%) were monitored due to paroxysmal events concerning for seizures, but never had electrographic seizures. cEEG monitoring helped confirm or rule out ongoing seizures in more than one third of the cases. This finding helps to support the use of cEEG in critically ill neonates. PMID:26129976

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

    PubMed Central

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

    2011-01-01

    Summary West J, Manchester B, Wright J, Lawlor DA, Waiblinger D. Reliability of routine clinical measurements of neonatal circumferences and research measurements of neonatal skinfold thicknesses: findings from the Born in Bradford study. Paediatric and Perinatal Epidemiology 2011. Assessing neonatal size reliably is important for research and clinical practice. The aim of this study was to examine the reliability of routine clinical measurements of neonatal circumferences and of skinfold thicknesses assessed for research purposes. All measurements were undertaken on the same population of neonates born in a large maternity unit in Bradford, UK. Technical error of measurement (TEM), relative TEM and the coefficient of reliability are reported. Intra-observer TEMs for routine circumference measurements were all below 0.4 cm and were generally within ±2-times the mean. Inter-observer TEM ranged from 0.20 to 0.36 cm for head circumference, 0.19 to 0.39 cm for mid upper arm circumference and from 0.39 to 0.77 cm for abdominal circumference. Intra and inter-observer TEM for triceps skinfold thickness ranged from 0.22 to 0.35 mm and 0.15 to 0.54 mm, respectively. Subscapular skinfold thickness TEM values were 0.14 to 0.25 mm for intra-observer measurements and 0.17 to 0.63 mm for inter-observer measurements. Relative TEM values for routine circumferences were all below 4.00% but varied between 2.88% and 14.23% for research skinfold measurements. Reliability was mostly between 80% and 99% for routine circumference measurements and ≥70% for most research skinfold measurements. Routine clinical measurements of neonatal circumferences are reliably assessed in Bradford. Assessing skinfolds in neonates has variable reliability, but on the whole is good. The greater intra-observer, compared with inter-observer, reliability for both sets of measurements highlights the importance of having a minimal number of assessors whenever possible. PMID:21281329

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Immunotherapy for peanut allergy.

    PubMed

    Lee, T H; Chan, June; Lau, Vivian W Y; Lee, W L; Lau, P C; Lo, M H

    2014-08-01

    Peanut allergy is one of the commonest food hypersensitivities causing fatal or near-fatal reactions. There is, currently, no preventive treatment and the incidence of severe allergic reactions during peanut desensitisation has limited its clinical use. Anti-immunoglobulin E therapy has been shown to be effective in preventing peanut-induced reactions but it does not result in long-term tolerance. Two important advances have recently been reported. One involves gradual oral introduction of peanut protein to desensitise, whereas the other approach uses a combination of anti-immunoglobulin E and oral peanut immunotherapy. Both approaches could offer a way to desensitise with a far greater margin of safety than has, hitherto, been reported. This article provides an overview of the literature on peanut immunotherapy and describes the experience in a small group of children in Hong Kong who were treated successfully using anti-immunoglobulin E combined with oral peanut desensitisation.

  17. Immunotherapy for tularemia.

    PubMed

    Skyberg, Jerod A

    2013-11-15

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

  18. Immunotherapy for tularemia

    PubMed Central

    Skyberg, Jerod A.

    2013-01-01

    Francisella tularensis is a gram-negative bacterium that causes the zoonotic disease tularemia. Francisella is highly infectious via the respiratory route (~10 CFUs) and pulmonary infections due to type A strains of F. tularensis are highly lethal in untreated patients (>30%). In addition, no vaccines are licensed to prevent tularemia in humans. Due to the high infectivity and mortality of pulmonary tularemia, F. tularensis has been weaponized, including via the introduction of antibiotic resistance, by several countries. Because of the lack of efficacious vaccines, and concerns about F. tularensis acquiring resistance to antibiotics via natural or illicit means, augmentation of host immunity, and humoral immunotherapy have been investigated as countermeasures against tularemia. This manuscript will review advances made and challenges in the field of immunotherapy against tularemia. PMID:23959031

  19. Neonatal Venous Thromboembolism.

    PubMed

    Haley, Kristina M

    2017-01-01

    Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE), and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults. Platelet function, pro- and anticoagulant proteins concentrations, and fibrinolytic pathway protein concentrations are developmentally regulated and generate a hemostatic homeostasis that is unique to the neonatal time period. The clinical picture of a critically ill neonate combined with the physiologically distinct neonatal hemostatic system easily fulfills the criteria for Virchow's triad with venous stasis, hypercoagulability, and endothelial injury and puts the neonatal patient at risk for VTE development. The presentation of a VTE in a neonate is similar to that of older children or adults and is dependent upon location of the VTE. Ultrasound is the most common diagnostic tool employed in identifying neonatal VTE, but relatively small vessels of the neonate as well as frequent low pulse pressure can make ultrasound less reliable. The diagnosis of a thrombophilic disorder in the neonatal population is unlikely to change management or outcome, and the role of thrombophilia testing in this population requires further study. Treatment of neonatal VTE is aimed at reducing VTE-associated morbidity and mortality. Recommendations for treating, though, cannot be extrapolated from guidelines for older children or adults. Neonates are at risk for bleeding complications, particularly younger neonates with more fragile intracranial vessels. Developmental alterations in the coagulation proteins as

  20. 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

  1. Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design.

    PubMed

    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; Cohen-Wolkowiez, Michael

    2014-06-01

    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. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

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

    PubMed

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

    2011-03-01

    Assessing neonatal size reliably is important for research and clinical practice. The aim of this study was to examine the reliability of routine clinical measurements of neonatal circumferences and of skinfold thicknesses assessed for research purposes. All measurements were undertaken on the same population of neonates born in a large maternity unit in Bradford, UK. Technical error of measurement (TEM), relative TEM and the coefficient of reliability are reported. Intra-observer TEMs for routine circumference measurements were all below 0.4 cm and were generally within ± 2-times the mean. Inter-observer TEM ranged from 0.20 to 0.36 cm for head circumference, 0.19 to 0.39 cm for mid upper arm circumference and from 0.39 to 0.77 cm for abdominal circumference. Intra and inter-observer TEM for triceps skinfold thickness ranged from 0.22 to 0.35 mm and 0.15 to 0.54 mm, respectively. Subscapular skinfold thickness TEM values were 0.14 to 0.25 mm for intra-observer measurements and 0.17 to 0.63 mm for inter-observer measurements. Relative TEM values for routine circumferences were all below 4.00% but varied between 2.88% and 14.23% for research skinfold measurements. Reliability was mostly between 80% and 99% for routine circumference measurements and ≥ 70% for most research skinfold measurements. Routine clinical measurements of neonatal circumferences are reliably assessed in Bradford. Assessing skinfolds in neonates has variable reliability, but on the whole is good. The greater intra-observer, compared with inter-observer, reliability for both sets of measurements highlights the importance of having a minimal number of assessors whenever possible. © 2011 Blackwell Publishing Ltd.

  11. 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.

  12. 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. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  13. The study of etiological and demographic characteristics of neonatal mortality and morbidity - a consecutive case series study from Pakistan

    PubMed Central

    2012-01-01

    Background To determine the etiology, management, bacteriological spectrum and outcome of neonatal patients admitted in Civil Hospital Karachi (CHK) and to examine the factors associated with it. Methods This hospital based descriptive study of 1463 patients from both sexes who were admitted to Paediatric department, CHK from 1st January 2008 till 31st December 2010 with an established cause according to modified Wigglesworth classification and fulfilling other inclusion criteria were included in the study. Data regarding their demographic profile and potential risk factors was collected on a well structured proforma. Cases were followed until discharge or expiry. Data was analyzed using descriptive statistics. Results The male to female ratio in our study was 1.12:1. Seven hundred and thirty-four patients were delivered at home (50.2%) and 1010 were less than 7 days old (69%). Out of the total cohort of expired subjects, 89 participants (74.8%) were < 7 days of life. Mortality was more in neonates born at home in rural areas to illiterate mother; 74 patients (62.2%). Most of the deaths; 57 were in neonates suffering from specific infections (47.9%) followed by 38 deaths in immaturity group (31.9%) and 19 related to asphyxial conditions (15.9%). The most common isolates were Staphylococcus aureus (28.7%) followed by Klebsiella (24.8%) and Pseudomonas aeruginosa (16.6 ). One hundred and nineteen (8.13%) of the neonates died in our study group. Conclusions These results suggest that neonates with illiterate mothers with high parity and below average socioeconomic level were more susceptible to mortality in the early neonatal period. Most of the cases of mortality were due to specific infections. PMID:22925171

  14. 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

  15. 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.

  16. Poxviral vectors for cancer immunotherapy

    PubMed Central

    Kim, Joseph W.; Gulley, James L.

    2012-01-01

    Introduction Poxviral vaccines have been given to over 1 billion people in the successful global eradication of smallpox. Since then, recombinant poxviruses have been investigated extensively as a novel immunotherapy for cancer, undergoing several iterations to optimize their immunogenicity and efficacy. The current platform expressing multiple costimulatory molecules plus a tumor-associated antigen such as PSA, i.e., PSA-TRICOM (PROSTVAC-V/F), is promising and is currently in a phase III randomized, placebo-controlled clinical trial in metastatic castration-resistant prostate cancer. Areas covered This review discusses the clinical development of poxviral-based cancer vaccines, with a particular focus on the rationale for combining vaccines with other treatment modalities, including radiotherapy, chemotherapy, hormonal therapy, other immune-based therapies, and molecularly targeted therapy. We also discuss the importance of appropriate patient selection in clinical trial design. Expert Opinion Preclinical and early clinical studies with poxviral vector vaccines have shown promising results with this novel immunologic approach both as vaccine alone and combined with other therapies. The challenges of translating the science of immunotherapy to clinical practice include clinical trial design that includes appropriate patient selection, appropriate endpoints, and identification of meaningful surrogate biomarkers. PMID:22413824

  17. 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.

