What Is Inflammation? What Causes Inflammation?

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Main Category: Pain / Anesthetics
Also Included In: Bones / Orthopedics;  Immune System / Vaccines;  Arthritis / Rheumatology
Article Date: 31 Jul 2012 – 0:00 PDT

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Inflammation is the body’s attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens – and begin the healing process. When something harmful or irritating affects a part of our body, there is a biological response to try to remove it, the signs and symptoms of inflammation, specifically acute inflammation, show that the body is trying to heal itself.
Inflammation does not mean infection, even when an infection causes inflammation. Infection is caused by a bacterium, virus or fungus, while inflammation is the body’s response to it.

The word inflammation comes from the Latin “inflammo”, meaning “I set alight, I ignite”.

Inflammation is part of the body’s immune response. Initially, it is beneficial when, for example, your knee sustains a blow and tissues need care and protection. However, sometimes inflammation can cause further inflammation; it can become self-perpetuating. More inflammation is created in response to the existing inflammation.

According to Medilexicon’s medical dictionary, Inflammation is:

“A fundamental pathologic process consisting of a dynamic complex of histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent, including the local reactions and resulting morphologic changes; the destruction or removal of the injurious material; and the responses that lead to repair and healing.

The so-called cardinal signs of inflammation are rubor, redness; calor, heat (or warmth); tumor, swelling; and dolor, pain; a fifth sign, functio laesa, inhibited or lost function, is sometimes added. All these signs may be observed in certain instances, but none is necessarily always present.”

Inflammation helps wounds heal

Wrist inflammation
Our immediate reaction to a swelling is to try to bring it down. Bearing in mind that inflammation is an essential part of the body’s attempt to heal itself, patients and doctors need to be sure that the treatments to reduce swelling are absolutely necessary and to not undermine or slow down the healing process.

The first stage of inflammation is often called irritation, which then becomes inflammation – the immediate healing process. Inflammation is followed by suppuration (discharging of pus). Then there is the granulation stage, the formation in wounds of tiny, rounded masses of tissue during healing. Inflammation is part of a complex biological response to harmful stimuli. Without inflammation, infections and wounds would never heal.

Neuroscientists at the Lerner Research Institute at the Cleveland Clinic in Ohio found that inflammation actually helps to heal damaged muscle tissue. Their findings clash with how sportspeople with inflammation are treated – health professionals always try to control the inflammation to encourage healing. The researchers say their findings may lead to new therapies for acute muscle injuries caused by freeze damage, medications, chemicals and trauma.

Lan Zhou, M.D., Ph.D., said that patients should be very closely monitored when therapies to combat inflammation are used to make sure that the benefits of inflammation are not completely eliminated.

Inflammation is part of our innate immunity

Our innate immunity is what is naturally present in our bodies when we are born, and not the adaptive immunity we get after an infection or vaccination. Innate immunity is generally non-specific, while adaptive immunity is specific to one pathogen:

Whooping cough vaccine – example of immunity being specific to one pathogen

    After being vaccinated for whooping cough (pertussis), we develop immunity to Bordetella pertussis or Bordetella parapertussis, types of bacteria that cause pertussis. This is an example of adaptive immunity – the immunity was not there before receiving the vaccine.

Inflammation is seen as a mechanism of innate immunity.

What is the difference between chronic inflammation and acute inflammation?

Acute inflammation – starts rapidly (rapid onset) and quickly becomes severe. Signs and symptoms are only present for a few days, but in some cases may persist for a few weeks.

Examples of diseases, conditions, and situations which can result in acute inflammation include: acute bronchitis, infected ingrown toenail, sore throat from a cold or flu, a scratch/cut on the skin, exercise (especially intense training), acute appendicitis, acute dermatitis, acute tonsillitis, acute infective meningitis, acute sinusitis, or a blow.

Chronic inflammation – this means long-term inflammation, which can last for several months and even years. It can result from:

  • Failure to eliminate whatever was causing an acute inflammation
  • An autoimmune response to a self antigen – the immune system attacks healthy tissue, mistaking it (them) for harmful pathogens.
  • A chronic irritant of low intensity that persists

Examples of diseases and conditions with chronic inflammation include: asthma, chronic peptic ulcer, tuberculosis, rheumatoid arthritis, chronic periodontitis, ulcerative colitis and Crohn’s disease, chronic sinusitis, and chronic active hepatitis (there are many more).

Our infections, wounds and any damage to tissue would never health without inflammation – tissue would become more and more damaged and the body, or any organism, would eventually perish.

However, chronic inflammation can eventually cause several diseases and conditions, including some cancers, rheumatoid arthritis, atherosclerosis, periodontitis, and hay fever. Inflammation needs to be well regulated.

What happens during acute inflammation?

Within a few seconds or minutes after tissue is injured, acute inflammation starts to occur. The damage may be a physical one, or might be caused by an immune response.

