This study compared two methods for measuring serum levels of S100B protein: an ELISA assay and a commercially available Elecsys® kit. Blood samples were taken from 52 patients before and after meningioma surgery and analyzed using both methods. The study found that while the methods showed a generally linear relationship, ELISA values tended to be higher than the Elecsys® measurements, especially at concentrations over 0.7 μg/L. The discrepancy increased linearly with rising S100B levels. Additionally, the Elecsys® kit did not detect any age- or sex-related differences in S100B levels.
Crimson Publishers: Practical Issues of Inhibition in Forensic Body Fluid Ide...Crimson-ForensicScience
The main objectives of forensic biological examinations are body fluid analysis and identification of persons involved in a criminal act. Recent molecular biological techniques have enabled the analysis of trace and impure forensic samples. In particular, polymerase chain reaction (PCR)-based DNA typing is the standard test used in human identification worldwide [1]. PCR technology is suitable for analysis of trace particles of evidence; however, the problem with PCR inhibition is known for making proper amplification difficult
Prediction of the in vitro intrinsic clearance determined in suspensions of h...PPaixao
Use of in vitro suspensions of human hepatocytes is currently accepted as one of the most promising
tools for prediction of metabolic clearance in new drugs. The possibility of creating computational models
based on this data may potentiate the early selection process of new drugs.Wepresent an artificial neural
network for modelling human hepatocyte intrinsic clearances (CLint) based only on calculated molecular
descriptors. In vitro CLint data obtained in human hepatocytes suspensions was divided into a train group
of 71 drugs for network optimization and a test group of another 18 drugs for early-stop and internal
validation resulting in correlations of 0.953 and 0.804 for the train and test group respectively. The model
applicability was tested with 112 drugs by comparing the in silico predicted CLint with the in vivo CLint
estimated by the “well-stirred” model based on the in vivo hepatic clearance (CLH). Acceptable correlations
were observed with r values of 0.508 and 63% of drugs within a 10-fold difference when considering blood
binding in acidic drugs only. This model may be a valuable tool for prediction and simulation in the drug
development process, allowing the in silico estimation of the human in vivo hepatic clearance.
Crimson Publishers: Practical Issues of Inhibition in Forensic Body Fluid Ide...Crimson-ForensicScience
The main objectives of forensic biological examinations are body fluid analysis and identification of persons involved in a criminal act. Recent molecular biological techniques have enabled the analysis of trace and impure forensic samples. In particular, polymerase chain reaction (PCR)-based DNA typing is the standard test used in human identification worldwide [1]. PCR technology is suitable for analysis of trace particles of evidence; however, the problem with PCR inhibition is known for making proper amplification difficult
Prediction of the in vitro intrinsic clearance determined in suspensions of h...PPaixao
Use of in vitro suspensions of human hepatocytes is currently accepted as one of the most promising
tools for prediction of metabolic clearance in new drugs. The possibility of creating computational models
based on this data may potentiate the early selection process of new drugs.Wepresent an artificial neural
network for modelling human hepatocyte intrinsic clearances (CLint) based only on calculated molecular
descriptors. In vitro CLint data obtained in human hepatocytes suspensions was divided into a train group
of 71 drugs for network optimization and a test group of another 18 drugs for early-stop and internal
validation resulting in correlations of 0.953 and 0.804 for the train and test group respectively. The model
applicability was tested with 112 drugs by comparing the in silico predicted CLint with the in vivo CLint
estimated by the “well-stirred” model based on the in vivo hepatic clearance (CLH). Acceptable correlations
were observed with r values of 0.508 and 63% of drugs within a 10-fold difference when considering blood
binding in acidic drugs only. This model may be a valuable tool for prediction and simulation in the drug
development process, allowing the in silico estimation of the human in vivo hepatic clearance.
