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Tuesday, July 29, 2008
Rheumatoid arthritis is one of the most debilitating forms of arthritis, causing joints to ache and potentially become deformed. These symptoms can make even the simplest activities difficult to manage. But with proper treatment, it may not have to get that bad. Learn about treatment options that can help you live better with RA.
This HealthTalk program is supported through an unrestricted educational grant from
This program is produced by HealthTalk and supported through an unrestricted educational grant from Abbott Laboratories. We thank them for their commitment to patient education. Our panelist today reports he has received prior funding from the sponsor of this program. The opinions expressed on this program are solely the views of our guest. They are not necessarily the views of HealthTalk, our sponsor or any outside organization. As always, please consult your own physician for the medical advice most appropriate for you. Now, here's your host, Dick Foley.
Hello and welcome to our program, Treating RA: What You Need to Know. RA, rheumatoid arthritis, is one of the most debilitating forms of arthritis, causing joints to ache and potentially become deformed. These symptoms can make even the simplest activities difficult to manage. But with proper treatment, it may not have to get that bad. Today, you'll learn about treatment options that can help you live better with RA.
I'm pleased to welcome our guest, Dr. Alvin Wells, who is director of the Rheumatology and Immunotherapy Center in Oak Creek, Wisconsin. Dr. Wells is also clinical assistant professor at the Rosalind Franklin University of Medicine and Science [in North Chicago, Ill.] and adjunct assistant professor at Duke University Medical Center [in Durham, N.C.].
Dr. Wells, is there a certain type of person, according to gender or age or race, who is most likely to get rheumatoid arthritis?
Dr. Alvin Wells:
Not specifically. We know that rheumatoid arthritis can affect patients of all ages, all races and all genders. One of the things which is curious about the disease is that it does tend to affect females more often than males. Usually, [it's] about three to four times more likely in females than in males.
What we've also seen is that even in younger individuals there's a condition called juvenile rheumatoid arthritis that can affect people, and I've seen kids as young as 18 months old. So again, [there's] no specific profile, but it does tend to be a little bit more common in females compared to males.
But even childhood onset, then, is not uncommon?
Dr. Wells:
Absolutely. And there, of course, is a whole area of pediatric rheumatology to treat kids with juvenile arthritis. And also some adult rheumatologists like myself see patients 12 and up and that kind of age group, and begin to treat them and diagnose rheumatoid arthritis.
This is, I assume, considered an autoimmune disorder?
Dr. Wells:
It is. I make the analogy like a bystander attack. So whenever your immune systems get up to remove, let's say, a bacterial infection or viral infection and those cells become activated, as a result of that they end up damaging normal parts of your body, in this case, the joints. So the autoimmune response is where the body's own immune system turns against itself, damaging the joints and other tissues.
Simply stated, this is when our immune system makes a terrible mistake.
Dr. Wells:
[That's] exactly right. And that's why some of the treatment that we have is almost geared toward resetting the immune system.
What are some of the first signs and symptoms that a person might notice if it, in fact, is rheumatoid arthritis?
Dr. Wells:
One of the unique features of the disease is that it does involve the small joints, for example, of the hands or the feet. It's a very curious disease. If it affects the first finger on the right hand, it will affect the exact same finger on the opposite side. So it usually has a symmetrical pattern, meaning affecting both sides of the body.
And again, it's associated with other symptoms. One thing we see in patients is profound stiffness in the mornings. We have patients who wake up in the morning, and it can take them several hours really to feel that they're able to function almost normally.
And that stiffness would be in leg joints, in the lower back, where would they feel it?
Dr. Wells:
It could be all over but primarily in the small joints of the hands or the feet. But people can also be affected in the neck, the shoulders, the elbows and also the knees. It usually does not involve the hip. So if we have somebody that has hip or lower back pain, that probably is not rheumatoid arthritis.
The symptoms, do they appear gradually? Do they worsen slowly, or is the progression of the disease all over the map and somewhat unpredictable?
Dr. Wells:
It is all over the map. There are some patients who wake up dramatically. I've had some patients who said they went to bed healthy, and they wake up the next morning with their joints swollen and stiff. So that can happen.
But usually, this patient will have disease for a number of weeks. And actually, we have certain criteria that we go by. If someone has swollen, tender joints that are present for at least six weeks, that probably does suggest rheumatoid arthritis.
Once the symptoms have appeared, doctor, does that mean that the disease has already done some damage to the joints in the body?
Dr. Wells:
Yes. And believe it or not, many patients, by the time they come into the clinic to see a rheumatologist, a significant amount of them already have some structural damage, meaning if you do X-ray the hands or the feet, you begin to see some small changes around the bone and the cartilage of the joints. So one of the things we're really teaching patients and other physicians is to recognize the symptoms early on and get them to a rheumatologist rapidly, so we can reverse or even prevent any further damage to the joints.
So starting treatment early is something that is recommended?
Dr. Wells:
That is a key. This is a new paradigm in rheumatology. Years ago, we would wait and gradually add newer medications. And now we've actually - we call it inverting the pyramid, where we start aggressive medications early on and then begin to taper those medications down based on the patient's symptoms.
I see. Now, I heard you mention X-ray. Is that the chief tool in diagnosing RA?
Dr. Wells:
That is one of the ones we do to start off. They're very cost effective. They're easy to do - a simple X-ray of the hands or the feet. Even if somebody is not symptomatic, we use that as part of the diagnostic criteria. And actually, when you look at rheumatoid arthritis, having the presence of damage on the joints is one of the signs that we look for.
Now we've actually gone a step further, what I call more of the 21st century, beginning to do ultrasound and MRIs, which actually pick up even changes that might not be seen on X-rays.
Okay. So other kinds of imaging now are being used, and that will guide the doctor even more precisely in the treatment of the disease?
Dr. Wells:
Absolutely. For example, I have an ultrasound in my practice that we use routinely to pick up changes in the joints. We can look for swelling. And one of the nice things about the ultrasound, we can put a patient on medication and then see if they actually are improving over several months.
That would be very helpful indeed. Is rheumatoid arthritis ever diagnosed as something else?
Dr. Wells:
Yes, unfortunately, sometimes it can be misdiagnosed. Many patients - particularly the male patients, they're the tougher ones - will self-medicate. As you know, in this country we have a lot of medications over the counter, things like ibuprofen, Aleve [naproxen] and Tylenol [acetaminophen], and those do relieve the symptoms. So when patients take those medications, they get some relief. But over a period of time, those medications will lose their effect. So people might think they have, for example, backaches or maybe sprained their foot or their wrist, and they're treating with those assumptions, when it turns out they might actually have rheumatoid arthritis.
I'm hearing you say that it's a mistake for people to self-diagnose and just treat the symptoms.
Dr. Wells:
I think so. I think, again, if somebody has some swelling in the small joints of the hands or the feet that's been present for more than a few days, the first place to start is with their primary care physician, a nurse practitioner or a physician assistant, and then with them recognize the disease and get them to quickly make a referral to a rheumatologist.
Once a person is diagnosed with RA, doctor, how do you measure the progression of the disease? How do you know if it's going to progress rapidly or gradually, or do you know?
Dr. Wells:
There are several tools that we use to give us an idea of where on the spectrum of the disease activity a patient will fall. One of the things we talked about already, how this is an autoimmune disease, and there are certain factors, there are certain things that we'll look for in the bloodstream that can give us an idea about how active the disease is.
And one of those is something called the rheumatoid factor. We know that this factor is present in the bloodstream of about 80 percent of the patients with rheumatoid arthritis. And, again, if people have high levels of this rheumatoid factor, they are more likely to have a more aggressive course of the disease.
When there is a misdiagnosis early on, what other conditions are likely to be identified, or what might we see RA disguised as?
Dr. Wells:
Some of the things that you can see that mimic rheumatoid arthritis, for example, will be gout. Gout can usually affect the small digits of the feet and of the hands. As you know, Lyme disease is an infectious arthritis that is caused by a bite from an infected tick, and you get this bacterium that gets into the joints. It can also mimic rheumatoid arthritis.
But those are the most common things that we see. Sometimes people can have other conditions like psoriasis, and that can also cause an arthritis that looks like and mimics rheumatoid arthritis as well.
Is Lyme disease a form of RA, or is it a completely different structure?
Dr. Wells:
It is a completely different disease. If you think about rheumatology, there are over a hundred different types of arthritis.
Some of those are caused by trauma, some are caused by infection, and some are caused by autoimmunity. Lyme disease will fall in that category, where a person gets an infection from a tick bite, and the bacterium then gets into the joints and starts its inflammatory process. That can lead to some joint damage.
Is RA one of the most severe forms of arthritis out of the many that you mentioned?
Dr. Wells:
It really is [one of the most severe forms]. There are other forms that are, fortunately, very rare that can cause more crippling changes, but rheumatoid arthritis is one of the more severe forms of the disease. Again, years ago, it used to be almost a kiss of death because we would see patients that would get crippling changes. We could not reverse the disease or halt it.
Patients had increased cardiovascular events, meaning you could have a 52-year-old lady with rheumatoid arthritis and a 52-year-old lady without rheumatoid arthritis, and that lady with rheumatoid arthritis was more likely to die anywhere between 10 to 15 years earlier than the lady without arthritis, mainly because of the disease process. And so we know that not only is it the joints that can be affected.
When I do my lecture to the doctors, I tell them you need to think outside the joint. So you think about the heart, you think about other tissues that can be involved. And even though we focus on the joints in patients with rheumatoid arthritis, it is a systemic disease. People can have eye disease, they can have lung disease, and they can have heart disease.
Pain and stiffness, as you have mentioned, are very common rheumatoid arthritis symptoms. Are there any less common symptoms that a person should look out for?
