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1.
BMC Health Serv Res ; 24(1): 688, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816869

ABSTRACT

BACKGROUND: Existing knowledge on healthcare use and costs in the last months of life is often limited to one patient group (i.e., cancer patients) and one level of healthcare (i.e., secondary care). Consequently, decision-makers lack knowledge in order to make informed decisions about the allocation of healthcare resources for all patients. Our aim is to elaborate the understanding of resource use and costs in the last six months of life by describing healthcare use and costs for all causes of death and by all levels of formal care. METHOD: Using five national registers, we gained access to patient-level data for all individuals who died in Norway between 2009 and 2013. We described healthcare use and costs for all levels of formal care-namely primary, secondary, and home- and community-based care -in the last six months of life, both in total and differentiated across three time periods (6-4 months, 3-2 months, and 1-month before death). Our analysis covers all causes of death categorized in ten ICD-10 categories. RESULTS: During their last six months of life, individuals used an average of healthcare resources equivalent to €46,000, ranging from €32,000 (Injuries) to €64,000 (Diseases of the nervous system and sense organs). In terms of care level, 63% of healthcare resources were used in home- and community-based care (i.e., in-home nursing, practical assistance, or nursing home care), 35% in secondary care (mostly hospital care), and 2% in primary care (i.e., general practitioners). The amount and level of care varied by cause of death and by time to death. The proportion of home- and community-based care which individuals received during their last six months of life varied from 38% for cancer patients to 92% for individuals dying with mental diseases. The shorter the time to death, the more resources were needed: nearly 40% of all end-of-life healthcare costs were expended in the last month of life across all causes of death. The composition of care also differed depending on age. Individuals aged 80 years and older used more home- and community-based care (77%) than individuals dying at younger ages (40%) and less secondary care (old: 21% versus young: 57%). CONCLUSIONS: Our analysis provides valuable evidence on how much healthcare individuals receive in their last six months of life and the associated costs, broken down by level of care and cause of death. Healthcare use and costs varied considerably by cause of death, but were generally higher the closer a person was to death. Our findings enable decision-makers to make more informed resource-allocation decisions and healthcare planners to better anticipate future healthcare needs.


Subject(s)
Cause of Death , Terminal Care , Humans , Norway , Terminal Care/economics , Male , Female , Aged , Aged, 80 and over , Middle Aged , Health Care Costs/statistics & numerical data , Adult , Registries , Patient Acceptance of Health Care/statistics & numerical data , Home Care Services/economics , Infant
2.
J Immunol ; 205(5): 1248-1255, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32699157

ABSTRACT

T follicular helper (Tfh) cells play a very important role in mounting a humoral response. Studies conducted in mouse models have revealed with good kinetic and spatial resolution the dynamics of these cells in germinal centers (GC) and their cross-talk with B cells upon an immune response. However, whether a similar migratory behavior is performed by human Tfh cells is unclear, as technology to track them in situ has been lacking. In this study, we combined traditional immunohistochemistry and real-time fluorescent imaging approaches on fresh human adenoid slices to provide static and dynamic information on Tfh cells. Our data indicate that GC light zones are composed of two distinct areas in terms of Tfh cell distribution and migration. In the outer GC light zones, Tfh cells migrate actively and with a high ability to form dynamic clusters showing intense and rapid reorganization. In these outer regions, Tfh cells demonstrate multiple interactions between each other. Conversely, in central regions of GC light zones, Tfh cells are much more static, forming long-lasting conjugates. These findings reveal for the first time, to our knowledge, the dynamic behavior whereby Tfh cells migrate in human GC and highlight the heterogeneity of GC for Tfh cell motility.


