Tuesday, July 29, 2008

ptsd

Although terror-attack survivors often rebound emotionally, their bodies stay on heightened alert long after such traumas, a new investigation suggests।
http://ljsheehan.blogspot.com

Psychiatrist Phebe M. Tucker of the University of Oklahoma Health Sciences Center in Oklahoma City examined 60 people who had been directly exposed to the 1995 Oklahoma City bomb blast and 60 other people who lived near the bombing site but didn't witness the blast or have friends or relatives killed in the incident.

Despite exhibiting relatively good emotional health in interviews conducted 7 years after the explosion, survivors displayed substantially higher heart rates and blood pressures while discussing the bombing than members of the comparison group did, Tucker and her coworkers say in the February American Journal of Psychiatry.

The two groups of participants reported similarly low levels of depression। Post-traumatic stress disorder (PTSD), a severe anxiety response to trauma, affected 16 survivors and 1 comparison individual।
http://ljsheehan.blogspot.com

Survivors showed biological sensitivity to reminders of the bombing, regardless of whether they exhibited PTSD, the researchers say. They suspect that this reaction initially fosters resilience by readying a person to survive future traumas

Sunday, July 20, 2008

disease

To fight off an infection or illness, the body shifts into a slow-down mode that mirrors some symptoms of depression. http://louis3j3sheehan.blogspot.comIn fact, scientists now think the immune response itself may even cause the mood disorder.

From Sick to DownImmune cells secrete cytokines (shown as red dots in this simplified drawing, click on image to see larger version) that trigger inflammatory responses. But when cytokine levels in the brain stay high fo too long, people susceptible to mood disorders may develop depression. Cytokines released in the body may enter the brain directly, by passing through leaky areas in the blood-brain barrier, or indirectly by initiating a chain reaction of "middlemen" that lead to brain cells called microglia releasing cytokines. Cytokines may alter mood by changing brain processes and levels of brain chemicals such as serotonin and dopamine. Synthetic version of interferon-alpha and interferon-beta, used to treat cancers, hepatitis C and multiple sclerosis, may engage the same pathway.Amadeo Bachar

When one of psychiatrist Andrew Miller’s patients asked about receiving the best drug available for treating hepatitis C, Miller said: “No way.” The patientin his early 20s and accompanied by his mom to the appointmenthad no job, few friends and a history of depression. While Miller knows that hepatitis C patients often benefit from the new generation of immune-boosting treatments, he’s keenly aware that those same immune therapies have a strong tendency to bring people downand, in people predisposed to depression, dangerously down.

Certain immune proteins in the body appear to mess with the minds of otherwise healthy, but depressed people as well. Those who suffer from major depression have higher levels of cytokines, immune proteins the body makes to fend off infections and to patrol the body for disease, and which laboratories mimic. Excess cytokines have also been found lurking in the postmortem brains of suicide victims. “It raises the issue, how much of how we feelhow much of who we are as peopleis dictated in terms of our immune system?” says Miller, a researcher at Emory University in Atlanta.

Though the connection between the body’s immune response and depression has only gained firm support in the last five years, it’s already catalyzing a revolution in antidepressant drug development. In hindsight, an emotional reaction to surging immune molecules does not seem so surprising. Cytokines are among the first immune proteins to respond to infection. Some direct swelling and fevers. Others order the body to rest, and so the sick take to the bed and decline party invitations, showers and even homemade dinners. The powerful molecules influence wants and needs by altering levels of substances like serotonin in the brain. Essentially, cytokines command the body to conserve energy when it’s sick. “A little depressed behavior is a survival mechanism in that sense,” Miller says. But when inflammation is artificially or erroneously triggered, prolonged sickness behavior may morph into depression and do more harm than good.

Figuring out the biology behind depression should help doctors combat the disorder, which strikes an estimated 14.8 million American adults each year, according to the National Institute of Mental Health. More than one in six individuals will experience major depression in their lifetime. And when depression coincides with chronic diseases like multiple sclerosis, cancer or diabetes, patients’ conditions are less likely to improve.