Objective(s):
There is a rising use of gold nanoparticles (AuNPs) in goods and in the medical fields but there is concern about the toxicity of them. So in this study spherical AuNPs with 3 different concentrations were applied for investigating their effects in vivo.
Materials and Methods:
40 male albino mice were randomly divided into sham, control, 25 ppm, 50 ppm, 100 ppm groups and were treated by intraperitoneal injection for period of 14 days. Blood was taken for measuring of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase (SGOT and SGPT) enzyme levels and Complete Blood Count (CBC).
Results:
After the treatment and comparing groups with sham group, in 50 ppm group significant increases on RBC, HCT, HGB, MCHC and in 25 ppm group significant increase on MCHC and significant decrease on MCV and in 100 ppm group significant increase on MCHC were observed. Also in 50 ppm group an increase on SGOT enzyme level was observed. However, it was nonsignificant.
Conclusion:
By observing the abnormality on the RBC count and SGOT enzyme level in the 50 ppm group, we concluded a slight toxicity effect for AuNPs and the threat potential of their use in human.
This is nice presentation given by Vishal Goyani, an Analytical student of National Institute Of Pharmaceutical education and research-INDIA.
mail your query at - vngoyanii@gmail.com
Objective(s):
There is a rising use of gold nanoparticles (AuNPs) in goods and in the medical fields but there is concern about the toxicity of them. So in this study spherical AuNPs with 3 different concentrations were applied for investigating their effects in vivo.
Materials and Methods:
40 male albino mice were randomly divided into sham, control, 25 ppm, 50 ppm, 100 ppm groups and were treated by intraperitoneal injection for period of 14 days. Blood was taken for measuring of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase (SGOT and SGPT) enzyme levels and Complete Blood Count (CBC).
Results:
After the treatment and comparing groups with sham group, in 50 ppm group significant increases on RBC, HCT, HGB, MCHC and in 25 ppm group significant increase on MCHC and significant decrease on MCV and in 100 ppm group significant increase on MCHC were observed. Also in 50 ppm group an increase on SGOT enzyme level was observed. However, it was nonsignificant.
Conclusion:
By observing the abnormality on the RBC count and SGOT enzyme level in the 50 ppm group, we concluded a slight toxicity effect for AuNPs and the threat potential of their use in human.
This is nice presentation given by Vishal Goyani, an Analytical student of National Institute Of Pharmaceutical education and research-INDIA.
mail your query at - vngoyanii@gmail.com
Immunoassay basic concepts for clinical pathologistDr. Rajesh Bendre
Immunoassays as technique have evolved considerably since the invention of Radioimmunoassay, monoclonal antibody, Recombinant technology & successfully achieved automation. However, many of the hormonal assays still lack standardization and/or Harmonization resulting in significant variability in test results. Using alternate methods, adopting procedures for sample pre-treatment, serial dilution of sample are some of the ways to troubleshoot these discrepant result
Subacute sclerosing panencephalitis (SSPE) In Iraqiosrjce
IOSR Journal of Computer Engineering (IOSR-JCE) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of computer engineering and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in computer technology. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Background: It is often difficult to predict which newborn with HIE will develop neurological sequlae so there is an urgent need for predictors for adverse neurological outcomes in these infants. Aim of Study: To evaluate the serum levels of serum amyloid A (SAA) protein in newborns with HIE during the first week of life and after 3 and 6 months of follow up to assess its correlation with degree of HIE neurological sequlee. Patients and Methods; This case-control study was conducted on 72 infants; group (1) included 36 full term neonates diagnosed as HIE and group (2)included 36 age and sex matched, infants as a control group, Serum amyloid A by ELIZA technique was measured at post natal age of 1 and 7 days, CT scan was done in justified cases .with follow up at age of 3 and 6 months for neurological sequlee. Results: SAA protein level was elevated in the asphyxiated group in comparison to the control group at day 1 and day 7, SAA level was significantly correlated to the Sarnat scoring system of HIE. SAA level significantly differ on follow up of developmental milestone at age of 3 and 6 months. ROC curve for validity of SAA for severity of HIE at cut off point > 25μg/ml at day 1 and at cut off point > 20 μg/ml at day 7 of HIE diagnosis reported sensitivity 100% and specificity 100% .Conclusion: SAA correlates with the severity of HIE and higher SAA expression is a prognostic marker for morbidity in these infants.