Subject(s)
Germinal Center/immunology , T Follicular Helper Cells/immunology , Adenoids/immunology , B-Lymphocytes/immunology , Cell Movement/immunology , Humans
3.
Methods Mol Biol ; 1930: 75-82, 2019.
Article in English | MEDLINE | ID: mdl-30610601

ABSTRACT

In order to mount a potent immune response, immune cells must move actively through tissues. As an example, T-cell need to migrate within lymph nodes in order to scan the surface of many dendritic cells and recognize rare expressed antigens. The recent development of improved imaging approaches, such as two-photon microscopy, and the use of powerful mouse models have shed light on some of the mechanisms that regulate the migration of immune cells in many organs. Whereas such systems have provided valuable insights, they do not always predict human responses. In human, our knowledge in the field mainly comes from a description of fixed tissue samples. However, these studies lack a temporal dimension since samples have been fixed. In order to overcome some of these limitations, we describe, in this methodology chapter, an experimental system of fresh human adenoid slices to monitor the dynamics of resident T-lymphocytes that have been stained with directly-coupled fluorescent antibodies. Combined with confocal fluorescent imaging, this preparation offers an effective approach to imaging immune cells in a three-dimensional (3D) human lymphoid tissue environment.


Subject(s)
Cell Movement , Cell Tracking/methods , Lymphoid Tissue/cytology , Microscopy, Confocal/methods , Molecular Imaging/methods , T-Lymphocytes/cytology , T-Lymphocytes/physiology , Cells, Cultured , Humans , Signal Transduction
4.
Qual Life Res ; 28(5): 1129-1143, 2019 May.
Article in English | MEDLINE | ID: mdl-30506179

ABSTRACT

PURPOSE: So far there is no Norwegian value algorithm to inform healthcare decision making. The 15D health state values estimated with the original 15D valuation procedure tend to be higher than the values of other generic preference-based health-related quality of life (HRQoL) instruments. The main purpose of this study was to use a new 15D valuation procedure to estimate Norwegian 15D health state values and to explore their empirical performance. METHODS: The visual analogue scale was used to collect 15D valuation data in a representative sample of the Norwegian general population. The new procedure used fewer valuation tasks and anchored the 15D health state values in an empirically assessed range. The Norwegian 15D health state values were compared to the values of five HRQoL instruments which were provided by Norwegian residents belonging to seven disease groups and a healthy population. RESULTS: The Norwegian 15D health state values ranged from 1 to - 0.52. Compared to 15D health state values estimated with the original procedure, the Norwegian 15D health state values were lower and more in line with values of other HRQoL instruments. CONCLUSIONS: The new 15D valuation procedure is simpler, links the 15D health state values better to the requirements of the QALY model, and provides an empirically-based range. We recommend using the new valuation procedure in future 15D valuation studies, and the Norwegian health state values for use in 15D-based health economic analyses in Norway.


Subject(s)
Quality of Life/psychology , Adolescent , Adult , Aged , Algorithms , Female , Humans , Male , Middle Aged , Norway , Surveys and Questionnaires , Young Adult
5.
Value Health ; 21(4): 462-470, 2018 04.
Article in English | MEDLINE | ID: mdl-29680104

ABSTRACT

BACKGROUND: The 15D is a generic preference-based health-related quality-of-life instrument developed in Finland. Values for the 15D instrument are estimated by combining responses to three distinct valuation tasks. The impact of how these tasks are combined is relatively unexplored. OBJECTIVES: To compare 15D valuation studies conducted in Norway and Finland in terms of scores assigned in the valuation tasks and resulting value algorithms, and to discuss the contributions of each task and the algorithm estimation procedure to observed differences. METHODS: Norwegian and Finnish scores from the three valuation tasks were compared using independent samples t tests and Lin concordance correlation coefficients. Covariance between tasks was assessed using Pearson product-moment correlations. Norwegian and Finnish value algorithms were compared using concordance correlation coefficients, total ranges, and ranges for individual dimensions. Observed differences were assessed using minimal important difference. RESULTS: Mean scores in the main valuation task were strikingly similar between the two countries, whereas the final value algorithms were less similar. The largest differences between Norway and Finland were observed for depression, vision, and mental function. CONCLUSIONS: 15D algorithms are a product of combining scores from three valuation tasks by use of methods involving multiplication. This procedure used to combine scores from the three tasks by multiplication serves to amplify variance from each task. From relatively similar responses in Norway and Finland, diverging value algorithms are created. We propose to simplify the 15D algorithm estimation procedure by using only one of the valuation tasks.


