ABSTRACT
AIMS: FAST-Forward and UK-FAST-trials have demonstrated the safety and efficacy of five-fraction breast adjuvant radiation therapy (RT) and have become the standard of care for selected early breast cancer patients. In response to the additional burden caused by the COVID-19 pandemic, we implemented "One-Week Breast RT," an innovative program delivering five-fraction whole breast RT in a complete 5-day workflow. The primary objective of this study was to demonstrate the feasibility and safety of our program. The secondary objective was to evaluate cosmetic results. MATERIAL AND METHODS: A total of 120 patients treated from February 2021 to March 2022, received whole breast RT without lymph node irradiation nor boost, with 26 Gy in five fractions over one week. Inverse planning with restricted optimization parameters offers systematic deep inspiration breath-hold aimed to provide treatment plans compliant with FAST-Forward recommendations. Toxicity and cosmetic evaluations were prospectively registered prior (pre-RT), at the end (end-RT), and 6 months after RT (6 months) based on Common Terminology Criteria for Adverse Events v. 4.03 and Harvard scale. RESULTS: With a median age of 70 years (interquartile range (IQR): 66-74) and a median follow-up of 6 months (IQR: 6.01-6.25), most patients (93.3%) completed their RT in one week from baseline to the end of the treatment consultation. The most common acute toxicities (at end-RT) were skin-related: radio-dermatitis (72%), induration (35%), hyperpigmentation (8%), and breast edema (16%). The rate of radio-dermatitis decreased from end-RT to 6 months (71.7% vs 5.4%, P< 0.001). No patient experienced grade ≥3 toxicity. At 6 months, cosmetic results were generally good or excellent (94.1%). CONCLUSION: This study confirms the feasibility and acute safety of the "One-Week Breast RT" in real life. Favorable toxicity profiles and good cosmetic outcomes are in line with FAST-Forward results. A prospective national cohort, aimed at decreasing treatment burden, maintaining safety, efficacy, and improving RT workflow efficiency with longer follow-up is ongoing.
Subject(s)
Breast Neoplasms , COVID-19 , Feasibility Studies , Humans , Breast Neoplasms/radiotherapy , Female , Aged , COVID-19/epidemiology , Radiotherapy, Adjuvant/methods , Radiotherapy, Adjuvant/adverse effects , Dose Fractionation, Radiation , Middle Aged , Prospective Studies , SARS-CoV-2 , Radiodermatitis/etiologyABSTRACT
During the past years, there has been an alarming increase in cases of food allergy and anaphylaxis in ever-younger children. Often, these children have multiple food allergies and food sensitizations, involving allergens with high anaphylactic potential, such as peanuts and nuts, which have a major influence on their quality of life and future. After reviewing the current epidemiological data, we discuss the main causes of the increase in food allergies. We analyze data from studies on the skin barrier and its fundamental role in the development of sensitization and food allergies, data on the tolerogenic digestive tract applied in particular to hen eggs and peanuts, as well as data on the prevention of allergy to cow milk proteins. In light of these studies, we propose a practical guide of recommendations focused on infants and the introduction of cow milk, the management of eczema, and early and broad dietary diversification including high-risk food allergens, such as peanut and nuts while taking into account the food consumption habits of the family.
Subject(s)
Allergens/immunology , Arachis/immunology , Food Hypersensitivity/prevention & control , Allergists , Anaphylaxis/prevention & control , Animals , Cattle , Chickens , Child , Dermatitis, Atopic/prevention & control , Female , Food Hypersensitivity/epidemiology , Humans , Infant , Primary Prevention/trends , Quality of LifeABSTRACT
BACKGROUND AND AIMS: Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. METHODS: We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. RESULTS: With a median follow-up of 9.4 years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. CONCLUSIONS: With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.