Three main processes occur before and during acute inflammation:

  • Arterioles, small branches of arteries that lead to capillaries that supply blood to the damaged region dilate, resulting in increased blood flow
  • The capillaries become more permeable, so fluid and blood proteins can move into interstitial spaces (spaces between tissues).
  • Neutrophils, and possibly some macrophages migrate out of the capillaries and venules (small veins that go from a capillary to a vein) and move into interstitial spaces. A neutrophil is a type of granulocyte (white blood cell), it is filled with tiny sacs which contain enzymes that digest microorganisms. Macrophages are also a type of white blood cells that ingests foreign material.

    Klaus Ley, M.D., a scientist at the La Jolla Institute for Allergy Immunology, reported in a study published in Nature that neutrophils are the human body’s first line of defense; they are the main cells that protect us from bacterial infections. Their protective function is a positive one, however, they also have inflammatory properties that may eventually lead to heart disease and several autoimmune diseases, such as lupus. Effectively manipulating neutrophils is vital in disrupting inflammatory diseases.

When our skin is scratched (and the skin is not broken), one may see a pale red line. Soon the area around that scratch goes red, this is because the arterioles have dilated and the capillaries have filled up with blood and become more permeable, allowing fluid and blood proteins to move into the space between tissues.

Edema – the area then swells as further fluid builds up in the interstitial spaces.

The five cardinal signs of acute inflammation – “PRISH”

An ingrown toenail
An ingrown toenail with the five PRISH signs; pain, redness, immobility, swelling and heat

  • Pain – the inflamed area is likely to be painful, especially when touched. Chemicals that stimulate nerve endings are released, making the area much more sensitive.
  • Redness – this is because the capillaries are filled up with more blood than usual
  • Immobility – there may be some loss of function
  • Swelling – caused by an accumulation of fluid
  • Heat – as with the reason for the redness, more blood in the affected area makes it feel hot to the touch

The five classical signs of inflammation

Although Latin terms are still used widely in Western medicine, local language terms, such as English, are taking over. PRISH is a more modern acronym which refers to the signs of inflammation. The traditional Latin based terms have been around for two thousand years:

  • Dolor – Latin term for “pain”
  • Calor – Latin term for “heat”
  • Rubor – which in Latin means “redness”
  • Tumor – a Latin term for “swelling”
  • Functio laesa – which in Latin means “injured function”, which can also mean loss of function

Dolor, Calor, Rubor, and Tumor were first described and documented by Aulus Cornelius Celsus (ca 25 BC-ca 50), a Roman encyclopaedist. Celcius is famous for creating De Medicina, which is thought to be the only surviving section of a vast encyclopedia. De Medicina was the main source of medical reference in the Roman world for pharmacy, surgery, diet and some other medical fields.

Functio laesa – it is not clear who first described and documented the fifth sign. The majority of attributions have gone to Thomas Sydenham (1624-1689) an English physician and Rudolph Carl Virchow (1821-1902), a German doctor, biologist, politician and pathologist. Virchow is seen as one of the founders of social medicine.

These five acute inflammation signs are only relevant when the affected area is on or very close to the skin. When inflammation occurs deep inside the body, such as an internal organ, only some of the signs may be detectable. Some internal organs may not have sensory nerve endings nearby, so there is be no pain, as is the case with some types of pneumonia (acute inflammation of the lung). If the inflammation from pneumonia pushes against the parietal pleura (inner lining of the surface of the chest wall), then there is pain.

Acute and chronic inflammation compared

The lists below show the difference between chronic and acute inflammation regarding the causative agents, which major cells are involved, features regarding onset, duration, and outcomes:

Acute Inflammation

  • Causative agents – harmful bacteria or injury to tissue
  • Major cells involved – mainly neutrophils, basophils (in the inflammatory response), and eosinophils (response to parasites and worms), and mononuclear cells (macrophages, monocytes)
  • Primary mediators – eicosanoids, vasoactive amines
  • Onset (when does the inflammation start) – straight away
  • Duration – short-lived, only a few days
  • Outcomes – the inflammation either gets better (resolution), develops into an abscess, or becomes a chronic inflammation

Chronic inflammation

  • Causative agent – non-degradable pathogens that cause persistent inflammation, infection with some types of viruses, persistent foreign bodies, overactive immune system reactions
  • Major cells involved – Macrophages, lymphocytes, plasma cells (these three are mononuclear cells), and fibroblasts
  • Primary mediators – reactive oxygen species, hydrolytic enzymes, IFN-γ and other cytokines, growth factors
  • Duration – from several months to years
  • Outcomes – the destruction of tissue, thickening and scarring of connective tissue (fibrosis), death of cells or tissues (necrosis)

Sleep quality and duration impacts on inflammation risk

Scientists at Emory University School of Medicine in Atlanta, Georgia, found in a study that sleep deprivation or poor sleep quality raise inflammation, which in turn increase the risk of developing heart disease and stroke.

The team gathered data on 525 middle-aged volunteers who had completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire, which asked detailed questions about sleep quality and duration.