  18. 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.

  19. Oral and sublingual immunotherapy for food allergy.

    PubMed

    Wang, Julie; Sampson, Hugh A

    2013-09-01

    Food allergies continue to be an increasingly common disorder, however, no treatment strategies are currently approved for the routine management of individuals with food allergies. Encouraging results from early open-label studies have sparked great interest in oral and sublingual immunotherapy, and thus several randomized controlled trials have recently been conducted to establish the safety and efficacy of these treatment strategies. The aim of this review is to examine the recent studies for peanut, milk and egg allergies. Open-label and randomized control trials are discussed. Studies focusing on peanut, milk and egg allergies are included. Current evidence indicates that desensitization is possible for the majority of subjects who undergo oral immunotherapy. Clinical improvement has been associated with favorable immunologic changes, including smaller skin prick test wheal sizes and increased allergen-specific IgG4 levels. Adverse reactions are common, however, and thus safety concerns remain. Sublingual immunotherapy thus far has not proven to be as effective as oral immune-therapy. Oral and sublingual immunotherapy are promising treatments for food allergy. Optimization and standardization of protocols, along with additional assessments of safety are still needed.

  20. 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

  1. 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.

  2. Trajectory of cause of death among brought dead neonates in tertiary care public facilities of Pakistan: A multicenter study.

    PubMed

    Mustufa, Muhammad Ayaz; Sheikh, Munir Ahmed; Taseer, Ijaz-Ul-Haque; Raza, Syed Jamal; Arshad, Muhammad Sohail; Akhter, Tasleem; Arain, Ghazala Mohyuddin; Habibullah, Sultana; Safdar, Sohail; Firdous, Rukhsana; Adnan, Muhammad

    2017-02-01

    Considering the fact that Pakistan is amongst the countries with very high neonatal mortality rates, we conducted a research study to determine the possible causes and characteristics of neonates presenting dead to the emergency department of tertiary public health care facilities of Pakistan using verbal autopsies. A descriptive case series study was conducted in emergency department/pediatrics ward/neonatal ward/nursery unit of ten tertiary care public health facilities, situated in seven major cities of Pakistan from November, 2011 to June, 2013. Precoded verbal autopsy proforma was used to collect information regarding cause of death, family narratives and other associated risks accountable for pathway to mortality. We identified 431 neonates presenting dead to the emergency department (238 males and 193 females). Sepsis (26.7%), birth asphyxia (18.8%) and persistent pulmonary arrest (17.2%) were main primary causes of brought death. Around 72% brought dead neonates were referred from doctors/health care facilities and more than 28% caregivers mentioned that they were not informed about the diagnosis/ailment of their deceased newborn. Findings of our study suggest that infectious disease remains the main primary cause of neonatal mortality. Underweight in newborns (64%) was estimated as a leading associated risk. Delays in referrals to respective health care facility enlightened the concern of sub-standard prerequisites of neonatal care that could be one of the major contributing risk factor of high mortality rates.

  3. Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study.

    PubMed

    Mirone, C; Albert, F; Tosi, A; Mocchetti, F; Mosca, S; Giorgino, M; Pecora, S; Parmiani, S; Ortolani, C

    2004-09-01

    The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002). Injective immunotherapy is safe and clinically effective

  4. 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.

  5. Occurrence of Fetal Macrosomia Rate and Its Maternal and Neonatal Complications: A 5-Year Cohort Study

    PubMed Central

    Najafian, Mahin; Cheraghi, Maria

    2012-01-01

    Background. Macrosomia is defined as an infant's birth weight of more than 4000 g at term which is to different maternal and neonatal complications. Several studies have been done on factors influencing risk of macrosomia, but there is lack of information and study in our country regarding macrosomia complications. Objective. The aim of this study was to determine the prevalence of macrosomia and its complications. Method. A cohort study was conducted from 2007 to 2011 at Obstetrics and Gynecology Department, Razi Hospital in Ahvaz city, Iran. All pregnant mothers who were referred to Obstetrics and Gynecology Department for delivery were included in this study. The total number of 201,102 pregnant mothers was recruited and divided into case and control groups after delivery (macrosomia (case) and normal weight infants (control) groups). Results. Out of total deliveries (201,102), there were 1800 macrosomia, (9%). Gestational diabetes, maternal obesity (BMI), maternal aged and positive history of previous macrosomia were the major risk factors for macrosomia which were compared with the normal weight infant groups (P < 0.001 for all parameters). Neonatal complications associated with macrosomia included humerus—clavicle fractures and arm—brachial plexus injury which were significant compared to the control group (P < 0.001 for all parameters). Conclusion. The macrosomia is potentially dangerous for the mother and the neonate. It is important to recognize the suspected fetal macrosomia to prevent its risk factors and complications. There is a need to provide all delivery facilities and care services to prevent and reduce the maternal and neonatal macrosomia complications. PMID:23209925

  6. Occurrence of fetal macrosomia rate and its maternal and neonatal complications: a 5-year cohort study.

    PubMed

    Najafian, Mahin; Cheraghi, Maria

    2012-01-01

    Background. Macrosomia is defined as an infant's birth weight of more than 4000 g at term which is to different maternal and neonatal complications. Several studies have been done on factors influencing risk of macrosomia, but there is lack of information and study in our country regarding macrosomia complications. Objective. The aim of this study was to determine the prevalence of macrosomia and its complications. Method. A cohort study was conducted from 2007 to 2011 at Obstetrics and Gynecology Department, Razi Hospital in Ahvaz city, Iran. All pregnant mothers who were referred to Obstetrics and Gynecology Department for delivery were included in this study. The total number of 201,102 pregnant mothers was recruited and divided into case and control groups after delivery (macrosomia (case) and normal weight infants (control) groups). Results. Out of total deliveries (201,102), there were 1800 macrosomia, (9%). Gestational diabetes, maternal obesity (BMI), maternal aged and positive history of previous macrosomia were the major risk factors for macrosomia which were compared with the normal weight infant groups (P < 0.001 for all parameters). Neonatal complications associated with macrosomia included humerus-clavicle fractures and arm-brachial plexus injury which were significant compared to the control group (P < 0.001 for all parameters). Conclusion. The macrosomia is potentially dangerous for the mother and the neonate. It is important to recognize the suspected fetal macrosomia to prevent its risk factors and complications. There is a need to provide all delivery facilities and care services to prevent and reduce the maternal and neonatal macrosomia complications.

  7. 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

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

    PubMed

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

    2010-08-21

    The reproductive implications of mutagenic treatments given to children with cancer are not clear. By studying the risk of untoward pregnancy outcomes, we indirectly assessed the risk of transmission of germline damage to the offspring of survivors of childhood cancer who were given radiotherapy and chemotherapy. We did a retrospective cohort analysis, within the Childhood Cancer Survivor Study (CCSS), of the risk of stillbirth and neonatal death among the offspring of men and women who had survived childhood cancer. Patients in CCSS were younger than 21 years at initial diagnosis of an eligible cancer, were treated at 25 US institutions and one Canadian institution, and had survived for at least 5 years after diagnosis. We quantified the chemotherapy given to patients, and the preconception radiation doses to the testes, ovaries, uterus, and pituitary gland, and related these to the risk of stillbirth or neonatal death using Poisson regression analysis. Among 1148 men and 1657 women who had survived childhood cancer, there were 4946 pregnancies. Irradiation of the testes (16 [1%] of 1270; adjusted relative risk 0.8 [95% CI 0.4-1.6]; mean dose 0.53 Gy [SD 1.40]) and pituitary gland (17 [3%] of 510, 1.1 [0.5-2.4] for more than 20.00 Gy; mean dose 10.20 Gy [13.0] for women), and chemotherapy with alkylating drugs (26 [2%] of 1195 women, 0.9 [0.5-1.5]; ten [1%] of 732 men, 1.2 [0.5-2.5]) were not associated with an increased risk of stillbirth or neonatal death. Uterine and ovarian irradiation significantly increased risk of stillbirth and neonatal death at doses greater than 10.00 Gy (five [18%] of 28, 9.1 [3.4-24.6]). For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1.00-2.49 Gy significantly increased the risk of stillbirth or neonatal death (three [4%] of 69, 4.7 [1.2-19.0]). Our findings do not support concern about heritable genetic changes affecting the risk of stillbirth and neonatal death in the offspring of men

  9. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy.

    PubMed

    Narisety, Satya D; Frischmeyer-Guerrerio, Pamela A; Keet, Corinne A; Gorelik, Mark; Schroeder, John; Hamilton, Robert G; Wood, Robert A

    2015-05-01

    Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these approaches are limited. This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT. In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged. Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT (P < .001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion. OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  10. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual versus Oral Immunotherapy for the Treatment of Peanut Allergy

    PubMed Central

    Narisety, Satya D.; Frischmeyer-Guerrerio, Pamela A.; Keet, Corinne A.; Gorelik, Mark; Schroeder, John; Hamilton, Robert G.; Wood, Robert A.

    2015-01-01

    Background Although promising results have emerged regarding oral and sublingual immunotherapy (OIT and SLIT) for the treatment of peanut allergy, direct comparisons of these approaches are limited. Objective This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut oral and sublingual immunotherapy. Methods In this double-blind study, children with peanut allergy were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7mg/day (SLIT) or 2000mg/day (OIT), and subjects were re-challenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 month were taken off treatment for 4 weeks and re-challenged. Results Twenty-one subjects, age 7–13 years, were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a >10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141-fold versus 22-fold, P=0.01). Significant within group changes in skin tests and peanut-specific IgE and IgG4 were found with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT (P<0.001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion. Conclusion OIT appeared far more effective than SLIT for the treatment of peanut allergy, but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects. PMID:25528358

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Immunotherapy of Prostate Cancer: Facts and Hopes.