Subject(s)
Hepatoblastoma , Liver Neoplasms , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/therapeutic use , Child , Child, Preschool , Cisplatin/adverse effects , Humans , Infant , Infant, Newborn , Liver Neoplasms/drug therapy , Morbidity , SurvivorsABSTRACT
PURPOSE OF THE STUDY: Several studies have confirmed the impact of confinement on the population, resulting in disruption of care, somatic and psychological effects. Our study looks at adverse effects and problems of adherence to oral immunotherapy therapy (OIT) during this period. PATIENTS AND METHODS: A total of 132 patients, mostly children (95%), with an atopic history (60%) followed for an OIT were included in 3 allergology centers in Île-de-France, during the period of confinement from 03/16 to 05/11/20. The main food allergens used for OIT were peanut (38%), cow's milk (24%), hazelnut (14%), egg (9%), cashew nut and pistachio nut (8%). RESULTS: Adverse effects were found in 13 patients or 10% of the cases. These reactions were mainly grade 1 and 2 according to the Ring and Messmer classification. Three patients had grade 3 reactions and six patients used epinephrine at home. Adherence was correct in 81% of cases with no omissions. Three patients increased their daily dose without medical advice. No significant difference was found in the subgroup analysis comparing age-matched children followed up in OIT in 2019 and 2020 over the same period in the same hospital. CONCLUSION: There was no increase in adverse events in OIT during the confinement period. Therapeutic education during OIT is paramount and helps to reduce the occurrence of adverse events.
ABSTRACT
The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.
Subject(s)
Biomedical Research/organization & administration , Cloud Computing , Diffusion of Innovation , Practice Guidelines as Topic , Biomedical Research/methods , European Union , Information Dissemination/legislation & jurisprudence , Information Dissemination/methodsABSTRACT
While some low-cost inertial motion capture (IMC) systems are now commercially available, generally, they have not been evaluated against gold standard optical motion capture (OMC). The objective was to validate the low-cost Neuron IMC system with OMC. Whole-body kinematics were recorded on five healthy subjects during manual handling of boxes for about 32 min while wearing 17 magnetic and inertial measurement units with Optotrak clusters serving as a reference. The kinematical model was calibrated anatomically for OMC and with poses for IMC. Local coordinate systems were aligned with angular velocities to dissociate differences due to technology or kinematical model. Descriptive statistics including the root mean square error (RMSE), coefficient of multiple correlation (CMC) and limits of agreement (LoA) were applied to the joint angle curves. The average technological error yielded 5.8° and 4.9° for RMSE, 0.87 and 0.96 for CMC and 0.4 ± 8.6° and -0.3 ± 6.0° for LoA about the frontal and transverse axes respectively, whereas the longitudinal axis yielded 10.5° for RMSE, 0.78 for CMC and 3.3 ± 13.1° for LoA. Differences due to technology and to the model contributed similarly to the total difference between IMC and OMC. For many joints and axes, RMSE stayed under 5°, CMC over 0.9 and LoA under 10°, especially for the transverse axis and lower limb. The Neuron low-cost IMC system showed potential for tracking complex human movements of long duration in a normal laboratory environment with a certain error level that may be suitable for many applications involving large IMC distribution.
Subject(s)
Costs and Cost Analysis , Mechanical Phenomena , Movement , Adult , Biomechanical Phenomena , Calibration , Female , Humans , Young AdultABSTRACT
Foot placement strategy is an essential aspect in the study of movement involving full body displacement. To get beyond a qualitative analysis, this paper provides a foot placement classification and analysis method that can be used in sports, rehabilitation or ergonomics. The method is based on machine learning using a weighted k-nearest neighbors algorithm. The learning phase is performed by an observer who classifies a set of trials. The algorithm then automatically reproduces this classification on subsequent sets. The method also provides detailed analysis of foot placement strategy, such as estimating the average foot placements for each class or visualizing the variability of strategies. An example of applying the method to a manual material handling task demonstrates its usefulness. During the lifting phase, the foot placements were classified into four groups: front, contralateral foot behind, ipsilateral foot behind, and parallel. The accuracy of the classification, assessed with a holdout method, is about 97%. In this example, the classification method makes it possible to observe and analyze the handler's foot placement strategies with regards to the performed task.
Subject(s)
Foot/physiology , Machine Learning , Movement/physiology , Adult , Humans , Male , Research Design , Task Performance and Analysis , Young AdultABSTRACT
Nanoparticles (NPs) and in particular TiO2-NPs are increasingly included in commercial goods leading to their accumulation in sewage sludge which is spread on agricultural soils as fertilizers in many countries. Crop plants are thus a very likely point of entry for NPs in the food chain up to humans. So far, soil influence on NP fate has been under-investigated. In this article, we studied the partitioning of TiO2-NPs between soil and soil leachate, their uptake and biotransformation in wheat seedlings and their impact on plant development after exposure on 4 different types of soil with different characteristics: soil texture (from sandy to clayey), soil pH, cationic exchange capacity, organic matter content. Results suggest that a NP contamination occurring on agricultural soils will mainly lead to NP accumulation in soil (increase of Ti concentration up to 302% in sand) but to low to negligible transfer to soil leachate and plant shoot. In our experimental conditions, no sign of acute phytotoxicity has been detected (growth, biomass, chlorophyll content). Clay content above 6% together with organic matter content above 1.5% lead to translocation factor from soil to plant leaves below 2.5% (i.e. below 13mgTi·kg-1 dry leaves). Taken together, our results suggest low risk of crop contamination in an agro-ecosystem.