Subject(s)
Health Care Costs , Health Status Indicators , Health Status , Process Assessment, Health Care/economics , Quality of Life , Adult , Aged , Aged, 80 and over , Algorithms , Cost-Benefit Analysis , Female , Finland , Humans , Male , Mental Health , Middle Aged , Models, Economic , Norway , Social Behavior , Treatment Outcome , Young Adult
6.
Health Qual Life Outcomes ; 14(1): 164, 2016 Nov 28.
Article in English | MEDLINE | ID: mdl-27894349

ABSTRACT

BACKGROUND: In health economic analyses, health states are typically valued using instruments with few items per dimension. Due to the generic (and often reductionist) nature of such instruments, certain groups of respondents may experience challenges in describing their health state. This study is concerned with generic, preference-based health state instruments that provide information for decisions about the allocation of resources in health care. Unlike physical measurement instruments, preference-based health state instruments provide health state values that are dependent on how respondents interpret the items. This study investigates how individuals with spinal cord injury (SCI) interpret mobility-related items contained within six preference-based health state instruments. METHODS: Secondary analysis of focus group transcripts originally collected in Vancouver, Canada, explored individuals' perceptions and interpretations of mobility-related items contained within the 15D, Assessment of Quality of Life 8-dimension (AQoL-8D), EQ-5D-5L, Health Utilities Index (HUI), Quality of Well-Being Scale Self-Administered (QWB-SA), and the 36-item Short Form health survey version 2 (SF-36v2). Ritchie and Spencer's 'Framework Approach' was used to perform thematic analysis that focused on participants' comments concerning the mobility-related items only. RESULTS: Fifteen individuals participated in three focus groups (five per focus group). Four themes emerged: wording of mobility (e.g., 'getting around' vs 'walking'), reference to aids and appliances, lack of suitable response options, and reframing of items (e.g., replacing 'walking' with 'wheeling'). These themes reflected item features that respondents perceived as relevant in enabling them to describe their mobility, and response strategies that respondents could use when faced with inaccessible items. CONCLUSION: Investigating perceptions to mobility-related items within the context of SCI highlights substantial variation in item interpretation across six preference-based health state instruments. Studying respondents' interpretations of items can help to understand discrepancies in the health state descriptions and values obtained from different instruments. This line of research warrants closer attention in the health economics and quality of life literature.


Subject(s)
Health Status Indicators , Mobility Limitation , Quality of Life , Spinal Cord Injuries/psychology , Walking/psychology , Canada , Comprehension , Female , Focus Groups , Humans , Male , Wheelchairs/psychology
7.
J Pain Res ; 8: 295-302, 2015.
Article in English | MEDLINE | ID: mdl-26203272

ABSTRACT

OBJECTIVE: The objective of this case series was to investigate the feasibility and safety of a novel method for the management of chronic lower back pain. Injections of recombinant human growth hormone and testosterone to the painful and dysfunctional areas in individuals with chronic lower back pain were used. In addition, the participants received manual therapies and exercise addressing physical impairments such as motor control, strength, endurance, pain, and loss of movement. Pain ratings and self-rated functional outcomes were assessed. STUDY DESIGN: This is a case series involving consecutive patients with chronic lower back pain who received the intervention of injections of recombinant human growth hormone and testosterone, and attended chiropractic and/or physical therapy. Outcomes were measured at 12 months from the time of injection. SETTING: A community based hospital affiliated office, and a private practice block suite. PARTICIPANTS: A total of 60 consecutive patients attending a pain management practice for chronic lower back pain were recruited for the experimental treatment. Most participants were private pay. INTERVENTIONS: Participants who provided informed consent and were determined not to have radicular pain received diagnostic blocks. Those who responded favorably to the diagnostic blocks received injections of recombinant human growth hormone and testosterone in the areas treated with the blocks. Participants also received manipulation- and impairment-based exercises. OUTCOME MEASURES: Outcomes were assessed at 12 months through pain ratings with the Mankowski Pain Scale and the Oswestry Disability Index. RESULTS: Of the 60 patients recruited, 49 provided informed consent, and 39 completed all aspects of the study. Those patients receiving the intervention reported a significant decrease in pain ratings (P<0.01) and a significant improvement in self-rated Oswestry Disability Index scores (P<0.01). In addition, in the Oswestry Disability Index results, 41% of the patients demonstrated a 50% or greater change in their disability score. Of the subjects who withdrew from the study, one was due to the pain created by the injections and nine were for nonstudy factors. CONCLUSION: The intervention appeared to be safe and the results provide a reasonable expectation that the intervention would be beneficial for a population of individuals with chronic nonradicular lower back pain. Due to the design of the study, causality cannot be inferred, but the results do indicate that further study of the intervention may be warranted.