This ppt file represents a simple overview on what is antibody validation & how to validate an antibody before performing any research.
Used references are also included.
Internship - FMRI, Gurgaon (Dec '18 - Jan '19) AryanDugar
This is a presentation detailing the knowledge I acquired at my observational internship in the Clinical Pathology laboratory at Fortis Memorial Research Institute, Gurgaon, India.
The aim of the study is to establish new accurate
Turbidometrical measurement of Sickle Hemoglobin using
spectrophotometer instead of using naked eyes. Moreover, the
study aimed to find out the most suitable filter and reducing
reagent, which gives best result to improve the outcome of
Solubility test. The study also intended to find out correlation
between readings and previous transfusions as well as Jaundice.
The study was carried out in Khartoum state among patients
with sickle cell trait who were attending Khartoum educational
hospital, Gafer Ibn Aouf Clinic and STAC International Centre
Laboratory.
Forty, 26 female and 14 male patients were recruited for the
study. Of them, 34 were children and 6 were adults over 20 years
old. There were also 30 normal persons recruited as control
group for comparison.
Results showed that 600 Nanometer is the best filter, which
yielded highest light absorbance with significant statistical
difference, and Na Meta-bisulphite is the best reducing agent
because it produced turbidity more intense than Na Dithionate
reagent. There is no significant correlation between reading and
previous transfusion and jaundice. Therefore, the study
recommend to use Na Meta-bisulphite for processing blood
samples in Solubility test and to read the final reaction
(Turbidity) by spectrophotometer using 600 Nanometer filter.
CLASE ASCITIS
DR. RAUL CARRILLO ORTIZ
MODULO MEDICINA INTERNA
ROTACIÓN PATOLOGÍA CLÍNICA
DEPARTAMENTO DE MEDICINA Y NUTRICIÓN
UNIVERSIDAD DE GUANAJUATO
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
2. BMC Clinical Pathology 2008, 8:9 http://www.biomedcentral.com/1472-6890/8/9
Background measurement at maximal proximity to surgical insult to
Protein S100 is an acidic, disulfide-linked, dimeric, cal- the central nervous system. Previous data have demon-
cium-binding, low molecular weight protein. The beta strated that at this time S100B concentrations are highly
subtype of this protein exists in astrocyte cells in relatively correlated with post-craniotomy neurological deteriora-
high concentrations. Rises in serum concentrations of tion and unfavorable 6-month outcome [12]. Since the
S100B have been shown to relate to clinical evidence of ELISA array allows batch testing of forty samples at a time,
CNS damage in the three accepted models of brain injury eighty samples were selected at random for the current
in humans-trauma [1-3], ischemia [4] and hypoxia [5]. study, 40 pre-operative and 40 postoperative.
Significantly higher concentrations of S100B have been
demonstrated in brain death [3] and in non survivors Laboratory testing and workup of blood samples
from cardiopulmonary arrest, compared to survivors Blood samples were first allowed to clot for 30 min at
[5,6]. room temperature and then centrifuged. Following cen-
trifugation for 15 minutes at 2000 rpm, serum samples
The value of using S100B as an indicator of neurological were stored at -70°c for up to ~3 months for batch analy-
injury in the clinical setting is limited by the relatively sis. The serum samples were then thawed to room temper-
high cost and lengthy performance time of the enzyme- ature, divided into two aliquots and analyzed in parallel
linked immunosorbent assay (ELISA) (currently consid- by the ELISA and Elecsys® methods. Diluted serum was
ered the best method of analysis), poor substantiation of used for higher values in both assays.