    PubMed

    Bilusic, Marijo; Madan, Ravi A; Gulley, James L

    2017-06-29

    In the last few years immunotherapy has become an important cancer treatment modality and while the principles of immunotherapy evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiation therapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity. The goal of prostate cancer immunotherapy does not have to be complete eradication of advanced disease, but rather the return to an immunologic equilibrium with an indolent disease state. In addition to determining the optimal combination of treatment regimens, efforts are also ongoing to discover biomarkers of immune response. With such concerted efforts, the future of immunotherapy in prostate cancer looks brighter than ever. Copyright ©2017, American Association for Cancer Research.

  16. 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.

  17. 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.

  18. Current progress in immunotherapy for pancreatic cancer.

    PubMed

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

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. 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.

  20. 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.

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

    PubMed

    Arichi, T; Gordon-Williams, R; Allievi, A; Groves, A M; Burdet, E; Edwards, A D

    2013-09-01

    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. 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). 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. The described system is therefore suitable for detailed studies of the ontology of olfactory sensation and perception during early human brain development. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  2. 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

  3. A cost analysis of neonatal care in the UK: results from a multicentre study. ECSURF Study Group.

    PubMed

    O'Neill, C; Malek, M; Mugford, M; Normand, C; Tarnow-Mordi, W O; Hey, E; Halliday, H L

    2000-03-01

    A number of papers have recently been published examining the magnitude of scale economies in neonatal care and the level of activity at which these become attainable. Although these agree there is scope for economies in the production of neonatal care, they debate the extent to which such economies are attainable and how they might best be detected. A major multicentre study of neonatal units in the United Kingdom has produced costing and activity data allowing these issues to be explored afresh. A postal questionnaire was used to determine neonatal cost and activity levels in 57 UK neonatal units. Costs for the financial year 1990-1991 related to clinical staffing, support (such as pathology) and overheads (such as heat, light, power and administrative overheads). Activity related to the total number of care days provided and the number of these that were intensive in nature. All data were scrutinized to ensure consistent definitions. A multivariate regression analysis was used to investigate the relationship between costs and activity. A double-log function relating variations in total costs to total days, case-mix and an interaction term provided the best fit to the data. The analysis suggests that significant economies of scale are possible within the observed range of provision of intensive care. Significant economies of scale may be attainable. Nevertheless, these results should be carefully interpreted. In particular, the costs of neonatal care should not be examined in isolation but in relation to outcomes. In certain instances, units of inefficient scale but acceptable outcome may be defensible on grounds of ease of access.

  4. Sublingual (SLIT) versus oral immunotherapy (OIT) for food allergy.

    PubMed

    McGowan, Emily C; Wood, Robert A

    2014-12-01

    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.

  5. 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

  6. Preimplantation genetic diagnosis: a national multicenter obstetric and neonatal follow-up study.

    PubMed

    Bay, Bjorn; Ingerslev, Hans Jakob; Lemmen, Josephine Gabriela; Degn, Birte; Rasmussen, Iben Anne; Kesmodel, Ulrik Schiøler

    2016-11-01

    To study whether women conceiving after preimplantation genetic diagnosis (PGD) and their children have greater risks of adverse pregnancy and birth outcomes compared with children conceived spontaneously or after IVF with or without intracytoplasmic sperm injection (ICSI). Historical cohort study. Not applicable. All deliveries following PGD treatment for single gene and sex-linked disorders or structural chromosomal aberrations (n = 126 deliveries/149 children), IVF/ICSI treatment (n = 30,418 deliveries/36,115 children), and spontaneous conception (n = 896,448 deliveries/909,624 children). None. Adverse obstetric and neonatal outcomes, such as pre-eclampsia, preterm primary rupture of membranes, placenta previa, abruption of placenta, preterm birth, low birth weight, malformations, and neonatal admission. Compared with spontaneously conceived pregnancies, PGD pregnancies were at significantly increased risk of placenta previa (adjusted odds ratio [ORa] 9.1; 95% confidence interval [95% CI] 3.4, 24.9), cesarean section (ORa 2.0; 95% CI 1.3, 2.9), preterm birth (ORa 1.6; 95% CI 1.0, 2.7), shorter gestation (mean difference -3.4 days; 95% CI -5.7, -1.1 days), and longer neonatal admission (mean difference 21 days; 95% CI 15, 28 days). The risks were comparable to that of pregnancies following IVF/ICSI. In subanalyses, adverse outcomes were only present in children conceived by PGD owing to parental monogenetic disorder and comparable to those of children born to parents with monogenic disorders conceiving without PGD, except for a higher risk of placenta previa. In this cohort study, the risk of adverse obstetric and neonatal outcomes was mainly related to the underlying parental condition rather than the PGD procedure. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Maternal fish consumption, fetal growth and the risks of neonatal complications: the Generation R Study.

    PubMed

    Heppe, Denise H M; Steegers, Eric A P; Timmermans, Sarah; Breeijen, Hanneke den; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2011-03-01

    Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age. In total, 3380 mothers completed a 293-item semi-quantitative FFQ to obtain information about fish consumption during the first trimester of pregnancy. Head circumference, femur length and fetal weight were estimated in the second and third trimesters by ultrasound. Information about birth anthropometrics and neonatal complications was available from hospital and midwife registries. Maternal older age, higher educational level, folic acid supplement use, alcohol use and not smoking were associated with higher fish consumption (P < 0·01). After adjustment, we observed no consistent associations of maternal total-fish consumption or specific consumption of lean fish, fatty fish or shellfish with fetal growth characteristics in the second and third trimesters and at birth. Likewise, total-fish consumption or specific consumption of any type of fish was not consistently associated with the risks of neonatal complications. These findings suggest that in a population with a relatively low fish intake, consumption of lean fish, fatty fish or shellfish in the first trimester is not associated with fetal growth or the risks of neonatal complications.

  8. Development of visual evoked potentials in neonates. A study using light emitting diode goggles.

    PubMed Central

    Chin, K C; Taylor, M J; Menzies, R; Whyte, H

    1985-01-01

    We used a signal averager with light emitting diode goggles as the photostimulator to study the development of the visual evoked potentials in 40 normal neonates of between 23 and 42 weeks' gestation. All except two infants of less than 24 weeks' gestation had replicable visual evoked potentials. A negative peak of latency (mean (SD), 308 (21) msec) was present in all infants, but the development of the primary positive peak depended on maturity. Only infants of 37 weeks or more had a consistent positive peak of latency (mean (SD), 220 (22) msec). The practical simplicity and reliability of this technique has distinct advantages over previous conventional recording systems. Neonatal visual evoked potentials are shown to change with maturity. PMID:4091582

  9. 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.

  10. Gold nanoparticle mediated cancer immunotherapy.

    PubMed

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

    2014-04-01

    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. Cancer immunotherapy approaches are rapidly evolving and are some of the most promising avenues to approach malignancies. This review summarizes the role of gold nanoparticles in immunotherapy agent delivery, and in the development of synergistic therapies such as photothermal ablation. © 2013.

  11. Immunological study of IFNbeta-1a-treated and untreated multiple sclerosis patients: clarifying IFNbeta mechanisms and establishing specific dendritic cell immunotherapy.

    PubMed

    Berghella, Anna Maria; Totaro, Rocco; Pellegrini, Patrizia; Contasta, Ida; Russo, Tomassina; Carolei, Antonio; Adorno, Domenico

    2005-01-01

    A comparative immunological evaluation of multiple sclerosis (MS) patients receiving IFNbeta treatment and patients who are not receiving treatment may help clarify IFNbeta neurological mechanisms and lead the way to an effective dendritic cell (DC) immunotherapy. This type of study helps clarify the pathological function of T cells and DCs within the TH1/TH2/TH3 network as well as the specific interactions between TH1/TH2/TH3 cytokines implicated in MS pathological mechanisms and determine the best way of reestablishing the TH1/TH2/TH3 network equilibrium. We studied network interactions between TH1/TH2/TH3 cytokine levels in serum and supernatants of whole blood and CD14+ monocyte-derived DCs in the remission phase of the disease and in correlation to the Expanded Disability Status Scale (EDSS). We found that TH1 dysregulation results in a disruption of the maturation and activation of dendritic and T cells, and a lack of T-regulating cells for the induction of self-tolerance; IFNbeta mechanisms restore regulation by reestablishing the network balance but fail to resolve the disease completely due to in vivo IL12p70 network interactions leading to the deletion of self-aggressive cells. Our results indicate that a specific DC immunotherapy could cure rather than treat MS. The best point to reestablish the normal physiological cycle is at the immature DC stage which can be done in vitro with treated peripheral blood CD14+ cells and used in vivo to stimulate the expansion of specific regulatory T cells.