They tested the participants’ levels of various inflammatory markers, and then tried to see whether they could link them to quality and duration of sleep.
The authors concluded:

“The researchers concluded that:
“Poor sleep quality, and short sleep durations are associated with higher levels of inflammation.”

Why does inflammation cause pain?

What is pain?
When people have inflammation it often hurts, they feel pain, stiffness, discomfort, distress and perhaps agony, depending on the severity of it. Pain can be constant and steady, in which case it is often referred to as an ache. Pain can be of a throbbing type, a pulsating pain, or it can be a stabbing or pinching pain.

Pain is a very individual experience and the only person who can describe it properly is the one who is feeling it.

Pain can be acute or chronic. It can also be:

  • Nociceptive pain – specific receptors are stimulated for us to feel this type of pain. These receptors sense changes in temperature, vibration, stretch, and chemicals which damaged cells release. “Nociceptive” means causing or reacting to pain – the cause of the pain comes from outside the nervous system, and the nervous system reacts to it. “Non-nociceptive” means the pain comes from within the nervous system itself.
  • Somatic pain – this is a kind of nociceptive pain. The sensation is felt in muscles, joints, bones, ligaments, and on the skin. Musculo-skeletal pain is somatic pain. Pain receptors are sentive to stretch in the muscles, vibration, temperature, as well as inflammation. When there is a lack of oxygen there may be painful ischemic muscle cramps.

    Somatic pain tends to be sharp and localized – touching or moving the affected area will result in more severe main.

  • Visceral pain – this is a kind of nociceptive pain. Pain is sensed deep down in the body, in the internal organs and main body cavities, such as the heart, lungs, bowels, spleen, liver, kidneys, bladder, uterus, and ovaries. The nociceptors (pain receptors) sense oxygen starvation (ischemia), stretch, and inflammation. It is harder to localize visceral pain than somatic pain. The pain is usually described as a deep ache. Cramping and colicky sensations are examples of visceral pain.

Inflammation primarily causes pain because the swelling pushes against the sensitive nerve endings, which send pain signals to the brain. Nerve endings send pain signals to the brain all day long; however, it learns to ignore most of them, unless pressure against the nerve endings increases.

Other biochemical processes also occur during inflammation which affect how nerves behave, and cause pain.

Inflammation risk much greater if you are obese

Diagram of painful joints in obese male
example of common painful joints in an overweight male

Fat men have more inflammatory markers (white blood cells) than men of the same age who are not obese or overweight. Raised white blood cell levels are markers which are linked to a higher risk of developing various illnesses, including coronary heart disease.

In a recent study, a team from Pennington Biomedical Research Center in Baton Rouge, Louisiana, focused on specific types of white blood cells; neutrophils, lymphocytes, monocytes, basophils, and eosinophils.

They measured resting levels of the white blood cells in the adult males, as well as their levels of fitness and BMIs (body mass indexes), and adjusted the results for age.

They found that:

  • Unfit men had higher white blood cell levels that fit men
  • Men with higher BMIs had raised levels of white blood cells
  • The combination of fitness levels and body weights impacted considerably on levels of white blood cells, and ultimately inflammation

Although scientists know that inflammation plays a key role in heart disease and several other illnesses, what drives inflammation in the first place is still a mystery.

Inflammation drops when women lose weight – scientists at the Fred Hutchinson Cancer Research Center in Seattle, Washington found that postmenopausal overweight or obese women who lost 5% or more of their body weight had measurable falls in levels of inflammation markers. Team leader, Anne McTiernan, M.D., Ph.D., said “Both obesity and inflammation have been shown to be related to several types of cancer, and this study shows that if you reduce weight, you can reduce inflammation as well.”

Autoimmune disorders and inflammation

An autoimmune disease, also known as autoimmune disorder, is one where the body initiates an immune response to healthy tissues, mistaking them for harmful pathogens or irritants. The immune response triggers an inflammatory response too.

There are literally hundreds of autoimmune diseases, and nearly all of them have inflammation as one of the signs, examples include:

