Abnormal Levels in HIV and CTE: Understanding Biomarkers and Brain Changes

23.09.197818.11.2021 by alexxlab

How do abnormal levels of biomarkers affect HIV patients despite early treatment. What insights does a new study reveal about CTE in NFL players’ brains. Can tau protein detection lead to improved diagnosis and treatment of neurodegenerative conditions.

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HIV Biomarkers: Persistent Abnormalities Despite Early Treatment

Human Immunodeficiency Virus (HIV) continues to present challenges even with early antiretroviral therapy (ART). A recent study investigated the immunologic pathways that remain abnormal in ART-suppressed people with HIV (PWH), potentially contributing to their higher risk of infections and infection-related cancers.

Study Design and Participant Demographics

The study compared ART-suppressed PWH with HIV-negative controls, all cytomegalovirus seropositive. Participants were stratified based on ART initiation timing:

Early ART: within 6 months of infection
Later ART: initiated after 6 months, further categorized by nadir CD4+ T-cell count

Notably, 92% of participants were male, reflecting the demographics of early-ART initiators in San Francisco.

Key Biomarkers Examined

The study focused on several biomarkers associated with immune activation and inflammation:

Kynurenine-tryptophan (KT) ratio
Interferon-inducible protein 10 (IP-10)
Soluble CD14 and CD163
Soluble tumor necrosis factor receptor 2 (sTNFR2)
Interleukin 6 (IL-6)
Soluble urokinase plasminogen activator receptor (suPAR)

Significant Findings in Early-ART Initiators

The study revealed intriguing results for those who initiated ART early:

Near-normal levels of sTNFR2, IL-6, and suPAR
Substantially higher KT ratio compared to HIV-negative controls (P = .008)
Trends towards higher levels of soluble CD14, CD163, and IP-10

Why does the kynurenine pathway remain abnormally elevated despite early ART? This persistent abnormality in tryptophan catabolism may contribute to adaptive immune defects and increased risks of tuberculosis and cancer progression in PWH.

The Kynurenine Pathway: A Potential Target for HIV Management

The kynurenine pathway’s role in tryptophan catabolism has garnered significant attention in HIV research. This pathway, regulated by the enzyme indoleamine 2,3-dioxygenase-1 (IDO-1), plays a crucial role in immune regulation and tolerance.

Implications of Elevated KT Ratio

An elevated KT ratio in PWH, even with early ART, suggests persistent immune dysregulation. This finding has several potential consequences:

Impaired T-cell responses
Increased susceptibility to opportunistic infections
Higher risk of cancer development
Potential neurological complications

How might targeting the kynurenine pathway improve outcomes for PWH? Researchers are exploring IDO-1 inhibitors and other interventions to modulate this pathway, potentially enhancing immune function and reducing long-term health risks.

Beyond HIV: Abnormal Protein Levels in NFL Players’ Brains

Shifting focus to another area of medical research, a groundbreaking study led by Dr. Robert Stern of Boston University has revealed abnormal levels of a protein linked to Chronic Traumatic Encephalopathy (CTE) in the brains of living NFL players.

Study Overview and Methodology

The research team utilized advanced brain imaging techniques to examine 26 former NFL players aged 40 to 69, all experiencing various memory, mood, and mental problems associated with CTE. The study employed PET scans to detect tau protein levels in specific brain regions.

Key Findings on Tau Protein Accumulation

The study yielded several significant observations:

Marked elevation of tau proteins in brain areas typically affected by CTE
Higher average tau signal in players compared to a non-player control group
Positive correlation between abnormal tau levels and years of football played

What implications do these findings have for CTE diagnosis and treatment? The ability to detect abnormal tau accumulation in living individuals could revolutionize both the identification of CTE and the monitoring of potential therapeutic interventions.

Tau Detection: A Promising Frontier in Neurodegenerative Disease Research

The development of reliable tau protein detection methods represents a significant advance in neurodegenerative disease research. This progress extends beyond CTE to other conditions such as Alzheimer’s disease.

Challenges and Future Directions

Despite the promising results, several challenges remain in developing a definitive CTE test:

Refining ligands for more precise tau detection
Understanding the relationship between tau accumulation and CTE symptoms
Determining whether head trauma accelerates tau protein accumulation
Establishing clear links between tau levels and specific behavioral changes

How might improved tau detection methods impact the broader field of neurodegenerative disease research? Enhanced ability to monitor tau protein levels could lead to earlier diagnosis, more effective treatment strategies, and improved outcomes across a range of neurological conditions.

NRBC Blood Test: Assessing Nucleated Red Blood Cells

Transitioning to another aspect of medical diagnostics, the Nucleated Red Blood Cell (NRBC) blood test provides valuable insights into various health conditions. NRBCs are immature red blood cells that still contain a nucleus, typically not present in the peripheral blood of healthy adults.

Understanding NRBC Levels

NRBC levels can be indicative of several health issues:

Severe anemia
Bone marrow disorders
Certain types of leukemia
Thalassemia
Severe infections

What constitutes a normal NRBC count in adults? In healthy adults, NRBCs are typically absent from peripheral blood. Their presence often signifies an underlying health concern requiring further investigation.

Clinical Significance of Elevated NRBC Counts

Elevated NRBC counts can provide critical information for healthcare providers:

Indicator of increased erythropoietic activity
Potential sign of bone marrow stress or dysfunction
Prognostic marker in certain critical illnesses
Guide for further diagnostic testing

How do clinicians interpret and act upon abnormal NRBC results? The presence of NRBCs typically triggers a series of follow-up tests to determine the underlying cause and develop an appropriate treatment plan.

Integrating Biomarker Research: From HIV to CTE and Beyond

The studies on HIV biomarkers, CTE-related tau protein accumulation, and NRBC levels highlight the critical role of biomarker research in advancing medical diagnostics and treatment. These diverse areas of study share common themes of identifying abnormal protein or cell levels to better understand and manage complex health conditions.

Cross-Disciplinary Implications

The integration of findings from various biomarker studies can lead to:

Improved early detection methods for multiple conditions
Development of more targeted therapies
Enhanced understanding of disease progression mechanisms
Better risk assessment and prevention strategies

How might advances in one area of biomarker research benefit others? Technological improvements in protein detection, for instance, could have far-reaching implications across multiple medical fields, from infectious diseases to neurodegenerative disorders and hematological conditions.

The Future of Personalized Medicine: Leveraging Biomarker Insights

As biomarker research continues to evolve, it paves the way for more personalized and effective medical interventions. The ability to detect subtle changes in protein levels, cellular composition, or metabolic pathways allows for a more nuanced understanding of individual patient profiles.

Potential Advancements in Patient Care

Future applications of biomarker research may include:

Tailored treatment plans based on individual biomarker profiles
Early intervention strategies for at-risk populations
More accurate prognosis and disease progression predictions
Development of novel therapeutic targets
Improved monitoring of treatment efficacy

What role will artificial intelligence and machine learning play in biomarker analysis? These technologies hold immense potential for identifying complex patterns and correlations in biomarker data, potentially uncovering new insights and treatment approaches.

Ethical Considerations and Patient Privacy

As biomarker research advances, it’s crucial to address ethical considerations:

Ensuring patient confidentiality in large-scale biomarker studies
Addressing potential discrimination based on biomarker profiles
Balancing the benefits of early detection with the psychological impact of risk awareness
Ensuring equitable access to advanced biomarker-based diagnostics and treatments

How can healthcare systems and policymakers ensure that the benefits of biomarker research are accessible to all? This question underscores the importance of integrating ethical considerations into the development and implementation of biomarker-based medical advances.