Dr. Wells:
Pain and stiffness are the most common things that we look out for, particularly this profound stiffness in the morning that lasts for more than 30 minutes that is so profound that it affects the patient's ability to do their normal activities, whether work or function around the house. Those are the most common things.
And then the other thing we watch out for is the fatigue because it is a systemic disease. We know that some patients can have an anemia, which is a low red blood cell count. And as a result of that, they can have this profound fatigue and malaise, where they just can't shake any kind of symptoms or have any energy to do normal activities.
And that symptom because it's so common could lead you in a number of different directions as far as diagnosis is concerned?
Dr. Wells:
That is correct. In particular in younger ladies, it's very common to have a little bit of anemia mainly associated with their menses. But people have profound anemia and fatigue that is not associated with those other conditions, and that's one of the things that should raise a red flag that this could be a more systemic disease like rheumatoid arthritis.
When you see an RA patient for the first time or early in the course of a disease, how do you set treatment goals?
Dr. Wells:
When I see a patient with rheumatoid arthritis, we start out by talking about the disease. I almost put myself in the patient's shoes. And if it was myself, my wife or my daughter who had rheumatoid arthritis, I'd want to learn about the disease. I'd want to see, what does this really mean for me and my family?
One of the big questions when adults get it is, "Are my kids going to get this?" And fortunately, rheumatoid arthritis is not a condition that is passed on from the parents to the child. But we know that if one individual in the family has rheumatoid arthritis, others in the family are at increased risk for developing that.
So again, another red flag, if you have a kid who's been seeing a pediatrician and the mother has rheumatoid arthritis if that kid develops some knee pain, the pediatrician should think about rheumatoid arthritis. So education is the first thing that we think about.
Dr. Wells:
And then we talk about some of the different treatment options. As you know, we start very conservatively, in some cases using anti-inflammatory medications. That could be Tylenol [acetaminophen]. It could be Celebrex [celecoxib]. It could be Aleve [naproxen]. All these medications we use, but together with more powerful medications.
So education first, talk about treatment options, and then do blood work and X-rays to give us an idea of where in the spectrum [the person's disease might be]. For example, if somebody has milder disease, we'll start up with one of the milder medications. But if you have a patient who's already had some changes on their X-rays, ultrasounds or MRI, then we'll go with a more aggressive treatment regimen.
So it really depends on the work-up as to the stage of the disease as to the treatment option you might choose. But early on, if the disease is indeed mild or progressing slowly, you'd begin and spend some time working with the drugs that they call NSAIDs?
Dr. Wells:
Yes. We do start with the NSAIDs, which stands for nonsteroidal anti-inflammatory drugs. And then we also use another milder form of medication, one called methotrexate, which is geared toward resetting the immune system.
Is it a form of chemotherapy, if you will?
Dr. Wells:
It is. I make that analogy. I tell a patient that methotrexate is a type of chemotherapy. For example, this is the same drug that's given to ladies with breast cancer. Because, if you think about it, with breast cancer you've got these angry cancer cells that are growing and growing and growing, and methotrexate is like a poison that slows those cells down and kills them.
The difference with cancer compared to rheumatoid arthritis is that if a lady has breast cancer they give a huge dose of the drug intravenously, where we use the small doses of the drug that you give on one day a week. So they are 10,000-fold less amounts of the drug that we use in rheumatoid arthritis.
So I mention the term chemotherapy to people. Many people say, "Okay I'm going to lose my hair." It's the first thing most ladies think of, and it doesn't happen. We very rarely see any side effects. It's a safe medication to take. It is a type of chemotherapy geared at shutting down those angry cells of the immune system that have gone awry.
That's the mechanism that it uses. It attacks those cells that are doing damage.
Dr. Wells:
That is correct. [It attacks cells] very nonspecifically, though. And sometimes in rare cases, it can injure some normal cells. The biggest thing we see sometimes, people do get some stomach upset or some diarrhea. In rare cases, they can get some hair loss or even some changes in their blood counts.
But now we have more specific therapy that targets specific parts of the immune system. Whereas, methotrexate is out there targeting both parts of the normal and the abnormal immune system, we have newer agents now that are almost like a magic bullet. They go right to the target where we want to treat.
But in some cases, the methotrexate, though, it can create some side effects, works pretty effectively?
Dr. Wells:
It really does. And if you look at patients who get in early enough to a rheumatologist and get on a decent drug, and if they can tolerate the medication without any side effects, about 70 percent of them will get a good response. And those are the ones we first start off with.
It varies from rheumatologist to rheumatologist, but we start with a nonsteroidal drug and together with methotrexate. And if we can't get the patient under control after three to six months with just those medications, then we have the patient come in and we have another conversation about the next options for treatment.
How long can a patient stay with a course of methotrexate?
Dr. Wells:
Really, [a patient can remain on a course of methotrexate] indefinitely. And that's one of the things about this disease. We know that if we stop medications, the patient will begin to flare. They will have an increased amount of swelling, stiffness and all the other things that they initially presented with.
We are in several cases able to take the drug down. For example, to give you an idea of the doses of methotrexate, we start anywhere from 7-1/2 milligrams to 25 milligrams just one day a week. It's very convenient to take. If a patient does begin to respond, let's say, if I have them on 25 milligrams, then as they get better I back it down to 20 milligrams or 15 milligrams to slowly get them on the lowest effective dose possible.
How often are you seeing these patients, and does every visit include some sort of imaging?
Dr. Wells:
Not always. Usually, we do imaging as baseline, and then we also do imaging at certain turning points. It could be [done at] six months or at a year, mainly to guarantee the patients are responding to therapy and making sure now that there is no progression of any damage on the X-rays.
Most patients, since they are on methotrexate and we do some blood monitoring, are seen every three or four months - only three or four times a year do they come in to see the doctor.
What about your comments on methotrexate and pregnancy?
Dr. Wells:
One of the other uses of methotrexate is if a patient wants to have a medical abortion. It's one of the drugs that is used. So if I have a young lady who is thinking about having a family, we usually stop the medication and let the patients go through two normal cycles, and in that case there [are] no adverse events.
I'll tell you though, there have been patients who get pregnant on methotrexate. I've had that happen, and the baby does fine. So if a patient is trying to get pregnant, if they're on methotrexate, they usually won't be able to get pregnant while on the drug. But if they are able to get pregnant while on the drug, the baby will be fine.
My preference is usually to stop it and let them go through a couple of normal periods and then resume their therapy.
There's less of a concern for male patients. There have been no side effects associated with them, for example, the sperm counts. Other drugs have affected male patients, but it's usually more the female patient we're concerned about.
I understand there may be, in some patients, some sort of an impact on the liver. Is that correct?
Dr. Wells:
Yes. Of some of the other rare side effects on methotrexate, patients can have a decrease in their blood counts. For example, it can affect the red blood cells and the platelet cells, those cells that cause a clotting in our bloodstream.
Also, it can also cause some irritation of the liver. Remember that the liver is the organ in the body that does the metabolism or breaking down of all things in the body, and methotrexate is one of those. If patients are taking high doses of it or patients, for example, are drinking alcohol or taking other drugs that put a bigger strain on the liver, then methotrexate might lead to some elevation of what we call the liver function test.
So this is why we monitor the patients every three to four months. And usually we'll pick up any changes in the bloodstream before the patient even has any symptoms or anything. And in most cases when you stop the drug or decrease the dose, the tests actually go back to normal.
I see. There's been a great deal of attention recently focused on COX-2 inhibitors, largely because of those that have been pulled off the market due to some safety concerns. Are they being used less in connection with RA?
Dr. Wells:
Yes. We still use the COX-2 inhibitors, and right now the only current one available is celecoxib, or Celebrex. I tell my patients all drugs have some side effects, and I tell them my job as a rheumatologist is to maximize the benefit of the drug and to minimize any side effects. So with careful check-up and monitoring, blood tests and other studies, we're able to prevent anything.
With all the nonsteroidals, you take ibuprofen, or Aleve, and celecoxib, they're all in the same kind of class of medications. The most common thing we see is some irritation of the stomach, and we do see some decrease in the function of the kidneys. And in those patients, that can lead to retaining fluid. And then we see the blood pressure increasing, and that can lead to some increased heart attacks and strokes.
But if you look at all the data of the patients who have been treated with these types of drugs, the patients who have the cardiovascular side effects are usually the sicker patients. So they have some underlying heart disease. They might have some lung disease. They might have some severe uncontrolled diabetes, and they are at-risk for heart attacks or strokes already. And you put them on even Aleve or something, and you will see that that risk goes up.
So what I tell people, with celecoxib, I use it to get the disease under control. It's not what we use to cure or get the disease into remission. Then once they get under control, the drugs like Celebrex and Aleve are taken as needed. If patients need them every day, they're fine to take every day. But then back off on those doses or go to lower doses on the days when you're feeling relatively well.
But that was the area of concern. It was cardiovascular involvement, heart attack and stroke risk increase that caused most of the safety concerns?
Dr. Wells:
That is correct. And if you look at all the changes in the warnings on the bottles of the drugs that are over the counter and on the prescribing information or labels of the drugs that are given by prescription, all of them have been updated to include that - that both physicians and the patients should be aware of symptoms that might suggest there have been some cardiovascular event, for example, elevation of blood pressure, swelling of the ankles and things like that.
And the drugs we've been talking about so far, mostly over-the-counter medications, both the NSAIDs and the COX-2 inhibitors, really are designed to treat symptoms. They don't necessarily halt progression of RA, is that correct?