  • Rheumatoid arthritis – there is inflammation in the joins, tissues surrounding the joints, and sometimes some other organs in the body
  • Ankylosing Spondylitis – there is inflammation of the vertebrae, muscles, ligaments, and also the sacroiliac joints (where the spine and hips meet)
  • Celiac Disease – there is inflammation and destruction of the inner lining of the small intestine.
  • Crohn’s Disease – the gastrointestinal tract becomes inflamed. Inflammation is most common in the ileum (small intestine), but may occur anywhere in the GI tract, from the mouth to the anus.
  • Fibromyalgia – often a set of symptoms related to another autoimmune disorder, such as lupus or rheumatoid arthritis. There is pain in various parts of the body. Location and even the existence of inflammation is unclear.
  • Graves’ Disease – one of the signs is goiter; when the thyroid gland is inflamed. Exophthalmos, inflammation of the muscles behind the eyes. Grave’s dermopathy, inflammation of the skin, usually the shins and the top of feet (uncommon)
  • Idiopathic Pulmonary Fibrosis – the role of inflammation is unclear. Experts used to think that the disease was mainly caused by inflammation within the alveoli (tiny sacs within the lungs). However, treatments to reduce inflammation are often disappointing. Therefore, although there is inflammation, its impact on the disease is a bit of a mystery.
  • Lupus – there can be inflammation in the joints, lungs, heart, kidney and skin.
  • Psoriasis – there is inflammation of the skin. In some cases, as in psoriatic arthritis, the joints and tissue surrounding the joints may also become inflamed.
  • Type 1 Diabetes – inflammation in various parts of the body are likely if the diabetes is not well controlled.
  • Addison’s disease – inflammation of the adrenal glands. The stress to the body caused by this disease can also lead to inflammation elsewhere.
  • Vaslculitis – refers to a group of disorders in which inflammation eventually destroys blood vessels, both arteries and veins.
  • Transplant rejection – there is already substantial inflammation caused by the transplant operation. If the organ recipient’s immune system rejects the new organ, there is typically inflammation in and around the donated organ.
  • Various allergies – all allergies have inflammation. Asthma has inflammation of the airways, in hay fever the nose, ear and throat mucous membranes become inflamed, people who are allergic to bee stings may have serious life-threatening inflammation which affects the whole body (anaphylaxis).
  • Vitamin A deficiency – inflammatory responses are much more likely if the person is deficient in vitamin A.

The disorders mentioned above are just a tiny example of the hundreds of autoimmune disorders which have inflammation as one of their signs.

What are the possible treatments for inflammation

As mentioned earlier in this article, patients (and many health care professionals) must remember that inflammation is part of the healing process. Sometimes reducing inflammation is necessary, but not always.

Anti-inflammatory medications

Ibuprofen is commonly used to alleviate pain
NSAIDs (non-steroidal anti-inflammatory drugs) are taken to alleviate pain caused by inflammation. They counteract the COX (cyclooxygenase) enzyme, which synthesizes prostaglandins which create inflammation. If prostaglandin synthesis can be blocked, pain is either eliminated or reduced.

Examples of NSAIDs include naproxen, ibuprofen and aspirin.

People should not use NSAIDs long-term without being under the supervision of a doctor, because there is a risk of stomach ulcers, and even severe and life-threatening hemorrhage. NSAIDs may also worsen asthma symptoms and cause kidney damage. NSAID medications, with the exception of aspirin, can also increase the risk of stroke and myocardial infarction (heart attack).

Acetaminophen (paracetamol, Tylenol) can reduce pain associated with inflammatory conditions, but have no anti-inflammatory effects. They may be ideal for those wishing to treat just the pain, while allowing the inflammation to run its course.

Corticosteroids – these are a class of steroid hormones naturally produced in the cortex (outer portion) of the adrenal gland. They are synthesized in laboratories and added to medications.

Corticosteroids, such as cortisol are anti-inflammatory; they prevent phospholipid release, which undermines eosinophil action and a number of other mechanisms involved in inflammation.

There are two sets of corticosteroids:

  • Glucocorticoids, which are produced as a reaction to stress, and are also involved in metabolizing fats, proteins and carbohydrates. Synthetic glucocorticoids are prescribed for inflammation of the joints (arthritis), temporal arteritis dermatitis, inflammatory bowel disease, systemic lupus, hepatitis, asthma, allergic reactions, and sarcoidosis. Creams and ointments (topical formulations) may be prescribed for inflammation of the skin, eyes, lungs, bowels and nose.
  • Mineralocorticoids, which regulate our salt and water balance. Medications with mineral corticoids are used for the treatment of cerebral salt wasting, and to replace missing aldosterone (a hormone) for patients with adrenal insufficiency.

Corticosteroid side effects are more likely if taken in oral form, compared to inhalers or injections. The higher the dosage and/or the longer they are taken for, the greater the risk of side effects. Side effect severity is also linked to dosage and duration of treatment. Patients taking oral corticosteroids for over three months have a considerably greater chance of experiencing undesirable side effects. Inhaled medications, such as those to treat asthma over the long-term raise the risk of developing oral thrush – rinsing the mouth out with water after each application can help prevent oral thrush. Gucocorticoids can also induce Cushing’s syndrome, while mineralocorticoids can cause high blood pressure (hypertension), low blood potassium levels (hypokalemia), high blood-sodium levels (hypernatremia), connective tissue weakness and metabolic alkalosis.

ImSAIDs (Immune Selective Anti-Inflammatory Derivatives)

ImSAIDs are a class of peptides being developed by IMULAN BioTherapeutics, LLC. Scientists found that they have anti-inflammatory properties. They alter the activation and migration of immune cells involved in amplifying the inflammatory response. This is a new category of anti-inflammatory medication which has nothing to do with steroids or non-steroidal anti-inflammatories. ImSAIDs have shown promise as potential veterinary drugs for controlling and reducing inflammation. Experts believe that they might eventually be suitable for human use.