Subject(s)
Agriculture , Ecosystem , Environmental Monitoring , Nanoparticles/analysis , Soil Pollutants/analysis , Titanium/analysis , Soil/chemistryABSTRACT
We report the results of a study of survival, liver and kidney functions, and growth with a median follow-up of 24 years following liver transplantation in childhood. From 1988 to 1993, 128 children underwent deceased donor liver transplantation (median age: 2.5 years). Twenty-year patient and graft survival rates were 79% and 64%, respectively. Raised serum aminotransferase and/or γ-glutamyl transferase activities were present in 42% of survivors after a single transplantation. Graft histology (35 patients) showed signs of chronic rejection in 11 and biliary obstruction in 5. Mean total fibrosis scores were 4.5/9 and 3/9 in patients with abnormal and normal serum liver tests, respectively. Glomerular filtration rate was <90 mL·min-1 in 35 survivors, including 4 in end-stage renal disease who were undergoing dialysis or had undergone renal transplantation. Median final heights were 159 cm for women and 172 cm for men; final height was below the target height in 37 patients. Twenty-year survival after childhood liver transplantation may be close to 80%, and final height is within the normal range for most patients. However, chronic kidney disease or altered liver biochemistries are present in over one third of patients, which is a matter of concern for the future.
Subject(s)
Graft Rejection/mortality , Graft Survival , Kidney Failure, Chronic/mortality , Liver Transplantation/mortality , Postoperative Complications , Renal Dialysis/statistics & numerical data , Survivors/statistics & numerical data , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , France/epidemiology , Glomerular Filtration Rate , Graft Rejection/epidemiology , Humans , Incidence , Infant , Kidney Failure, Chronic/epidemiology , Kidney Function Tests , Male , Prognosis , Risk Factors , Survival Rate , Young AdultABSTRACT
We have performed three-dimensional characterization of the TPA effective laser spot size in silicon using an integrated knife-edge sensor. The TPA-induced response of a CMOS integrated circuit is analyzed based on these results and compared to simulation; we have found that the charge injection capacity in IC's active layer could be influenced by irradiance energy and focus depth.
ABSTRACT
Seclusion with or without restraint is a measure used to manage patients with challenging behaviours. Although controversial, the intervention remains poorly documented, especially in Canadian psychiatric hospitals. The purpose of this study is to assess the prevalence of the measure and identify any correlated demographic characteristics and psychiatric disorders. Episodes of seclusion with or without restraint were extracted from a computerized, hospital-based system introduced specifically to track such interventions. Of 2721 patients hospitalized during that time, 23.2% (n = 632) were secluded with or without restraint, and 17.5% (n = 476) were secluded with restraint. Younger age, schizophrenia or other psychosis, bipolar and personality disorder, and longer stay in hospital are predictors of an episode of seclusion with or without restraint. Younger age, bipolar and personality disorders and a longer stay in hospital are predictors of an episode of seclusion with restraint. For patients who spent longer in seclusion and under restraint, there is a positive association with longer stay in hospital. In this inpatient psychiatric facility, seclusion with or without restraint thus appears to be common. More research is warranted to better identify the principal factors associated with seclusion and restraint and help reduce resort to these measures.
