Conie we need to talk now!

[Guest guest]

Back in May 1998 I worked in the main LAB lab at Great Lakes Navel

(durring my intern), I did be come very ill 4 months into my MLT

studies (I drew blood and proccecd the blood) and urine samples! I

had to stop my intern in Aug of 99. Could thid be it? it sure as hell

makes sence now! I drew all the new recruts HIV tests and di all the

female blood Preg tests!

PS. I dont think I can sleep tomightnow thnking about all of this!

And how many of us were MT's, MLT', or Phlebotomists?

Caonnie e-mail me at westernairegal @aol.com eith you # so we can

talk more about this! Also The navy made me take TONS of shots before

I was accepted in the LAB and I have no idea what they gave me, it

was 7 shots.

-------------------------------------------------

> Hi ,

>

> In today's (5-17-02) issue of the Wall Street Journal, there was an

> article that reminded me of our earlier discussion....that of the

> lack of clinical trials due to the lack of funds. I thought the

> article was very interesting in and of itself, but if you

substitute

> antibiotics instead of the prednisone and substitute RP instead of

> sepsis....you will see the similarities. It seems that this

> situation happens over and over again.

>

> Sending hugs,

>

> Connie

> here's the article:

> Why Cheap Drugs That Appear

> To Halt Fatal Sepsis Go Unused

>

> By THOMAS M. BURTON

> Staff Reporter of THE WALL STREET JOURNAL

>

>

> It was strictly happenstance that sent the doctor off on his quest.

A

> young mother hovering near death in a Connecticut hospital was

> misdiagnosed, and given a drug she wouldn't otherwise have gotten.

> She recovered.

>

> Then the doctor, G. Umberto Meduri, learned that what the woman

> actually had was sepsis, a devastating condition that has long been

> as baffling as it is deadly. Often beginning as a blood infection

> after surgery, sepsis can quickly turn lethal. It kills an

estimated

> 215,000 people in the U.S. annually -- more than the combined toll

of

> the worst cancers, of the lung and colon.

>

>

> 4th in a series: See previous articles in series

>

>

> The puzzling thing was that the drug this woman got was a steroid,

> supposedly worthless for sepsis. Research seeming to show this

> futility was common at the time. " In the late 1980s, anyone in our

> field would have said you're an idiot if you use steroids " for

> sepsis, says Dr. Meduri, who is now at the University of Tennessee

> Health Science Center in Memphis.

>

> What followed was 15 years of tantalizing but tiny studies that

> seemed to jibe with what happened in the Connecticut hospital. Now,

> Dr. Meduri and colleagues in the U.S. and Europe have accumulated a

> modest body of evidence that the deadliest forms of sepsis often

> yield to cheap, common steroids such as cortisone. A researcher at

> the University of Paris recently found that steroids led to nearly

a

> 30% drop in deaths from septic shock, a severe form of sepsis in

> which blood pressure plunges.

>

> If the approach is indeed effective, it would be big economic news:

> It typically costs less than $50. The only drug specifically

approved

> for severe sepsis is about $7,000 a dose.

>

> That drug, Eli Lilly & Co.'s newly approved Xigris, was the fruit

of

> huge studies costing hundreds of millions of dollars, and Lilly is

> spending lavishly to promote it. The Meduri approach languishes,

> because no one has ever done the large-scale studies that most

> doctors need to be convinced.

>

> • See what happens when an infection invades the body and how

it

can

> lead to sepsis, using the example of a respiratory infection.

>

>

>

>

> The steroids saga illustrates one reason expensive brand-name drugs

> don't face more competition from low-priced generics. There is

little

> incentive for big pharmaceutical companies -- the main financiers

of

> drug research -- to pay for studies of using steroids against

sepsis,

> because the steroids' patents have expired. The National Institutes

> of Health also turned Dr. Meduri down. It primarily funds basic

> scientific research, not human trials of drugs.

>

> Dr. Meduri, who finally got modest funding from a church-affiliated

> health-care foundation in Tennessee, has recently had to slash the

> size of what he hoped would be a major study, as his funding runs

> low. He has laid off some researchers and he lost one of his labs

> when the University of Tennessee reassigned it. Sitting in freezers

> are thousands of blood-plasma samples that might reveal which

> patients' genetics make them likeliest to benefit -- samples there

is

> no money to analyze.

>

> " Meduri has been a voice crying in the wilderness, " says J.

> Marini, a University of Minnesota medical professor and specialist

in

> critical care. " His data are intriguing, and consistent with my

> clinical experience. I have no doubt whatever that steroids have

> saved patients of my own. "

>

> It's a Catch-22: Because money is unavailable, only small studies

are

> possible. Because they are small, they are viewed as less than

> convincing, allowing skepticism to persist -- and money to remain

> unavailable. The drugs that draw the industry's heavy research and

> promotional money are the branded ones, which are also far more

> expensive.

>

> By all accounts, the prime skeptic is Gordon R. Bernard, a

prominent

> Vanderbilt University critical-care specialist. He was the chief

> investigator both on a 1987 study showing steroids ineffective, and

> on the main large study of Lilly's Xigris. Dr. Bernard has been

> sarcastic in his criticism of Dr. Meduri's work, attacking him in

> unusually personal terms. In a medical-conference debate with Dr.