Some herbs have anti-inflammatory properties

  • Harpagophytum procumbens – also known as devil’s claw, wood spider or grapple plant comes from South Africa and is related to sesame plants. European colonists brought devil’s claw back home to treat arthritis, fever and pain. According to the British Herbal Pharmacopoeia, Devil’s Claw has diuretic, sedative and analgesic properties.
  • Hyssop Hyssopus – from the plant family Lamiaceae, is added to eau de Cologne and Chartreuse (liqueur drink). It is also used to color some spirits. Hyssop is mixed with other herbs, such as liqourice for the treatment of some lung conditions, including inflammation. Beware of the essential oils of hyssop, as they can lead to life-threatening convulsions in laboratory animals.
  • Ginger, also known as ginger root, is the mass of roots (rhizome) of the Zingiber officinale plant. It is used as a medicine or a spice. Jamaican ginger was the traditional medical form of this root, and has been used as a carminative (to treat gas or wind) and a stimulant. It has been used for hundreds of years to treat dyspepsia, constipation, colic, other gastrointestinal problems, as well as rheumatoid arthritis pain.

    Researchers from Michigan Medical School reported that ginger supplements were found to reduce the markers of colon inflammation. Chronic colon inflammation is associated with a higher risk of developing colon cancer. They added that ginger supplements may help prevent colon cancer.

  • Turmeric (Curcuma longa) – also a plant of the ginger family. Current research is looking into the possible beneficial effects of turmeric in treating arthritis, Alzheimer’s disease, and some other inflammatory conditions. Curcumin, a substance found in turmeric, is under investigation for the treatment of several illnesses and disorders, including inflammation.
  • Cannabis – contains a cannabinnoid called cannabichromene, which has been shown to have anti-inflammatory properties.

    Other treatments for inflammation

    Applying ice – do not place the ice in direct contact with skin, wrap it in a cloth or a purpose-made ice bag. Applying ice has been shown to reduce inflammation. Athletes commonly use ice treatment for managing pain and inflammation. Inflammation can go down more rapidly if you rest, apply ice, compression, and elevate the affected area (have your ankle raised if the swelling is there, for example).

    Fish oil (Omega-3) – scientists form Ohio State University Center for Clinical and Translational Science reported on a study in the journal Brain, Behavior and Immunity that the daily consumption of fish oil, omega-3 reduced both inflammation and anxiety in a group of young healthy people.

    Green tea – researchers from the Laura W. Bush Institute for Women’s Health at the Texas Tech University Health Sciences Center found that regular green tea drinking enhances bone health and reduces inflammation in postmenopausal women. They added that Tai-Chi appears to have the same beneficial effect.

    Tart cherries – sports scientists found that tart cherries have powerful anti-inflammatory properties which may help millions of Americans who suffer from joint pain and arthritis. The team, from Oregon Health Science University even went as far as saying that “(tart cherries) have the highest anti-inflammatory content of any food”. They believe that tart cherries could help patients with osteoarthritis manage their pain effectively. Twenty females aged from 40 to 70 years drank tart cherry juice twice a day for three weeks; they all suffered from inflammatory osteoarthritis. At the end of the three weeks there were significant falls in levels of key inflammation markers.

    Written by Christian Nordqvist

    Copyright: Medical News Today

    Not to be reproduced without permission of Medical News Today

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  • Increase In Diagnostic Imaging Among Stage IV Cancer Patients On Medicare

    Main Category: Radiology / Nuclear Medicine
    Also Included In: Cancer / Oncology;  Medicare / Medicaid / SCHIP
    Article Date: 31 Jul 2012 – 4:00 PDT

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    The use of diagnostic imaging in Medicare patients with stage IV cancer has increased faster than among those with early-stage (stages I and II) disease, according to a study published July 30 in the Journal of the National Cancer Institute.

    The costs of diagnostic imaging have increased more rapidly than the overall costs of cancer care, making diagnostic imaging the fastest-growing division of Medicare-reimbursed services. The net costs of cancer care are the highest in the last year of life; yet little is known about the use of high-cost imaging in cancer patients during the last year of life.

    In order to determine the usage of high-cost imaging in cancer patients at the end of life, Yue-Yung Hu, M.D., M.P.H. and colleagues in the Center for Outcomes and Policy Research at Dana-Farber Cancer Institute, the Center for Surgery and Public Health at Brigham and Women’s Hospital, and Wisconsin Surgical Outcomes Research Program at the University of Wisconsin, looked at claims within the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1994 and 2009 for computed tomography, magnetic resonance imaging, positron emission tomography, and nuclear medicine scans for patients diagnosed with stage IV breast, colorectal, lung, or prostate cancer between 1995-2006. The rate of imaging per-patient per-month of survival was determined for each phase of care. For reference, trends in imaging use in early-stage patients with the same tumor types during the same time period were also considered.