Dr. Wells:
That is correct. And that's where the challenge is, not only for a patient but also for the primary care physician. For example, Celebrex is approved for rheumatoid arthritis. It treats the signs and symptoms, but it really does nothing to halt the disease. So patients, if they're taking Celebrex or Aleve or Tylenol, will feel better, but the disease can smolder and slowly go on to cause some joint damage. And by the time they get to the rheumatologist, the cat is already out of the bag.
There is a newer group of medications that are used to treat rheumatoid arthritis, and they're called biologics. I'd like to have you introduce our audience to these medications and tell us how they differ from the older therapies.
Why don't we start with the first one approved for the treatment of RA, and then we'll go through to the most recent. The first one, of course, was called Enbrel [etanercept], and we'd love to know how it works and how effective it is, and does it have side effects?
Dr. Wells:
What you mentioned is this new class of drugs, which are called the biologic drugs or disease-modifying drugs. When these drugs were first approved in 1998 and 1999, they revolutionized the treatment and the care of patients with rheumatoid arthritis. We've been talking a little bit about anti-inflammatory medications like Celebrex [celecoxib]. We've talked a little bit about methotrexate, which is a poison that gets rid of all activated cells, including some normal cells; hence they cause some side effects.
The difference with the newer drugs like Enbrel, it really goes to one of the main focuses of the things that drive the disease. For example, the biologic drugs are designed to target certain proteins in our systems, which are called cytokines. Cytokines are one component of the immune system that, when they are at increased levels, lead to swelling, pain, stiffness, and over the course of years can lead to damage of joints and tendons.
We now have these newer drugs like Enbrel that can block the production of those cytokines or block their function. And as a result of that, you shut off the disease and patients feel dramatically better. So Enbrel is the first class of these, and they block the main cytokine, which we usually abbreviate, called TNF, which stands for tumor necrosis factor. That's essentially how they work.
Is all this accomplished without bringing about overall immunosuppression?
Dr. Wells:
That's correct. These drugs are immunomodulators, we call them, because they modulate or change or modify the immune system. And as a result of that, we do see certain signals. The most common thing that we see from these drugs is a slight increased risk of infections. The most common things are sinusitis, bronchitis and pneumonia.
And that's why before starting these types of medications, most rheumatologists, including myself, will give our patients a pneumonia vaccine. They get their flu shot each year. We make sure their tetanus shot is up to date. All those things we do before initiating therapy with these newer drugs.
These new drugs, are they all injectables?
Dr. Wells:
Yes. If you think about how these new drugs work, if you were to take a pill, pills, once they hit the stomach [they] are broken down by the acid of the stomach. You can make the analogy of protein, like a piece of meat. Those protein molecules are broken down by the acid of the stomach.
These newer drugs, like Enbrel, Remicade [infliximab] and Humira [adalimumab], are those types of proteins. So if they were to be taken orally, they would be broken down by the stomach acid and would be inactive. They're given either subcutaneously - under the skin, same as how we do for a diabetic who's taking insulin - or they're given intravenously through an IV infusion. That way, they get directly into the bloodstream and bypass the stomach, so they're not broken down by the acids of the stomach.
How is it determined then which method is preferable, subcutaneous or intravenous?
Dr. Wells:
It varies in which method we choose and which drug the patient decides to go on. I have some patients who would never be able to give themselves an injection, and therefore they come in to get the infusions. Whereas, some patients have no trouble giving themselves an injection, or they have a spouse or another family member or someone to do the injection for them. So we make that decision together. We present the different options, the different choices of the drug, and then together with the patient help them to make a decision.
So some patients, then, can take these medications themselves without a visit to the doctor's office and can be unrestricted as far as travel is concerned?
Dr. Wells:
Absolutely, and that's one of the nice things about it. For example, we have one of our drugs, Humira, which is only given twice a month. So even if a patient is going to be going away for like a two-week vacation, they can take an injection of the medication, go for the two-week vacation, and they don't have to worry about taking needles through security or having a little refrigerated cooler and things like that. So it makes it very convenient for the patient.
So long as you have mentioned Humira, we'll touch on that one next. Is this one of the newer drugs?
Dr. Wells:
It is a newer one, newer in the sense that it's been approved in December 2002. And again, as you think about newer drugs coming out, one of the things we're always looking for is that they can be a little stronger, a little better or that they're given on a more patient-friendly regimen. All the drugs work about the same as far as radiographic protection of the joints and signs and symptoms, but the convenience is a huge factor with Humira only being given twice a month.
How long can a patient stay on a drug like Humira?
Dr. Wells:
Since rheumatoid arthritis is a chronic and inflammatory disease, unfortunately, we don't have a cure yet for the disease. For example, if you take an oncologist who's treating a cancer, you hear them talk about a cure or remission. And those are patients where they're essentially cancer-free, and they're in remission on no drug at all.
The difference in rheumatology, and when we talk about patients with rheumatoid arthritis, we are able to get a significant amount of our patients into remission, but that does require them to be on therapy to maintain that remission. So even though we are able to decrease the dose of the medications and the frequency at which they're given, patients will have to be on some medications probably for the rest of their lives in order to keep the disease under control.
But for many patients, that can be a maintenance dose, greatly reduced from active treatment?
Dr. Wells:
That is correct. For example, if you take somebody who is on Humira, usually we start off twice a month, and to control the disease they go to once a month. And the same thing if we have someone, for example, who's on Remicade. Usually, they get an infusion every eight weeks. In some cases, a few patients can go to every 10 or every 12 weeks.
Now, you've mentioned Remicade. How does it differ from the others that we've mentioned, Enbrel and Humira?
Dr. Wells:
Remicade blocks one of those cytokines, one of those human proteins that leads to the swelling, the pain, the stiffness and ultimately joint damage. It is a little different because it is actually given intravenously, but its structure is actually different.
I've done research for over 15 years in looking at all these different molecules in the labs. And what really revolutionized our use of these types of drugs is that we can take information from what we learned from doing animal studies of arthritis and combine that with our patients.
The way Remicade is constructed, it has about 10 percent mouse component, and the other 90 percent is human. What makes it unique is that it's what we call a chimeric molecule, a combination of part human and part mouse, and that gives it some unique properties, allowing it to be given intravenously for our patients with rheumatoid arthritis.
Is this a drug that is also sometimes used in combination with methotrexate?
Dr. Wells:
Yes. If you think about many of the diseases that we treat, rheumatoid arthritis being the most common one, all of our patients are on methotrexate. And it turns out that when you look at all the biologic drugs we've mentioned thus far, they work a little bit better when you are on methotrexate. You get a little bit better bang for your buck with a combination.
And by using two drugs, you can actually use a lower dose of two drugs and get a better response than a high dose of one.
That combination has been shown then to produce a better response with the disease?
Dr. Wells:
Absolutely. Across the board, with all the different drugs, we've found that if patients don't respond completely to methotrexate - meaning they still have swelling, stiffness and pain - that when you add the biologic drugs to methotrexate the patients are then able to get into remission. And we can get anywhere from 30 to 39 percent of our patients into complete remission on these drugs. That means no swollen joints, no tender joints, no morning stiffness and no pain.
Patients are liking the sound of that, Dr. Wells.
Dr. Wells:
And I tell you it's even more dramatic when you think about the juvenile patients. If you have a 10-year-old kid who for years has not been able to play soccer or to run, you put them on one of these drugs, and these patients are able to have a normal life. With these drugs, patients get back to more normal living, and it's rewarding, as a rheumatologist, to be able to offer that to patients.
Almost like the magic bullet.
Dr. Wells:
Now, there's an agent called Orencia [abatacept]. Is it new? Is it different? Tell us about Orencia.
Dr. Wells:
Yes. We talked about Enbrel, Humira and Remicade. They block one part of the immune system, which are these cytokines. There are two newer drugs that have been approved. And now the next thing that we want to do with these newer drugs is look at different arms, the different parts of the immune system.
Remember, with the immune system, we have different types of cells. We have one group of cells called the T cell and another group of cells called the B cell. Well, the T cell, it turns out, when you slow down its activity or blunt its response, you actually get some benefit in patients with rheumatoid arthritis.
And that's what Orencia is. It actually is a molecule that interacts with one of the signals that tells the T cells not to proliferate and not to divide and not to grow. And as a result of that, you get a slowing of the swelling and pain in patients with rheumatoid arthritis.
Is it as effective or more effective, or right for certain patients and not for others?
Dr. Wells:
Yes. And I think when you look at the efficacy of all the different drugs, it's hard to say whether one is more efficacious than the others because there have been no head-to-head trials where you look at drug A compared to drug B in the same trial. But when we look at the levels of response that we get, all the drugs seem to be very similar.
With Orencia being the newer drug, we don't have much data yet to say how many of our patients are able to get into remission. I'm sure that data will come as we get more and more information about it. So I think its efficacy right now is comparable to the other drugs.
The only thing that's a little different is, again, being newer, we still haven't seen any of the long-term protection on the X-rays. In other words, if I take an X-ray of a patient's hand today and then put him on a treatment and then follow up that X-ray a year from now, we would like to see that not only have the joints not gotten any worse but maybe in some cases that we begin to see some improvement.
And to date with Orencia, we do see some mild amount of improvement, but it's not as strong or not at the same level of protection as we get with the TNF drugs.
How long has Orencia been available?
Dr. Wells:
Orencia was approved earlier this year. But when they were approved, they already had three years' worth of data that was presented to the FDA, and that's what's captured in their packaging label.
And then the next benchmark for most of these agents, I assume, is the five-year data.
Dr. Wells:
That is correct. We're looking at five-year data. Because, remember, being a chronic disease, we want to show that we can treat patients over several years without several things, without any loss of efficacy, so we want the drug still to work. And we also don't want to see any adverse events, any side effects. And over a five-year time period, that seems to be the minimum of what the FDA allows. So even once the drug is approved, the companies then are all obligated to show some long-term data to the FDA, to physicians and to patients as well.