8.
J Nerv Ment Dis ; 202(7): 513-20, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24594678

ABSTRACT

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 µg of LSD (n = 8) or 20 µg of LSD with an open-label crossover to 200 µg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.


Subject(s)
Anxiety Disorders/therapy , Anxiety/therapy , Lysergic Acid Diethylamide/pharmacology , Psychotherapy/methods , Serotonin Antagonists/pharmacology , Adult , Anxiety/drug therapy , Anxiety/etiology , Anxiety Disorders/drug therapy , Anxiety Disorders/etiology , Combined Modality Therapy , Cross-Over Studies , Female , Follow-Up Studies , Humans , Lysergic Acid Diethylamide/administration & dosage , Lysergic Acid Diethylamide/adverse effects , Male , Middle Aged , Neoplasms/psychology , Pilot Projects , Placebos , Psychiatric Status Rating Scales , Serotonin Antagonists/administration & dosage , Serotonin Antagonists/adverse effects , Treatment Outcome
9.
J Nurs Meas ; 21(2): 156-65, 2013.
Article in English | MEDLINE | ID: mdl-24053049

ABSTRACT

PURPOSE: To move beyond the correlation analysis between glucose statistics and patient outcome and to benchmark summary statistics calculated on all glucose values taken during an entire individual patient-stay. METHOD: The sample consisted of 141 patient-stays with multiple finger-stick blood glucose (BG) measurements resulting in 5,428 total BGs. Glucose control assessments of the BG profiles for each patient-stay were independently conducted by two endocrinologists. Summary statistics (mean, standard deviation, mean absolute glucose [MAG], percentage of hours of patient-stay with BG over threshold) were calculated for BG using patient-stay as the unit of analysis. RESULTS: Produced numerical benchmarks for the mean (148 mg/dL), SD (40 mg/dL), MAG (6.2), and the percentage of patient-stay hours over 200 mg/dL (10%). Specificity and sensitivity were high, ranging from 91% to 89% for specificity and from 90% to 81% for sensitivity. CONCLUSION: This study demonstrated that benchmarks developed on specific patient populations can be used to evaluate glycemic control in a straightforward, computationally simple system.


Subject(s)
Blood Glucose/analysis , Inpatients , Aged , Benchmarking , Comorbidity , Female , Hospitals, Community , Humans , Length of Stay/statistics & numerical data , Male , Outcome Assessment, Health Care , Patient Care Team , Sensitivity and Specificity , South Carolina
10.
Int J Radiat Oncol Biol Phys ; 86(4): 785-90, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23664323

ABSTRACT

BACKGROUND: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). METHODS AND MATERIALS: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. RESULTS: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. CONCLUSION: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.


Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Head and Neck Neoplasms/therapy , Neoplasm Proteins/metabolism , Transcription Factor RelA/metabolism , Analysis of Variance , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/adverse effects , Disease Progression , Dose Fractionation, Radiation , Female , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , NF-kappa B/metabolism , Survival Rate , Treatment Outcome
11.
Dysphagia ; 28(4): 528-38, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23559454

ABSTRACT

Reducing fluoroscopic pulse rate, a method used to reduce radiation exposure from modified barium swallow studies (MBSSs), decreases the number of images available from which to judge swallowing impairment. It is necessary to understand the impact of pulse rate reduction on judgments of swallowing impairment and, consequentially, treatment recommendations. This preliminary study explored differences in standardized MBSS measurements [Modified Barium Swallow Impairment Profile (MBSImP™©) and Penetration Aspiration Scale (PAS) Scores] between two pulse rates: 30 and simulated 15 pulses per second (pps). Two reliable speech-language pathologists (SLPs) scored all five MBSSs. Five SLPs reported treatment recommendations based on those scores. Differences in judgments of swallowing impairment were found between 30 and simulated 15 pps in all five MBSSs. These differences were in six physiological swallowing components: initiation of pharyngeal swallow, anterior hyoid excursion, epiglottic movement, pharyngeal contraction, pharyngeal-esophageal segment opening, and tongue base retraction. Differences in treatment recommendations were found between 30 and simulated 15 pps in all five MBSSs. These findings suggest that there are differences in both judgment of swallowing impairment and treatment recommendations when pulse rates are reduced from 30 to 15 pps to minimize radiation exposure.