  12. A new suction mask to reduce leak during neonatal resuscitation: a manikin study.

    PubMed

    Lorenz, Laila; Maxfield, Dominic A; Dawson, Jennifer A; Kamlin, C Omar F; McGrory, Lorraine; Thio, Marta; Donath, Susan M; Davis, Peter G

    2016-09-01

    Leak around the face mask is a common problem during neonatal resuscitation. A newly designed face mask using a suction system to enhance contact between the mask and the infant's face might reduce leak and improve neonatal resuscitation. The aim of the study is to determine whether leak is reduced using the suction mask (Resusi-sure mask) compared with a conventional mask (Laerdal Silicone mask) in a manikin model. Sixty participants from different professional categories (neonatal consultants, fellows, registrars, nurses, midwives and students) used each face mask in a random order to deliver 2 min of positive pressure ventilation to a manikin. Delivered airway pressures were measured using a pressure line. Inspiratory and expiratory flows were measured using a flow sensor, and expiratory tidal volumes and mask leaks were derived from these values. A median (IQR) leak of 12.1 (0.6-39.0)% was found with the conventional mask compared with 0.7 (0.2-4.6)% using the suction mask (p=0.002). 50% of the participants preferred to use the suction mask and 38% preferred to use the conventional mask. There was no correlation between leak and operator experience. A new neonatal face mask based on the suction system reduced leak in a manikin model. Clinical studies to test the safety and effectiveness of this mask are needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

    PubMed

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

    2000-01-01

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

  14. 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

  15. 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.

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

    PubMed

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

    2011-01-01

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

  17. 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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Neonatal sepsis and neurodevelopment in very low birth weight infants in Matanzas, Cuba 2006-2010: a prospective cohort study.

    PubMed

    Robaina Castellanos, Gerardo Rogelio; Riesgo Rodríguez, Solangel de la Caridad

    2016-04-07

    Neonatal sepsis has been associated with poor neurodevelopmental outcome in very low birth weight infants (VLBW infants). The impact of neonatal sepsis on neurodevelopment in very low birth weight infants discharged from Cuban neonatal intensive care units is unknown. To determine the impact of neonatal sepsis as a risk factor of neurodevelopmental disorders in a Cuban very low birth weight infants’ population. A cohort study was carried out that enrolled 89 infants with birth weight less than 1500 g who were admitted during the period 2006-2010 to the Teaching Provincial Gynecological and Obstetrical Hospital of Matanzas. All patients were followed-up at the outpatient clinic until two years of corrected gestational age. Then they were divided into two groups: those who had been diagnosed with neonatal sepsis (n=19) and those who had not (n=70). The association power of neonatal sepsis with neurodevelopmental disorders was determined with calculation of relative risk (RR) and their confidence intervals at 95% (CI95%). A multivariate analysis with logistic regression enabled us to compare sepsis with other neonatal variables as risk factors. Very low birth weight infants with neonatal sepsis had an increased risk of neurodevelopmental disorders (47.4 vs 17.1%; RR 2.7 CI95% 1.3-5.5; p=0.005). This risk was significant after correction for other variables (male sex, mechanical respiratory assistance, bronchopulmonary dysplasia and hyperbilirrubinemia >15 mg/dl) (odds ratio 4.0; CI95% 1.1-14.3; p=0.03). Neonatal sepsis should be considered an important factor among the multiple events related to poor neurodevelopmental outcome in the preterm newborn.

  19. Oral Immunotherapy for Food Allergies.

    PubMed

    Feuille, Elizabeth; Nowak-Węgrzyn, Anna

    2016-01-01

    Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice. © 2016 S. Karger AG, Basel.

  20. Immunotherapy for cow's milk allergy.

    PubMed

    Taniuchi, Shoichiro; Takahashi, Masaya; Soejima, Kazukiko; Hatano, Yasuko; Minami, Hirotaka

    2017-08-21

    Oral immunotherapy (OIT) is used regularly for young children with cow's milk (CM) allergy and has been shown to be effective in several studies. However, adverse events occur frequently during OIT. Furthermore, there are only five randomized controlled trial studies of CM-OIT and these are low-powered single center trials. Therefore, evidence levels are also low and sometimes frequent and severe allergic events occur during the OIT. Furthermore, there are no standardized protocols in pediatric allergy guidelines from several countries and studies with long-term follow-up observations and clinical tolerance defined as sustained unresponsiveness are rare. Additionally, clinical tolerance by OIT is generally not well defined and obscure. Thus, several problems remain to be resolved, however we hope OIT in combination with omalizumab and less allergenic heated CM products will resolve these problems in the future.

  1. 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

  2. Maternal drug use and its effect on neonates: a population-based study in Washington State.

    PubMed

    Creanga, Andreea A; Sabel, Jennifer C; Ko, Jean Y; Wasserman, Cathy R; Shapiro-Mendoza, Carrie K; Taylor, Polly; Barfield, Wanda; Cawthon, Laurie; Paulozzi, Leonard J

    2012-05-01

    To estimate the effect of maternal illicit and prescription drug use on neonates in Washington State between 2000 and 2008. We used state-linked birth certificate and hospital discharge (mother and neonate) data to calculate prenatal drug exposure and neonatal abstinence syndrome rates, and compared state neonatal abstinence syndrome rates with national-level data from the Nationwide Inpatient Sample. We identified the drugs of exposure, examined predictors of drug exposure and neonatal abstinence syndrome, and assessed perinatal outcomes among drug-exposed and neonatal abstinence syndrome-diagnosed neonates compared with unexposed neonates. Drug exposure and neonatal abstinence syndrome rates increased significantly between 2000 and 2008, neonatal abstinence syndrome rates being consistently higher than national figures (3.3 compared with 2.8 per 1,000 births in 2008; P<.05). The proportion of neonatal abstinence syndrome-diagnosed neonates exposed prenatally to opioids increased from 26.4% in 2000 to 41.7% in 2008 (P<.05). Compared with unexposed neonates, drug-exposed and neonatal abstinence syndrome-diagnosed neonates had a lower mean birth weight, longer birth hospitalization, were more likely to be born preterm, experience feeding problems, and have respiratory conditions (all P<.001). Maternal use of illicit and prescription drugs was associated with considerable neonatal morbidity and significantly higher rates of drug exposure and neonatal abstinence syndrome in recent years. Data suggest that opioid analgesics contributed to the increase in prenatal drug exposure and neonatal abstinence syndrome in Washington State. In accordance with current guidelines, our findings emphasize the need for clinicians to screen pregnant women for illicit and prescription drug use and minimize use of opioid analgesics during pregnancy. II.

  3. Clinical trials in neonatal sepsis.

    PubMed

    Oeser, Clarissa; Lutsar, Irja; Metsvaht, Tuuli; Turner, Mark A; Heath, Paul T; Sharland, Mike

    2013-12-01

    Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy.

  4. 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.

  5. 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.

  6. Clinical trials of drugs used off-label in neonates: ethical issues and alternative study designs.

    PubMed

    Amin, Sanjiv B; McDermott, Michael P; Shamoo, Adil E

    2008-01-01

    The use of drugs for indications unapproved by the Food and Drug Administration (FDA), often called "off label use, "is widespread in children, including neonates. The widespread off-label use of drugs in neonates presents ethical and safety challenges. Since the passage of the Best Pharmaceuticals for Children Act (BPCA) in 2002, both the FDA and National Institutes of Health (NIH) have taken initiatives to facilitate and encourage research to achieve the necessary labeling for drugs routinely used in infants and children. Federal regulations provide broad rules and guidance for the protection of human subjects in research. However, there are ethical issues that a physician may face when designing clinical trials of drugs in neonates that are routinely used off-label and widely believed to be beneficial. We attempt to describe these ethical challenges and provide recommendations, including alternative study designs, to resolve them in an ethical framework that takes into account the Belmont Report, the statement of the World Medical Association (WMA), and federal regulations.

  7. Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study.

    PubMed

    Wiles, Jason R; Isemann, Barbara; Mizuno, Tomoyuki; Tabangin, Meredith E; Ward, Laura P; Akinbi, Henry; Vinks, Alexander A

    2015-12-01

    To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol. Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. There was substantial interindividual variability in methadone concentrations. Blood concentrations of methadone were best described by a 1-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of neonatal abstinence syndrome followed by an expedited weaning phase. The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. ClinicalTrials.gov: NCT01754324. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. [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

  9. 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.

  10. Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia, 2015: Unmatched Case Control Study.

    PubMed

    Gebremedhin, Destaalem; Berhe, Haftu; Gebrekirstos, Kahsu

    2016-01-01

    Neonatal sepsis is a leading cause of neonatal morbidity and mortality, particularly in the developing countries. Delays in the identification and treatment of neonatal sepsis are among the main contributors to the high mortality. The aim of this study was to determine the risk factors of neonatal sepsis in public hospitals of Mekelle City, Tigray Region, North Ethiopia, 2015. A hospital based case control study was done in public hospitals of Mekelle City, Tigray region. Cases were neonates who had sepsis with their index mothers and controls were neonates who hadn't had sepsis with their index mothers. Hematologic findings were used to diagnose sepsis once the neonates were being clinically suspected. Cases and controls were selected using the systematic sampling technique. Data were entered using Epi info version 7 and then analyzed using SPSS window 20. The binary logistic regression model was used to test the association between dependent and independent variables and multivariable logistic regression was used to identify the associated risk factors to neonatal sepsis. A total of 78 cases and 156 controls were included in this study. More than three quarters (76.8%) of cases had early onset sepsis. The multivariable logistic regression analysis showed that the possible risk factors of neonatal sepsis in this study were; history of maternal urinary tract infection or sexually transmitted infection [AOR = 5. 23; 95% CI (1.82, 15.04)], prolonged rupture of membrane [AOR = 7. 43; 95% CI (2.04, 27.1)], Place of delivery; health center delivery [AOR = 5. 7; 95% CI (1.71, 19.03)], intrapartum fever [AOR = 6. 1 95% CI (1.29, 28.31)], APGAR score <7 at 5th minute [AOR = 68. 9; 95% CI (3.63, 1308)] and not crying immediately at birth [AOR = 124. 0; 95% CI (6.5, 2379)]. Both maternal and neonatal factors had contributed to the risk of neonatal sepsis. Strengthening of the existing risk based prevention strategies as well as improvement of institutional delivery practices

  11. 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

  12. 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.