Collaborative Research: A Key to Unlocking Biomarker Potential

The complex nature of biomarker research necessitates collaboration across various scientific disciplines. From molecular biologists to clinical researchers, data scientists, and healthcare providers, a multidisciplinary approach is essential to fully realize the potential of biomarker discoveries.

Building Interdisciplinary Research Networks

Effective collaboration in biomarker research involves:

Sharing of data and resources across institutions
Development of standardized protocols for biomarker measurement
Integration of clinical observations with laboratory findings
Cross-pollination of ideas between different medical specialties

How can research institutions foster a more collaborative environment for biomarker studies? Initiatives such as multi-center studies, shared databases, and interdisciplinary conferences play crucial roles in advancing the field.

Translating Research into Clinical Practice

The ultimate goal of biomarker research is to improve patient outcomes. This requires a seamless transition from laboratory discoveries to clinical applications. Key steps in this process include:

Rigorous validation of biomarker findings in diverse populations
Development of standardized, cost-effective testing methods
Integration of biomarker testing into clinical guidelines
Education of healthcare providers on the interpretation and application of biomarker results

What strategies can accelerate the translation of biomarker research into clinical practice? Close collaboration between researchers, clinicians, and regulatory bodies is essential to navigate the complex pathway from discovery to implementation.

As we continue to unravel the complexities of human biology through biomarker research, we move closer to a future where medical interventions are increasingly precise, personalized, and effective. From understanding the intricacies of HIV progression to detecting neurodegenerative changes in living individuals, biomarker studies are reshaping our approach to health and disease. The journey from abnormal levels to actionable insights is ongoing, promising a new era of medical understanding and patient care.

Abnormal Levels of Some Biomarkers of Immune Activation Despite Very Early Treatment of Human Immunodeficiency Virus

Background:

Despite early antiretroviral therapy (ART), ART-suppressed people with human immunodeficiency virus (HIV) (PWH) remain at higher risk for infections and infection-related cancers than the general population. The immunologic pathways that remain abnormal in this setting, potentially contributing to these complications, are unclear.

Methods:

ART-suppressed PWH and HIV-negative controls, all cytomegalovirus seropositive and enriched for HIV risk factors, were sampled from an influenza vaccine responsiveness study. PWH were stratified by timing of ART initiation (within 6 months of infection [early ART] vs later) and nadir CD4+ T-cell count among later initiators. Between-group differences in kynurenine-tryptophan (KT) ratio, interferon-inducible protein 10, soluble CD14 and CD163, soluble tumor necrosis factor receptor 2, interleukin 6, and soluble urokinase plasminogen activator receptor were assessed after confounder adjustment.

Results:

Most participants (92%) were male, reflecting the demographics of early-ART initiators in San Francisco. Most biomarkers were higher among later-ART initiators. Participants in the early-ART group achieved near-normal soluble tumor necrosis factor receptor 2, interleukin 6, and soluble urokinase plasminogen activator receptor levels, but substantially higher KT ratio than those without HIV after confounder adjustment (P = .008). Soluble CD14, soluble CD163, and interferon-inducible protein 10 trended similarly.

Conclusions:

While early-ART initiators restore near-normal levels of many inflammatory markers, the kynurenine pathway of tryptophan catabolism remains abnormally high. Because this pathway confers adaptive immune defects and predicts tuberculosis and cancer progression, this it may contribute to persistent risks of these complications in this setting.

Keywords:

3-dioxygenase-1; HIV; IP-10; antiretroviral therapy; immune activation; indoleamine 2; inflammation; kynurenine; sCD14; sCD163; tryptophan.

Abnormal Levels of a Protein Linked to C.T.E. Found in N.F.L Players’ Brains, Study Shows

The new study was led by Dr. Robert Stern of Boston University, which thus far has the largest collection of donated brains from former pro football players. He led a coalition of investigators at multiple centers who took brain images from 26 former pro players, aged 40 to 69, who had a variety of memory, mood and mental problems associated with C.T.E.

Those images showed marked elevation of tau proteins in the areas of the brain that display the tau signature when diagnosed post-mortem. The players’ tau signal in those areas was higher, on average, than the tau signal from a control group of men who had not played.

“We found, as well, that the amount of abnormal tau detected in these PET scans was associated with the number of years playing football,” Dr. Stern said.

His collaborators included brain scientists from the Mayo Clinic Arizona, Brigham and Women’s Hospital and Avid Radiopharmaceuticals. Avid makes a molecule, called a ligand, that binds to proteins, in this case in the brain. Avid’s ligand is the most studied of the so-called tau detectors, and the company helped finance the study.

Experts said the findings were encouraging, because any reliable marker for abnormal tau accumulation would allow doctors not only to identify people with C.T.E., but also to monitor progress from potential drug treatments.

But, these experts said, much more work is required to develop a reliable test for a disorder that is still not well understood. As in tests for people suffering from Alzheimer’s and other diseases that affect the brain, researchers have spent years trying to precisely refine the ligands that are ingested by patients before they receive PET scans and other imaging tests.

There are also many open questions about the tau protein that is a signature of C.T.E. Researchers are trying to determine whether the protein, which occurs naturally in the brain, accumulates faster in people who have received repeated head trauma, and how those accumulating levels are related to behaviors associated with C.T.E., which include not only memory deficits but also impulse control issues and symptoms of depression.

NRBC (Nucleated RBC) Blood Test: Normal & Abnormal Levels

Nucleated red blood cells (NRBC) are immature red blood cells. Their presence in the bloodstream may indicate serious problems with RBC production or the bone marrow. Read on to learn more details about the presence of NRBC in your blood and what you can do about it.

What are Nucleated RBCs?

As red blood cells mature, they lose their nucleus – a part of the cell where DNA is stored. This enables them to carry more hemoglobin (and therefore more oxygen) and become highly flexible in shape.

Nucleated RBCs (NRBCs, normoblasts) are immature red blood cells (RBCs) that still contain a nucleus. Unlike the mature ones, nucleated red blood cells are unable to “squeeze” through portholes in the bone marrow and enter the circulation [1, 2, 3].

In healthy adults and children, NRBCs are usually only found in the bone marrow where they develop and mature. Their presence in the blood signifies the disruption of the blood-bone marrow barrier or increased red blood cell production outside the bone marrow [1, 2, 3].

However, NRBCs are common in the blood of fetuses and newborn babies, especially if they are experiencing growth retardation or a lack of oxygen [1, 2, 3].

Nucleated red blood cells are immature red blood cells. In adults, their presence in the blood indicates a problem.

NRBC Blood Test

NRBC test is often requested as a follow-up to abnormal results on a complete blood count (CBC) test in order to check for blood cell abnormalities. It may also be of use when a person has signs and symptoms of a condition affecting blood cell production or lifespan.

When automatic counters are used for CBC analysis, sometimes NRBCs can be misclassified as white blood cells. This can have negative consequences for patient treatment and outcome. In those cases, NRBCs in the blood film should be counted manually [4, 5, 6].

Your doctor may order an NRBC test if your complete blood count test results indicate issues. To avoid mistakes, NRBC count should be confirmed manually.

Normal NRBC Levels

Nucleated RBCs are quantified by counting the number of NRBCs per 100 white blood cells. Counts with even 1 NRBC/100 WBCs are to be reported, as only a few NRBCs can have dangerous implications [5].

A normal result is 0 NRBCs/100 WBCs.

Abnormal Nucleated RBC Levels

The presence of nucleated RBCs in the blood is known as normoblastemia—a complex condition with many possible causes [5].