Subject(s)
Decision Making , Deglutition Disorders/diagnostic imaging , Deglutition Disorders/therapy , Fluoroscopy/methods , Adult , Aged , Aged, 80 and over , Barium Sulfate , Contrast Media , Deglutition Disorders/physiopathology , Female , Humans , Male , Middle Aged , Observer Variation , Radiation Dosage , Retrospective Studies , Severity of Illness Index
12.
J Psychopharmacol ; 27(1): 28-39, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23172889

ABSTRACT

We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for chronic, treatment-resistant post-traumatic stress disorder (PTSD) (Mithoefer et al., 2011). All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study's final MDMA session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness Personality Inventory-Revised (NEO PI-R) Personality Inventory. We also collected a long-term follow-up questionnaire. Results for the 16 CAPS completers showed there were no statistical differences between mean CAPS score at LTFU (mean = 23.7; SD = 22.8) (t (matched) = 0.1; df = 15, p = 0.91) and the mean CAPS score previously obtained at Study Exit (mean = 24.6, SD = 18.6). On average, subjects maintained statistically and clinically-significant gains in symptom relief, although two of these subjects did relapse. It was promising that we found the majority of these subjects with previously severe PTSD who were unresponsive to existing treatments had symptomatic relief provided by MDMA-assisted psychotherapy that persisted over time, with no subjects reporting harm from participation in the study.


Subject(s)
N-Methyl-3,4-methylenedioxyamphetamine/therapeutic use , Psychotherapy/methods , Stress Disorders, Post-Traumatic/therapy , Substance-Related Disorders/drug therapy , Adult , Female , Follow-Up Studies , Humans , Illicit Drugs/adverse effects , Male , N-Methyl-3,4-methylenedioxyamphetamine/adverse effects , Outcome Assessment, Health Care , Prospective Studies , Stress Disorders, Post-Traumatic/drug therapy , Surveys and Questionnaires , Treatment Outcome
13.
Dysphagia ; 27(2): 178-84, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21748449

ABSTRACT

This study was designed to further our understanding of a potentially significant clinical event of negative nasal airflow near the end of the respiratory pause (inhibition) to accommodate swallowing. This negative flow, referred to as "SNIF," or swallow noninspiratory flow, occurs at the onset of airway reestablishment at the conclusion of the oropharyngeal swallow. Using simultaneous digital video fluoroscopic and nasal respiratory airflow recordings on 82 healthy adults (21-97 years old), the objectives of this study were to determine (1) the frequency of occurrence of SNIF during a 5-ml natural cup-drinking task, (2) differences in SNIF occurrence by age group, and (3) the temporal relationship between SNIF and other swallowing events. Results revealed that for most participants SNIF was observed in both swallowing trials. There was a statistically significant difference in SNIF occurrence by age category, with SNIF observed less frequently in the oldest participants. The peak onset of SNIF is closely related to the first release of contact between the soft palate and tongue base with the posterior pharyngeal wall and opening of the laryngeal vestibule. Based on this, and in agreement with previous investigators, we suggest that this negative flow may be related to a partial vacuum established by the relaxation of pharyngeal contraction near the conclusion of the pharyngeal swallow. The more frequent occurrence of SNIF in younger adults and less in older adults suggests a reduction in pharyngeal pressure associated with healthy aging.