reference levels, lack of standardization of serum S-100B
testing and the paucity of data regarding the relationship Assessment by ELISA
between measurement methods. Most studies demon- Testing was performed using the Sangtec 100 ELISA
strating the potential diagnostic value of serum S-100B in immunosorbent assay for quantitative measurement of
neurological diseases used an ELISA method (Sangtec S100B protein in human serum (DiaSorin Inc., Stillwater,
Medical) [1,5,7,8]. Recently a kit for rapid quantification Minnesota, USA). Each sample was incubated together
of S-100B in human serum has become available (Roche with an appropriate marker. Washout was performed with
Pharmaceuticals, Elecsys®). a buffer and tetramethylbenzidine was added as a sub-
strate. Following further incubation a tetramethylbenzi-
The current study was designed to quantitatively compare dine-arresting substance was added. Spectrophotometric
the commercially available Elecsys® assay for serum S100B reading of light absorbance at 450 nm was performed.
protein concentrations with the gold standard ELISA Calculation of the result was performed using a cubic
method and to examine whether this test detects sex- and spline algorithm. The calculation range is accurate to a
age-related differences in serum S100B protein concentra- measured concentration of 5 μg//L.
tions similar to those demonstrated with ELISA by Gaz-
zolo et al. [9] and Nyberg et al. [10] in pediatric Assessment by Elecsys®
populations. Testing was performed using the Roche Elecsys® S100 rea-
gent kit (assay duration 18 minutes, measuring range
Methods 0.005–39 μg/L, cross reactivity against S100α < 1%). Less
Sampling technique than 24 hr prior to testing calibration was performed per
Following institutional review board approval (Hadassah reagent kit and control values were determined to be
Hebrew University Medical Center, reference number 14– within the limits required for calibration (0.206 μg/L and
19/12/03) as well as individual patient informed consent, 2.54 μg/L). The test kit is based on the sandwich principle;
52 consecutive adult patients aged 18–80 who underwent the 1st incubation is performed with a biotinylated mono-
supratentorial meningioma surgery over a 10 month clonal S100-specific antibody and a monoclonal S100-
period provided pre- and post operative blood samples specific antibody labeled with a ruthenium complex react
for analysis of S100B concentrations. to form a sandwich complex. The 2nd incubation: After
addition of streptavidin-coated microparticles the com-
Blood samples were drawn into sterile, preservative-free plex becomes bound to the solid phase via interaction of
vacuum containers for the evaluation of S100B in the peri- biotin and streptavidin. The reaction mixture is aspirated
operative period as described elsewhere [11]. For the pur- into the measuring cell where the microparticles are mag-
pose of the current study, samples drawn prior to surgery netically captured onto the surface of the electrode.
(after insertion of an intravenous cannula upon admis- Unbound substances are then removed with ProCell.
sion) and immediately after surgery were used. These sam- Application of a voltage to the electrode then induces
pling times were selected based on the assumption that chemiluminescent emission which is measured by a pho-
the broadest range of serum concentrations would be tomultiplier. Results are determined via a calibration
obtained between the baseline measurement and the curve which is instrument-specifically generated by 2-
Page 2 of 7
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3. BMC Clinical Pathology 2008, 8:9 http://www.biomedcentral.com/1472-6890/8/9
point calibration and a master curve provided via the rea-
gent barcode.
The two laboratory analyses were performed by different
technicians in different times. Both were blinded to the
results of the alternative method.