    The researchers found that most patients with stage IV breast, colorectal, lung, and prostate cancer undergo high-cost imaging procedures throughout the course of their care and that the usage of imaging has steadily increased between 1995 and 2006. The increase may reflect a lack of guidelines in this area or the use of imaging to guide symptom management, detect disease progression and assess treatment effect. “Because scans help clinicians determine whether a change in (or cessation of) treatment is indicated, the expanding use of advanced imaging in stage IV disease is likely a manifestation of the increasing number and types of treatment options available to these patients,” the authors write. “Imaging, although it often leads to (appropriate) palliative measures, may also distract patients from focusing on achievable end-of-life goals, require them to spend more of their limited time in medical care settings and/or provoke anxiety.” The authors point out the importance of examining such patient-centered outcomes in future research to define the role of advance imaging in Stage IV solid tumors.

    In an accompanying editorial, Drs. Robin Yabroff and Joan Warren, of the Health Services and Economics Branch at the National Cancer Institute, feel that assessing the appropriateness of care for patients with stage IV disease is complex. “Physicians tend to overestimate survival for terminally ill cancer patients, which may influence their treatment and related imaging recommendations,” the editorialists write. “Development of practice guidelines for advanced imaging in patients with stage IV disease, with explicit statements about the state of evidence will be critical, particularly for care outside of the window surrounding patient diagnosis.”

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    Rheumatoid Arthritis New Major Clinical Target After Mesoblast Obtains Positive Results In Inflammatory Arthritis

    Main Category: Arthritis / Rheumatology
    Article Date: 27 Jul 2012 – 5:00 PDT

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    Regenerative medicine company Mesoblast Limited (ASX:MSB) have announced positive results in a large animal model of Rheumatoid Arthritis (RA) following a single intravenous injection of its proprietary allogeneic, or “off-the-shelf”, immunomodulatory adult Mesenchymal Precursor Cells (MPCs).

    Mesoblast Chief Executive Professor Silviu Itescu said that the results indicated that the Company’s immunomodulatory MPCs may have a mechanism of action that is unique from other biological therapies by shutting down multiple cytokine pathways simultaneously, and that this could become a first line treatment with a superior and sustained benefit on reducing inflammation and destruction of joints in people suffering from severe RA.

    RA is an autoimmune disease driven and perpetuated by pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-17. Treatments targeting any of these pathways alone are only moderately effective in RA, need to be administered chronically, and may cause unacceptable infectious adverse events. A single intravenous injection of allogeneic MPCs in sheep with collagen-induced arthritis concomitantly affected T cells, monocytes/macrophages, and synoviocytes to simultaneously shut down TNF-alpha, IL-6, and IL-17 cytokine pathways, and improve joint pathology.

    Severe joint synovial inflammation with cartilage loss and bony erosions, characteristic of human RA, occurs in sheep injected with collagen. In a pilot study, significant numbers of allogeneic MPCs were detected in involved joints or lymph nodes of arthritic sheep at 24 hours after a single intravenous injection, but not in normal sheep, indicating that MPCs selectively migrate to sites of immune-mediated inflammation.

    A randomized, placebo-controlled study was next performed in 30 sheep with established collagen-induced arthritis, comparing a single intravenous injection of allogeneic MPCs at one of three doses (0.3, 1 and 2 million MPCs/kg) to saline. Thirty days later, joint synovial tissues from arthritic sheep were examined. In comparison with saline treated controls, synovial tissue from arthritic sheep receiving a single intravenous injection of 2 million MPCs/kg showed 88% mean reduction in IL-6 levels (p=0.029), 83% mean reduction in TNF-alpha levels (p=0.049), 53% mean reduction in IL-17 levels (p=0.005), and 52% mean reduction in infiltrating monocytes/macrophages (p=0.009).

    MPC-treated animals had a 31% mean reduction in histopathology severity scores compared with controls (p=0.025). Intermediate effects were seen with 1 million MPCs/kg, and the lowest MPC dose was least effective. These findings demonstrate that MPCs are immunoregulatory and concomitantly suppress the activation and proliferation of T-cells, monocytes, and synoviocytes seen in active Rheumatoid Arthritis. Mechanistically, the data suggest that MPCs inhibit the Th17 CD4 T cell subset, with the subsequent simultaneous reduction in the key cytokines, IL-17, IL-6, and TNF-alpha.

    Mesoblast has an upcoming scheduled meeting with the United States Food and Drug Administration (FDA) to discuss its Phase 2 clinical program in patients with RA. Subject to FDA clearance, the Company intends to commence a randomized, placebo-controlled Phase 2 trial in the fourth quarter of 2012.

    “Rheumatoid Arthritis represents the second indication, after Type 2 diabetes, in a growing list of major market segments that will be targeted by Mesoblast’s intravenous product formulation,” Professor Itescu added.