Causes

The causes discussed below are commonly associated with elevated NRBCs, but a high lab result here is not sufficient to diagnose any of these conditions. Work with your doctor or other health care professional to determine an accurate diagnosis and appropriate strategies for improving your health.

1. Low Oxygen

Conditions that reduce the tissue oxygen supply (hypoxia) increase red blood cell production, which, in turn, leads to the presence of nucleated RBCs in the blood. These include [5, 1, 7]:

Hemorrhage (blood loss)
Anemia (hemolytic anemia, iron deficiency anemia, megaloblastic anemia)
Thalassemia major
Severe lung disease
Congestive heart failure

NRBCs can show up in the blood due to low oxygen caused by blood loss or different health conditions.

2. Spleen Dysfunction

Normally, spleen clears nucleated RBCs that escape from the bone marrow. Conditions that affect spleen function can result in the presence of nucleated RBCs in the blood. These include [5, 1]:

Sickle cell anemia
Essential thrombocytosis (a rare disorder with the overproduction of platelets)
Hemolytic anemia
Malaria
Splenectomy (surgical removal of the spleen)

Conditions that affect the spleen can prevent the removal of NRBCs from the blood.

3. Bone Marrow Damage

Conditions that damage the bone marrow can break down the blood-bone marrow barrier and release NRBCs and into the circulation. These conditions include [5, 8]:

Blood cancers (e.g. preleukemia, leukemia, lymphoma, multiple myeloma, myelofibrosis, and myelodysplasia)
Neuroblastoma (cancer of immature nerve cells)
Gaucher disease (the buildup of fats in certain organs, especially the spleen and liver)
Tuberculosis
Collagen vascular disease (e.g. lupus)
Fungal infections
Sarcoidosis (inflammation in the lungs, skin, eyes, and lymph nodes)

4. RBC Production Outside of the Bone Marrow (Extramedullary Hematopoiesis)

Bone marrow damage or severe anemia can lead to the production of red blood cells in other organs such as the liver or spleen, which may release NRBCs into the circulation. Such conditions include [5, 9]:

Myelophthisis (severe anemia resulting from bone marrow failure)
Myeloid metaplasia (progressive bone marrow scarring)
Chronic hemolytic anemia
Polycythemia vera (excess RBC production)
Leukemia

5. Other

Other causes of NRBC in the blood (normoblastemia) include [5, 1, 10]:

It is unclear why normoblastemia occurs in some of these, but the breakdown of the blood-bone marrow barrier may play a key role [5].

Consequences

The presence of nucleated RBCs in the blood is associated with poor disease prognosis.

In two studies of over 600 intensive care patients, NRBCs in the blood were associated with increased mortality [3, 11].

Ways to Decrease Nucleated RBCs

The primary way to decrease nucleated RBCs is to address any underlying conditions. Work with your doctor to find an accurate diagnosis and to determine the appropriate next steps to improve your health.

We recommend strongly against making significant exercise, diet, or supplement changes without consulting a physician, as unexpected interactions may arise.

If you have anemia:

Exercise: Moderate physical activity signals your body to increase red blood cell production in order to increase the oxygen supply to your muscles [12].

Avoid more intense and strenuous forms of exercise as these can damage and destroy red blood cells. This is one of the reasons that endurance athletes often have anemia [13].

Make sure you are not nutrient deficient. Your body should have all the nutrients it needs to produce red blood cells (iron, vitamin B12, folate, copper, and vitamin B6).
Reduce or stop your alcohol consumption. It decreases red blood cell production [14].
Avoid NSAIDs such as ibuprofen – they can cause gut injuries and increase blood loss [15].
Be cautious with antacids and other drugs that suppress stomach acid. These decrease iron levels, leading to low RBCs [16].
Avoid products that contain lead, such as lead paints; it will help prevent red blood cell damage [17].
Boost testosterone levels by getting good quality sleep, losing weight if you are overweight, and exercising regularly [18, 19, 20, 21].

To reduce NRBCs, address the underlying cause. If you have anemia, get regular exercise and enough iron, B vitamins, and copper; avoid alcohol and NSAID painkillers.

According to some studies, these supplements may help with anemia:

Note that the supplements above have not been approved by the FDA. The data supporting their use is still considered insufficient, so talk to your doctor about them to make the best possible decisions to support your health.

Takeaway

Nucleated red blood cells (NRBCs) are immature red blood cells produced in the bone marrow. In adults, their presence in the blood indicates a problem with bone marrow integrity or red blood cell production.

Your doctor may order an NRBC test if other blood test results (such as CBC) indicate blood cell issues. A normal result is 0 NRBCs/100 WBCs or a complete absence of NRBCs in the blood.

Possible causes of NRBCs in the blood include anemia, low oxygen, spleen dysfunction, and bone marrow damage and disorders. You can reduce NRBCs by addressing the underlying cause.

If you have anemia, make sure to exercise regularly, eat a nutritious diet, and reduce alcohol. Avoid NSAIDs and drugs that suppress stomach acid and consider taking folate, iron, selenium, spirulina, and vitamins B12, D, and E.

Abnormal blood levels of proteins linked to dementia, Alzheimer’s disease

The development of dementia, often from Alzheimer’s disease, late in life is associated with abnormal blood levels of dozens of proteins up to five years earlier, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health. Most of these proteins were not known to be linked to dementia before, suggesting new targets for prevention therapies.

The findings are based on new analyses of blood samples of over ten thousand middle-aged and elderly people–samples that were taken and stored during large-scale studies decades ago as part of an ongoing study. The researchers linked abnormal blood levels of 38 proteins to higher risks of developing Alzheimers within five years. Of those 38 proteins, 16 appeared to predict Alzheimer’s risk two decades in advance.

Although most of these risk markers may be only incidental byproducts of the slow disease process that leads to Alzheimer’s, the analysis pointed to high levels of one protein, SVEP1, as a likely causal contributor to that disease process.

The study was published May 14 in Nature Aging.

This is the most comprehensive analysis of its kind to date, and it sheds light on multiple biological pathways that are connected to Alzheimer’s. Some of these proteins we uncovered are just indicators that disease might occur, but a subset may be causally relevant, which is exciting because it raises the possibility of targeting these proteins with future treatments. “

Josef Coresh, MD, PhD, MHS, Study Senior Author, George W. Comstock Professor, Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University

More than six million Americans are estimated to have Alzheimer’s, the most common type of dementia, an irreversible fatal condition that leads to loss of cognitive and physical function. Despite decades of intensive study, there are no treatments that can slow the disease process, let alone stop or reverse it. Scientists widely assume that the best time to treat Alzheimer’s is before dementia symptoms develop.

Efforts to gauge people’s Alzheimer’s risk before dementia arises have focused mainly on the two most obvious features of Alzheimer’s brain pathology: clumps of amyloid beta protein known as plaques, and tangles of tau protein. Scientists have shown that brain imaging of plaques, and blood or cerebrospinal fluid levels of amyloid beta or tau, have some value in predicting Alzheimer’s years in advance.

But humans have tens of thousands of other distinct proteins in their cells and blood, and techniques for measuring many of these from a single, small blood sample have advanced in recent years. Would a more comprehensive analysis using such techniques reveal other harbingers of Alzheimer’s? That’s the question Coresh and colleagues sought to answer in this new study.