  13. [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.

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

    PubMed

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

    2014-09-01

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

  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. 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.

  17. 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.

  18. 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.

  19. Breast feeding and insulin levels in low birth weight neonates: a randomized study.

    PubMed

    Gupta, Mukesh; Zaheer; Jora, Rakesh; Kaul, Vijay; Gupta, Rajeev

    2010-05-01

    To evaluate the influence of early infancy feeding practices on fasting insulin levels, as marker of insulin resistance, in low birthweight neonates. Eighty successive low birth weight (<2.5 kg) neonates <10 days of age born at >38 wk of gestation at this tertiary care centre, were successively invited for participation in the study; parents of 52 (65%) consented to participate. Group 1 children (n=26) were randomized to receive only breast feeding and Group 2 (n=26) received fortified breast feeding with a commercially available human milk fortifier. Routine anthropometry and evaluation of health status was performed. The babies were followed-up every 15 day up to three months. 4-hour fasting glucose and insulin levels were measured at baseline and at 3 month. Statistical analyses were performed using t-test and Mann-Whitney test. In excusively breast-fed Group 1 neonates vs Group 2 the mean birthweight was similar (1.99+/-0.23 vs 1.87+/-0.30 kg). There was no difference in body length, head circumference and chest circumference. Mean hemoglobin levels, fasting glucose (63.9+/-9.8 vs 64.3+/-8.0 mg/dl) and fasting insulin levels (1.44+/-1.19 vs 1.73+/-1.38 microU/ml), were also similar. At three month follow-up in Group 1 children receiving exclusive breast feeding, there was significantly lower weight as compared to Group 2 (3.40+/-0.3 vs 4.75+/-0.5 kg, p<0.01). This was associated with significantly lower fasting glucose (79.0+/-9.4 vs 85.6+/-8.4 mg/dl) and fasting insulin levels (6.95+/-4.27 vs 15.73+/-3.29 microU/ml) (p<0.001). The difference persisted even after adjustment for weight gain in Group 2 (weight adjusted insulin 11.26+/-3.3 microU/ml; p<0.001). Low birthweight neonates fed fortified breast milk had greater fasting insulin levels compared to those with exclusive breast feeding, at three month of age. The difference persisted after adjustment for excessive gain in fortified milk fed neonates and, suggests adverse glucometabolic programming.

  20. Umbilical cord bilirubin as a predictor of neonatal jaundice: a retrospective cohort study.

    PubMed

    Jones, Kelsey D J; Grossman, S E; Kumaranayakam, Dharshini; Rao, Arati; Fegan, Greg; Aladangady, Narendra

    2017-09-20

    Hyperbilirubinaemia is a major cause of neonatal morbidity. Early identification of those infants most at risk might allow the development of targeted primary preventative therapy and follow-up. The objective of this study was to assess whether arterial umbilical cord bilirubin (aUCB) level at delivery predicts the development of neonatal jaundice in term deliveries. Retrospective analysis of hospital biochemistry records identified term deliveries with recorded aUCB. Infant medical records were reviewed to identify those who developed neonatal hyperbilirubinaemia (requiring treatment according to UK NICE guidelines) with/without a positive direct antiglobulin test (DAT). Of 1411 term deliveries with a clearly recorded aUCB, 30 infants developed clinically-significant jaundice (2.7%), of whom 8 were DAT + ve (0.6%) mostly due to ABO incompatibility. aUCB strongly predicted the development of DAT + ve jaundice (area under the ROC curve = 0.996), as well as all-cause jaundice (area under the ROC curve = 0.74). However, this effect was critically dependent on maternal blood group. Amongst infants at risk of ABO incompatibility (maternal blood groups O + ve/O-ve, 39.7%) the predictive value of aUCB for all cause jaundice was strengthened (area under the ROC curve = 0.88). Amongst those not at risk (defined maternal blood group not O + ve/O-ve, 51.0%) it disappeared completely (area under the ROC curve = 0.46). A cutoff of 35 μmol/l for mothers with blood group O + ve/O-ve increased the pre-test probability for all-cause jaundice of 4% to a post-test probability of 30%. For infants of mothers with blood group O, aUCB predicts development of neonatal jaundice. There was no evident utility for infants of mothers with other blood groups. Estimation of aUCB should be considered as a strategy for early identification of those at risk of neonatal haemolytic jaundice.

  1. 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.

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

    PubMed Central

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

    2013-01-01

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

  3. [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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25026155

  5. 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.

  6. Study of intraventricular hemorrhage in VLBW neonates admitted in Al-Zahra Hospital, Tabriz, Iran.

    PubMed

    Jodeiry, B; Heidarzadeh, M; Sahmani-Asl, S; Hoseini, M; Javaherizadeh, H; Eliasi, S; Abedini, K

    2012-01-01

    Intra-ventricular hemorrhage (IVH) is an important predictor of adverse neurodevelopmental outcome. IVH risk factor identification may conduct improvement of quality of care in neonatal intensive care units. The aim of the current study was to determine possible risk factors associated with IVH in VLBW neonates admitted in our hospital. All neonates with birth weight below 1500 gr admitted to NICU. Cranial ultrasonography was done for premature neonates weighed <1000 g in 3 to 5 days and in 1 month again. In premature infants weighed >1000 g, sonography was done in 7 days and 30 days of life respectively. If there is any conditions such as apnea, seizure, significant decrease in level of hemoglobin, increased head circumference, increased oxygen consumption, and other significant changes another sonography was done again. Exclusion criteria were cerebral malformations, metabolic disturbances, chromosomal anomalies, central nervous system infection, and genetic syndromes. Data was analyzed by SPSS ver 16.0 (SPSS Inc, Chicago, IL, USA). In this study 64 cases with IVH and without IVH were included. Mean of gestational age was 28.78 +/- 12.08. From neonates, 54.6% were boys and 45.4% were girls. Vaginal delivery and cesarean section was done in 56 (32.2%) and 118 (67.8%) cases respectively. Mean +/- SD of pH in cases with IVH and without IVH was 7.19 +/- 0.22 and 7.30 +/- 0.12 respectively (p = 0.001). Mean ISD of pco2 in cases with IVH and without IVH was 65.15 +/- 29.89 and 49.88 +/- 40.89 respectively(p = 0.001). Mean of 5th min APGAR score in patients required CPR was 7.36 +/- 1.57 and in patients without CPR was 8.68 +/- 1.25 (P = 0.001). From cases with IVH, hydrocephaly was detected in 20 cases. From cases without IVH, hydrocephaly was detected in 6 cases. Result of chi-square show significant correlation between IVH and prematurity (chi2 = 21.94, df=1, P < 0.001). From cases with IVH, 18 cases (28.1%) expired. From cases without IVH, 11 cases (10%) expired

  7. Immunotherapy for invasive mold disease in severely immunosuppressed patients.

    PubMed

    Safdar, Amar

    2013-07-01

    Response to systemic antifungal therapy alone remains disproportionately less satisfactory in immunosuppressed transplant and oncology patients. As insight in fungal immunopathogenesis forges ahead, interventions for boosting immune functions along with antimicrobial drugs has shown promise in preclinical experiments. The clinical experience with immunotherapy for invasive mold disease is limited. Most studies have involved small numbers of patients at a single institution or data collected retrospectively. An overview of various facts of immune modulatory drug intervention is presented, including major considerations in antifungal immunotherapy in immunosuppressed patients. Patients in whom immunotherapy is being considered must be critically evaluated to identify the underlying immune defects, including treatment-induced immunosuppression. Antifungal immunotherapy is appealing; however, before routine clinical use is recommended, well-designed prospective comparative clinical trials are urgently needed.

  8. Toxoplasmic encephalitis during mycophenolate mofetil immunotherapy of neuromuscular disease

    PubMed Central

    Chahin, Nizar

    2015-01-01

    Objective: To show that immunotherapy with medications such mycophenolate mofetil (MMF) can cause serious complications in patients with neuromuscular disorders. Methods: Two patients with neuromuscular disorders on immunotherapy with long-term MMF who developed toxoplasmic encephalitis (TE) were included in this case series. Results: One patient with myasthenia gravis and one patient with inflammatory myopathy on immunotherapy with long-term MMF developed severe TE. Diagnosis was based on clinical presentation, MRI brain imaging characteristics, and CSF PCR positivity for Toxoplasma gondii. Both patients were treated with pyrimethamine, sulfadiazine, and leucovorin for 2 months without clinical improvement, and both died. Conclusions: Immunotherapy with medications such as MMF can cause devastating TE in non-HIV patients with neuromuscular disorders. Early consideration and recognition of this complication is important to possibly prevent unfavorable outcomes. The utility of screening and prophylaxis against toxoplasmosis in individuals with neuroimmunologic disorders and other autoimmune disorders who receive immunosuppressive therapy requires future study. PMID:25635260

  9. 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.

  10. 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…

  11. 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…

  12. 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.

  13. Frequent brief on-site simulation training and reduction in 24-h neonatal mortality--an educational intervention study.