Psychiatrists and pharmaceutical companies have noted the downpour of evidence linking inflammation to depression। Miller says he and his colleagues have considered creating a new diagnostic category: Major Depressive Disorder with Increased Inflammation। To combat this depression, he says, researchers must find a way to alter the body’s immune response. It is a risky strategy but one that offers hope to the nearly 30 percent of all depressed patients who don’t respond to the antidepressants currently on the market. http://louis3j3sheehan.blogspot.com

Jekyll-and-Hyde changes

Cytokines emerged as the primary suspects for what’s since become known as inflammation-induced depression after Miller and others noticed that cancer patients became inexplicably upset during treatment with synthetic type 1 interferons, cytokines that block viral replication in infected cells. One of these, interferon-alpha, is among the most effective drugs for patients battling cancer and the hepatitis C virus. Yet the treatment has become notorious for causing major depression and other behavioral changes in more than half of these patients, depending on the dose of the immune booster.

Miller describes a “Jekyll-and-Hyde– type change” in one of his patients after interferon therapy. Eight weeks into it, the patient dumped his girlfriend, began dressing in black and grew a goatee. And there was another woman, Miller recalls, who took a drastic downward turn. “One of my most positive patients had been battling cancer for years, yet four weeks into the cytokine therapy she was distraught,” he says. “She told me, ‘I love my husband and my children, but I don’t want to be around them. I want to be left alone, and I don’t know why.’

As observations of sadness, irritability, insomnia, fatigue and loss of appetiteall classic symptoms of depressionmounted in patients treated with immune boosters in the 1990s, papers published nearly a decade earlier in veterinary journals resurfaced. Benjamin Hart had been writing about the behavior of sick animals since the mid-1980s. “Depression was the first sign we had that an animal was sick,” says Hart, an animal behavior researcher at the University of California, Davis. In a seminal 1985 paper in the Journal of the American Veterinary Medical Association, he put forth the argument that animal malaise serves a purpose। http://louis3j3sheehan.blogspot.com

“People would call in and say that the dog is sleeping more than usual. They give the dog its favorite treat, and it only nibbles at it and then drops it, or they’d say the cat looks scruffy,” Hart explains. “Cats usually groom all the time.” He says that when he ran blood and urine tests on such animals, he usually discovered signs of bacterial or viral infection. Instead of assuming the pet acted sad because it wasn’t feeling well, he suggested that the pet’s behavior was part of its immune response. Fido’s body forced the animal to devote its energy to battling illness, instead of to chasing squirrels.

Furthermore, since all mammals act similarly when sick, Hart suggested that the behavior had been inherited from a common ancestor who survived infection better than other animals who had not evolved the behavioral response.

In the 1990s, researchers in the Netherlands reported that patients with major depression showed signs of inflammation, with elevated levels of cytokines in their blood and cerebrospinal fluid. And in 2001, Robert Dantzer, now at the University of Illinois at Urbana-Champaign, injected rats with cytokines. Sure enough, Dantzer says, the rats lost interest in previous pleasures and activities: They didn’t care for sugary water, they didn’t run on the wheel and, when placed in a pool of water they swam lethargically, barely keeping their heads above water.

Miller compares this sickness behavior to “holing up in a cave.” Although the animal has little drive to do much of anything, it does stay alert to major threats. “While in the cave, the organism rests but keeps one eye open,” he says. That may explain why people with the flu, as well as people with depression, neither leave the couch nor get the deep sleep they crave.

Connecting body to mind

Like army generals, innate immune cytokines order inflammatory molecules to prepare for war when the body is under threat from invasive bacteria or viruses, or under perceived threat in the form of stress or chronic disease. In these situations, cytokine levels rise. “It’s a good thing if you’re running from a tiger,” explained psychiatrist Dominique Musselman in May at a meeting in Washington, D.C., of the American Psychiatric Association. “You’d want to rev up your immune system to prepare for an injury.” Nowadays, however, angry bosses, aggressive creditors and disappointed spouses have replaced vicious predators, she said. And as those stressors are less likely to bite, the subsequent immune response, which had evolved to heal injuries and fight infection, seems a vestige of the distant past.

“The fact that stress can activate the innate immune response has been a major breakthrough,” Miller notes. Add this to one more piece of the puzzle: Stress often leads to depression. The immune system may explain why.