Subject(s)
Air , Deglutition/physiology , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Nose/physiology , Respiration , Young Adult
14.
J Biol Chem ; 286(50): 43103-11, 2011 Dec 16.
Article in English | MEDLINE | ID: mdl-21990360

ABSTRACT

Anaphylaxis mediated by carbohydrate structures is a controversially discussed phenomenon. Nevertheless, IgE with specificity for the xenotransplantation antigen α1,3-Gal (α-Gal) are associated with a delayed type of anaphylaxis, providing evidence for the clinical relevance of carbohydrate epitopes in allergy. The aim of this study was to dissect immunoreactivity, interaction, and fine epitope of α-Gal-specific antibodies to obtain insights into the recognition of carbohydrate epitopes by IgE antibodies and their consequences on a molecular and cellular level. The antigen binding moiety of an α-Gal-specific murine IgM antibody was employed to construct chimeric IgE and IgG antibodies. Reactivity and specificity of the resulting antibodies were assessed by means of ELISA and receptor binding studies. Using defined carbohydrates, interaction of the IgE and human serum was assessed by mediator release assays, surface plasmon resonance (SPR), and saturation transfer difference NMR analyses. The α-Gal-specific chimeric IgE and IgG antibodies were proven functional regarding interaction with antigen and Fc receptors. SPR measurements demonstrated affinities in the micromolar range. In contrast to a reference antibody, anti-Gal IgE did not induce mediator release, potentially reflecting the delayed type of anaphylaxis. The α1,3-Gal epitope fine structures of both the recombinant IgE and affinity-purified serum were defined by saturation transfer difference NMR, revealing similar contributions of carbohydrate residues and participation of both galactose residues in interaction. The antibodies generated here constitute the principle underlying α1,3-Gal-mediated anaphylaxis. The complementary data of affinity and fine specificity may help to elucidate the recognition of carbohydrates by the adaptive immune response and the molecular requirements of carbohydrate-based anaphylaxis.


Subject(s)
Epitopes/immunology , Galactose/immunology , Immunoglobulin E/immunology , Magnetic Resonance Spectroscopy/methods , Animals , Antibody Specificity/immunology , Cell Line , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Humans , Immunoblotting , Rats , Surface Plasmon Resonance
15.
Mol Immunol ; 48(9-10): 1236-44, 2011 May.
Article in English | MEDLINE | ID: mdl-21474184

ABSTRACT

The scarcity of monoclonal human IgE antibodies with specificity for defined allergens is a bottleneck for the molecular characterisation of allergens and their epitopes. Insights into the characteristics of such antibodies may allow for analyses of the molecular basis underlying allergenicity and cross-reactivity, standardisation of allergens as well as improvement of allergy diagnostics and therapeutics. Here we report the generation and application of the first set of authentic human IgG, IgE and IgA antibodies. On the basis of a Phl p 5a specific antibody fragment, a lambda light chain and the IgG1, IgG4, IgE, IgA1, and IgA2 heavy chains, the corresponding human immunoglobulins were constructed and produced in mammalian cells. In parallel, a murine hybridoma line with specificity for Phl p 5a was established, recloned and produced as human chimeric IgE. After purification, immunoreactivity of the antibodies with the allergen was assessed. Applicability in allergy diagnostics was confirmed by establishment of artificial human sera. Functionality of both antibodies was further demonstrated in receptor binding studies and mediator release assays using humanised rat basophil leukaemia cells (RBL-SX38) suggesting the presence of spatially separate epitopes. By using Phl p 5 fusion proteins and recombinant IgE in immunoblotting and mediator release assays we assigned the epitope of the authentic IgE to a looped stretch exclusively present in Phl p 5a. In summary, the Phl p 5-specific antibodies are the first full set of allergy-related antibody isotypes of their kind and represent valuable tools for studies of fundamental mechanisms and structure/function relationships in allergy.


Subject(s)
Allergens/immunology , Antibodies, Monoclonal/biosynthesis , Antibody Specificity/immunology , Epitopes/immunology , Immunoglobulin Isotypes/immunology , Phleum/chemistry , Plant Proteins/immunology , Allergens/chemistry , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , Cell Line , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Epitopes/chemistry , Humans , Immunoglobulin E/immunology , Mice , Microspheres , Models, Molecular , Molecular Sequence Data , Mutant Proteins/chemistry , Mutant Proteins/immunology , Plant Proteins/chemistry , Rats , Receptors, Fc/immunology , Recombinant Proteins/immunology
16.
Protein Pept Lett ; 18(4): 415-22, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21171948