    PubMed

    Mduma, Estomih; Ersdal, Hege; Svensen, Erling; Kidanto, Hussein; Auestad, Bjørn; Perlman, Jeffrey

    2015-08-01

    "Helping Babies Breathe" (HBB) is a simulation-based educational program developed to help reduce perinatal mortality worldwide. A one-day HBB training course did not improve clinical management of neonates. The objective was to assess the impact of frequent brief (3-5 min weekly) on-site HBB simulation training on newborn resuscitation practices in the delivery room and the potential impact on 24-h neonatal mortality. Before/after educational intervention study in a rural referral hospital in Northern Tanzania. Baseline data was collected from 01.02.2010 to 31.01.2011 and post-intervention data from 01.02.2011 to 31.01.2012. All deliveries were observed by research assistants who recorded information about labor, newborn delivery room management, perinatal characteristics, and neonatal outcomes. A newborn simulator was placed in the labor ward and frequent brief HBB simulation training was implemented on-site; 3-min of weekly paired practice, assisted by local-trainers. Local-trainers also facilitated 40-min monthly re-trainings. Outcome measures were; delivery room management of newborns and 24-h neonatal outcomes (normal, admitted to a neonatal area, death, or stillbirths). There were 4894 deliveries pre and 4814 post-implementation of frequent brief simulation training. The number of stimulated neonates increased from 712(14.5%) to 785(16.3%) (p = 0.016), those suctioned increased from 634(13.0%) to 762(15.8%) (p ≤ 0.0005). Neonates receiving bag mask ventilation decreased from 357(7.3%) to 283(5.9%) (p = 0.005). Mortality at 24-h decreased from 11.1/1000 to 7.2/1000 (p = 0.040). On-site, brief and frequent HBB simulation training appears to facilitate transfer of new knowledge and skills into clinical practice and to be accompanied by a decrease in neonatal mortality. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Neonatal morbidity by week of gestational age for twins compared to singletons: a population-based cohort study.

    PubMed

    Wolfe, Katherine; Tabangin, Meredith; Meinzen-Derr, Jareen; Snyder, Candice; Lewis, David; DeFranco, Emily

    2014-02-01

    Quantify neonatal morbidity by week of gestation for twins compared with singletons. We performed a population-based retrospective cohort study of all Ohio births from 2006 to 2007. Composite neonatal morbidity consisting of Apgar score < 7 at 5 minutes, assisted ventilation > 6 hours, neonatal transport, or seizures was compared between singletons and twins from 34 to 41 weeks. Neonatal morbidity was the lowest in twins delivered at 37 completed weeks and 2 weeks later for singletons at 39 weeks. Twin morbidity rapidly increased after 37 weeks and reached 15.8% at 41 weeks versus the singleton morbidity rate of 3.4% at 41 weeks. Twins delivered at 39 weeks and beyond were more than twice as likely to incur neonatal morbidity compared with singletons. The lowest rate of neonatal morbidity occurs at 37 weeks for twins versus 39 weeks for singleton births. The increased risk after 37 weeks for twins accelerates at a faster rate compared with that for singletons born past 39 weeks. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Maternal and antenatal risk factors for stillbirths and neonatal mortality in rural Bangladesh: a case-control study.

    PubMed

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

    2013-01-01

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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

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

    PubMed

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

    2014-07-10

    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. 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. 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. 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

  6. 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.

  7. 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.

  8. Immunotherapy for bladder cancer

    PubMed Central

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

    2015-01-01

    It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  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. 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.

  11. Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case-control study on 171 patients. The EFESO-children multicenter trial.

    PubMed

    Acquistapace, Franca; Agostinis, Fabio; Castella, Vincenzo; Kantar, Ahmad; Novembre, Elio; Perrone, Maria Rosaria; Pietrasanta, Michele; Sambugaro, Renato; Milani, Massimo

    2009-11-01

    Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in 'real life' in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case-control study to evaluate the effect of SLIT in children (age 6-18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case-control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean +/- SD) was 4.5 +/- 2.5 in cases and 9.0 +/- 3.0 in controls (-50%) (p = 0.0001). MS (mean +/- SD) was 2.5 +/- 1.9 and 3.6 +/- 2.1 in the case and control groups, respectively (-31%) (p = 0.0001). At the end of

  12. 3D Models of Immunotherapy

    Cancer.gov

    This collaborative grant is developing 3D models of both mouse and human biology to investigate aspects of therapeutic vaccination in order to answer key questions relevant to human cancer immunotherapy.

  13. Outcomes at 7 years for babies who developed neonatal necrotising enterocolitis: the ORACLE Children Study.

    PubMed

    Pike, Katie; Brocklehurst, Peter; Jones, David; Kenyon, Sarah; Salt, Alison; Taylor, David; Marlow, Neil

    2012-09-01

    Within the ORACLE Children Study Cohort, the authors have evaluated long-term consequences of the diagnosis of confirmed or suspected neonatal necrotising enterocolitis (NEC) at age of 7 years. Outcomes were assessed using a parental questionnaire, including the Health Utilities Index (HUI-3) to assess functional impairment, and specific medical and behavioural outcomes. Educational outcomes for children in England were explored using national standardised tests. Multiple logistic regression was used to explore independent associates of NEC within the cohort. The authors obtained data for 119 (77%) of 157 children following proven or suspected NEC and compared their outcomes with those of the remaining 6496 children. NEC was associated with an increase in risk of neonatal death (OR 14.6 (95% CI 10.4 to 20.6)). At 7 years, NEC conferred an increased risk of all grades of impairment. Adjusting for confounders, risks persisted for any HUI-3 defined functional impairment (adjusted OR 1.55 (1.05, 2.29)), particularly mild impairment (adjusted OR 1.61 (1.03, 2.53)) both in all NEC children and in those with proven NEC, which appeared to be independent. No behavioural or educational associations were confirmed. Following NEC, children were more likely to suffer bowel problems than non-NEC children (adjusted OR 3.96 (2.06, 7.61)). The ORACLE Children Study provided opportunity for the largest evaluation of school age outcome following neonatal NEC and demonstrates significant long-term consequences of both gut function (presence of stoma, admission for bowel problems and continuing medical care for gut-related problems) and motor, sensory and cognitive outcomes as measured using HUI-3.

  14. Monitoring neonatal abstinence syndrome in buprenorphine-exposed in vitro fertilization twins: A case study.

    PubMed

    Brandt, Laura; Swoboda, Patrick; Fischer, Gabriele; Unger, Annemarie

    2016-01-01

    Prior studies have reported on the pregnancies and outcomes of in vitro fertilization (IVF) in special subpopulations; however, there is a lack of studies on opioid-exposed IVF-conceived neonates. A young adult IVF-pregnant woman was maintained on buprenorphine throughout pregnancy and received follow-up from the addiction clinic from estimated gestational week 32. She delivered healthy dichorionic twins via cesarean section at 38 weeks gestational age (buprenorphine dose at time of delivery: 16 mg). All maternal supervised urinalysis taken as of gestational week 32 were negative for concomitant substances (prior to treatment initiation at the addiction clinic, only self-reports of abstinence from concomitant substances were available). Both healthy children (male birth weight: 3140 g, female birth weight: 2650 g) developed an unusual course of neonatal abstinence syndrome (NAS) requiring extensive treatment (total morphine dose male: 22 mg, and female: 26.75 mg; length of treatment: 33 and 34 days, respectively; duration of hospitalization: 40 days). The highly severe and long-lasting NAS in both neonates represents a very unusual course following an uneventful pregnancy, and influencing iatrogenic factors cannot be ruled out. Given the multiple variables influencing infant outcomes, this highlights the importance of high-quality, evidence-based standard operating procedures, which (1) are initiated as early as possible during pregnancy to minimize risk factors for adverse infant outcomes, such as concomitant substance use during pregnancy; (2) support the substance-dependent woman throughout the postpartum period, especially in cases of multiple and/or IVF-conceived pregnancies, where additional challenges may arise; and (3) consider the right of everyone to the enjoyment of the highest attainable standard of physical and mental health.

  15. Frequency of newborn behaviours associated with neonatal abstinence syndrome: a hospital-based study.

    PubMed

    Elliott, M Ruth; Cunliffe, Pemme; Demianczuk, Nestor; Robertson, Charlene M T

    2004-01-01

    To determine the frequency of neonatal abstinence syndrome (NAS) among unselected term newborns, using newborn behaviour data only. This hospital-based prospective exploratory study used clinical observations of newborn behaviours, mothers' observations of their newborns, and newborn chart data to determine the prevalence of suspected and confirmed cases of NAS in a convenience sample of unselected term newborns "rooming in" with their mothers in a large central city acute-care referral hospital. Over a 4-month period, 824 out of 1008 newborns were observed at between 8 and 30 hours of life by specially trained nurse observers. Behaviours recorded and their weighting were adapted from the Neonatal Abstinence Scoring System (NASS) by Finnegan and Kaltenbach. Newborns with scores of 5 or greater and "suspect for NAS" were referred to their physicians for confirmation or refutation of the clinical findings. The prevalence of "suspect for NAS" and confirmed NAS, as well as of individual neonatal behaviours, was calculated. Thirty-one (3.8%) of 824 term "rooming in" newborns were identified with findings suggestive of NAS. Four newborns were positively identified as having NAS and treated. The identification was confirmed by post hoc affirmation of maternal drug use. Individual behaviours occurring in 10% or more of newborns included excessive sneezing, nasal stuffiness, unsustained suck, tremor, and abnormal nipple latch. Clinical observation of newborn behaviour may identify NAS. Further studies are recommended to correlate this methodology with laboratory findings, as are more in-depth maternal questionnaires concerning use of mood-altering substances. The prevalence of NAS is likely underestimated because of early hospital discharge. A coordinated system of early identification and infant-specific assessment and treatment, both in hospital and following discharge home, is advocated.