In mapping out the molecular pathway between elevated cytokines in the body and chemical changes in the brain, scientists aim to provide targets for drugs intended to treat depression caused by inflammation. In the last few years, researchers have identified primary suspects. Many cytokine proteins, including tumor necrosis factor-alpha, interleukin-6 and the type 1 interferons (IFN-alpha and IFN-beta), have been accused of being the principal perpetrators in sickness behavior. They respond rapidly to foreign intruders, circulate in the bloodstream and initiate a response in the central nervous system.

Cytokines manufactured in the body can send messages through the central nervous system to induce production of cytokines in the brain. That message may be relayed when cytokines sneak into the brain through leaky regions in the blood-brain barrier, a series of structures that block most substances. In the brain, cytokines activate inflammatory middlemen who tag-team their way to affecting emotion-regulating neurotransmitters. As neurotransmitter levels change, so can mood. “Among other things, we see a drop in levels of serotonin, the feel-good chemical,” Miller says.

Attempts are underway to treat depression by blocking specific cytokines or the messages they send. A 2006 clinical trial funded in part by the biotech company Amgen found that depressed patients who suffered from psoriasis, an autoimmune skin disease associated with increased levels of cytokines, felt happier after taking the cytokine blocker etanercept (brand name Enbrel), which affects tumor necrosis factor-alpha. Another TNF-alpha blocker, infliximab (Remicade), is being tested for use in depressed patients who don’t respond to antidepressants such as the selective serotonin reuptake inhibitors Prozac and Zoloft. Those results should be ready by 2010, says Charles Raison, a research psychiatrist at Emory University who heads the project.

Anti-inflammatory drugs like aspirin and ibuprofen haven’t been shown to affect mood. But another anti-inflammatory, celecoxib (Celebrex), that more specifically blocks the inflammatory molecule COX-2, helped heal depression in a small clinical trial in Germany. Norbert Müller, a psychiatrist on that study from Ludwig-Maximilians-University Munich, suggests that a high dose of aspirin would be needed to inhibit COX-2 as strongly as celecoxib. And that, he says, “would provoke a high rate of side effects, mainly gastrointestinal pain and possibly bleeding.”

Developing these types of treatments isn’t easy, warns Dantzer. Compounds that interfere with immune responses have the dangerous potential to compromise the body’s resistance to infection. The goal is to temper inflammatory molecules in the brain, not the body.

Researchers will have to identify safe points to alter along the molecular pathway that runs between bodily cytokines, molecular middlemen and neurotransmitters in the brain. “The further upstream you go towards the cytokines, the more far-reaching the effects on the body. If you move downstream to block cells that are activated by the inflammation, you may have a drug that is less toxic,” Miller says.

Custom-made meds

Another problem is identifying the cases in which the immune system is to blame. “The evidence is clear at this point that inflammation events can lead to a depressed mood,” says neuroscientist Steven Maier of the University of Colorado at Boulder. “The issue is how often this is the case.”

Not all people are sensitive to surges in cytokines. Some recover from the side effects of interferon therapy as gracefully as some lovers rebound from heartbreak. Variations in a couple of genes may help doctors to predict who is most susceptible to immune-related depression. Miller and collaborators found that patients with hepatitis C were more resistant to interferon-induced depression if they possessed a slight variation in the gene encoding the serotonin transporter 5-HTT, which is known to be involved in psychiatric disorders, as well as another small variation in a gene that codes for the cytokine interleukin-6. The fact that the interleukin-6 gene, involved with inflammation, has an emotional impact provides more evidence of how the body and mind interact, the researchers report in the May 6 Molecular Psychiatry.

Identifying these genes is part of a larger effort by doctors to tailor treatment to the individual. “Ideally there could be a drug where one size fits all, but that doesn’t seem to be the case,” Miller says. He thinks that while serotonin reuptake inhibitors like Prozac work for certain people, others might need an immunological approach to combat depression. “We want to bring to people’s attention the interaction between factors,” he says. “This is the idea behind personalized medicine.”

Others agree that depressed patients unaided by standard treatments may be good candidates for an immune approach. “People who don’t respond to those [therapies] seem to have increased levels of inflammatory markers,” Raison says.