Statistical analysis
In the first stage, several regression models were used to
examine the Elecsys® method as a function of the ELISA
method using all the samples. These included linear,
quadratic, cubic, logarithmic, inverse, compound, power,
s and growth. Among those models with the best fit
(judged by the R2 value) the most parsimonious was cho-
sen. In the second stage, Bland-Altman analyses [13] were
used to compare the quantification of S100 between Elec-
sys® and ELISA and to detect the existence of systematic S100B measured using ELISA and Elecsys®, with regression
Figure 1
line
errors. The statistical analyses were performed using SPSS S100B measured using ELISA and Elecsys®, with
12 software (SPSS Inc, Chicago, IL). The study endpoint regression line. The formula for the regression line of the
was examination of the relationship between the two test relationship between the two test methods was y = 0.045269
methods. + 0.276976*x, with x = ELISA value. All serum concentra-
tions are given in μg/L.
Preoperative samples were used for detection of age- and
sex-related changes in serum S-100B levels using the Elec-
sys® assay. Statistical analyses included the Mann-Whitney ancy was very large (>2 SD) at values above 0.7 μg/L (i.e.
test for comparison between sexes, the Spearman correla- in the region of values suggestive of brain injury).
tion coefficient to evaluate correlation between serum
S100B and age and post-hoc ANOVA to test for differences
between serum S100B levels and age groups.
Results
Quantitative comparison between the two methods
The best fitting models that assessed Elecsys® values as a
function of ELISA values were linear, quadratic and cubic
regressions, with R2values of 0.732, 0.752 and 0.753
respectively. As the R2 values were very similar, the more
parsimonious (in terms of the number of parameters in
the model) linear model was selected to represent the rela-
tionship between the two test methods. The formula for
the regression line of the relationship between the two test
methods was y = 0.045269 + 0.276976*x, with x = ELISA
value (Figure 1).
The mean difference in measurement between the two
tests (ELISA minus Elecsys®) was 0.214 ± 0.277 μg/L.
However, this value is determined by the distribution of
the measured concentrations (i.e. the patient mix) with as measured by ELISA and Elecsys® measurements
Bland and Altman comparison of serum S100 concentrations
Figure 2
Bland and Altman comparison of serum S100 con-
the discrepancy being a linear function of the S100B con-
centrations as measured by ELISA and Elecsys®
centration. The Bland-Altman analysis clearly demon- measurements. The x-axis represents the average meas-
strated that the values determined by ELISA were higher urement and the y-axis represents the difference (in μg/L) in
than by Elecsys®, with the discrepancy increasing in linear measurements when these were made using ELISA and Elec-
mode as the S100B concentration increased so that the sys® methods. The mean difference ± 2 SDs are represented
ELISA values markedly exceeded the Elecsys® values at the by horizontal complete and dotted lines respectively. The
higher concentrations (Figure 2). The degree of discrep- value of the R2 for the regression line is 0.88.
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Relationship between S100B and age damage) that may cause misclassification of patient status
No statistically significant sex difference was noted in and prognosis; hence the need for standardization. The
serum S100B concentrations measured by the Elecsys® current paper relates to brain damage as a result of an
method (p = 0.643), nor was there a correlation between intracranial operative procedure and may therefore be
S100B concentration and age (p = 0.728) (figure 3). more pertinent to the range of test values to be expected
in direct injury to the brain.
Discussion
The current study provides a quantitative comparison of Sex and age related differences in serum S100B levels were
two tests for measuring the serum concentration of not detected using the Elecsys®. This result is consistent
S100B; ELISA and the commercially available Elecsys®. In with other studies that used alternative measurement
terms of R2 and the number of parameters in the model, methods which demonstrated no sex and age differences
the linear model provided the best fit for the relationship in normal adult populations [10,15,16], contrary to pedi-
between the results achieved by these tests. However, in atric populations [9,10].