  16. Permanent neonatal diabetes mellitus: prevalence and genetic diagnosis in the SEARCH for Diabetes in Youth Study.

    PubMed

    Kanakatti Shankar, Roopa; Pihoker, Catherine; Dolan, Lawrence M; Standiford, Debra; Badaru, Angela; Dabelea, Dana; Rodriguez, Beatriz; Black, Mary Helen; Imperatore, Giuseppina; Hattersley, Andrew; Ellard, Sian; Gilliam, Lisa K

    2013-05-01

    Neonatal diabetes mellitus (NDM) is defined as diabetes with onset before 6 months of age. Nearly half of individuals with NDM are affected by permanent neonatal diabetes mellitus (PNDM). Mutations in KATP channel genes (KCNJ11, ABCC8) and the insulin gene (INS) are the most common causes of PNDM. To estimate the prevalence of PNDM among SEARCH for Diabetes in Youth (SEARCH) study participants (2001-2008) and to identify the genetic mutations causing PNDM. SEARCH is a multicenter population-based study of diabetes in youth <20 yr of age. Participants diagnosed with diabetes before 6 months of age were invited for genetic testing for mutations in the KCNJ11, ABCC8, and INS genes. Of the 15,829 SEARCH participants with diabetes, 39 were diagnosed before 6 months of age. Thirty-five of them had PNDM (0.22% of all diabetes cases in SEARCH), 3 had transient neonatal diabetes that had remitted by 18 months and 1 was unknown. The majority of them (66.7%) had a clinical diagnosis of type1 diabetes by their health care provider. Population prevalence of PNDM in youth <20 yr was estimated at 1 in 252 000. Seven participants underwent genetic testing; mutations causing PNDM were identified in five (71%), (two KCNJ11, three INS). We report the first population-based frequency of PNDM in the US based on the frequency of PNDM in SEARCH. Patients with NDM are often misclassified as having type1 diabetes. Widespread education is essential to encourage appropriate genetic testing and treatment of NDM. © 2012 John Wiley & Sons A/S.

  17. 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

  18. 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

  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. 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

  1. 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

  2. NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol.

    PubMed

    Askie, Lisa M; Brocklehurst, Peter; Darlow, Brian A; Finer, Neil; Schmidt, Barbara; Tarnow-Mordi, William

    2011-01-17

    The appropriate level of oxygenation for extremely preterm neonates (<28 weeks' gestation) to maximise the greatest chance of survival, without incurring significant morbidity, remains unknown. Infants exposed to lower levels of oxygen (targeting oxygen saturations of <90%) in the first weeks of life are at increased risk of death, cerebral palsy, patent ductus arteriosus, pulmonary vascular resistance and apnoea, whilst those maintained in higher levels of oxygen (targeting oxygen saturations of >90%) have been reported to have greater rates of morbidity including retinopathy of prematurity and chronic lung disease. In order to answer this clinical dilemma reliably, large scale trial evidence is needed. To detect a small but important 4% increase in death or severe disability in survivors, over 5000 neonates would need to be recruited. As extreme prematurity affects 1% of births, such a project undertaken by one trial group would be prohibitively lengthy and expensive. Hence, the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration has been formed. A prospective meta-analysis (PMA) is one where studies are identified, evaluated, and determined to be eligible before the results of any included studies are known or published, thereby avoiding some of the potential biases inherent in standard, retrospective meta-analyses. This methodology provides the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility. The NeOProM Collaboration protocol (NCT01124331) has been agreed prior to the results of individual trials being available. This includes pre-specifying the hypotheses, inclusion criteria and outcome measures to be used. Each trial will first publish their respective results as they become available and the combined meta-analytic results, using individual patient data, will be published when all trials are complete. The primary outcome to be assessed is a composite outcome of death or

  3. 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.

  4. 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

  5. Mathematical modeling of the effect of boosting tumor infiltrating lymphocyte in immunotherapy.

    PubMed

    Kartono, Agus; Subiyanto

    2013-10-15

    This study, we analyzed the effect of boosting tumor infiltrating lymphocyte in immunotherapy using mathematical modeling. In this model, tumor growth is described as a tumor cells population with immunotherapy. This model also describes the effect of Tumor Infiltrating Lymphocytes (TIL), interleukin-2 (IL-2) and interferon alpha (INF-alpha) on dynamics of tumor cells. Numerical modeling of immunotherapy with or not boosted Tumor Infiltrating Lymphocyte (TIL) are presented in this study. We obtained that boosting Tumor Infiltrating Lymphocyte (TIL) in immunotherapy have a very significant role in killing of tumor cells.

  6. A study of neonatal swimming (water therapy) applied in clinical obstetrics.

    PubMed

    Zhao, S; Xie, L; Hu, H; Xia, J; Zhang, W; Ye, N; Chen, B

    2005-01-01

    To study the significance of some clinical parameters related to neonatal 'swimming' (water therapy) during hospitalization. Normal newborns were randomly divided into two groups to observe their birth weight, weight before discharge,time of first defecation and meconium turning yellow. Group one was the swimming (study) group, comprising a total of 223 newborns including 127 babies delivered after spontaneous vaginal delivery and 96 babies after Cesarean section. Group two was the bathing (control) group, comprising 154 newborns including 109 babies delivered after spontaneous vaginal delivery and 45 babies after Cesarean section. There was no significant difference in birth weight between the two groups (p > 0.05). However, the mean weight before discharge of the babies in the study group was 3.29 + 0.35 and 3.51 + 0.40 kg, spontaneous vaginal delivery vs. Cesarean section, compared with 3.09 + 0.38 and 3.17 + 0.48 kg, respectively, in the control group (p < 0.01). The corresponding mean times of meconium turning yellow were 39.15 + 15.88 and 39.02 + 13.60 h in the study group compared with 48.01 + 19.42 and 55.67 + 25.05 h in the control group. This difference was significant (p < 0.01), as was the difference between the time of first defecation (p < 0.05). Neonatal swimming can accelerate babies' growth in the early stage.

  7. Patient adherence to allergy immunotherapy.

    PubMed

    Reisacher, William R; Visaya, Jiovani M

    2013-06-01

    This article reviews the literature on patient adherence to two different approaches to allergen-specific immunotherapy for allergic disease. Factors related to adherence in general, as well as the various methods used to measure adherence, will be discussed. Although a complex interaction of factors related to both the physician and the patient influence the adherence to a particular therapeutic regimen, effective communication between these two parties and the simplicity of the regimen are frequently noted to be of primary importance. Variability with respect to the definition of adherence, the method of measuring adherence, and the length of the measuring period has resulted in a wide range of adherence rates to allergy immunotherapy reported in the literature. Patients most often site inconvenience, side-effects, and poor efficacy as reasons for discontinuing allergy immunotherapy. Adherence to therapy not only improves individual patient outcomes, but also helps determine the best treatment modalities and reduces the burden of disease on society. As new methods of delivering immunotherapy are being developed, such as allergy immunotherapy tablets and oral mucosal immunotherapy, the factors associated with patient adherence should be carefully considered.

  8. 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

  9. Enterovirus infection in febrile neonates: A hospital-based prospective cohort study.

    PubMed

    Lv, Xiao-Qing; Qian, Ling-He; Wu, Tai; Yuan, Tian-Ming

    2016-08-01

    This study aims to investigate clinical characteristics and microbiological results and to assess the predictors for enterovirus infection in febrile neonates. A prospective cohort study was conducted on 334 febrile patients (age: 0.33-28 days) in 2011-2012 years. Enterovirus RNA was detected by reverse transcription polymerase chain reaction on faeces or cerebrospinal fluid (CSF). Clinical characteristics were compared, and non-conditional logistic regression analysis was performed to determine independent predictors for enterovirus infection. There were 131 episodes of neonatal enterovirus infection (39.22%). Forty-eight (36.64%) developed respiratory symptoms, 69 (52.67%) had diarrhoea, 22 (16.79%) had poor feeding and 34 (25.95%) had rash. Eighteen (13.74%) had lower platelet counts, and CSF specimens were positive for enterovirus RNA in 44.27% (58/131) whose CSF revealed a mean white blood cell counts of 100.38 ± 147.97 cells/mm(3) (range: 2-668 cells/mm(3) ). The positivity of stool 38.92% (130/334) was significantly higher than that of CSF specimens 26.24% (58/221) for enterovirus RNA (P < 0.01). By logistic regression analysis, the following independently predicted enterovirus infection: abnormal CSF test (odds ratio (OR): 12.426, 95% confidence interval (CI): 5.633-27.413), thrombocytopenia (OR: 3.647, 95% CI: 1.312-10.136), duration of fever >3.25 (d) (OR: 2.293, 95% CI: 1.279-4.113), highest temperature >38.35 (°C) (OR: 2.094, 95% CI: 1.342-4.123) and negative bacterial culture (OR: 5.073, 95% CI: 1.504-17.114). Our data indicated that enteroviruses should be routinely considered in the differential diagnosis of febrile neonates. The factors, which may predict the risk of neonatal enterovirus infection, were abnormal CSF test, thrombocytopenia, duration of fever >3.25 (d), highest temperature >38.35 (°C) and negative bacterial culture. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  10. Infant pupillary response to methadone administration during treatment for neonatal abstinence syndrome: a feasibility study.