ABSTRACT

Allergic reactions to hymenoptera stings are one of the major reasons for IgE-mediated anaphylaxis. However, proper diagnosis using venom extracts is severely affected by molecular cross-reactivity. In this study recombinant honeybee venom major allergen phospholipase A2 (Api m 1) was produced for the first time in insect cells. Using baculovirus infection of different insect cell lines allergen versions providing a varying degree of cross-reactive carbohydrate determinants as well as a non glycosylated variant could be obtained as secreted soluble proteins in high yields. The resulting molecules were analyzed for their glycosylation and proved to show advantageous properties regarding cross-reactivity in sIgE-based assays. Additionally, in contrast to the enzymatically active native protein the inactivated allergen did not induce IgE-independent effector cell activation. Thus, insect cell-derived recombinant Api m 1 with defined CCD phenotypes might provide further insights into hymenoptera venom IgE reactivities and contribute to an improved diagnosis of hymenoptera venom allergy.


Subject(s)
Allergens/chemistry , Antigens, Plant/chemistry , Bee Venoms/enzymology , Bees/enzymology , Insect Proteins/chemistry , Phospholipases A/chemistry , Recombinant Proteins/chemistry , Allergens/genetics , Allergens/immunology , Animals , Antigens, Plant/genetics , Antigens, Plant/immunology , Cell Line , Cross Reactions/immunology , Humans , Hypersensitivity/diagnosis , Immunoglobulin E/blood , Immunoglobulin E/immunology , Insect Bites and Stings/diagnosis , Insect Proteins/genetics , Insect Proteins/immunology , Mutagenesis, Site-Directed , Phospholipases A/genetics , Phospholipases A/immunology , Rats , Recombinant Proteins/genetics , Recombinant Proteins/immunology
17.
Head Neck ; 32(4): 481-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19780056

ABSTRACT

BACKGROUND: Unstable respiratory-swallowing coordination has been associated with disorders and disease. The goals of this study were (1) to describe respiratory-swallow patterns in patients with dysphagia consequent to treatments for cancers of the oropharynx and (2) to determine the association between respiratory-swallow patterns, airway invasion, and overall severity of swallowing impairment. METHODS: This prospective, cross-sectional design compared respiratory-swallow patterns in 20 patients treated for oropharyngeal cancer and 20 healthy, age-matched control participants. Nasal airflow direction was synchronously recorded with videofluoroscopic imaging in participants who swallowed 5-mL thin liquid barium boluses. RESULTS: Respiratory-swallow patterns differed between groups. Most control participants initiated and completed swallowing bracketed by expiratory airflow. Swallowing in patients often interrupted inspiratory flow and was associated with penetration or aspiration of the bolus. CONCLUSIONS: We suggest nonexpiratory bracketed respiratory-swallowing phase patterns in patients with oropharyngeal cancer may place patients at greater risk of airway penetration or aspiration during swallowing.


Subject(s)
Deglutition/physiology , Oropharyngeal Neoplasms/therapy , Oropharynx/surgery , Respiratory Aspiration/diagnosis , Adult , Aged , Barium Sulfate , Chemotherapy, Adjuvant , Combined Modality Therapy , Cross-Sectional Studies , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Female , Fluoroscopy/methods , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Oropharyngeal Neoplasms/complications , Oropharyngeal Neoplasms/pathology , Oropharynx/drug effects , Oropharynx/radiation effects , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Probability , Prospective Studies , Radiotherapy, Adjuvant , Reference Values , Respiratory Aspiration/etiology , Video Recording
18.
Dysphagia ; 23(4): 392-405, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18855050

ABSTRACT

The aim of this study was to test reliability, content, construct, and external validity of a new modified barium swallowing study (MBSS) tool (MBSImp) that is used to quantify swallowing impairment. Multiple regression, confirmatory factor, and correlation analyses were used to analyze 300 in- and outpatients with heterogeneous medical and surgical diagnoses who were sequentially referred for MBS exams at a university medical center and private tertiary care community hospital. Main outcome measures were the MBSImp and index scores of aspiration, health status, and quality of life. Inter- and intrarater concordance were 80% or greater for blinded scoring of MBSSs. Regression analysis revealed contributions of eight of nine swallow types to impressions of overall swallowing impairment (p < or = 0.05). Factor analysis revealed 13 significant components (loadings >/= 0.5) that formed two impairment groupings (oral and pharyngeal). Significant correlations were found between Oral and Pharyngeal Impairment scores and Penetration-Aspiration Scale scores, and indexes of intake status, nutrition, health status, and quality of life. The MBSImp demonstrated clinical practicality, favorable inter- and intrarater reliability following standardized training, content, and external validity. This study reflects potential for establishment of a new standard for quantification and comparison of oropharyngeal swallowing impairment across patient diagnoses as measured on MBSS.