The researchers’ initial analysis covered blood samples taken during 2011-13 from more than 4,800 late-middle-aged participants in the Atherosclerosis Risk in Communities (ARIC) study, a large epidemiological study of heart disease-related risk factors and outcomes that has been running in four U.S. communities since 1985. Collaborating researchers at a laboratory technology company called SomaLogic used a technology they recently developed, SomaScan, to record levels of nearly 5,000 distinct proteins in the banked ARIC samples.

The researchers analyzed the results and found 38 proteins whose abnormal levels were significantly associated with a higher risk of developing Alzheimer’s in the five years following the blood draw.

They then used SomaScan to measure protein levels from more than 11,000 blood samples taken from much younger ARIC participants in 1993-95. They found that abnormal levels of 16 of the 38 previously identified proteins were associated with the development of Alzheimer’s in the nearly two decades between that blood draw and a follow-up clinical evaluation in 2011-13.

To verify these findings in a different patient population, the scientists reviewed the results of an earlier SomaScan of blood samples taken in 2002-06 during an Icelandic study. That study had assayed proteins including 13 of the 16 proteins identified in the ARIC analyses. Of those 13 proteins, six were again associated with Alzheimer’s risk over a roughly 10-year follow-up period.

In a further statistical analysis, the researchers compared the identified proteins with data from past studies of genetic links to Alzheimer’s. The comparison suggested strongly that one of the identified proteins, SVEP1, is not just an incidental marker of Alzheimer’s risk but is involved in triggering or driving the disease.

SVEP1 is a protein whose normal functions remain somewhat mysterious, although in a study published earlier this year it was linked to the thickened artery condition, atherosclerosis, which underlies heart attacks and strokes.

Other proteins associated with Alzheimer’s risk in the new study included several key immune proteins–which is consistent with decades of findings linking Alzheimer’s to abnormally intense immune activity in the brain.

The researchers plan to continue using techniques like SomaScan to analyze proteins in banked blood samples from long-term studies to identify potential Alzheimer’s-triggering pathways–a potential strategy to suggest new approaches for Alzheimer’s treatments.

The scientists have also been studying how protein levels in the ARIC samples are linked to other diseases such as vascular (blood vessel-related) disease in the brain, heart and the kidney.

First author Keenan Walker, PhD, worked on this analysis while on faculty at the Johns Hopkins University School of Medicine and the Bloomberg School’s Welch Center for Prevention, Epidemiology and Clinical Research. He is currently an investigator with the National Institute of Aging’s Intramural Research Program.

“Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk” was co-authored by Keenan Walker, Jingsha Chen, Jingning Zhang, Myriam Fornage, Yunju Yang, Linda Zhou, Morgan E. Grams, Adrienne Tin, Natalie Daya, Ron Hoogeveen, Aozhou Wu, Kevin Sullivan, Peter Ganz, Scott Zeger, Elias Gudmundsson, Valur Emilsson, Lenore Launer, Lori Jennings, Vilmundur Gudnason, Nilanjan Chatterjee, Rebecca Gottesman, Thomas Mosley, Eric Boerwinkle, Christie Ballantyne, and Josef Coresh.

Source:

Johns Hopkins University Bloomberg School of Public Health

Journal reference:

Walker, K. A., et al. (2021) Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk. Nature Aging. doi.org/10.1038/s43587-021-00064-0.

High vs Low, Normal Range

A prolactin (PRL) test measures how much of a hormone called prolactin you have in your blood. The hormone is made in your pituitary gland, which is located just below your brain.

When women are pregnant or have just given birth, their prolactin levels increase so they can make breast milk. But it’s possible to have high prolactin levels if you’re not pregnant, and even if you’re a man.

Your doctor may order a prolactin test when you report having the following symptoms:

For women

For men

Decreased sex drive
Difficulty in getting an erection
Breast tenderness or enlargement
Breast milk production (very rare)

For both

Causes of Abnormal Prolactin Levels

Normally, men and nonpregnant women have just small traces of prolactin in their blood. When you have high levels, this could be caused by:

Also, kidney disease, liver failure, and polycystic ovarian syndrome (a hormone imbalance that affects ovaries) all can affect the body’s ability to remove prolactin.

How the Test Is Done

You don’t need to make any special preparations for a prolactin test. You will get a blood sample taken at a lab or a hospital. A lab worker will insert a needle into a vein in your arm to take out a small amount of blood.

Some people feel just a little sting. Others might feel moderate pain and see slight bruising afterwards.

After a few days, you’ll get the results of your prolactin test in the form of a number.

The normal range for prolactin in your blood are:

Males: 2 to 18 nanograms per milliliter (ng/mL)
Nonpregnant females: 2 to 29 ng/mL
Pregnant females: 10 to 209 ng/mL

If Your Prolactin Levels Are High

If your value falls outside the normal range, this doesn’t automatically mean you have a problem. Sometimes the levels can be higher if you’ve eaten or were under a lot of stress when you got your blood test.

Also, what’s considered a normal range may be different depending on which lab your doctor uses.

If your levels are very high — up to 1,000 times the upper limit of what’s considered normal — this could be a sign that you have prolactinoma. This tumor is not cancer, and it is usually treated with medicine. In this case, your doctor may want you to get an MRI.

You’ll lie inside a magnetic tube as the MRI device uses radio waves to put together a detailed image of your brain. It will show whether there’s a mass near your pituitary gland and, if so, how big it is.

If Your Levels Are Low

If your prolactin levels are below the normal range, this could mean your pituitary gland isn’t working at full steam. That’s known as hypopituitarism. Lower levels of prolactin usually do not need medical treatment.

Certain drugs can cause low levels of prolactin. They include:

Dopamine (Intropine), which is given to people in shock
Levodopa (for Parkinson’s disease)
Ergot alkaloid derivatives (for severe headaches)

Treatment

Not all cases of high prolactin levels need to be treated.

Your treatment will depend on the diagnosis. If it turns out to be a small prolactinoma or a cause can’t be found, your doctor may recommend no treatment at all.

In some cases, your doctor may prescribe medicine to lower prolactin levels. If you have a prolactinoma, the goal is to use medicine to reduce the size of the tumor and lower the amount of prolactin.

Cholesterol Testing and the Lipid Panel

Cholesterol is a form of fat we need. It helps make the outer membranes of our bodies’ cells stable. But for decades, doctors have known that people with high total cholesterol levels are more likely to get heart disease. They’ve also found that the different forms of cholesterol (“good” and “bad”) play a role. High total cholesterol, high bad cholesterol, or low good cholesterol could raise your chances.

For example, low-density lipoprotein (LDL), or “bad” cholesterol, can stick to blood vessel walls. Over time, it can play a role in clogging arteries in a process called atherosclerosis. Narrowed arteries in your heart can then develop sudden blood clots, causing heart attacks.

Triglycerides are another fat that doctors measure with cholesterol testing. High levels can raise your chances of having a heart attack or stroke . This is especially true when you have low levels of “good” cholesterol, called high-density lipoprotein (HDL). High triglyceride levels also make you more likely to develop diabetes.

The American Heart Association recommends that everyone over age 20 get a cholesterol test so you know what your levels are and can do something about them if you need to.

Cholesterol Tests: The Good, the Bad, and the Fatty

The different kinds of cholesterol and other fats in your blood are together called lipids. Doctors measure and diagnose lipid problems with a simple blood test. Some doctors ask you to fast for 9 to 12 hours before it to make sure it’s not affected by any food you recently ate. But not all situations require fasting. You may not need it if you’re younger than 25, or if you require only a partial lipid panel, or if your doctor is looking for a “non-fasting” result.

In particular, some doctors are especially interested in “non-fasting” triglyceride levels, but it is not yet clear how this helps calculate risk for heart disease and other cholesterol-related illnesses. Ask your health care provider if you need to fast for your test.