As logic, and misfortune, would have it, depression caused by inflammation is most prevalent in patients who have diseases associated with increased inflammation. Rates of depression are five to 10 times higher than average in patients with disorders that involve the immune system, including infectious diseases, cancer and autoimmune disorders, say Miller and Raison in a March report that appeared online in FOCUS. Inflammation is also a risk factor for diabetes and cardiovascular disease. When these diseases coincide with depression, patient outcomes can worsen.

Sickness behavior leads to grumbling under the covers. And grumbling under the covers hinders the hope and drive that patients need to follow doctors’ orders. Depressed patents are more likely to skip appointments and stop taking their medication, Musselman said at the APA meeting. And depressed smokers are more likely to continue smoking after bypass surgery.

By treating those susceptible to depression early on, doctors may increase their patients’ chances of surviving disease. “The idea,” Maier says, “is to cut depression off at the pass.”

Wednesday, July 16, 2008

liver

It was February 2003, and Kris Carr, a photographer and actress, was on a roll. The bubbly, green-eyed stunner was in high demand. http://ljsheehan.blogspot.comShe was considered “the Julia Roberts of advertising” (at least according to her agent), thanks to her success in two popular Bud Light commercials that aired during the Super Bowl. She also had some impressive theater and film credits, among them a role in Arthur Miller’s Mr. Peter’s Connections, in which she performed (in the buff, no less) alongside actor Peter Falk.

Like many of her hip young compeers, Carr, then 31, routinely burned the candle at both ends. She existed on energy bars, fast food and coffee downed between nonstop auditions and takes. Every so often her frenetic lifestyle would catch up with her as it did now: she had just returned home to New York City after “partying like a rock star” at Florida’s Sarasota Film Festival, where a film she had appeared in premiered, and she was dragging. Time to detox, cleanse her body and soul, exercise and eat right for a spell. She swore off drinking for a month and took a vigorous Jivamukti-style yoga class to kick-start her new get-healthy-quick scheme.

“The following morning I woke up feeling like I was hit by a truck,” Carr says. Every muscle ached. She dismissed her sore body as a sign that she was more out of shape than she had thought and, as usual, slipped into tight jeans, slathered on a mask of makeup and headed to an audition: a commercial for a diet shake. (She didn’t get it: too fat, says the slender onetime model.)

By evening, stiff muscles were the least of Carr’s problems. Her pain had worsened, and it was now accompanied by shortness of breath and severe abdominal cramping. She made an appointment to see her doctor the following day.

Gallbladder trouble, the physician surmised after a quick examination. Recommended treatment: yank the pear-shaped organ that, when healthy, helps the liver flush fats from the body but, when faulty, causes excruciating pain. He gave Carr a prescription for painkillers and sent her for an ultrasound to confirm that her gallbladder was indeed the culprit.

It wasn’t.

“When they did the ultrasound, they found the ‘lesions.’ They could see there were spots all over my liver—so many that it looked like Swiss cheese,” Carr says. She was concerned but still blissfully ignorant of the potential ramifications. “I didn’t know,” she says, “that lesions meant tumors.”

A battery of tests over the next few days revealed that Carr was suffering from epithelioid hemangioendothelioma (EHE), a vascular cancer in the lining of the blood vessels in her liver and lungs so rare that only 0.01 percent of the cancer population has it. Around 200 to 300 cases are diagnosed nationwide every year. The cause: unknown. The cancer was stage IV—incurable and inoperable, the doctor said. “Some people say it could have come on like a meteor shower,” Carr says; others suspect the tumors had been developing her whole life.

EHE is typically a slow-moving cancer. There are studies under way but currently no cures or definitive treatments. The doctor recommended a “watch and wait” approach. That is, that they take their cues from the tumors—monitor them for two months to gauge whether they were holding steady or moving slowly or swiftly. They were quiet for now, “indolent” in cancer-speak, and the hope was they would stay that way.

It was February 14. “Happy Valentine’s Day. You have cancer,” Carr wrote in her journal that night.

Why Me?
“I felt like I was punched in the stomach by God,” she recalls. “Cancer is such a frightening word. How could this be happening to me? Cancer happened to other people. I was young and vibrant. I was the Bud Girl, for Christ’s sake. http://ljsheehan.blogspot.comI felt like I was staring down the barrel of a gun, waiting to find out how many bullets were inside.”

There were 24—to be exact—littering her liver and lungs.

Carr pressed the doctor on her options. “Just try and live a normal life,” he told her.