The final agent that we'll talk about here, and I think this one is one that has been around for a while, is called Rituxan [rituximab]. Is it in very common use?
Dr. Wells:
Yes, it is. Rituxan has been around for a while. Again, I talk about different arms of the immune system, the T cell being one that is targeted by Orencia. The other arm of that is the B cell. And this is a cell that is targeted by Rituxan. Rituxan has been around and used worldwide for treating patients with certain types of lymphoma, which are B-cell lymphomas, and the most common treatment is actually standard of care for lymphoma.
It turns out the same thing applies for rheumatoid arthritis. So you can imagine these B cells are growing and growing and growing, making all these different factors, making this rheumatoid factor that I mentioned earlier. It turns out that if we are able to get rid of the B cells or reduce the number of the B cells, we do see a clinical improvement in patients with rheumatoid arthritis. And that's how it's been used.
The nice thing about this drug is the way it's given. It's also given intravenously. And we take a rheumatoid patient, and we do an infusion today and one two weeks from today, and then we wait and see how the patients do. Many patients will not need any other drug, other than methotrexate, for six to nine months. And then at that time, we can give another treatment of Rituxan if we need to.
You have already told us why these drugs can't be given orally. And I know when you talk about the certain types of cells in the immune system, when we use an agent to reduce the number of those kinds of cells, are there any other side effects that may creep in from the reduction of that cellular activity?
Dr. Wells:
The biggest thing we alluded to already. When we decrease the different cells of the different arms of the immune system, we do see different signals. The most common things are infections. Remember, again, the immune system is mainly designed to kind of make sure that any invading organism, a pathogen like a bacterium or virus, that gets into the body is quickly immobilized and removed.
So if we've blunted one part of the immune system - it might be the T cells, it might be the B cells, it might be these other cytokines or proteins - then we do see slight increased risk of infections.
It turns out that if you look at a patient with rheumatoid arthritis, even without any drug in their system they are at slightly increased for infections already because their immune system is so busy causing the arthritis, so it's almost sidetracked by doing that. And so organisms and bugs can get in, and patients do get sick just from infections.
And so when we add these drugs on, there might be a little bit of increased infection. But it turns out that with the newer biologic drugs the risks for infection, and particularly serious infections, are no different than what we've seen with the older drugs like methotrexate and some of the drugs that have been around for 20 or 30 years.
Hearing you talk about the immune system going awry leads one to hope that there's a lot of serious work being done on figuring out why this happens. That really does represent the future, doesn't it?
Dr. Wells:
It really does, and I'll tell you where we're headed. I'll be able to have a patient come into my office one day and take some blood from them, I might be able to take some of the cells from the joints, and analyze those cells and see which part of the immune system has actually gone awry. So we'll be able to tailor drugs and make these cocktails that for one patient might be different than what the other patient is getting.
Right now, all of these drugs are given to all the patients, but they don't work in everybody. Some work better in some patients compared to others. But one day, based on all the studies that we're doing, we'll be able to have genetic markers to tell which part of the immune system is affected and who might be more likely to respond to drug A versus drug B.
Because our strong focus today has been these biologic medications as the new wave of treatment for RA, can you make some comments for us about their safety?
Dr. Wells:
Yes. I tell my patients, when I start talking about the drugs like methotrexate and even the biologic drugs, "You're going to get the same treatment or same advice I would give if you were a member of my family. "
And I don't like to ever downplay any potential side effects from any drug, but I tell my patients, first of all, I'm more concerned about the disease process than the drugs. Because, I tell them, if I do not treat the arthritis and reverse it, they are at increased risk for having cancer. They are at increased risk for having cardiovascular death. They are at increased risk for having infection, just by having rheumatoid arthritis.
And we know now that newer data is coming out that when we shut off this or change part of the immune system that's affecting the joints, that we'd see not only are there less cases of cancers and lymphomas or less cardiovascular deaths, that we are really changing the patients, their whole body and their whole lives with these drugs.
I do spend time talking about infections. We talk about how we can give the immunizations like the flu shot and the pneumonia vaccine for patients before they start these drugs. But the biggest thing we are concerned about is looking for infections.
But at the end of the day, I am more concerned about the disease process than any potential side effect for the drug because we have 30, 40 years of data showing that if we don't treat the disease that these patients do die earlier, and most of them are dying from infections from cardiovascular events.
That's a very important observation, that RA can in fact open the door to increased risk of other illness.
Dr. Wells:
That is correct. And that's why as I work with my primary care physicians, for example, if I have a rheumatoid patient who has hypertension, I ask the primary care physician to give me very aggressive control to the blood pressure. For many patients, one medication might do it to lower their blood pressure, but some patients might need to be on two or more drugs to get their blood pressure nice and low to make sure that is not a reason for them to have any cardiovascular event. And, as well, [I tend to be] looking for things like cholesterol levels and screening for diabetes and things like that. So I work very closely in conjunction with my primary care physicians and other physicians as well.
So has it been your finding, then, that the biologics can be taken safely then in conjunction with medications for other conditions such as hypertension or depression?
Dr. Wells:
Absolutely. That's one of the biggest questions patients have when I start them on these new medications. Is this going to affect or interact with my other medications? And we'll say there are no drug interactions that we worry about. So patients can be on their blood pressure medications, they can be on their blood thinners, they can be on their diabetes medicines without any problems at all.
What I'm also hearing you say is that each case of RA is very different, and you have to work up treatment plans for patients on a very individual basis.
Dr. Wells:
Absolutely. For example, if I have an older patient, let's say, about a 70-year-old patient who's in a nursing home, will these new biologic drugs be right for that patient? [They are] probably not [right] because, again, we don't want to put any patient at increased risk for having anything.
But if I have a 32-year-old mother who's married with three kids, she cannot take care of her kids or can't do her activity or work, then I think that patient deserves and demands aggressive control of the disease to get them back to a more normal life. So we have the whole spectrum. I make the analogy of the 32-year-old, but there are a lot of 60- and 70-year-old patients that we treat very aggressively as well.
And I think one of the most dramatic things we heard you say today is talking about the juvenile RA and the kids who aren't able to enjoy a normal life and play soccer or basketball or whatever. And with the proper treatment, these youngsters literally get their lives back.
Dr. Wells:
I tell you, it's been really amazing. When I was at Duke, we would see kids come into the rheumatology clinic. They are on crutches and in wheelchairs and really, really crippled. And when I was visiting there in February and doing a lecture with the faculty, they said for the last five years you can count on the hand the number of times they've seen kids come in in wheelchairs. We really have been able to reverse the disease in these kids and indeed made a profound effect.
And just like we talk about heart disease and everything in adult patients, there are other things that are brought under control too in the juvenile patients. For example, the rheumatoid arthritis can affect the growth of a limb. So if a kid has arthritis in their left knee, that leg would actually grow differently than the right leg, and patients would get crippled as a result of that. So we don't see those kinds of things happening anymore with these newer drugs. So they really have revolutionized our care of our patients.
That is very exciting.
Dr. Wells, if you're willing, some of our listeners have e-mailed some questions to us, and we'll put a couple of those to you.
Sarah from Philadelphia sent us this e-mail, and she says, "I've opted not to use methotrexate after using it for about eight years. My rheumatologist has now prescribed prednisone, which I'm doing very well on. What are the side effects and what are the benefits of prednisone?"
Dr. Wells:
Right. As she mentioned, methotrexate can be used long term, and some patients decide not to take that. I still feel it's safe. I make the analogy, I tell them it's safer than taking ibuprofen. Because if you look at all the data across the world, there's usually only one or two deaths a year from methotrexate. But if you look at a drug like ibuprofen, which everybody thinks is benign, there [are] about 17,000 deaths a year just from that.
But prednisone is a great drug. I use it in significant amounts of my patients because it does work. We know that the side effects of prednisone are dose-related. So if I have a patient who's on 10 milligrams or more, they're more likely to have some side effects. And the most common things with the prednisone at higher doses, we do see some weight gain, we see elevation of the blood pressure and then elevation of blood sugars. So in some patients, it will look like they're developing a form of diabetes. And because it blunts the immune system, we do see slightly increased risk of infections. So we use it. But when I use prednisone, I like to use as low a dose as possible to give them the best benefit.
And are there limitations, then, in the use of prednisone in terms of course of treatment, how long a person could take it?
Dr. Wells:
Usually not. For example, in my younger patients, I don't like to use it long term. But I have a significant amount of patients in their 70s and 80s that when I weigh all the different choices of medication that a low dose of prednisone might be the safest for them.
Like I made the analogy about the 72-year-old lady in the nursing home, that would be a person I would probably put on a low dose of prednisone compared to even methotrexate or one of the other biologic drugs because they're around other sick individuals, people who might have tuberculosis or pneumonia and all those different things. But yes, the lower the dose the less side effects we see with prednisone.
Here's an e-mail from Chad in Texas who knows some of his medical terminology. He says, "Having RA and taking the drug to suppress the disease, will the body rebuild the synovium?"
Dr. Wells:
Yes. It's really amazing. We not only think about the synovium but the bone. Because, remember, with rheumatoid arthritis, these angry cells that have gone awry get into the joints. And they actually lead to damage, and you see this crippling formation of the hands. And it turns out that when you put patients on these drugs and you shut off those angry cells that the bone is able to recover, to repair.
And I make the analogy, if you take a patient who breaks their bone and the surgeon puts that bone back together in a cast, the bone will regrow. Or if you take a patient who has had, for example, a surgical procedure where you've had a screw in the bone and we take that screw out, the bone will begin to fill in.