Subject(s)
Hospitals, Psychiatric/statistics & numerical data , Mental Disorders/nursing , Nursing Audit , Patient Isolation/statistics & numerical data , Restraint, Physical/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Bipolar Disorder/epidemiology , Bipolar Disorder/nursing , Bipolar Disorder/psychology , Canada , Cross-Sectional Studies , Female , Humans , Length of Stay/statistics & numerical data , Male , Mental Disorders/epidemiology , Mental Disorders/psychology , Middle Aged , Patient Isolation/psychology , Personality Disorders/epidemiology , Personality Disorders/nursing , Personality Disorders/psychology , Psychotic Disorders/epidemiology , Psychotic Disorders/nursing , Psychotic Disorders/psychology , Restraint, Physical/psychology , Retrospective Studies , Risk Factors , Schizophrenia/epidemiology , Schizophrenia/nursing , Statistics as Topic , Utilization Review , Young AdultABSTRACT
Seclusion with or without restraint is a measure for managing aggressive or agitated clients and promoting site security, particularly in an emergency psychiatric setting. The decision to control a potentially dangerous person's behaviour by removal or seclusion seems ethically justifiable in such a setting. However, although the decisions on these restrictive measures are based on rational needs, they are also influenced by the healthcare team's perceptions of the client and by the characteristics of the team and the environment. The purpose of this paper is to set out and categorize the factors in play in aggression- and agitation-management situations as perceived by the healthcare teams, particularly the nurses. The first part of the paper deals briefly with the settings in which control measures are applied in a province in eastern Canada and the effect of such measures on patients and healthcare teams. The second part identifies the factors involved in the management of agitation and aggression behaviour. The final part discusses the current spin-offs from this knowledge as well as promising paths for further research on the factors involved. The ultimate objective is to reduce recourse to coercive measures and enhance professional practices.
Subject(s)
Decision Making , Psychiatric Nursing , Restraint, Physical/psychology , Aggression/psychology , Awareness , Emergencies , Emergency Services, Psychiatric/organization & administration , Environment , Humans , Nurse-Patient Relations , Quebec , Social Isolation/psychologyABSTRACT
Ambulatory assessment of trunk posture is important in improving our understanding of the risk of low back injury. Recently, small inertial sensors combining accelerometers, gyroscopes and magnetometers were developed and appear to be promising for measuring human movement. However, the validity of such sensors for assessing three-dimensional (3D) trunk posture in motion has not been documented. The purpose of this study was to evaluate a hybrid system (HS) composed of two inertial sensors for the 3D measurement of trunk posture. A secondary purpose was to explore the utility of adding another source of information, a potentiometer, to measure the relative rotation between both sensors in order to improve the validity of the system. The first sensor was placed over the sacrum and the second on the upper part of the thorax. Both sensors were linked by a flexible rod with a potentiometer. A complementary quaternion filter algorithm was used to estimate trunk orientation by taking advantage of the nine components of each sensor and the potentiometer. The HS's orientations were compared to those obtained from a 3D optoelectronic system. Validation of the HS was performed in three steps in which six subjects had to perform manual handling tasks in: (1) static postures; (2) dynamic motions of short duration (30s); and (3) dynamic motions of long duration (30min). The results showed that the root mean square (RMS) error of the HS was generally below 3 degrees for the flexion and lateral bending axes, and less than 6 degrees for the torsion axis, and that this error was lower for the short-duration tests compared to the long-duration one. The potentiometer proved to be an essential addition, particularly when the magnetometer signals were corrupted and only the gyroscope and accelerometer could be combined. It is concluded that the HS can be a useful tool for quantifying 3D trunk posture in motion.
Subject(s)
Data Display , Monitoring, Ambulatory/instrumentation , Movement , Posture/physiology , Thorax , Adult , Humans , Male , QuebecABSTRACT
A survey of the work with Ig response to allergens carried out previously reveals an allergen-specific response both by IgE and all of IgG subclasses. Response of non-sensitive people is characterized by the appearance of a variety of the IgG subclasses. We have reexamined ragweed and Amb a 1 specific Ig response in 54 nonsensitive and 147 atopic or atopic-allergic people using a new inverse sandwich immunoassay allowing discrimination based on antibody affinity. We show that non-sensitive people present no, 0 out of 54, Ig response with affinities higher than Ka 10(7) M(-1). The subpopulation of 66 atopics who never have experienced desensitization responds vigorously and solely (56 out of 66) with genes of the sequence gamma2-alpha2. Only ten showed an additional weak response from gamma1-alpha1. This suggests a possible association between the atopic state and selective activation of part of the gene sequence.