    About Rheumatoid Arthritis

    Rheumatoid arthritis (RA) is a chronic systemic disease characterized by progressive joint deformity and joint destruction driven by synovial inflammation and hyperplasia in which cytokines play central pathogenic roles. The prevalence of RA is estimated to be 0.8% worldwide, with women twice as likely to develop the disease as men. In the United States, RA afflicts 1.3 million people. It is responsible for 250,000 hospitalizations and 9 million physician visits each year. According to Global Data, the RA therapeutics market was valued at $10.3 billion globally in 2010, and has doubled over a four-year period after growing at a Compound Annual Growth Rate (CAGR) of 12.3%.

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    ‘Rheumatoid Arthritis New Major Clinical Target After Mesoblast Obtains Positive Results In Inflammatory Arthritis’

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    Medical Imaging Study In Health Affairs Incomplete And Potentially Misleading According To ACR

    Main Category: Radiology / Nuclear Medicine
    Also Included In: Medicare / Medicaid / SCHIP;  Primary Care / General Practice
    Article Date: 27 Jul 2012 – 1:00 PDT

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    In response to a study published in the August issue of Health Affairs regarding declining medical imaging use in recent years, the American College of Radiology (ACR) released a statement explaining that physician education efforts and quality assurance steps have resulted in more efficient use of imaging, but that arbitrary Medicare cuts are damaging patient access to care.

    The ACR also cited a December 2011 Health Affairs article that shows Medicare imaging cuts may have resulted in physical harm to patients.

    “This Health Affairs study further supports the fact that medical imaging scans are being more efficiently used and are not a primary driver of rising healthcare costs. Medicare spends the same amount on imaging services now as in 2003 – virtually unheard of in the healthcare arena. This is likely the case among the privately insured as well. Those who contend that imaging is primarily responsible for rising costs are either misinformed or purposefully misinforming others…Arbitrary, backward looking limits on care may slow or even reverse gains against cancers and other serious illnesses and deny patients access to potentially lifesaving services,” said Paul Ellenbogen, MD, FACR, chair of the American College of Radiology Board of Chancellors.

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    Expanding Medicaid To Low-Income Adults Leads To Improved Health, Fewer Deaths

    Main Category: Medicare / Medicaid / SCHIP
    Also Included In: Public Health
    Article Date: 27 Jul 2012 – 1:00 PDT

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    A new study from Harvard School of Public Health (HSPH) finds that expanding Medicaid to low-income adults leads to widespread gains in coverage, access to care, and – most importantly – improved health and reduced mortality. It is the first published study to look specifically at the effect of recent state Medicaid expansions on mortality among low-income adults, and the findings suggest that expanding coverage to the uninsured may save lives.

    “The recent Supreme Court decision on the Affordable Care Act ruled that states could decide whether or not they wanted to participate in the health care law’s Medicaid expansion. Our study provides evidence suggesting that expanding Medicaid has a major positive effect on people’s health,” said Benjamin Sommers, assistant professor of health policy and economics at HSPH and the study’s lead author.

    The study was published online and will appear in the September 13, 2012 print issue of the New England Journal of Medicine.

    In the past decade, several states expanded Medicaid from its traditional coverage of low-income children, parents, pregnant women, and disabled persons to include “childless adults,” poor adults without any children living at home and the population most directly targeted by the Affordable Care Act (ACA). Medicaid currently covers 60 million people, and the ACA will extend eligibility to millions more beginning in 2014. However, the Supreme Court decision gives states the option of choosing whether or not to expand coverage and, because of budget pressures, some states are considering cutbacks, not expansion.

    The HSPH researchers, including senior author Arnold Epstein, chair of the Department of Health Policy and Management, and Katherine Baicker, professor of health economics, analyzed data from three states – Arizona, Maine, and New York – that had expanded their Medicaid programs to childless adults (aged 20-64) between 2000 and 2005. They selected four neighboring states without major Medicaid expansions – New Hampshire (for Maine), Pennsylvania (for New York), and Nevada and New Mexico (for Arizona) – as controls. The researchers analyzed data from five years before and after each state’s expansion.

    The results showed that Medicaid expansions in three states were associated with a significant reduction in mortality of 6.1% compared with neighboring states that did not expand Medicaid, which corresponds to 2,840 deaths prevented per year for each 500,000 adults gaining Medicaid coverage. Mortality reductions were greatest among older adults, non-whites, and residents of poorer counties. Expansions also were associated with increased Medicaid coverage, decreased uninsurance, decreased rates of deferring care due to costs, and increased rates of “excellent” or “very good” self-reported health.

    The groups that benefitted from Medicaid expansion in this study – older adults, racial and ethnic minorities, and those living in poor areas – are groups that have traditionally had higher mortality rates and faced greater barriers to care. The study results provide valuable evidence for state policymakers deciding whether or not to expand Medicaid, say the authors.

    “Sometimes the political rhetoric is at odds with the evidence, such as claims that Medicaid is a ‘broken program’ or worse than no insurance at all; our findings suggest precisely the opposite,” said Epstein.