So [it's] the same thing with rheumatoid arthritis. You can have a condition where for years and years these angry cells have eaten away at the bone and caused this bone damage. And when you shut off the inflammation, the body's normal healing mechanisms can go in to repair those areas. And that's what we see. We can do an X-ray of somebody at baseline and see some damage. We put them on one of these drugs that suppresses the immune system and the inflammation, and we see that the bones begin to repair themselves over six months to a year.
So we don't leave everybody in the dust, why don't you define synovium for us?
Dr. Wells:
Synovium is the soft tissue that lines the joints. If you think about a joint that moves, like the knee or the elbow joints, the synovium is that piece of tissue that bathes the joint and gives lubrication to the joint.
Here's an e-mail from Jim in Seattle, and he asks, "Can physical therapy be helpful for RA?"
Dr. Wells:
Yes, absolutely. I work very, very closely with physical therapists doing therapy for the hand. For example, some people have these wax baths that they use, using the exercise balls or grips. One of the things that I tell my patients, even though they might be a little stiff or sore, they really want to still do some stretching. And that could just be maybe five or 10 minutes first thing in the morning to really get those joints moving because we know if we don't move those joints, the tendons and the muscle around those joints will actually begin to get stiffer. So I work very, very aggressively with the physical therapy, particularly the hand therapy to keep the patient's hand functioning.
Here's an e-mail from Rachel in Portland, Oregon. She says, "I have RA and fibromyalgia. [I'm] not sure which one flares up, sometimes, as they are so close in symptoms. Will biologic treatment help both?"
Dr. Wells:
Yes and no. We know that, for example, patients with rheumatoid arthritis are more likely to get fibromyalgia. For patients or people who don't know, fibromyalgia is a condition where people get these just trigger points, tenderness, and severe fatigue and pain, some of the similar symptoms that you see with rheumatoid arthritis. And it turns out that as you get the patient's pain and swelling under control from the arthritis, some of the fibromyalgia symptoms actually do improve.
I don't want to give the impression if you have somebody who just has fibromyalgia if I put them on one of these drugs, like methotrexate or a biologic, it will work. We don't have the data to support that.
I think if I've heard a theme throughout our conversation today, it has been one of hope. It looks as though we're making some headway. And would you say the patients are better off today than they were 10 years ago in terms of their treatment options?
Dr. Wells:
I think they are [better off]. It is rewarding to see patients come in now, to get them diagnosed and treated aggressively. It still is a little bit heartbreaking to see patients who've had the disease for 10, 20 years before these drugs were available, and just wishing and hoping that I had had this drug 10 years ago for these patients and could have gotten them some better control.
But we can take patients who have had disease for 10 or 11 or 12 years, and still they get some benefit from these drugs. So I don't want people to think, "Okay, I've had the disease, there's really nothing else for you to do." That's not true. Even if people had long-term rheumatoid arthritis, going on these drugs, patients do get better, and that's one of the exciting things about these drugs and being a rheumatologist today.
But I'm assuming that damage done to joints can't be reversed. Once the damage is done, it's done?
Dr. Wells:
That is correct. But once we turn off these angry cells from the immune system, then we work with some of our orthopedic colleagues to maybe give me some joint replacements or realign the wrist and the fingers. So we control the disease and then work with the surgeons to help get them structural control.
These days, would you say that an RA patient should in most or at least many cases be able to avoid the crippling effects of this disease?
Dr. Wells:
Absolutely, and I think that's the goal here. The goal is, one, to get people into remission and prevent this crippling. We know that since we've been using methotrexate for over 20 years, we see less of the crippling changes. And over the last five years since these biologic drugs have been used more and more, we see even less of that. Very rarely do I see a patient coming in with a diagnosis of the last 10 years with rheumatoid arthritis and do they have any crippling changes. I always tell my patients and other physicians if somebody has rheumatoid arthritis, you definitely want to get them in to a rheumatologist because we can do something now.
So there are clear benefits, then, to getting a referral to a rheumatologist, a specialist, over simply working with the family doctor?
Dr. Wells:
Absolutely, and one of the differences is all the drugs that we've mentioned. These drugs simply are chemotherapies. We are essentially like the oncologists of the joints because what we are actually able to do is come up with which cocktail, which solution, which of these biologic drugs are going to be the best for the patient.
As rheumatologists, we've trained for over two or three years, at least, in rheumatology to study these drugs. We know the side effects, we know the benefits, and we know what to look out for. Whereas, other doctors are just reading the information that's sent to them in the mail, or they're being told by the pharmaceutical rep. It's a lot different than having specialized in this.
Would you say that most rheumatologists are pretty up to speed on the newer therapies like the biologics?
Dr. Wells:
I think they are because this has really become standard of care now. At most places where you see, and even with some community rheumatologists that have been around for years, they're using these newer drugs that give a significant benefit. I think all of them are up-to-date with this.
Are there any drugs in the pipeline that our audience should be aware of, anything promising out there that we should keep an eye on?
Dr. Wells:
There are two things that are going to be exciting. We know now one of the things that leads to joint damage in patients with rheumatoid arthritis, where the cells essentially eat away at the bone. It turns out that these are the same cells that cause osteoporosis, the thinning of the bones or the changes to the spine that we see in older female patients.
Well, it turns out if we use the biologic drugs together with drugs that you use to treat osteoporosis that we even get more of a benefit on the X-rays, more protection of the bone itself. So we'll be seeing newer drugs that will be targeting not only the immune system, but also drugs that will target the cells that cause a breakdown of the bone like we see for osteoporosis.
Then we've identified other cytokines, other proteins, other parts of the immune system that can be turned off or that can be modulated. So there are several different drugs that will be used for not only rheumatoid arthritis but for other conditions like psoriasis and the arthritis associated with psoriasis, and for other conditions as well.
Just to reiterate something that I think you mentioned earlier, there can be a genetic component in this. So if a parent has RA, would it be wise to have a child screened?
Dr. Wells:
I don't think they need to have the child screened. I don't want to get patients to become hypochondriacs.
But if you have a young mother who has a kid, let's say a 10-year-old son, and all of a sudden he stops playing soccer - because one of the things you find is that kids don't really complain. They adapt or they change their habits. They won't play soccer, or they won't go out and run or do as much. They might have one little swollen knee or a swollen ankle.
So in somebody with a history of rheumatoid arthritis, if there's something different about the kids or another family member, that should be alerted to the physician. "My mother has rheumatoid arthritis," or "My father has severe rheumatoid arthritis," - that should be the marker then. In that case, the physician should do the screening for rheumatoid factors or get the patient to a referral, so we can do the appropriate screening.
[There's] nothing environmental, as far as we know, that may impact this disease?
Dr. Wells:
Yes or no. For example, some of my Hispanic patients feel that eating red meat triggers your arthritis, and that is not true. Other people believe by taking high doses of vitamins that they can actually change the disease, and that's not really true.
Environmental in the sense that we know, for example, there are some people that could be exposed to certain viruses and the viral infection can trigger arthritis that looks just like rheumatoid arthritis. But there's no chemical or anything that people could be exposed to [that can impact the disease].
We know that in some cases people get trauma. I've had patients who've actually injured their knee or their wrist and develop arthritis in those areas, so trauma can trigger it. But I can't think of any food, any vitamin, any chemical that patients are exposed to that can cause them to develop the arthritis.
I'm guessing that there may be some patients out there who would love to ask you, "What about the future of biologics without needles?"
Dr. Wells:
Yes, that's what's being revolutionized. One of the newer trends in patients with diabetes who have to take insulin, you can take a device that essentially looks like a large pen, almost like a little magic marker, and that's loaded with some gas, like carbon dioxide. And that will shoot the medication into the skin without any needles. So these newer systems are being looked at, these injectable devices that don't involve needles.
And there's been a new insulin approved, which is given by a nasal spray, given into the lungs, because the lungs are essentially full of blood vessels. So we might theoretically have, one day, a nasal spray of one of these types of [arthritis] medications that we will use. I think those are going to be the next wave in delivery systems, ones that don't have to be given necessarily every month or every other month but can be given with an inhaled spray or with a needle assistance.
I suspect you've probably seen a patient or two in your experience who sees a hypodermic needle and runs the other way.
Dr. Wells:
[That's] exactly right. Some patients would just never want to put a needle near them.
One of the great values of these conversations is to hear really current discussion of therapies from a specialist such as yourself. And I know that our patients would also find great value in any take-home message that you would like to leave for them. What would you like a listener to take away from our conversation?
Dr. Wells:
I think the take-home message is that there is hope, that we can actually do something for the disease now. I think when many patients get the diagnosis or think they have rheumatoid arthritis or rheumatism or arthritis, they go to the Internet and they try all these other sources, some of which might get them benefit. But now we can take patients who've had the disease for 10, 11 or 12 years and definitely even in some cases halt the disease and maybe even reverse it.
So my take-home message is not only for the patients. If you have family, friends, people at church or work who you think are suffering from arthritis or other inflammatory conditions, get them into a rheumatologist because, remember, rheumatologists treat patients with diseases of the skin, muscle, bones and joints, and sometimes rheumatoid arthritis can mimic other conditions. Get them to a rheumatologist, get evaluated and if needed to be, get on therapy.
But clearly, it's a great benefit to the patient to get to that specialist?
Dr. Wells:
Absolutely. I think the primary care physicians do a great job to help to monitor the patient and follow some of these other things like we talked about, diabetes and hypertension in patients with rheumatoid arthritis. But to treat the disease specifically itself, they need to be managed by a specialist. Just like if a patient had cancer they would go in to an oncologist and not to a family physician.