A lipid profile usually gives results for four different types:

Total cholesterol
LDL (low-density lipoprotein), the “bad cholesterol”
HDL (high-density lipoprotein), the “good cholesterol”
Triglycerides, the most common type of fat in your body

Some lipid panels can give even more detailed information, like the presence and sizes of various fat particles in your blood. Researchers are looking into what, if any, effect these traits have on heart disease. There are no clear guidelines on when this more advanced testing is needed.

Your Cholesterol Test Results

Once you’ve had your test, what do the numbers mean?

For total cholesterol:

200 milligrams per deciliter (mg/dL) or less is normal.
201 to 240 mg/dL is borderline.
More than 240 mg/dL is high.

For HDL (“good cholesterol”), more is better:

60 mg/dL or higher is good — it protects against heart disease.
40 to 59 mg/dL is OK.
Less than 40 mg/dL is low, raising your chance of heart disease.

For LDL (“bad cholesterol”), lower is better:

Less than 100 mg/dL is ideal.
100 to 129 mg/dL can be good, depending on your health.
130 to 159 mg/dL is borderline high.
160 to 189 mg/dL is high.
190 mg/dL or more is very high.

For triglycerides, lower is better:

150 mg/dL or less may be the goal your doctor recommends, though the American Heart Association suggests that a lower level is best for health.
151 to 200 mg/dL means you’re on your way to a higher risk for heart disease.
More than 200 mg/dL means you have a higher risk of heart disease.

Your doctor will consider your overall likelihood of heart disease to set your personal LDL goal. For people who are at higher risk of heart disease or who already have it, your LDL should be less than 100 mg/dL. (Your heart doctor might recommend an even lower LDL — less than 70 mg/dL — if your risk of heart disease is very high.)

If you have a moderately high chance of heart disease, an LDL less than 130 mg/dL is your target. If your risk of heart problems is fairly low, less than 160 mg/dL is probably fine.

What You Can Do About Abnormal Lipid Levels

Lifestyle changes are the first thing to tackle to reduce your chance of heart disease. Your doctor may also recommend that you start taking prescription drugs to help your cholesterol level.

Lifestyle habits to lower cholesterol

A cholesterol-lowering diet can bring down bad cholesterol by up to 30%. A diet low in saturated fat and simple carbohydrates and that has no more than 200 miliigrams of cholesterol daily can lower LDL cholesterol. Fiber and plant sterols (found in special margarines and other foods) help, too.

Keep these dietary tips in mind:

Cut saturated fat to less than 7% of your total calories.
Avoid trans fat completely. Check the ingredients label for “partially hydrogenated” oils. Those are trans fats. Even if a product says “0 grams trans fat,” it can have a small amount of trans fat (less than half a gram per serving), and that adds up.
Read food labels. Products that say “low cholesterol” or “no cholesterol” could be too high in saturated fats or sugar.

Regular aerobic exercise can lower bad cholesterol (LDL) and raise good cholesterol (HDL). If you smoke, quit.

Lifestyle changes such as diet, exercise, and weight loss are also effective ways to improve your triglyceride levels. Ask your doctor for a sensible diet that will help. If you smoke, get suggestions on ways to help you quit.

Medications and procedures

If lifestyle changes don’t lower cholesterol levels enough, you can try medications or a combination of treatments. If you stick with your new healthy habits, however, you may be able to work with your doctor to reduce the amount of medicine you take or stop it altogether.

Your doctor may prescribe:

Statins. These are the most effective and commonly used cholesterol drugs. They block your liver’s ability to make cholesterol. They usually don’t cause problems, but in rare instances, they can damage the liver and muscle. Because of this, your doctor will do blood tests to check your liver function after you start treatment and if there are any signs of problems. There have also been reports of memory loss and a small increased risk of type 2 diabetes. The benefits may outweigh the risks, so talk with your doctor about them.

Statins available in the U.S. are:

Niacin. Doctors may prescribe this to help raise HDL (“good”) cholesterol. To be effective, it must be taken in large doses. In these amounts, it often causes skin flushing and an upset stomach. Newer versions of niacin made to minimize these side effects may be easier to take. Despite its effects on cholesterol levels, an important scientific study recently found that adding niacin to statin therapy did not lower the risk of heart problems.

Fibrates. Doctors sometimes prescribe fibric acid derivatives, fibrates, to raise HDL cholesterol and lower triglyceride levels. They also mildly lower LDL.

Ezetimibe (Zetia). This drug limits the amount of cholesterol the small intestine can absorb. People who take it also usually take a statin, which can reduce cholesterol another 25%. Zetia is controversial, however, because of less evidence that it lowers the risk of heart attack or death from heart disease.

Bile acid sequestrants. Also known as cholestyramine and colestipol, these may lower total and LDL cholesterol in some people. Side effects include bloating, gas, and constipation. If your cholesterol level can’t be controlled by using medication, your doctor may try to combine a bile acid sequestrant and a statin.

PCSK9 inhibitors. This is a newer class of cholesterol-lowering drugs that’s used in patients with in heterozygous familial hypercholesterolemia who cannot control their cholesterol through diet and statin treatments. It’s also used in those with clinical atherosclerotic heart disease. The drugs alirocumab (Praluent) or evolocumab (Repatha) block the liver protein PCSK9, which hinders the liver’s ability to remove LDL-cholesterol from the blood. This reduces the amount of bad cholesterol in the bloodstream. Evolocumab in particular, has proven to be effective in lowering the risk of heart attack and strokes in people who have cardiovascular disease.

Triglyceride medications. Your doctor may also prescribe medicine if your triglyceride number is above 500 mg/dL. You may need to take these meds for a long time to keep your triglyceride levels out of the danger zone.

LDL apheresis. This isn’t a drug. It’s a blood-cleansing procedure that may help with severe genetic cholesterol disorders. Over several hours, blood is removed from the body, chemically cleansed of LDL cholesterol, and then returned to the body. Treatments every 2 to 3 weeks can cut average LDL cholesterol by 50% to 80%, but they’re costly in both time and money.

Other Risks and Follow-up Testing

Your cholesterol numbers don’t determine your destiny. Remember, other things besides cholesterol can also lead to heart disease. Diabetes, smoking, high blood pressure, obesity, exercise, and genetics are important as well.

People with normal cholesterol can have heart disease; people with high cholesterol can have healthy hearts. Overall, though, more people whose cholesterol levels are off will get heart disease.

Experts recommend follow-up cholesterol testing every 5 years for most people. If your lipid results aren’t what you and your doctor had hoped for, or if you have other reasons to be concerned about heart disease, you’ll need cholesterol tests more often.

Plasma protein tests: how to interpret abnormal results | Hot topic

Read this article to learn more about:

constituents of plasma protein and their functions in the body

when plasma protein tests are required and what information they provide

techniques used for the identification of specific proteins and antibodies.

Key points

Implementation actions for STPs and ICSs

Guidelines Learning

After reading this article, ‘ Test and reflect ’ on your updated knowledge with our multiple-choice questions. We estimate that this activity will take you 30 minutes—worth 0.5 CPD credits.

Plasma protein is the collective term for the proteins present in the blood. Plasma proteins fall into several different groups and have numerous functions, including maintaining osmotic pressure, and transporting lipids, hormones, vitamins, and minerals. Some plasma proteins are enzymes, while others have functions in blood clotting and the immune system. Excluding immunoglobulins, all major blood proteins are synthesised in the liver.