> Meduri at Chicago's Drake Hotel in 1998, for instance, Dr. Bernard

> seemed to question Dr. Meduri's IQ. At the same conference, in a

> remark citing one of the steroids, Dr. Bernard said, " Elvis was

> spotted again in Memphis ... only three hours after Dr. Meduri was

> seen at the grave-site of Elvis at Graceland attaching

> methylprednisolone to the grave. "

>

> Dr. Bernard says he regrets his IQ remark. As for whether steroids

> used the way Dr. Meduri proposes could help with sepsis, he says

> it " is a fair hypothesis -- but give me some data. "

>

> Sepsis -- which is often the culprit when a newspaper story says

> someone died of " complications " from surgery or illness -- can

savage

> a young body as well as an old one. Shanna Carel, a member of the

> pompom squad at the University of Memphis, went out for pizza one

> night in 1998 and felt ill. Twenty-four hours later, she was

> diagnosed with meningitis from airborne bacteria. It swiftly

> progressed to septic shock and acute respiratory distress syndrome.

>

> Within hours, Ms. Carel was on a ventilator, fighting for her life.

> Given four weeks of low-dose, intravenous steroids in one of Dr.

> Meduri's studies, she survived. She now is 24 and a nursing student.

>

>

> Her story suggests why sepsis and the closely related acute

> respiratory distress syndrome have escaped broad awareness. No one

> suffers from them chronically. Patients usually either die -- as

> about a third of those with severe sepsis do -- or return to

general

> health in a few months. This doesn't make for support groups or

> publicity.

>

> Out of Control

>

> The body reacts to bacterial invaders such as Ms. Carel's with

> inflammation, a response that is normally beneficial. But in severe

> sepsis, the inflammation gets out of hand and turns into a raging

> forest fire instead of a controlled blaze. It can cause the liver,

> the lungs or other organs to simply shut down.

>

> The body normally regulates its inflammatory response with

steroids.

> A signal sent from the pituitary gland in the brain to the adrenal

> glands, sitting atop the kidneys, tells them to send out a steroid

> called cortisol. The cortisol's role is to prevent overproduction

of

> inflammatory chemicals. However, in sepsis, cells become less

> sensitive to the cortisol. It can't curb the inflammation.

>

> Two decades ago, doctors tried common steroids for sepsis. They

gave

> them in megadoses, for 24 hours or so. By 1987, this approach had

> been widely discredited by large-scale studies of human patients,

the

> most prominent of which was published by Vanderbilt's Dr. Bernard.

>

> The approach of Dr. Meduri and others such as Djillali ne at

the

> University of Paris is quite different. Instead of megadoses, they

> give steroids for days or weeks, intravenously, at doses of only 2%

> or less of those used in the 1980s. They believe synthetic steroids

> such as hydrocortisone and methylprednisolone can reactivate the

> cells' sensitivity to cortisol, curtailing inflammation.

>

> This may have been what helped Grady Marlow Jr., a retired

accountant

> and lawyer in Germantown, Tenn., who had a heart attack in late

1998.

> During a cardiac procedure, he breathed in stomach contents he had

> coughed up, developing sepsis and acute respiratory distress

> syndrome. He lingered for seven days on a ventilator. Then, given a

> low dose of methylprednisolone in a Meduri study, he improved

enough

> to have heart surgery. Now the 80-year-old widower is back home and

> doing well. He says he has become a regular at a Baptist Church in

> Memphis, where " there's a lot of widows. "

>

>

> Most doctors facing a sepsis case don't try the treatment Mr.

Marlow

> got. There's little legal or economic reason not to, because the

> steroids are approved drugs with long safety records. But some

> doctors aren't interested unless they see results from a large

trial,

> and many others have never heard of the treatment. Many doctors get

> most of their knowledge of new drug treatments from pharmaceutical

> companies, which have no interest in dispatching emissaries to talk

> about low-priced drugs with long-expired patents.

>

> By contrast, Lilly promotes Xigris through a large sales force and

> also pays 250 critical-care specialists to speak to colleagues

about

> the IV drug, for $1,000 to $1,500 per talk. Lilly also recently

> treated critical-care doctors to a concert by jazz singer-guitarist

> Benson during a conference in San Diego, and last year it

gave

> a dinner for other critical-care specialists during a Brussels

> medical conference. It says it has decided to stop providing such

> entertainment because of adverse public perceptions. Lilly has sold

> $43 million of Xigris in the drug's first full quarter on the

market.

>

> The case that piqued Dr. Meduri's interest came in 1987. He was on

> staff at Norwalk Hospital in Connecticut when Janet Machala, an

> artist, was hospitalized for a severe respiratory infection. A

> pathologist misread a biopsy slide and concluded she had a rare

> pneumonia, which called for a low dose of steroids over many days.

> Lingering near death on a mechanical respirator, Ms. Machala was

> hooked up to a steroid IV drip for four weeks. After the first four

> days, she was able to get off the respirator.