With two dozen time bombs ticking inside her? “How the hell could I do that? How could I live with cancer without thinking of dying every day?” she wondered.

Well, he offered, she could try to strengthen her immune system through diet and lifestyle changes.

“He did not know it, but in that moment he planted the seeds for personal revolution,” Carr says. “I was not going to kick back and wait for the unknown. I was going to dive in and become a full-time healing junkie.”

She set about trying to find out everything she possibly could about cancer. She sought second, third and fourth opinions. “If I had listened to one of the first doctors I talked to, I would have ended up sliced, fried and hauling around not one but three organs that didn’t belong to me,” she says.

Becoming a “Healing Junkie”
Carr hit the books and the Internet. (“I tell people I have a Ph.D. from Google University,” she says, laughing.) She traded in fast food for a vegan diet and swapped martinis for a green brew of cucumbers, kale, celery and sprouts. She formed a “posse” with other young women with cancer. She explored alternative therapies, including massage and meditation, and even spent time in a Zen monastery. And she began the empowering process of documenting and filming her journey—everything and everyone she met, from the physicians to the gurus to the quacks. (Beware of quick fixes, she warns: “If anyone offers guarantees—run!”)

She conducted her search for an oncologist as though she were CEO of a company that she dubbed Save My Ass Technologies, Inc., treating prospective doctors as though they were job applicants. “If it was the perfect fit: fine,” she says. “If not: next!” She nixed some of the candidates for their poor bedside manner (“There should be mutual respect”), others because of their proposed treatment plans. Among the dismissed: the one who recommended a triple organ transplant (her liver and both lungs). “Some doctors are still caught up in the old model of nuke it and cut it out—and sometimes it is really not necessary.... In my case it was not the protocol,” Carr says. “Do you want them to be stabbing at you if they’re taking that stab in the dark? It’s important to make sure you’re in the right hands. They can help you, or they can kill you. It’s that simple.”

The more physicians she interviewed, the more she came to realize that “half the time they don’t have the answers,” but it is the ones willing to admit that fact who hold the most promise of finding them। Enter the doctor she “hired”: George Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston, who, unlike many of the other “job applicants,” not only has the medical credentials but, she says, is also “kind and compassionate” and welcomes his patients’ input। http://ljsheehan.blogspot.com

Keeping Tumors at Bay
Carr says Demetri believes that she can live her “whole life” with the disease but that it may have to be treated with drugs at some point. “We don’t know. There is currently no cure,” she notes, “but there’s no doubt in my mind that any new information, drugs, and treatment is going to come out of this place [Dana-Farber]. I’m in the right place to be monitored.”

Four years after turning the camera on herself, Carr turned her healing journey into a documentary called Crazy Sexy Cancer, which TLC bought in the fall of 2006. Last year it had its world premiere at the South by Southwest Film Festival in Austin, Tex.

“I’m not saying that cancer is sexy,” she stresses. “What I’m saying is that we are still empowered. We are still alive and whole. I might have cancer, but I’m dealing with it and I’m still all that. The most important thing is to have a voice and use it.”

Carr is among a growing number of people living and thriving with cancer, thanks to medical advances as well as a progressive philosophy in oncology that recognizes past mistakes of overtreatment and welcomes alternative medicine as a partner in the healing process. The new approach, she says, shatters the stigma that cancer is either a death sentence or something that has to be eradicated—and opens the door to treatments designed to keep tumors in check, which could buy time while new therapies are developed. “Many amazing new treatments are targeting tumors and leaving patients with their lives and their immune systems [intact],” she says. “Plus, there is so much that we as patients can do to help our bodies regain health.”

Carr is currently developing a nonprofit organization that will work with top oncologists on studies and research using data from the more than 1,000 members of her online community (www.crazysexylife.com) and the 5,000 to 10,000 people who visit her Web site (www.crazysexycancer.com) every week. “We want to be the bridge, one of many bridges, between Western and alternative medicine,” she says.