The total protein test gives an approximate measure of all plasma protein (excluding fibrinogen when testing is on clotted samples). With a typical reference range of 60–80 g/l,¹ plasma proteins constitute around 7% of plasma by weight² and 0. 5% of total body mass.

Serum albumin accounts for around 55% of plasma protein (typical reference range: 35–55 g/l).^3,4 It maintains the osmotic pressure of plasma and functions in the transport of calcium, lipids, and steroid hormones.

Globulins make up approximately 35% of plasma protein (typical reference range: 20–35 g/l).^5,6 Globulins are involved in a range of processes including transport of ions, hormones, and lipids; acute-phase responses; and, as immunoglobulins, immune response. Globulins and are divided into four subgroups:²

alpha₁ (comprising mainly alpha₁ antitrypsin)

alpha₂ (including haptoglobin and ceruloplasmin)

beta (comprising transferrin and some complement components)

gamma (predominantly immunoglobulins and C-reactive protein [CRP]).

Fibrinogen is a soluble protein which constitutes around 6. 5% of plasma protein.⁷ Conversion of fibrinogen to the insoluble protein fibrin, is a process central to blood clotting.

The remaining plasma proteins comprise hundreds of distinct protein molecules. Individually, they are present in small amounts, but together they make up approximately 1% of plasma protein, and have crucial roles as regulatory proteins such as enzymes, proenzymes, and hormones.⁸

Reasons for protein measurement in practice

Plasma proteins are heterogenous in nature and involved in many complex functions within the body. Abnormalities in plasma proteins may be primary (the cause of specific pathologies) or secondary (the result of a wide range of disease processes). Abnormal proteinuria can also result from various medical conditions.

The reasons why a GP may request measurement of plasma protein include investigations of symptoms, allergies, and immunity (see Box 1).

Box 1: Plasma protein measurement in practice⁹

A GP may request measurement of plasma protein when:

investigating a specific symptom, such as peripheral oedema

diagnosing an inflammatory process or autoimmune disorder (for example, antinuclear antibody testing in the assessment of systemic lupus erythematosus [SLE])

diagnosing bone marrow disorders, including multiple myeloma

assessing allergies

testing for immunodeficiency in patients with recurrent infections

assessing immunity to infections, such as hepatitis B or rubella, through specific antibody assays

investigating possible coeliac disease through the measurement of total immunoglobulin A (IgA) and IgA tissue transglutaminase antibody.

Liver panel tests, for example, those requested as part of drug monitoring, may reveal protein abnormalities that require further investigation.¹⁰

Pregnancy-associated plasma protein A (PAPP-A) assessment, together with plasma human chorionic gonadotropin (hCG) measurement and nuchal translucency ultrasound (together known as first-trimester screening), is offered in early pregnancy (10–14 weeks) to assess the risk of a foetal chromosomal disorder such as Down’s syndrome (trisomy 21) or Edwards’ syndrome (trisomy 18).¹¹

Testing urine for protein may assist in the diagnosis of urinary infection, primary renal disease including nephrotic syndrome, secondary renal disease for example in diabetes, multiple myeloma, and pre-eclampsia in pregnancy.¹²

Liver panel blood tests (liver function tests)

‘Routine’ liver panel testing typically includes measurement of total protein and albumin. ¹⁰ Total protein is a measure of both serum albumin and globulin, so test results outside the reference range may represent abnormal levels of either one or both of these components. The conditions associated with abnormal globulin and albumin levels are detailed below and summarised in Table 1.

Decreased globulin levels as a fraction of total protein are seen in individuals with malnutrition and patients with nephrotic syndrome when there is renal protein loss. High total protein levels associated with increased globulin may be seen in dehydration, in response to acute infections such as pneumonia and hepatitis, and in chronic inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus (SLE). Other causes include Waldenström macroglobulinaemia, a type of non-Hodgkin lymphoma in which abnormal cells synthesise large amounts of macroglobulin, and multiple myeloma, a malignant neoplasm of plasma cells characterised by excessive synthesis of monoclonal globulin that can usually be detected in blood and urine. ⁹

Albumin is only synthesised in the liver and serum albumin level may be reduced when the liver’s synthetic function is significantly impaired, for example in long-standing liver disease or advanced cirrhosis. Other causes of a low serum albumin level include severe malnutrition (which may accompany alcohol-related liver disease). Low serum albumin may also be evident when there is protein malabsorption, for example in Crohn’s disease, or when excessive protein is being lost, for example from the gut in protein-losing enteropathy, through the skin in exfoliating dermatitis or after severe burns, or from the kidney in nephrotic syndrome. Severe inflammatory conditions or shock may also be associated with low serum albumin levels, when a catabolic state develops and the synthetic function of the liver switches to the production of other proteins. An important symptom of low serum albumin is the development of peripheral oedema. High serum albumin levels generally reflect dehydration. ⁴

Table 1: Conditions associated with abnormal globulin and albumin levels^4,9
Serum protein	Levels	Associated conditions
Globulin	Decreased	Malnutrition Nephrotic syndrome with renal protein loss
Globulin	Increased	Dehydration Acute infections, such as pneumonia or hepatitis Chronic inflammatory conditions, such as rheumatoid arthritis or SLE Waldenström macroglobulinaemia Multiple myeloma
Albumin	Decreased	Long-standing liver disease including advanced cirrhosis Severe malnutrition (which may accompany alcohol-related liver disease) Conditions involving protein malabsorption, such as Crohn’s disease Conditions involving excessive protein loss, for example from the gut in protein-losing enteropathy, the skin in exfoliating dermatitis/after severe burns, or the kidney in nephrotic syndrome Severe inflammatory conditions Shock
Albumin	Increased
SLE=systemic lupus erythematosus

Urine protein testing

Some loss of protein by the kidneys is normal, at levels of up to 150 mg/day. Causes of transient elevated proteinuria include:¹³

strenuous exercise

febrile illness

urinary tract infection

orthostatic proteinuria (rare after the age of 30 years)

pregnancy.

Urine may test falsely positive for protein when the sample has been contaminated by vaginal mucous. Causes of persistent proteinuria include:¹³

primary kidney disease, including nephrotic syndrome and glomerulonephritis

secondary renal disease, for example, that associated with diabetes and hypertension.

If serum albumin is low and nephrotic syndrome is suspected, testing the urine for protein will help inform the diagnosis.¹⁴ If total protein and globulins are high and multiple myeloma or Waldenström macroglobulinaemia are possible differential diagnoses, dipstick testing for protein followed by measurement of Bence Jones protein (a monoclonal protein found in the urine) may be useful. ⁹

C-reactive protein

C-reactive protein is an acute-phase reactant; a protein synthesised by the liver and released into the blood in response to tissue injury, infection, or other inflammatory processes. Its physiological role is thought to involve binding to the surface of dead or dying cells (and some types of bacteria) to activate the complement system.

C-reactive protein may be acutely raised:¹⁵

following myocardial infarction

in sepsis

in tissue trauma

after surgery.

In infection or acute inflammation, a patient’s CRP level may rise before the onset of clinical symptoms.

Chronic inflammatory conditions, including rheumatoid arthritis, seronegative arthritides such as Reiter’s syndrome, vasculitic syndromes, and inflammatory bowel disease (although levels tend to be higher in Crohn’s disease than in ulcerative colitis), are also associated with a raised CRP level. However, SLE produces almost no increase in CRP unless there is coincident infection. In chronic inflammatory conditions, CRP level can be valuable in monitoring disease activity, with high levels suggestive of an acute exacerbation or ineffective treatment and falling or low levels indicative of remission.¹⁶

Raised CRP is a feature of infection or inflammation, but it is a non-specific marker of an acute response.¹⁶ Clinical history, examination, and specific diagnostic tests are needed to establish the cause of raised CRP. C-reactive protein typically returns to normal when the acute infective or inflammatory process is resolved.