    PubMed

    Heil, Sarah H; Gaalema, Diann E; Johnston, Anne M; Sigmon, Stacey C; Badger, Gary J; Higgins, Stephen T

    2012-11-01

    Pupil diameter is a frequently assessed objective index of the pharmacodynamic effects of opioids in adults, but to our knowledge has never been examined in infants. Such a measure could improve assessment and treatment of neonates exposed to opioids in utero. The present study examined changes in pupil diameter after opioid administration in opioid-exposed infants who required pharmacological treatment for neonatal abstinence syndrome (NAS) to test the feasibility of using pupil diameter as a measure of opioid effects in these infants. Ten infants (2-7 days old) receiving methadone (0.4-0.5 mg every 12 h) for the treatment of NAS participated. A picture of one of each infant's eyes was taken under controlled illumination conditions with a standard digital camera just prior to dosing and 0-1, 2-4, 5-7, and 8-10h after dosing. The diameters of the pupil and iris were measured and relative pupil diameter (pupil diameter expressed as a percentage of iris diameter) was analyzed. Mean (±SE) relative pupil diameter decreased significantly after dosing from 41±2% to 29±2%. After dosing, a significant increasing linear trend was observed over time, with values of 29±2%, 33±3%, 38±3%, and 41±3% at 0-1, 2-4, 5-7, and 8-10h after dosing. Infant pupils respond to opioid administration in the same sensitive, orderly manner as is commonly observed in adults. Pupil diameter appears to be an objective, sensitive measure of neonatal response to opioids that may be a useful complement to, or perhaps at times a replacement for, observer-rated scale scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Infant Pupillary Response to Methadone Administration During Treatment for Neonatal Abstinence Syndrome: A Feasibility Study

    PubMed Central

    Heil, Sarah H.; Gaalema, Diann E.; Johnston, Anne M.; Sigmon, Stacey C.; Badger, Gary J.; Higgins, Stephen T.

    2012-01-01

    Background Pupil diameter is a frequently assessed objective index of the pharmacodynamic effects of opioids in adults, but to our knowledge has never been examined in infants. Such a measure could improve assessment and treatment of neonates exposed to opioids in utero. The present study examined changes in pupil diameter after opioid administration in opioid-exposed infants who required pharmacological treatment for neonatal abstinence syndrome (NAS) to test the feasibility of using pupil diameter as a measure of opioid effects in these infants. Methods Ten infants (2–7 days old) receiving methadone (0.4–0.5 mg every 12 hours) for the treatment of NAS participated. A picture of one of each infant's eyes was taken under controlled illumination conditions with a standard digital camera just prior to dosing and 0–1, 2–4, 5–7, and 8–10 hours after dosing. The diameters of the pupil and iris were measured and relative pupil diameter (pupil diameter expressed as a percentage of iris diameter) was analyzed. Results Mean (±SE) relative pupil diameter decreased significantly after dosing from 41±2% to 29±2%. After dosing, a significant increasing linear trend was observed over time, with values of 29±2%, 33±3%, 38±3%, and 41±3% at 0–1, 2–4, 5–7, and 8–10 hours after dosing. Conclusions Infant pupils respond to opioid administration in the same sensitive, orderly manner as is commonly observed in adults. Pupil diameter appears to be an objective, sensitive measure of neonatal response to opioids that may be a useful complement to, or perhaps at times a replacement for, observer-rated scale scores. PMID:22682657

  12. 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

  13. Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: study protocol for a cluster randomised controlled trial.

    PubMed

    Rahn, Anne Christin; Köpke, Sascha; Kasper, Jürgen; Vettorazzi, Eik; Mühlhauser, Ingrid; Heesen, Christoph

    2015-03-21

    Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of evidence-based patient information and shared decision-making, has the potential to facilitate participation of individuals in the decision-making process. This cluster randomised controlled trial follows the assumption that decision coaching by trained nurses, using evidence-based patient information and preference elicitation, will facilitate informed choices and induce higher decision quality, as well as better decisional adherence. The decision coaching programme will be evaluated through an evaluator-blinded superiority cluster randomised controlled trial, including 300 patients with suspected or definite relapsing-remitting multiple sclerosis, facing an immunotherapy decision. The clusters are 12 multiple sclerosis outpatient clinics in Germany. Further, the trial will be accompanied by a mixed-methods process evaluation and a cost-effectiveness study. Nurses in the intervention group will be trained in shared decision-making, coaching, and evidence-based patient information principles. Patients who meet the inclusion criteria will receive decision coaching (intervention group) with up to three face-to-face coaching sessions with a trained nurse (decision coach) or counselling as usual (control group). Patients in both groups will be given access to an evidence-based online information tool. The primary outcome is 'informed choice' after six months, assessed with the multi-dimensional measure of informed choice including the sub-dimensions risk knowledge (questionnaire), attitude concerning immunotherapy (questionnaire), and immunotherapy uptake (telephone survey

  14. 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.

  15. 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

  16. [Prevention of neonatal conjunctivitis. A comparative clinical and bacteriologic study of 2 eyedrops: silver nitrate and oxytetracycline chlorhydrate].

    PubMed

    Brussieux, J; Boisivon, A; Théron, H P; Faidherbe, C; Machado, N; Michelon, B

    1991-11-01

    This study carried out at the Saint-Germain-en-Laye Hospital maternity ward included all the neonates delivered between February and September 1989 who exhibited no abnormal manifestations during their stay in the ward, except for ocular symptoms in some subjects. Nine hundred neonates were enrolled. Each day, one of two eyedrop preparations for the prevention of neonatal ocular infections was selected at random. Investigators were blinded to the preparation used. Study subjects were evaluated twice, between D1 and D7 (900 infants) and between D15 and D30 (407 infants). Ocular findings were classified as follows: normal, minimally abnormal (isolated swelling of the eyelids, clear discharge), or frankly abnormal (conjunctivitis, purulent discharge). A bacteriologic study was performed in all patients with minimally abnormal or abnormal findings. Between D1 and D7, ocular symptoms were significantly (p less than 0.05) more prevalent in neonates treated with silver nitrate than in neonates treated with oxytetracycline hydrochloride. This difference was no longer present between D15 and D30. Bacteriologic studies recovered no gonococci. One enfant in the oxytetracycline group had bacteriologically confirmed Chlamydia trachomatis ocular infection. The other organisms recovered were mainly Staphylococcus aureus and non-hemolytic streptococci. In inclusion, no currently available eyedrop preparation offers complete protection against C. trachomatis but tolerance is considerably better with oxytetracycline hydrochlorate than with silver nitrate.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

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

    SciTech Connect

    Snyder, F.

    1992-11-01

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

  3. Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study

    PubMed Central

    Wiles, Jason R.; Isemann, Barbara; Mizuno, Tomoyuki; Tabangin, Meredith E.; Ward, Laura P.; Akinbi, Henry; Vinks, Alexander A.

    2015-01-01

    Objective To characterize the population pharmacokinetic (PK) of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome (NAS) and to develop a PK model towards an evidence-based treatment protocol. Study design Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed via high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. Results There was substantial inter-individual variability in methadone concentrations. Blood concentrations of methadone were best described by a one-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of NAS followed by an expedited weaning phase. Conclusions The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. Trial registration ClinicalTrials.gov: NCT01754324 PMID:26364984

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

    PubMed

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

    2014-01-01

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

  5. Maternal and neonatal outcomes following induction of labor: a cohort study.

    PubMed

    Grivell, Rosalie M; Reilly, Aimee J; Oakey, Helena; Chan, Annabelle; Dodd, Jodie M

    2012-02-01

    To evaluate maternal and neonatal outcomes associated with birth at term by week of gestational age and also by onset of labor. Cohort study. A state-wide perinatal outcome database. 28,626 women with spontaneous onset of labor, induction of labor for recognized indications and induction of labor for non-recognized indications. Cohort study utilizing a validated dataset comparing outcomes with type of onset of labor using a log binomial model. Cesarean section, assisted vaginal birth, important measures of maternal and neonatal morbidity. Induction of labor for non-recognized indications was associated with a significantly increased risk of a range of outcomes, including cesarean section (RR 1.67, 95% CI 1.55-1.80). The lowest risk of adverse maternal and infant outcome occurred with birth between 38 and 39 weeks and with the spontaneous onset of labor. Induction of labor for non-recognized indications at term is associated with an increased risk of adverse outcomes. Caution is warranted with a liberal policy of induction of labor at term in an otherwise uncomplicated pregnancy. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

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

    PubMed

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

    2015-01-01

    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. 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. 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). 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.

  7. 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

  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. 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.

  10. 'Clinical trials in Alzheimer's disease': immunotherapy approaches.

    PubMed

    Delrieu, Julien; Ousset, Pierre Jean; Caillaud, Céline; Vellas, Bruno

    2012-01-01

    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 (Aβ) peptide represents an important molecular target for intervention in Alzheimer's disease. Several types of Aβ peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic intact Aβ(42) , active immunization involving the administration of synthetic fragments of Aβ peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aβ peptide. Pre-clinical studies showed that immunization against Aβ peptide can provide protection and reversal of the pathology of Alzheimer's disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. 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 Aβ peptide immunotherapy approaches are under investigation but also against tau pathology. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  11. 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.

  12. Neonatal infection with Neisseria meningitidis: analysis of a 97-year period plus case study.

    PubMed

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

    2014-09-01

    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). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Discrimination of emotional prosodies in human neonates: A pilot fNIRS study.

    PubMed

    Zhang, Dandan; Zhou, Yu; Hou, Xinlin; Cui, Yun; Zhou, Congle

    2017-08-23

    Very early in development, vocal emotional cues are more critical than facial expressions in guiding infants' behavior. However, the processing of emotional prosody in the very early days of life is still far from clearly understood. To address the issue, this study used functional near-infrared spectroscopy to examine brain response of neonates when they passively listened to fearful, angry, happy and neutral prosodies. It was found that while the right temporal cortex (mainly located in the middle temporal gyrus and superior temporal gyrus) exhibited enhanced response to emotional, relative to neutral, prosody, a right parietal area (approximately located in the supramarginal gyrus) showed a heightened sensitivity to fearful, relative to happy and neutral, prosody. These findings highlight the crucial importance of the right hemisphere in the perception of emotional prosody in neonates. Furthermore, the result is consistent with the notion of a negativity bias, supporting the evolutionary importance of threatening information that could be processed at birth. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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