Subject(s)
Allergens , Hypersensitivity, Immediate/immunology , Hypersensitivity/immunology , Immunoglobulin Heavy Chains/biosynthesis , Immunoglobulin Isotypes/biosynthesis , Plant Proteins/immunology , Antibody Specificity , Antigens, Plant , Asteraceae/immunology , Asthma/immunology , Cross Reactions , Gene Expression Regulation , Genes, Immunoglobulin , Humans , Hypersensitivity/therapy , Hypersensitivity, Immediate/therapy , Immunoassay , Immunoglobulin E/biosynthesis , Immunoglobulin G/biosynthesis , Immunoglobulin G/classification , Immunoglobulin Heavy Chains/genetics , Immunotherapy , Pollen/immunology , Rhinitis/immunology , Skin TestsABSTRACT
To determine the forms of cardiac troponin I (cTnI) circulating in the bloodstream of patients with acute myocardial infarction (AMI) and patients receiving a cardioplegia during heart surgery, we developed three immunoenzymatic sandwich assays. The first assay involves the combination of two monoclonal antibodies (mAbs) specific for human cTnI. The second assay involves the combination of a mAb specific for troponin C (TnC) and an anti-cTnI mAb. The third assay was a combination of a mAb specific for human cardiac troponin T (cTnT) and an anti-cTnI mAb. Fifteen serum samples from patients with AMI, 10 serum samples from patients receiving crystalloid cardioplegia during heart surgery, and 10 serum samples from patients receiving cold blood cardioplegia during heart surgery were assayed by the three two-site immunoassays. We confirmed that cTnI circulates not only in free form but also complexed with the other troponin components (TnC and cTnT). We showed that the predominant form in blood is the cTnI-TnC binary complex (IC). Free cTnI, the cTnI-cTnT binary complex, and the cTnT-cTnI-TnC ternary complex were seldom present, and when present, were in small quantities compared with the binary complex IC. Similar results were obtained in both patient populations studied. These observations are essential for the development of new immunoassays with improved clinical sensitivity and for the selection of an appropriate cTnI primary calibrator.
Subject(s)
Heart Arrest, Induced/methods , Myocardial Infarction/blood , Myocardium/metabolism , Troponin I/blood , Fetal Blood , Humans , Immunoenzyme Techniques , Sensitivity and SpecificityABSTRACT
The Center for Community Alternatives (CCA) operates an array of programs that primarily serve students whose parents are incarcerated. The authors explore outreach and programmatic approaches and discuss the benefits of a holistic, multifaceted, open approach to identifying, assessing, and meeting the needs of adolescent children of incarcerated parents. The article concludes with policy recommendations regarding further development of programs targeting this population.
Subject(s)
Adolescent Health Services/organization & administration , Community Health Centers/organization & administration , Community-Institutional Relations , Parents , Prisoners , Students/psychology , Adolescent , Child Welfare , Health Services Needs and Demand , Humans , New York , Program Development , Program Evaluation , Self-Help Groups/organization & administration , Social SupportABSTRACT
The presence of cardiac troponin I in the serum is now considered as one of the most specific biochemical markers of acute myocardial infarction. To improve the knowledge of the antigenic properties of cardiac Troponin I, a set of monoclonal antibodies and polyclonal antibodies against human cardiac troponin I has been tested with overlapping peptides covering the cardiac troponin I sequence. The results indicate that N-terminal and C-terminal cardiac troponin I regions were most often recognized by poly- and monoclonal antibodies. These observations are valuable for choosing the best combination of monoclonal antibodies to set up new immunoassays to detect serum cardiac troponin I earlier after myocardial damage, to understand better which forms are released, and finally to propose appropriate cardiac troponin I standards.
Subject(s)
Antibodies, Monoclonal/immunology , Myocardium/immunology , Troponin I/immunology , Amino Acid Sequence , Antibodies, Monoclonal/chemistry , Antigens/immunology , Biomarkers , Epitope Mapping , Humans , Isomerism , Myocardial Infarction/diagnosis , Myocardial Infarction/physiopathology , Sensitivity and Specificity , Troponin I/blood , Troponin I/chemistryABSTRACT
The presence of human cardiac troponin I (hcTnI) in serum is considered to be a highly specific biochemical marker of acute myocardial infarction. To better understand the antigenic properties of hcTnI, a set of 68 overlapping peptides covering the complete amino acid sequence of hcTnI was prepared and used in epitope mapping experiments. All 16 anti-hcTnI monoclonal antibodies tested were found to recognize a peptide epitope, indicating that recognition by anti-hcTnI monoclonal antibodies was not dependent on the tertiary structure of the protein. Furthermore, the peptide reactivity with anti-hcTnI polyclonal antibodies indicated that most of the sequence of the protein was antigenic; in particular, the N- and C-terminal extremities were found to be the strongest antigenic regions. By using accurate secondary structure prediction methods, hcTnI was found to be an all-alpha type protein, with five regions predicted as helices. Matching the results of the epitope analysis with the structural prediction led us to the view that hcTnI is not a globular protein but probably adopts an extended conformation, allowing a large part of the amino acid sequence of this molecule to be recognized by the immune system. This improved knowledge of the antigenic and structural properties of hcTnI may help in developing new antibodies and immunoassays for use in diagnosing myocardial infarction.