Subject(s)
Deglutition Disorders/diagnosis , Deglutition , Data Interpretation, Statistical , Deglutition Disorders/physiopathology , Humans , Photofluorography/instrumentation , Regression Analysis , Reproducibility of Results , Statistics as Topic , United States
19.
Issues Ment Health Nurs ; 28(11): 1247-65, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17987480

ABSTRACT

The decision to examine the phenomenon of lateral violence within the nursing workforce of a Southeastern tertiary care medical center evolved from the strong response of attendees to a nursing presentation on lateral violence. This paper describes the development and testing of the Lateral Violence in Nursing Survey. This questionnaire, designed to measure perceived incidence and severity of lateral violence, was administered online to 663 nursing staff participants. Forty-six percent of the study participants reported lateral violence as a "very serious" or "somewhat serious" problem, and 65% reported frequently observing lateral violence behaviors among coworkers. Education and effective leadership were found to mediate oppressive and negative behaviors, whereas ineffective leadership was found to exacerbate lateral violence.


Subject(s)
Interpersonal Relations , Nursing Staff, Hospital , Violence , Adult , Aged , Female , Humans , Male , Middle Aged , Models, Psychological , Nursing Staff, Hospital/psychology , Pilot Projects , Southeastern United States , Violence/prevention & control , Violence/psychology , Violence/statistics & numerical data
20.
Biol Res Nurs ; 9(1): 70-80, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17601858

ABSTRACT

Chronic inflammation and microcirculatory disturbances of the skin have been implicated as causative factors of complications associated with chronic venous disease (CVD). The purpose of this study is to describe the mean differences between and correlations among three measures of microcirculation: skin temperature (Tsk), tissue perfusion/blood flow (BF), and tissue oxygen (tcPO(2)) of CVD-inflamed skin compared to normal controls. In a convenience sample of 55 patients with CVD (n = 31) and without CVD (n = 24), Tsk was measured with an infrared thermometer, BF with a laser Doppler flowmeter, and tcPO( 2) with a transcutaneous oximeter across three measurements periods 1 week apart (Times 1, 2, and 3) at the medial aspect of both lower legs. Tsk was higher (1.2 degrees C) across all measurement periods (p < .05), BF was higher at Times 1 and 3 (p = .002 and .012, respectively), and tcPO(2) was lower at Times 1 and 3 (p = .013 and .050, respectively) in the CVD group as compared to the non-CVD group. BF and Tsk were positively correlated at Times 1 and 2 (r = .516, p < .005; r = 0.278, p = .04) but not at Time 3 (r = 0.235, p > .05). No consistently significant correlations were found between tcPO(2) and BF or tcPO(2) and Tsk (p > .05). Tsk and BF were higher in the skin of lower legs affected by CVD than in those not affected. Pathological processes in the skin produce heat detectable by an infrared thermometer. Measurement and monitoring of Tsk can augment clinical findings and guide treatment when localized inflammation is suspected. Future studies of Tsk should be directed toward the usefulness of infrared technology to develop a CVD leg ulcer prediction model.


Subject(s)
Oxygen , Skin Temperature/physiology , Tissue Distribution/physiology , Venous Insufficiency/metabolism , Venous Insufficiency/physiopathology , Aged , Aged, 80 and over , Analysis of Variance , Blood Flow Velocity , Blood Gas Monitoring, Transcutaneous , Body Mass Index , Case-Control Studies , Chronic Disease , Clinical Nursing Research , Diabetes Complications/complications , Female , Humans , Hypertension/complications , Inflammation , Laser-Doppler Flowmetry , Male , Microcirculation , Middle Aged , Nursing Assessment , Obesity/complications , Oxygen/analysis , Oxygen/metabolism , Oxygen/physiology , Venous Insufficiency/etiology
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