Protein electrophoresis

Although standard liver panel tests and on-site urine protein testing give a general indication of protein levels, protein electrophoresis can be used to separate the mixture of proteins present in either plasma or urine into subdivisions to provide additional diagnostic information.⁹ In this process, an electric current is used to move the protein mixture across a thin layer of gel. The distance travelled by each protein depends on a range of variables, including its molecular size and electrical charge. The separated proteins are then visualised using a stain, which reveals a characteristic pattern of bands. Serum proteins are separated into six major groups by protein electrophoresis: albumin and alpha₁, alpha₂, beta₁, beta₂, and gamma globulins. The size of each band gives a qualitative indication of the amount of that protein fraction. This pattern of bands is often converted into a graph, with vertical spikes or peaks where there are large amounts of protein and smaller peaks or valleys where there are small amounts of protein.

Abnormal electrophoresis patterns are associated with a variety of different pathological conditions.

Increased gamma fraction

When the gamma fraction is increased, spike-like monoclonal increase is suggestive of malignant or pre-malignant clonal conditions such as multiple myeloma and Waldenström macroglobulinaemia, whereas a broader-based, polyclonal increase typically reflects a more general inflammatory response. ¹⁷ Although a monoclonal increase may be of concern, the most common cause is monoclonal gammopathy of uncertain significance (MGUS), which is generally benign but may progress to a malignant condition over time. The most common elevation in gamma globulin levels is polyclonal and typically due to increased immune system activity caused by acute or chronic infection, tissue damage or autoimmune connective tissue diseases such as rheumatoid arthritis, SLE, scleroderma, chronic active autoimmune hepatitis, and primary biliary cholangitis.⁹

Causes of low immunoglobulin levels include:⁹

congenital and acquired immunodeficiency syndromes

other conditions associated with reduced immunoglobulin production, such as protein malnutrition

conditions causing excessive loss of immunoglobulins, such as sepsis, nephrotic syndrome, burns, and protein-losing enteropathy.

Increased alpha fraction

Isolated alpha₁ abnormalities are usually due to changes in alpha₁ antitrypsin, with decreased levels occurring in congenital alpha₁ antitrypsin deficiency. Increased levels may be found in acute inflammatory disorders.⁹

Alpha₂ macroglobulin levels may be raised in nephrotic syndrome and haptoglobin levels are increased in stress, infection, inflammation, and tissue necrosis. Haptoglobin levels may be decreased in haemolytic conditions.⁹

Increased beta fraction

Beta globulin level may be raised in severe iron deficiency when there are high levels of transferrin. It may be decreased in malnutrition and cirrhosis.⁹

Immunofixation electrophoresis and enzyme immunoassays

When required, specific proteins can be identified using one of a family of tests termed immunofixation electrophoresis.⁹ In these tests, proteins are first separated by electrophoresis and then reacted with a specific antibody. If the antibody reacts with the protein being investigated, the antibody–protein complex remains in the gel while other proteins are washed away, allowing the protein to be identified and quantified. This technique is useful in the assessment of multiple myeloma.

Immunoglobulin E (IgE) antibodies to specific antigens can be measured using the radioallergosorbent testing (RAST) or enzyme-linked immunosorbent assay (ELISA) techniques. These techniques are valuable in the assessment of allergies, for example when there is a risk of anaphylaxis.⁹

A range of other techniques, including enzyme immunoassays, can be used to quantify the serum levels of specific antibodies, such as rubella and hepatitis B antibodies. These techniques are used both to diagnose current infection and to confirm the presence of immunity. A preparation of a specific antigen (for example, hepatitis B surface antigen) is incubated with a specimen of a patient’s serum. If the antibody under investigation is present, it will become coupled to the antigen. Analytic processes are then used to quantify the amount of antibody present in the serum.¹⁸

Conclusion

Plasma proteins have myriad functions and metabolic roles. Abnormalities in their levels can be associated with a range of morbidities, either as a primary cause or as a secondary effect. Understanding of the tests available provides the physician with useful diagnostic tools.

Dr Jez Thompson

RCGP/British Liver Trust Clinical Champion for Liver Disease Clinical Director, Bevan Healthcare

Guidelines Learning

After reading this article, ‘ Test and reflect ’ on your updated knowledge with our multiple-choice questions. We estimate that this activity will take you 30 minutes—worth 0.5 CPD credits.

Key points

Abnormalities in plasma proteins may be the cause of specific pathologies, or result from a wide range of disease processes
Albumin levels may be:
decreased in cirrhosis, severe malnutrition, protein-losing enteropathy, and nephrotic syndrome

increased in dehydration

Globulin levels may be:
decreased in malnutrition and nephrotic syndrome

increased in dehydration, acute infections, chronic inflammatory conditions, Waldenström macroglobulinaemia, and multiple myeloma

Causes of transient proteinuria include strenuous exercise, febrile illness, urinary tract infection, orthostatic proteinuria, and pregnancy, whereas causes of persistent proteinuria include primary and secondary renal disease, multiple myeloma, and Waldenström macroglobulinaemia

First-trimester screening in early pregnancy, which is used to assess the risk of specific chromosome abnormalities, comprises plasma PAPP-A and hCG measurement and nuchal translucency ultrasound

Levels of CRP can acutely increase:
following myocardial infarction or surgery

in sepsis or tissue trauma

during chronic inflammatory conditions such as rheumatoid arthritis

Raised CRP is a non-specific marker of infection or inflammation; clinical history taking, examination, and specific diagnostic tests are needed to establish its cause

Protein electrophoresis can be used to separate the proteins present in plasma or urine into six component groups:
polyclonal raised gamma globulin is seen in infectious and inflammatory conditions

monoclonal rises are a feature of MGUS, multiple myeloma, and Waldenström macroglobulinaemia

Immunofixation electrophoresis can be used to identify specific types of immunoglobulin, which is useful in confirming a diagnosis of multiple myeloma

IgE antibodies for specific allergens can be measured using RAST or ELISA, which can be valuable in the assessment of allergies

Enzyme immunoassays can be used to:
identify and quantify immunoglobulins produced in response to specific antigens

diagnose acute and chronic infections, such as hepatitis B infection

establish immunity, for example to rubella.

PAPP-A=pregnancy-associated plasma protein; hCG=plasma human chorionic gonadotropin; CRP=C-reactive protein; MGUS=monoclonal gammopathy of uncertain significances; IgE=immunoglobulin E; RAST=radioallergosorbent testing; ELISA=enzyme-linked immunosorbent assay

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources.

Create an online pathology handbook and clinical algorithm tool that can be accessed by all clinicians who request blood sampling:
list available tests with the indications for ordering them and guides to interpretation of results

link the handbook to any online electronic pathology ordering system that is used in the STP area

define any required tests in referral management systems and if possible link these electronically to the handbook

Audit and monitor requests for pathology samples to check these are being made appropriately and represent an efficient use of resources.

STP=sustainability and transformation partnership; ICS=integrated care system

References

Association for Clinical Biochemistry and Laboratory Medicine. Analyte monographs alongside the National Laboratory Medicine catalogue (AMALC): total protein. Available at: www.acb.org.uk/docs/default-source/committees/scientific/amalc/total-protein.pdf (accessed 10 July 2018).