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    Erectile Dysfunction Can Be A Warning Sign For Heart Disease In Younger And Middle-Aged Men And Men With Diabetes

    Main Category: Erectile Dysfunction / Premature Ejaculation
    Also Included In: Diabetes;  Heart Disease;  Obesity / Weight Loss / Fitness
    Article Date: 27 Jul 2012 – 1:00 PDT

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    Although erectile dysfunction (ED) has been shown to be an early warning sign for heart disease, some physicians – and patients – still think of it as just as a natural part of “old age.” But now an international team of researchers, led by physicians at The Miriam Hospital, say it’s time to expand ED symptom screening to include younger and middle-aged men.

    In an article appearing in the July issue of the American Heart Journal, they encourage physicians to inquire about ED symptoms in men over the age of 30 who have cardiovascular risk factors, such as smoking, obesity or family history, and in all men with type 2 diabetes.

    As many as 30 million American men suffer from ED, or the inability to maintain an erection sufficient for sexual intercourse. ED and cardiovascular disease share a common cause: narrowing of the arteries, resulting in reduced or obstructed blood flow to the organs. They also share similar risk factors, including smoking, diabetes, obesity and high blood pressure. Because the penile arteries are just a fraction smaller than the arteries supplying blood to the heart, symptoms of conditions that can narrow the arteries, such as arteriosclerosis, are likely to present first in the form of erection problems. That’s why it is also believed that the more severe the ED, the greater the risk of heart disease-related events, such as heart attack and stroke.

    “Erectile dysfunction represents an important first step toward heart disease detection and reduction, yet many health care providers and patients assume it’s just a sign of old age, so it may not be something that comes up during an annual physical with a younger man who doesn’t fit the ED ‘stereotype,'” says lead author Martin Miner, M.D., chief of family medicine and co-director of the Men’s Health Center at The Miriam Hospital.

    “That’s why we urge physicians to discuss sexual function with the majority of their male patients – including diabetic men of all ages and men over the age of thirty with some of the traditional heart disease risk factors, like smoking or a family history,” he adds.

    Although not all men with ED are at increased risk for cardiovascular disease, Miner says it is the physician’s responsibility to make that determination based on aggressive workup and testing. If the patient is found to be at risk, the patient can then receive intensive risk factor management.

    Miner and colleagues conducted a literature review of 40 studies that suggest ED is a significant predictor for cardiovascular disease in two populations: men under the age of 60 and men with diabetes. Their analysis supports several widely-held theories, including the role of ED as a significant red flag for cardiovascular disease in younger and middle-aged men.

    For example, in the Mayo Clinic’s Olmsted County Study, a large, epidemiological study cohort of men from Olmsted County, Minnesota, men 40 to 49 years old with ED were twice as likely to develop coronary artery disease as those who did not have ED. However, ED had less predictive value for men 70 years and older.

    Several studies, including a large analysis of more than 6,300 men enrolled in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation) trial, suggest ED is a particularly powerful indicator of cardiovascular disease in diabetic men as well, prompting researchers to call for ED symptom screening in all men with type 2 diabetes.

    Miner points out early identification of men at risk for cardiovascular disease has the potential to lower health care costs and improve outcomes.

    “There may be a ‘window of curability’ in which we can intervene early and stop the progression of heart disease,” he says. “Also, it may be possible to someday use erectile function as a measurement to tell us if preventive interventions for heart disease are working.”

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    Miner’s co-authors on the paper include Mark Sigman, M.D., co-director of the Men’s Health Center and chief of urology at Rhode Island and The Miriam hospitals; Peter Tilkemeier, M.D., interim chair, division of cardiology at Rhode Island and The Miriam hospitals; Allen D. Seftel, M.D., FACS, of the University of Medicine and Dentistry, New Jersey-Robert Wood Johnson Medical School; Ajay Nehra, M.D., of Mayo Clinic; Peter Ganz, M.D., of San Francisco General Hospital and University of California at San Francisco; Robert A. Kloner, M.D., Ph.D., of Good Samaritan Hospital, Los Angeles; Piero Montorsi, M.D., of the University of Milan; Charalambos Vlachopoulos, M.D., of Athens Medical School; Melinda Ramsey, Ph.D., of Melinda Ramsey, LLC; and Graham Jackson, M.D., FRCP, of Guys and St. Thomas Hospitals, London.

    Miner is also a clinical associate professor of family medicine and surgery (urology) at The Warren Alpert Medical School of Brown University. In addition, Sigman is a professor of surgery (urology) and Tilkemeier is an associate professor of medicine at Alpert Medical School.
    Lifespan

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    What Is Remicade (infliximab)?

    Remicade (infliximab) is a TNF inhibitor, a monoclonal antibody against tumor necrosis factor alpha (TNF-α), that is prescribed for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, chronic plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ankylosing spondylitis. Infliximab is used to alleviate the symptoms of pain and inflammation…