Subject(s)
Epitopes/analysis , Myocardium/chemistry , Protein Structure, Secondary , Troponin I/blood , Troponin I/chemistry , Amino Acid Sequence , Antibodies, Monoclonal , Antigen-Antibody Reactions , Biomarkers , Epitopes/chemistry , Humans , Models, Molecular , Molecular Sequence Data , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Peptide Fragments/immunology , Troponin I/immunologyABSTRACT
Our objective in experiments reported here was to identify myofilament proteins of rat hearts either lost or degraded by cardiac ischemia (15- or 60-minute duration) with and without 45 minutes of reperfusion. We correlated these changes with alterations in myofilament sensitivity to Ca2+ and maximum force generation. Protein degradation and loss were assessed by high-performance liquid chromatography, SDS-PAGE, Western blotting analysis, and amino acid sequencing. Compared with nonischemic control hearts, bundles of skinned fibers from hearts subjected to ischemia alone demonstrated a decrease in maximum force generation and an increase in sensitivity to Ca2+. These changes in function were increased with the duration of the ischemia and with reperfusion. With increasing duration of ischemia, there was an increased loss and degradation of myofibrillar alpha-actinin and troponin I (TnI) at its C-terminus. Alpha-actinin and TnI were most susceptible to ischemia, but with 60 minutes of ischemia/reperfusion, there was also degradation of myosin light chain-1 (MLC1) involving a clip of residues 1 to 19. The MLC1 degradation product was detected in the reperfusion effluent (along with troponin T, tropomyosin, and alpha-actinin) but not in the tissue with 60 minutes of ischemia with no reperfusion. Moreover, with ischemia the following proteins became associated with the myofibrils: GAPDH and proteins of the mitochondrial ATP synthase complex. Our results provide new evidence regarding the mechanism by which ischemia/reperfusion causes myocardial injury and support the hypothesis that an important element in the injury is altered activity and structure of the myofilaments.
Subject(s)
Actin Cytoskeleton/metabolism , Microfilament Proteins/metabolism , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Animals , Calcium/metabolism , Histological Techniques , In Vitro Techniques , Osmolar Concentration , RatsABSTRACT
The purposes of the present study were to evaluate cardiac troponin 1 (cTnl) in the diagnosis of percutaneous transluminal coronary angioplasty (PTCA)-related myocardial injury in comparison with cardiac troponin T (cTnT) and creatine kinase (CK) MB mass concentration, and to investigate the frequency of myocardial injury, as indicated by myocardial protein release, after clinically symptomless side-branch occlusion (SBO) which may occur in the proximity of the attempted stenosis. The final study population comprised 80 patients undergoing elective, single vessel PTCA. Blood samples were drawn before, 6, 24 and 48 h after PTCA. cTnI, cTnT and CKMB mass baseline values were within the reference intervals in all patients (cTnI < 0.1 microgram/l, cTnT < 0.2 microgram/l, CKMB < 5 micrograms/l). Two patients presented with primary failure of PTCA, and visually successful PTCA was performed in all remaining patients. Seven patients (four with SBO) subsequently developed acute myocardial infarction (AMI). Symptomless SBO occurred in 16 patients. In controls (n = 55) there were no significant increases in cTnI, cTnT, or CKMB concentrations compared with baseline values, and all markers stayed within their reference intervals. In half the patients with symptomless SBO (n = 8) all markers were slightly to moderately increased, in two additional patients only CKMB was elevated (cTnI: 0.1-1.0 microgram/l; cTnT: 0.25-0.81 microgram/l and CKMB: 7.9-25.6 micrograms/l). In the majority of patients with primary failure or AMI we found pronounced increases in all tested markers (cTnI: 0.2-12.0 micrograms/l; cTnT: 0.44-12.10 micrograms/l; CKMB: 19.2-423.0 micrograms/l). The results of this study indicate that cTnI is comparably useful to cTnT or CKMB mass for diagnosing myocardial injury in PTCA patients. From our results a preference for one of the tested parameters cannot be clearly derived. Post-procedural cTnI, cTnT, and CKMB mass values are not higher than baseline values in uncomplicated cases, whereas AMI after PTCA leads to pronounced marker increases. SBO, even when symptomless, leads frequently (in about half the patients) to slight marker increases.