>

> Then Dr. Meduri found out she had actually had sepsis and acute

> respiratory distress syndrome. He continued to treat some sepsis

> cases with steroids at a low dose, had success, and published his

> results. A paper he wrote for Chest, a leading respiratory-disease

> journal, carried the provocative title, " Is the Right Drug Used the

> Wrong Way? "

>

> What was needed was a large study matching the treatment against a

> placebo. He sent out numerous grant requests to drug companies,

> government agencies and foundations. They all said no, including

> Upjohn Co., the maker of methylprednisolone. It had partly funded

the

> study that showed megadoses of the steroid ineffective. In

addition,

> the steroid's patent had expired.

>

> A decade later, after Upjohn became part of Pharmacia Corp., Dr.

> Meduri made a plea to Pharmacia's chief executive, Fred

> Hassan. " Because of this drug developed by your company, we have

seen

> a precipitous drop in morbidity and mortality in patients with

[acute

> respiratory distress syndrome]. It is unfortunate and disappointing

> that your company is unwilling to support this promising and life-

> saving effort, " Dr. Meduri wrote. A Pharmacia spokeswoman

says, " Drug

> companies get loads of requests to do studies, but given this

> background, we chose other priorities. "

>

> Desperate for money, Dr. Meduri turned to an unlikely source and

> finally struck paydirt. An official at Baptist Health Care Corp. in

> Memphis, a foundation that operates 17 hospitals, had heard of his

> work. It gave him funding for a clinical trial in patients with

late-

> stage acute respiratory distress syndrome.

>

> This work resulted in a Journal of the American Medical Association

> paper in 1998 concluding that " prolonged administration of

> methylprednisolone " was associated with " improvement in lung

injury "

> and " reduced mortality " in respiratory distress, which often

results

> from sepsis. Specifically, none of 16 patients who got steroids

from

> the beginning died. Five of the eight who started out on a placebo

> did.

>

> Dr. Bernard criticizes both the study's size and its methodology.

Its

> 24 patients contrast with the 1,690 in one study he supervised of

> Lilly's Xigris. And the steroid researchers, though they didn't

know

> which patients were getting the drug and which a placebo, switched

> the patients who weren't responding after 10 days to the other

> treatment. That move made it harder to analyze the results.

>

> " Gordon [bernard] is skeptical and Umberto [Meduri] is a big

> advocate. The middle ground is probably correct, " says another

> leading critical-care doctor, Philip Dellinger in Camden, N.J. He

> says the Meduri research is " a very impressive study, and I found

> encouraging the fact that there was a broad effect on inflammation.

> But it was a small number of patients. "

>

> Drop in Mortality

>

> A study by Dr. ne in France linked low-dose steroids to a 29%

> fall in deaths from septic shock. That appears to be a larger drop

in

> mortality than Xigris has shown in severe sepsis, and without the

> bleeding risk the Lilly drug entails. Lilly officials say they

> believe Xigris is superior. But " if steroid researchers are

> successful, that's fantastic, " says Elaine Sorg, head of Lilly's

> critical-care business. The French doctor's study, like Dr.

Meduri's,

> was far smaller than Lilly's.

>

> Dr. Meduri had hoped to enroll 200 patients in a new sepsis study

but

> had to limit it to 80 for lack of funding. As a result, he worries

> that this, too, " may not have the statistical power to show a

> mortality benefit. "

>

> But Dr. Meduri's fortunes may be changing. His group recently

> published an analysis showing that steroids called glucocorticoids

> lowered the levels of inflammatory chemicals in patients who

survived

> acute respiratory distress syndrome. One co-author was

> Chrousos, an authority on that type of steroid, who is also the

> National Institutes of Health's chief of pediatric and reproductive

> endocrinology. Dr. Chrousos has become an influential believer in

Dr.

> Meduri's ideas.

>

> He believes the NIH, which once declined to pay for Dr. Meduri's

> research, will do so now. " This basically says that patients with

> [acute respiratory distress syndrome] and early septic shock should

> be on glucocorticoids, " Dr. Chrousos says.

>

> --------------------------------------------------------------------

--

> ----------

>

> How Sepsis Can Occur

> What happens when an infection invades the body and how it can lead

> to sepsis, using the example of a respiratory infection.

>

> 1. Bacterial products or other inflammatory agents enter the lungs,

> activating a protein called NFkB. NFkB stimulates the production

> of " fighting " proteins called cytokines.

> 2. These cytokines are sent into the bloodstream to organs. The

> resulting inflammation can kill bacteria, but if unabated,

> inflammation can turn into sepsis and threaten vital organs.

> 3. When cytokines reach the brain's pituitary gland, it releases a

> hormone called ACTH.

> 4. ACTH flows through the bloodstream and stimulates the adrenal

> glands to produce a steroid called cortisol.

> 5. Cortisol attaches to cell proteins, called glucocorticoid

> receptors, regulating the ability of NFkB to stimulate cytokine

> production. When the regulation doesn't occur properly,

inflammation

> can spread, leading to sepsis. Dr. Meduri contends additional

> cortisol-like steroids can restart the normal process.

>

> Sources: WSJ Research; Merck Manual; University of Tennessee