Rote N, McCance K. Structure and function of the hematologic system. In: McCance K, Huether S, editors. Pathophysiology: the biologic basis for disease in adults and children, 7 edition. Amsterdam: Elsevier Health Sciences, 2013: 946.

Anderson N, Anderson N. The human plasma proteome: history, character, and diagnostic prospects. Molecular & Cellular Proteomics 2002; 1 (11): 845–867.

Association for Clinical Biochemistry and Laboratory Medicine. Analyte monographs alongside the National Laboratory Medicine catalogue (AMALC): albumin. Available at: www.acb.org.uk/docs/default-source/committees/scientific/amalc/albumin.pdf

Chambers D, Huang C, Matthews G. Blood and immune system: plasma constituents. In: Chambers D, Huang C, Matthews G. Basic physiology for anaesthetists. Cambridge: Cambridge University Press, 2015: 366.

US National Library of Medicine, Medline Plus. Medical encyclopedia: serum globulin electrophoresis. Available at: medlineplus.gov/ency/article/003544.htm (accessed 10 July 2018).

Biochem Den. Plasma proteins: types and functions (basic notes). Available at: www.biochemden.com/plasma-proteins/ (accessed 10 July 2018).

Tripathi Y. Blood and plasma proteins. In: Tripathi Y. Concise textbook of physiology for dental students. Chennai: Elsevier India, 2011: 93.

Harding M. Globulins. Patient website, 2014. Available at: patient.info/doctor/globulins (accessed 10 July 2018).

Lab Tests Online UK. Liver function tests. Available at: www.labtestsonline.org.uk/tests/liver-function-tests (accessed 10 July 2018).

Shiefa S, Amargandhi M, Bhupendra J et al. First trimester maternal serum screening using biochemical markers PAPP-A and free beta-hCG for Down syndrome, Patau syndrome and Edward syndrome. Indian J Clin Biochem 2013; 28 (1): 3–12.

Lab Tests Online UK. Urine protein and urine protein to creatinine ratio. Available at: www.labtestsonline.org.uk/tests/urine-protein-and-urine-protein-creatinine-ratio (accessed 10 July 2018).

BMJ Best Practice. Assessment of proteinuria. Available at: bestpractice.bmj.com/topics/en-gb/875 (accessed 10 July 2018).

Hull R, Goldsmith D. Nephrotic syndrome in adults. BMJ 2008; 336 (7654): 1185–1189.

Lab Tests Online UK. C-reactive protein (CRP). Available at: labtestsonline.org.uk/tests/c-reactive-protein (accessed 10 July 2018).

Tidy C. Acute-phase proteins, CRP, ESR and viscosity. Patient website, 2014. Available at: patient.info/doctor/acute-phase-proteins-crp-esr-and-viscosity

O’Connell T, Horita T, Kasravi B. Understanding and interpreting serum protein electrophoresis. Am Fam Physician 2005; 71 (1): 105–112.

Lab Tests Online UK. Laboratory methods. About laboratory methods: enzyme-linked immunosorbent assay (ELISA). Available at: labtestsonline.org.uk/articles/laboratory-test-methods (accessed 1 August 2018).

90,000 Abnormal iron levels in the brain “may be biomarkers of ADHD”

01.12.2014

According to a recent study, the number of children diagnosed with attention deficit hyperactivity disorder in the United States increased by 42% between 2003-04 and 2011-12. was put by mistake . But a new study, published in the journal Radiology , detailed the biomarkers of ADHD, which are identified using new brain imaging technology, which the researchers believe can avoid misdiagnosis.

Attention deficit hyperactivity disorder (ADHD) is a developmental disorder that causes problems with concentration, uncontrollable behavior and hyperactivity. ADHD usually develops during childhood and the condition can persist into adulthood.

According to the research team, including dr. Vitria Adisetiyo, a research associate at the University of South Carolina, had many concerns about the rise in ADHD diagnoses in the United States, especially as about two-thirds of these diagnosed children were receiving psychostimulants such as Ritalin for treatment.

Psychostimulants are prescribed in order to regulate impulsive behavior and increase the duration of attention span. But these drugs also raise levels of dopamine in the brain, a neurotransmitter associated with drug addiction, which can increase the likelihood of drug abuse.

In a recent study, the researchers set out to find a way to avoid being overdiagnosed with ADHD so that children and adolescents do not take stimulants when not needed.

Patients with ADHD “may have abnormal absorption of iron in the brain”

The research team set out to determine if iron levels in the brain are a potential biomarker for diagnosing ADHD.

In 2006, a study by Dr. Joseph Helpern and Jens Jensen developed a new MRI technique called magnetic field correlation imaging.

Using this technique, the researchers measured brain iron levels in 22 children and adolescents with ADHD and 27 children and adolescents without ADHD.Of the ADHD patients, 12 did not receive psychostimulant medications. The level of iron in the blood of patients from the study group was also determined.

The results of the study showed that 12 patients with ADHD who did not take psychostimulants had much lower levels of iron in the brain compared to both those patients who took psychostimulants and in the control group of healthy children.

In fact, scientists found that ADHD patients who took psychostimulants had the same iron levels in the brain as healthy children, suggesting that psychostimulant use can normalize iron levels in the brain.

Our study suggests that iron absorption in the brain may be abnormal in ADHD patients, given that atypical levels of iron in the brain occur even when blood iron levels are normal, ”explains Dr. Adisetiyo.“ We found no difference in the level of iron in the blood in patients taking or not taking psychostimulants

Dr. Adisetiyo notes that at present, the diagnosis of ADHD is made only on the basis of clinical examination and the subjective assessment of the doctor.Therefore, according to the research team, their magnetic field correlation imaging technique can be used to improve the diagnosis and treatment of ADHD by detecting low levels of iron in the brain.

They note that if their findings are replicated in additional studies, this imaging technique can be used to identify patients who can actually benefit from psychostimulants and exclude those who do not need psychostimulants.

Dr. Adisetiyo adds:

We want the public to know that progress in identifying potential non-invasive biomarkers of ADHD can help prevent misdiagnosis. We are now testing our findings in a larger cohort of data to confirm that measuring brain iron levels in ADHD patients is indeed a reliable and clinically relevant biomarker.

Smolenskaya Gazeta – In Smolensk, a yellow level of weather hazard was declared due to anomalous heat

Habitat

Forecasters of the Hydrometeorological Center of Russia announced on Friday in the territory of the Smolensk region a yellow level of weather hazard due to an abnormally high temperature.This follows from the data of the predictive warning map for the Central Federal District on the institution’s website.

“ Very high temperature. The degree of intensity of dangerous phenomena: yellow – the weather is potentially dangerous “, – the message says.

It is noted that in some places the maximum air temperature will reach 32 degrees Celsius. The warning period for adverse weather events in Smolensk and the region is valid today, July 9, from 13:00 to 19:00.

As a reminder, the third class of fire hazard has also been established on the territory of the region, an increase to 4 (high) class is expected.In this regard, the risk of forest fires increases dramatically.

Photo: 67.mchs.gov.ru

Maria Obraztsova

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In Smolensk, an illegally installed football goal is being dismantled

In Smolensk, on Nikolaev Street, unauthorized garages will be demolished

90,000 How Moscow residents flee from the abnormal heat.Photo report – RBK

The heat in Moscow is breaking records. On June 22, the maximum air temperature for this date was recorded since 1917 – 33.7 degrees.In the metropolitan area, the orange level of weather hazard has been extended. How Moscow residents flee from the heat in parks and fountains – in a photo report by RBC