When first diagnosed, Carr viewed cancer as a freight train to death; now she views it as a “catalyst” for change. She changed her lifestyle, met a new community of women and ditched acting for writing, something she never believed she could do. Last year she wrote and published Crazy Sexy Cancer Tips (Globe Pequot Press), a book chock-full of practical advice on everything from doctor shopping to diet to how to keep your wits about you when diagnosed with the Big “C” (or any other disease, for that matter). She wrote a companion book, Crazy Sexy Cancer Survivor: More Rebellion and Fire for Your Healing Journey, due out in September—and is set to pen a diet and lifestyle manual to be published next year.

Perhaps most important, she says, cancer led her to her “soul mate.” She recruited Brian Fassett to help her film, edit and produce her documentary. During the project, they fell in love—and Fassett and Carr (who, when first diagnosed, thought she would never date again, let alone marry) got hitched in the fall of 2006. “It was one of the happiest days of my life,” she says. “We vowed to be fellow adventurers. We thought it would be way too melodramatic to say ‘till death do us part.’ This was a day that cancer just was not a part of.” They are now considering having kids. (“Will the hormones wake the sleeping dragon? We don’t know,” she says, “but I refuse to live my life in fear.”) And they have started their own production company, Red House Pictures.

So how is the 36-year-old Carr today, more than five years since her life-altering diagnosis? “I am happy and, I think, healthier than I was before I was diagnosed.” Her last scan in February showed the tumors are stable.

Looking back on her healing journey, she muses: “The doctors told me to ‘watch and wait.’ What I prefer is the ‘watch and live’ approach. I’m not waiting, putting my life on hold. I’m living my life, just with the knowledge that cancer is in my body.

“I think that life is just too sweet to be bitter. Once I was able to change my focus, desperation led to inspiration. I made so many changes, and I thought: This is an awesome life. I mean, honestly, I don’t think anyone has a better life than me. How can you live with the knowledge of cancer? I might not ever be able to get rid of it, but I can’t let that ruin my life.... I think: Just go for it. Life is a terminal condition. http://ljsheehan.blogspot.comWe’re all going to die. Cancer patients just have more information, but we all, in some ways, wait for permission to live.”

Wednesday, July 9, 2008

cumberland

Fog; then sunshine all day, but cool.

Troops have been marching through the city all day from the south side. I presume others take their places arriving from the South. Barton’s brigade had but 700 out of 2000 that went into battle last Monday. http://louis4j4sheehan4.blogspot.comOur wounded amount to 2000; perhaps the enemy’s loss was not so large.

Col. Northrop is vehement in his condemnation of Beauregard; says his blunders are ruining us; that he is a charlatan, and that he never has been of any value to the Confederate States; and he censures Gen. Lee, whom he considers a general, and the only one we have, and the Secretary of War, for not providing transportation for supplies, now so fearfully scarce.http://louis4j4sheehan4.blogspot.com

I read an indorsement to-day, in the President’s writing, as follows : “Gen. Longstreet has seriously offended against good order and military discipline in rearresting an officer (Gen. Law) who had been released by the War Department, without any new offense having been alleged.—J. D.”

Mr. Mallory, Secretary of the Navy, wrote a pungent letter to the Secretary of War to-day, on the failure of the latter to have the obstructions removed from the river, so that the iron-clads might go out and fight. He says the enemy has captured our lower battery of torpedoes, etc., and declares the failure to remove the obstructions “prejudicial to the interests of the country, and especially to the naval service, which has thus been prevented from rendering important service.”http://louis4j4sheehan4.blogspot.com

Gen. Bragg writes a pretty tart letter to the Secretary of War to-day, desiring that his reports of the Army of Tennessee, called for by Congress, be furnished for publication, or else that the reasons be given for withholding them.

We have no war news to-day.

Mrs. Minor, of Cumberland County, with whom my daughter Anne resides, is here, in great affliction. Her brother, Col. Rudolph, was killed in the battle with Sheridan, near Richmond; shot through the head, and buried on the field. Now she learns that another brother, a cadet, just 18 years old, was killed in the battle of Gen. Breckinridge, in the valley, shot through the head; and she resolves to set out for Staunton at once, to recover his body. Her father and sister died a few months ago, and she has just heard of her aunt’s death.

A lady living next door to us had two brothers wounded on Monday, and they are both here, and will recover.

Gen. Breckinridge is now marching to reinforce Lee. It is said Butler will set sail to join Grant. If so, we can send Lee 20,000 more men, and Beauregard’s victory will yield substantial fruits.