Are there any insights into causes of rheumatoid arthritis? Do we know why the immune system may go awry?
Dr. Wells:
Yeah. There are some genetic markers that we will or have identified that in some groups of patients does seem to predispose them to rheumatoid arthritis. So as we look more and more, looking for markers in the bloodstream, looking for markers in the joint itself, we will be able to have different genetic markers, different genes that we can identify that can tell if this patient might develop rheumatoid arthritis.
It's a double-edged sword there. That's one of the challenges. When this information is out there that goes back until the day when a patient is born, let's say, that he might develop rheumatoid arthritis in 10 years, what are some of the ethical ramifications of that? So it sounds really good, but it also creates another set of issues too.
But overall, there is room for hope for these patients?
Dr. Wells:
Absolutely. We can do a lot now. We've got all kind of medications. Not everybody has to take an injection or a needle. There are a number of different things that we can do for our patients and definitely get them better where they can lead a more normal life.
Dr. Alvin Wells has joined us today, and we appreciate your being with us.
Dr. Wells:
Thank you very much. [I] enjoyed it.
And from our studios here in Seattle, I'm Dick Foley. We wish you and your families the very best of health.
Last Updated: 5/30/2006


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Penn Reading Project Archives
The Penn Reading Project, now in its twenty-first year, was created as an introduction for incoming freshmen to academic life at Penn. Past PRP selections include The Big Necessity (George), The Gross Clinic (Eakins), Your Inner Fish (Shubin), The Omnivore's Dilemma (Pollan), Free Culture (Lessig), Benjamin Franklin's Autobiography, The Quiet American (Greene), Things Fall Apart (Achebe), Candide (Voltaire), Metamorphosis (Kafka), The Woman Warrior (Kingston), Frankenstein (Shelley), Arcadia (Stoppard) and The Tipping Point (Gladwell).
Faculty members in all twelve schools are invited to take part as PRP discussion leaders. A copy of the text will be sent to discussion leaders and students in July, along with additional information about the Reading Project.
To learn more about this year's Penn Reading Project, return to the Penn Reading Project Home Page
For more information, and to volunteer as a leader, contact:
David Fox
Director, Penn Reading Project
215-573-5636 / firstname.lastname@example.com
Penn Reading Project | New Student Orientation | University of Pennsylvania
3702 Spruce Street, Philadelphia, PA 19104 | 215-898-7000 | email@example.com
This page last updated on:
February 22, 2011 3:08 PM
| Copyright © 2008

subset: commoncrawl


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|Dec 27, 2009
This Girl Is Hot! Love the interaction between Melrose and cast group. It looks honest,true, it looks like she was having a great time. I know i had a great time watching her with those Fuck Machines. I would love to see Melrose again! . Great shoots with super lady with great sex drive. A+++ Hope to see her again. Thanks Melrose! :)
|Fucking Machines
18 U.S.C. 2257 Record-Keeping Requirements Compliance Statement All material shown on this website is consensual. No model was harmed during the filming of these movies. Copyright ©2016 Kink.com


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The ontogeny of major histocompatibility class II antigens in small intestine enterocytes of postnatal C3H/He mice was investigated. Cryosections of duodenal, jejunal, and ileal segments from 7-, 14-, 16-, 20-, 21-, 23-, 25-, 27-, 28-day-old and 7-week-old mice were stained for the class II antigens...
Quantitative regional variation in the expression of major histocompatibility class II antigens in enterocytes of the mouse small intestine
The qualitative and quantitative expression of major histocompatibility class II antigens was investigated in the absorptive epithelium of the duodenum, jejunum, and ileum from mice of C3H/He (H-2k haplotype) and C57BL/6 (H-2b haplotype) strains by peroxidase-antiperoxidase labelling and image analy...
Ultrastructural study of the late stages of Loma salmonae development in the gills of experimentally infected rainbow trout
The main objective of this investigation was to examine the ultrastructural features of gills from rainbow trout experimentally infected with Loma salmonae to determine the morphological events that occur during the late stages of development of this parasite. Peripheral distribution of the mature p...
Morphological and biochemical assessment of the liver response to excess dietary copper in Fischer 344 rats
The aim of this study was to determine the amount of excess dietary copper (Cu) necessary to experimentally induce liver lesions characteristic of Cu-associated disease in Fischer 344 rats. Male weanling Fischer 344 rats of uniform age were divided into 6 groups (n = 5) and fed a rodent diet contain...
Ultrastructural study of the early development and localization of Loma salmonae in the gills of experimentally infected rainbow trout
The early ultrastructural stages of Loma salmonae were studied in the gills of experimentally infected rainbow trout. No parasitic stages were identified during the first 2 wk of the infection. By week 3 postexposure (PE), uninucleate and binucleate meronts were recognized within host cells (no xeno...
Localization of the initial developmental stages of Loma salmonae in rainbow trout (Oncorhynchus mykiss)
The intracellular microsporidian parasite Loma salmonae affects salmonids of the genus Oncorhynchus and is a significant cause of economic losses in pen-reared Chinook salmon (O. tshawytscha) in British Columbia. Loma salmonae infection is easily recognized by the xenomas that form in the gills, but...
Use of genomic DNA probes for the diagnosis of acute sarcocystosis in experimentally infected cattle
Two clones of 1.4 and 4.33 kilobase pairs (kbp) DNA inserts, were selected from a Sarcocystis cruzi sporozoite genomic library constructed in bacteriophage lambda gt10. These clones strongly hybridized with sporozoite and merozoite DNA and were evaluated as probes for detection of merozoite DNA in c...
Production of monoclonal antibodies specific for antigens derived from tissue of chinook salmon (Oncorhynchus tshawytscha) affected with plasmacytoid leukemia
Two distinct monoclonal antibodies (MAB) were prepared for testing with kidney, spleen, and retrobulbar tissue imprints made from chinook salmon (Oncorhynchus tshawytscha) affected with plasmacytoid leukemia. (PL). Hybridomas were prepared from mice immunized with whole and lysed cells purified from...
Using a randomized controlled trial design, a randomly allocated intervention group of 15 cows received a slow-release bolus that delivered 100 days of monensin. The negative control group of 15 cows received a placebo bolus that was identical to the monensin bolus, except without the monensin. Two ...
Background: The proportion of geriatric horses within the equine population has increased in the past decade, but there is limited information on the immune function of these animals. Hypothesis: Aged horses will have a lesser increase in serum antibody response to vaccination. Animals: Thirty-four ...


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Welcome to the LP Questionnaire, special SXSW V2V Edition! In the coming days we'll be featuring many of the lovely talents who will be showcasing at our new event in Las Vegas taking place next week. (August 11-14, to be exact.) Its not too late to make your way to the desert for some heady times at The Cosmopolitan.
The good people of SXSW Music have put together two nights of fine sounds for you and your friends. If you're headed to V2V or if you're in Vegas, head on down to The Backstage Bar and Billiards.
First up is Mr. Jackie Chain, a half Korean, half Irish rapper who just moved to Los Angeles. He just dropped his new mixtape, the Bruce Lean Chronicles 2.
He has fresh beats and loves bacon.
And here is his...
The LP Questionnaire
Name: Jackie Chain
Do you have any nicknames? Aka Mr VIP, aka Bruce Lean, aka Johnny Cash, aka Mr Fuckedyomainbitch.
1. Pretend you're 15. Name three songs you'd put on a mix tape for your girlfriend/boyfriend. The year is 1998. I got Outkast "West Savannah", UGK "Diamonds and Wood" (even though it had been out awhile it's an instant classic), and Goodie Mob "Black Ice."
2. Which evil villain would make the best President? Dr Evil. We would have sharks with frickin' laser beams in their head.
3. What was your favorite cartoon as a child? Thundercats was pretty dope.
4. What superpower do you wish you had? I would wanna live forever. Is that a super power? If not it should be.
5. What would the title of your autobiography be? Ain't Slept in Weeks!
Thanks for joining us and please do come again next week when we've got LPQs from Kisses, Dizzy Wright, Palmbonen and more.
You'll be able to keep up with this wit and wisdom for the ages here. We are available on Twitter @SXSW, @SXSWV2V and @mspark.
It's like hot sauce out there, lp
Photo courtesy of the Artist


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Tahuti Lodge, Ordo Templi Orientis, NYC, is proud to present:
Alchemy and the Ascent of the Soul"by Special guest lecturer and noted author
Brian CotnoirAuthor of The Weiser Concise Guide to Alchemy
Open Event
Saturday, November 21, 2009 e.v.
In Constantinople June 617AD, Stephanos of Alexandra finished writing a series of lectures called the Art of Gold-making. This work is the synthesis of alchemy to that time and a synopsis of what was transmitted to the Arabs and on to the West. By examining excerpts from this work, we will see the broad outlines of Byzantine alchemy with its more overt spiritual emphasis — alchemy as the ascent of the soul.
In today's talk this idea of the ascent of the soul will be explored from a variety of perspectives and traditions. Please join noted author and practicing alchemist Brian Cotnoir, as he surveys the techniques and methods used by alchemists throughout history in their search for enlightenment and spiritual transformation.
This event will be held in Manhattan
440 Studios
440 Lafayette St. New York, NY 10003-6919
STUDIO 3C (3rd floor)
440 Studios is located between Astor Place and East 4th St. Directly across from The Public Theater. Take the elevator to the 3rd & 4th Floors.
For directions and transit info see here:
Admission is $11 in advance and $13 at the door
Seating is limited
Please reserve your seat using Paypal
Seats and books will still be available for purchase at the event
Copies of The Weiser Concise Guide to Alchemy will be available for purchase.