our hands ELISA measurements were higher than Elecsys®
measurements and particularly so at the higher values, There are several subunits of S100 proteins [17], many of
where the differences in the measurements made using which are expressed selectively by specific cell types. The B
the two methods were consistently outside the limits of subunit of the S100 protein (S100B) is found in particu-
agreement (2 SDs) as seen in the Bland-Altman display. larly high concentrations in astroglial cells of the central
nervous system and is therefore often referred to as Astro-
Mussack et al. [14] performed a similar analysis in a group cyte Derived Growth Factor [18,19]. S100B is implicated
of patients undergoing carotid revascularization. With the in the coordinated development and maintenance of the
exception of two patients with ongoing damage, the central nervous system; it stimulates differentiation of
results of ELISA testing in their series were curtailed at 0.4 immature neurons [18-23], promotes cell survival
μg/L whereas the current paper describes ranges up to 1.2 [23,24], induces neurite extension [25] and enhances glial
μg/L. In contrast with our study, Mussack et al. found cell proliferation. Observations of higher S100B concen-
small, inconsistent mean differences between the meth- trations humans in infants and adolescence have led some
ods and little or no change in the difference between researchers to suggest that the release of this neurotrophic
methods with increasing S100 concentrations. It is pre- factor decreases as the brain matures [9,10].
cisely the divergence at higher values reported in our
paper (i.e. those more likely to be associated with brain Serum S100B concentrations rise in clinical situations rep-
resenting the three models of human brain injury –
trauma [1-3], ischemia [4,26] and hypoxia [5,27]. The
degree of elevation is probably related to the severity of
blood-brain barrier disruption [28,29]. Although S100B is
eliminated by the kidneys, in-vivo studies have not shown
a detectable rise in S100B concentration in renal failure,
probably due to its estimated 2 hour biological half life
[30]. Prolonged post-insult elevation of serum S100B con-
centrations therefore most probably reflects ongoing cen-
tral nervous system damage.
Routine use of S100B for early diagnosis of brain injury
remains limited for a number of reasons. Lack of specifi-
city for the biologically active dimeric form of the S-100B
molecule using the actually available assays is a major
problem. This protein can be released from extracerebral
tissue, particularly after surgery [31], potentially con-
founding the association with brain injury and resulting
Figure 3 of S100B levels with age
Relationship in misclassification. S100B can be released from the heart
Relationship of S100B levels with age. Error bar for or mediastinum [32,33] and exists in adipose tissue
preoperative serum S100B levels (μg/L) by decade for [34,35], skin, testes [34], skeletal muscle [36] and placen-
patients with meningioma (n = 40). Data are presented tal tissue [37,38], albeit in significantly lower concentra-
together for male and female patients since no sex differ- tions than in brain tissue. The definition of "normal"
ences were found. values in humans has yet to be established in each assay
and cutoff values for diagnosis and quantification of the
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presence and extent of brain injury remain undefined. (approximately 90 minutes per test) and the test kit
Clinical applicability is also limited by the lack of stand- (which costs 1257 ) usually allows for performance of 40
ardization. Different laboratories using the same kit pro- tests. ELISA measurement remains the gold standard for
duced substantially different values [5,6,39,40] and S100B measurements. However, widespread use of ELISA
between-kit variance may be even larger. remains limited by cost/benefit considerations, mainly
due to its time-consuming nature.
Elecsys® analysis requires an electrochemiluminescence
measuring cell. Apart from the initial centrifuging, testing This study provides an assessment of the relationship
is fully automated; thus only a few minutes of laboratory between two currently used laboratory methods but does
staff time are needed for analysis. The reagent kit suffices not address the diagnostic accuracy of either (i.e. sensitiv-
for up to 100 tests. Calibration is required once monthly ity or specificity, optimal cutoff points). The inequality
and requires two calibration standards in duplicate (4 demonstrated between the tests at higher S100 values may
tests). Two control tests are required daily (2 tests). The have important implications for its use both as a prognos-
real cost of any test is subject to kit yield which depends tic marker and for clinical diagnosis as different cutoff
on several variables (e.g. daily number of tests, calibration points may be needed for the different test kits – an
and quality control procedures). Calculated yield may be overtly undesirable clinical situation. Coefficients of vari-
therefore be greatly affected by internal laboratory regula- ation are not given for the measurement methods. One
tions. Kit yield is close to maximal at 20 tests per day, at should also exercise caution in extrapolating the findings
which point additional costs are almost negligible (Table of this study to concentrations of S100B higher than those
1). In 2008 the local price for an Elecsys S100 kit was included in the study.