To RSVP for this event or to receive information or directions, please email email@example.com


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- Filed Under
PRESS RELEASE: Direct from LS3P
December 19, 2013 – (Greenville, SC ; Charleston, SC; Columbia, SC; Charlotte, NC; Wilmington, NC, Raleigh, NC) - Two projects designed by the Charleston office of architectural firm LS3P, received First Place Awards at the American Society of Interior Designers (ASID) Carolinas Design Excellence Awards Gala in Greenville, SC.
LS3P's winning projects, Le Creuset's North American Headquarters and a Private Yacht Club, are both located in Charleston.
The new headquarters building for Le Creuset, a high-end international cookware manufacturer, is located along a tranquil marsh and draws inspiration from its stunning natural setting as well as the client's sleek, brightly-colored cookware. The project transformed an aging seafood restaurant into a modern office space to showcase the company's products and includes conference facilities, a cooking demonstration kitchen, and outdoor event space. The resulting building is open, light-filled, and tranquil, with expansive marsh views throughout the interior.
The renovation project of the Private Yacht Club, originally built as a Shrine Temple in the early 1960's, transformed the space into a high-end private club with ballroom, dining rooms, and lounge. The aesthetic reflects the rich heritage of the city, drawing on both southern traditional and maritime themes for inspiration, and the interior space features incomparable views to Charleston's harbor.
LS3P provides architecture, interior architecture and planning services nationwide with offices in Charleston, Columbia, and Greenville, SC and Charlotte, Raleigh and Wilmington, NC. LS3P's combined offices have received over 400 awards for excellence in design and are honored to be included in Engineering News Record, Architectural Record, and Interior Design's top design firms. LS3P celebrates its 50th anniversary this year. For more information on LS3P, visit www.ls3p.com.
ASID, founded in 1975, is the oldest, largest, and leading professional organization for interior designers. The Carolinas Chapter has over 1,500 members in North and South Carolina, and provides education and support for design practitioners with a wide range of specialties.
Project Team, Le Creuset North American Headquarters: Cameron Wilson (PM), Richard Bing, Whitney Groves, Kristin Baker, Katie Sedor, and Brian Leounis.
Project Team, Private Yacht Club: Richard Bing (PM), Cameron Wilson, Whitney Groves, Kristin Baker


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While most Christian women today do not veil their heads, many are surprised to learn that wearing headcoverings was actually the rule throughout the history of the Church. It was taken for granted that when Paul spoke about a woman covering her head in 1 Corinthians 11:2-16, what was being prescribed was a universal practical that issued naturally from God's moral law, that symbolized the authority the husband has over the wife. Below is a list of quotations from historically important theologians that make it clear that wearing such coverings was the universal practice of the Christian Church. Various paintings and mosaics of Christian women throughout history likewise makes it clear that veils were universally donned by women throughout Church history.
"And let all the women have their heads covered with an opaque cloth, not with a veil of thin linen, for this is not a true covering"(Hippolytus)
"I also admonish you second group of women, who are married, not to outgrow the discipline of the veil. Not even for a moment of an hour. Because you can't avoid wearing a veil, you should not find some other way to nullify it. That is, by going about neither covered nor bare. For some women do not veil their heads, but rather bind them up with turbans and woollen bands. It's true that they are protected in front. But where the head properly lies, they are bare.
Others cover only the area of the brain with small linen coifs that do not even quite reach the ears.... They should know that the entire head constitutes the woman. Its limits and boundaries reach as far as the place where the robe begins. The region of the veil is co-extensive with the space covered by the hair when it is unbound. In this way, the neck too is encircled.
The pagan women of Arabia will be your judges. For they cover not only the head, but the face also. . . . But how severe a chastisement will they likewise deserve, who remain uncovered even during the recital of the Psalms and at any mention of the name of God? For even when they are about to spend time in prayer itself, they only place a fringe, tuft [of cloth], or any thread whatever on the crown of their heads. And they think that they are covered!" [Tertullian, The Veiling of Virgins The Ante-Nicene Fathers Vol. 4 pp. 27-29,33]
"If thou desirest to be one of the faithful, and to please the Lord, O wife, do not superadd ornaments to thy beauty, in order to please other men; neither affect to wear fine broidering, garments, or shoes, to entice those who are allured by such things. For although thou dost not these wicked things with design of sinning thyself, but only for the sake of ornament and beauty, yet wilt thou not so escape future punishment, as having compelled another to look so hard at thee as to lust after thee, and as not having taken care both to avoid sin thyself, and the affording scandal to others. But if thou yield thyself up, and commit the crime, thou art both guilty of thy own sin, and the cause of the ruin of the other's soul also. Besides, when thou hast committed lewdness with one man, and beginnest to despair, thou wilt again turn away from thy duty, and follow others, and grow past feeling; as says the divine word: "When a wicked man comes into the depth of evil, he becomes a scorner, and then disgrace and reproach come upon him."25752575 Prov. xviii. 3. For such a woman afterward being wounded, ensnares without restraint the souls of the foolish. Let us learn, therefore, how the divine word triumphs over such women, saying: "I hated a woman who is a snare and net to the heart of men worse than death; her hands are fetters."25762576 Eccles. vii. 26. And in another passage: "As a jewel of gold in a swine's snout, so is beauty in a wicked woman."25772577 Prov. xi. 22. And again: "As a worm in wood, so does a wicked woman destroy her husband."25782578 Prov. xii. 4 in LXX. And again: "It is better to dwell in the corner of the house-top, than with a contentious and an angry woman."25792579 Prov. xxi. 9, 19 You, therefore, who are Christian women, do not imitate such as these. But thou who designest to be faithful to thine own husband, take care to please him alone. And when thou art in the streets, cover thy head; for by such a covering thou wilt avoid being viewed of idle persons. Do not paint thy face, which is God's workmanship; for there is no part of thee which wants ornament, inasmuch as all things which God has made are very good. But the lascivious additional adorning of what is already good is an affront to the bounty of the Creator. Look downward when thou walkest abroad, veiling thyself as becomes women."
"IX. Avoid also that disorderly practice of bathing in the same place with men; for many are the nets of the evil one. And let not a Christian woman bathe with an hermaphrodite; for if she is to veil her face, and conceal it with modesty from strange men, how can she bear to enter naked into the bath together with men? But if the bath be appropriated to women, let her bathe orderly, modestly, and moderately. But let her not bathe without occasion, nor much, nor often, nor in the middle of the day, nor, if possible, every day; and let the tenth hour of the day be the set time for such seasonable bathing. For it is convenient that thou, who art a Christian woman, shouldst ever constantly avoid a curiosity which has many eyes"(The Apostolic Constitutions)
"Let the woman observe this, further. Let her be entirely covered, unless she happens to be at home. For that style of dress is grave, and protects from being gazed at. And she will never fall, who puts before her eyes modesty, and her shawl; nor will she invite another to fall into sin by uncovering her face. For this is the wish of the Word, since it is becoming for her to pray veiled." [Clement of Alexandria, The Instructor 3.12]
Demanding then a law of God, you have that common one prevailing all over the world, engraved on the natural tables to which the apostle too is wont to appeal, as when in respect of the woman's veil he says, "Does not even Nature teach you?" - as when to the Romans, affirming that the heathen do by nature those things which the law requires, he suggests both natural law and a law-revealing nature. Tertullian (A.D. 198) Ante-Nicene Fathers vol.3 pg. 96
Christ is the Head of the Christian man - (for his head) is as free as even Christ is, under no obligation to wear a covering, not to say a crown. But even the head which is bound to have the veil, I mean woman's, as already taken possession of by this very thing, is not open also to a crown. She has the burden of her own humility to bear. Tertullian (A.D. 198) Ante-Nicene Fathers vol.3 pg. 102
But that point which is promiscuously observed throughout the churches, whether virgins ought to be veiled or no, must be treated of. For they who allow to virgins immunity from head-covering, appear to rest on this; that the apostle has not defined "virgins" by name, but "women," as "to be veiled;" Tertullian (A.D. 198) Ante-Nicene Fathers vol.3 pg. 687
"Every woman," said he, "praying and prophesying with head uncovered, dishonors her own head." What is "every woman", but woman of every age, of every rank, of every condition? "Every man." As, then, in the masculine sex, under the name of "man" even the "youth" is forbidden to be veiled; so, too, in the feminine, under the name of "woman," even the "virgin" is bidden to be veiled… For indeed it is "on account of the angels" that he said women must be veiled, because on account of "the daughters of men" angels revolted from God. Who then, would contend that "women" alone - that is, such as were already wedded and had lost their virginity - were the objects of angelic concupiscence, unless "virgins" are incapable of excelling in beauty and finding lovers? Tertullian (A.D. 198) Ante-Nicene Fathers vol.3 pg. 688
Why do you denude before God what you cover before men? Will you be more modest in public than in the church? Be veiled, virgin, if virgin you are; for you ought to blush. If you are a virgin, shrink from (the gaze of) many eyes. Let no one wonder at your face; let no one perceive your falsehood. Tertullian (A.D. 198) Ante-Nicene Fathers vol.3 pg. 689
Nay, rather banish quite away from your "free" head all this slavery of ornamentation. In vain do you labor to seem adorned: in vain do you call in the aid of all the most skilful manufacturers of false hair. God bids you "be veiled." I believe (He does so) for fear the heads of some should be seen! Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.22
It behooves our virgins to be veiled from the time that they have passed the turning-point of their age: that this observance is exacted by truth, on which no one can impose prescription - no space of times, no influence of persons, no privilege of regions. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.27
Throughout Greece, and certain of its barbaric provinces, the majority of Churches keep their virgins covered. There are places, too, beneath this (African) sky, where this practice obtains; lest any ascribe the custom to Greek or barbarian Gentilehood. But I have proposed (as models) those Churches which were founded by apostles or apostolic men. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.28
"If any," he says, "is contentious, we have not such a custom, nor (has) the Church of God." So, too, did the Corinthians themselves understand him. In fact, at this day the Corinthians do veil their virgins. What the apostles taught, their disciples approve. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.32-33
But even if it is "on account of the angels" that she is to be veiled, doubtless the age from which the law of the veil will come into operation will be that from which "the daughters of men" were able to invite concupiscence of their persons, and to experience marriage. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.24
And as they veil their head in presence of heathens, let them at all events in the church conceal their virginity, which they do veil outside the church. They fear strangers: let them stand in awe of the brethren too. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.35
For some, with their turbans and woolen bands, do not veil their head, but bind it up; protected, indeed, in front, but, where the head properly lies, bare. Others are to a certain extent covered over the region of the brain with linen coifs of small dimensions - I suppose for fear of pressing the head - and not reaching quite to the ears. If they are so weak in their hearing as not to be able to hear through a covering, I pity them. Let them know that the whole head constitutes "the woman." Its limits and boundaries reach as far as the place where the robe begins. The region of the veil is co-extensive with the space covered by the hair when unbound; in order that the necks too may be encircled. For it is they which must be subjected, for the sake of which "power" ought to be "had on the head:" the veil is their yoke. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.37
Arabia's heathen females will be your judges, who cover not only the head, but the face also, so entirely, that they are content, with one eye free, to enjoy rather half the light than to prostitute the entire face. A female would rather see than be seen. And for this reason a certain Roman queen said that they were most unhappy, in that they could more easily fall in love than be fallen in love with; whereas they are rather happy, in their immunity from that second (and indeed more frequent) infelicity, that females are more apt to be fallen in love with than to fall in love. Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.37
To us the Lord has, even by revelations, measured the space for the veil to extend over. For a certain sister of ours was thus addressed by an angel, beating her neck, as if in applause: "Elegant neck, and deservedly bare! it is well for you to unveil yourself from the head right down to the loins, lest withal this freedom of your neck profit you not!" And, of course, what you have said to one you have said to all. But how severe a chastisement will they likewise deserve, who, amid (the recital of) the Psalms, and at any mention of (the name of) God, continue uncovered; (who) even when about to spend time in prayer itself, with the utmost readiness place a fringe, or a tuft, or any thread whatever, on the crown of their heads, and suppose themselves to be covered? Tertullian (A.D. 198) Ante-Nicene Fathers vol.4 pg.37
In a 1525 sermon, Martin Luther wrote:
Women, be subject to your husbands as to the Lord, for the husband is the head of the wife" [Eph 5:22-23]. Again to the Colossians in the third chapter [3:18]. Because of this, the wife has not been created out of the head, so that she shall not rule over her husband, but be subject and obedient to him.