1528 . Thus, the theoretical price per test was 15.28 . For
a daily routine of 5 reported results (kit yield 0.6451) the Clinical tools for early diagnosis of brain damage in criti-
real price per test was 23.69 and for a daily routine of 12 cally ill patients are lacking. Physical examination and intu-
reported results (kit yield 0.8235) the real price per test itive prediction are often the mainstays for both diagnostic
was 18.55 . Additional costs of calibrator and control and treatment decisions in these patients. This is a far from
materials should be noted: The estimated consumption of optimal situation in the intensive care environment where
S100 calibrator (price 80.00 /pack) and control (price judicious allocation of hospital resources is required; sur-
189.00 /pack) is 2 and 3 packs/year accordingly, yielding vival with overwhelming residual neurological disability
additional estimated costs of 727 /year. Analysis of and absent or poor quality of life following insult to the
S100B levels by ELISA requires specialized equipment, a central nervous system incurs expensive in- and out-of-hos-
substantial amount of laboratory technician time pital therapy and high indirect costs [40-45].
Table 1: Elecsys® rack-pack yield for 28 days.
n tests
For clinical use daily For clinical use monthly For calibration For Quality Control Total Kit yield
1 28 16 56 101 0.28
2 56 16 56 130 0.43
3 84 16 56 159 0.53
4 112 16 56 188 0.60
5 140 16 56 217 0.65
10 280 16 56 362 0.77
15 420 4 56 495 0.85
20 560 4 56 640 0.88
25 700 4 56 785 0.89
30 840 4 56 930 0.90
40 1120 4 56 1220 0.92
50 1400 4 56 1510 0.93
60 1680 4 56 1800 0.93
70 1960 4 56 2090 0.94
80 2240 4 56 2380 0.94
90 2520 4 56 2670 0.94
100 2800 4 56 2960 0.95
Data are correct provided manufacturer specifications and recommendations are followed. Kit yield is close to maximal at 20 tests per day, at
which point additional costs are close to negligible.
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Despite its limitations, serum S100B, one of the most 6. Rosen H, Rosenberg L, Herlitz J, Blomstrand C: Increased serum
levels of the S-100 protein are associated with hypoxic brain
studied biomarkers of brain damage in the clinical setting, damage after cardiac arrest. Stroke 1998, 29:473-477.
is currently the only one of which we are aware that holds 7. Weiss N, Sanchez-Peña P, Roche S, Beaudeux JL, Colonne C, Coriat
promise as an early marker of brain damage and a predic- P, Puybasset L: Prognosis value of plasma S100B protein levels
after subarachnoid aneurysmal hemorrhage. Anesthesiolog
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bility. Our study points to some shortcomings of currently 8. Heizmann CW: S100B protein in clinical diagnostics: assay spe-
available measurement methods and to the need for bet- cificity. Clin Chem 2004, 50:249-251.
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Conclusion 11. Einav S, Shoshan Y, Ovadia H, Matot I, Hersch M, Itshayek E: Postop-
Although a general linear relationship exists between erative serum S100B levels predict postoperative brain dam-
age in patients undergoing meningioma surgery. Crit Care
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to be higher than commercial kit measurements particu- pappa D, Sakas DE: Serum S-100B as an indicator of early post-
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Competing interests tomy. Clin Biochem 2006, 39:349-356.
The authors declare that they have no competing interests. 15. Wiesmann M, Missler U, Gottmann D, Gehring S: Plasma S-100b
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SE, YS and JDK are responsible for conceiving and design- LN, Silva CT, Busnello JV, Kapczinski F, Gonçalves CA, Souza DO:
The serum S100B concentration is age dependent. Clin Chem
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