For that reason the wife wears a headdress, that is, the veil on her head, as St. Paul writes in 1. Corinthians in the second chapter, that she is not free but under obedience to her husband.
John Calvin, in his commentary on 1 Corinthians 11, writes:
For it is all one as if she were shaven. He now maintains from other considerations, that it is unseemly for women to have their heads bare. Nature itself, says he, abhors it. To see a woman shaven is a spectacle that is disgusting and monstrous. Hence we infer that the woman has her hair given her for a covering. Should any one now object, that her hair is enough, as being a natural covering, Paul says that it is not, for it is such a covering as requires another thing to be made use of for covering it. And hence a conjecture is drawn, with some appearance of probability — that women who had beautiful hair were accustomed to uncover their heads for the purpose of showing off their beauty. It is not, therefore, without good reason that Paul, as a remedy for this vice, sets before them the opposite idea — that they be regarded as remarkable for unseemliness, rather than for what is an incentive to lust.


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Torrington, CT Japanese Restaurant
Fuji Japanese Restaurant
Fuji Japanese Restaurant of Torrington, CT is an upscale bar and restaurant offering delectable sushi options and traditional and contemporary Japanese cuisine. We are also a Hibachi steak house and liquor bar that serves the finest dining combinations on this side of town.
Here's what we offer:
Call Fuji Japanese Restaurant at 860-482-9308 for inquiries.
Contact Information
Hours of Business:
Monday - Thursday: 12:30am-10:00pm
Friday - Saturday: 11:30am-11:00pm
Sunday: 12:00noon-9:30pm
Methods of Payment:


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Custom Hunting, Tactical & Competition Rifles Built for Absolute Accuracy. Contact Aaron Roberts, Owner and Host of TV's Tactical Impact & Handguns on The Sportsman Channel. 281-651-5593 www.RPRIFLES.com
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Sierra, Scomberomorus sierra: The Sierra is one of the more common and feisty members of the Scombridae or Tuna, Bonito, and Mackerel Family found in Mexican waters.
The Sierra is characterized by its elongated body with short snout, bronze green on the back, silver-white sides and belly, and a series of medium-sized yellow spots on its sides.
It has 7 to 10 finlets between the second dorsal fin and the caudal fin and between the anal fin and the caudal fin.
The Sierra might be confused with the Monterey Spanish Mackerel, Scomberomorus concolor (no yellow spots).
The Sierra is a coastal pelagic schooling species found in all Mexican waters, normally in the first 50 feet of the water column.
The Sierra is reported to reach a length of three-and-one-half feet (24 inch models more common) and 12 pounds.
This fish species is caught on almost any lure or bait, but has a set of horrific teeth and wire leader is recommended.
It is viewed by locals as excellent table fare but one that must be prepared on the day of the catch.
Mexico Fishing Home Page < Fish Photo List < Sierra
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Health & Pregnancy
First Trimester of Pregnancy
In this article
What to Expect: Changes in Your Body continued...
Mood swings. Increased fatigue and changing hormones can put you on an emotional roller coaster that makes you feel alternately elated and miserable, cranky and terrified. It's OK to cry, but if you're feeling overwhelmed, try to find an understanding ear -- if not from your partner, then from a friend or family member.
Morning sickness. Nausea is one of the most universal pregnancy symptoms, affecting up to 85% of pregnant women. It's the result of hormone changes in the body, and it can last through the entire first trimester. For some pregnant women, nausea is mild; others can't start their day without vomiting. Nausea is usually worst in the morning (hence the name, "morning sickness"). To calm your nausea, try eating small, bland, or high-protein snacks (crackers, meat, or cheese) and sipping water, clear fruit juice (apple juice), or ginger ale. You may want to do even do this before getting out of bed. Avoid any foods that make you sick to your stomach. Nausea itself isn't anything to worry about, but if it persists or is severe, it can affect the amount of nutrition getting to your baby, so call your doctor if you can't stop vomiting or can't keep down any food.
Weight gain. Pregnancy is one of the few times in a woman's life when weight gain is considered a good thing, but don't overdo it. During the first trimester, you should gain about 3 to 6 pounds (your doctor may recommend that you adjust your weight gain up or down if you started your pregnancy underweight or overweight). Although you're carrying an extra person, don't go by the adage of "eating for two." You only need about an extra 150 calories a day during your first trimester. Get those calories the healthy way, by adding extra fruits and vegetables, milk, whole-grain bread, and lean meat to your diet.
Red Flag Symptoms
Any of these symptoms could be a sign that something is seriously wrong with your pregnancy. Don't wait for your prenatal visit to talk about it. Call your doctor right away if you experience:
- Severe abdominal pain.
- Significant bleeding.
- Severe dizziness.
- Rapid weight gain or too little weight gain.
WebMD Medical Reference


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Subtotal: $0.00
Customer Service
We want to make shopping for children's toys just as much fun as children love playing with toys. The Personal Shoppers and Customer Service Center at Kazootoys is designed to answer any and all questions you might have while shopping on our site. We know you have questions from time to time and unlike many other online sites, www.kazootoys.com provides many levels of customer service support. Support is available during the course of the day by phone or email
Don't have time to put your child's birthday party goody bags together? We can do it for you! Call us and we can customize and assemble your bag for you! We have a wide variety of party favors and toys to add to the bag whether we do it here or ship to you to help along the way.
Thank you for shopping at Kazoo Toys.


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An Italian scientist has suggested that an 8.2-magnitude earthquake that has been documented to have rocked Jerusalem in 33 A.D. may have provided the catalyst for the image imprinted on the historic Shroud of Turin. According to USA Today on Feb. 12, Professor Alberto Carpinteri's research into piezonuclear fission reactions has led him to believe that an earthquake could have caused the emission of neutrons that induced the image on the fibers. The neutrons could have also altered the carbon-14 dating that indicated its age at 728 when testing was done in 1988.
The ancient relic is purported to be the burial cloth that Jesus was buried in, but the Catholic church has not made a definitive declaration of its authenticity. This theory developed by Carpinteri and the team at Politecnico di Torino in Italy actually supports the Biblical record regarding a significant earthquake in 33 A.D. The events surrounding the death of Jesus Christ in Mathew 27 are as follows from the King James Version on BibleHub.
50Jesus, when he had cried again with a loud voice, yielded up the ghost. 51And, behold, the veil of the temple was rent in twain from the top to the bottom; and the earth did quake, and the rocks rent; 52And the graves were opened; and many bodies of the saints which slept arose, 53And came out of the graves after his resurrection, and went into the holy city, and appeared unto many. 54Now when the centurion, and they that were with him, watching Jesus, saw the earthquake, and those things that were done, they feared greatly, saying, Truly this was the Son of God.
It is always interesting when science supports the accuracy of the Holy Bible texts.
You can read here about Hitler's fascination with the Shroud of Turin.
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