Thursday, May 31, 2012

How safe are metal-on-metal hip implants?

This is the response from Depuy to Debbie Cohen's article in the British Medical Journal on the Depuy hip issue.  The BMJ article can be found here as well as Debbie Cohen's response to Depuy's comment on the article:The original post for the article can be found here: http://www.mydepuyhiprecall.com/2012/03/how-safe-are-metal-on-metal-hip.html



Graham Isaac PhD CEng FIMechE, Distinguished Engineering Fellow
Simon Sinclair PhD MB BChir, International Clinical Director
DePuy Orthopaedics Inc, Leeds, United Kingdom

While we respect the BMJ’s right to rigorously investigate issues, this article is unnecessarily alarmist and in a number of instances factually incorrect. We submit this letter to highlight some of the factual errors and omissions regarding metal-on-metal hip implants generally, and, in particular, DePuy’s ULTAMET® metal-on-metal implant, which is one of the available options used with the Pinnacle® Acetabular Cup System.

Adverse Reactions to Metal Debris and Ions:

It is well documented that all hip implants, no matter what materials are used, experience wear over time and generate wear debris. Indeed, it was the widely published concerns that wear debris from metal-on-polyethylene hip replacements used in the 1990’s caused bone damage to a significant number of patients that re-kindled the orthopaedic community’s interest in developing a new generation of metal-on-metal implants. Contrary to the suggestion in the article, the potential for reactions to wear debris from metal-on-metal hip implants has been known and studied for over two decades, and the reported incidence of such adverse reactions is very low. According to the U.S. Food and Drug Administration, “Based on the limited number of case reports in published literature, the true incidence or prevalence of adverse systemic effects from MoM hip implants is not known at this time, but is believed to be rare.” Similarly, the MHRA, in releasing updated guidelines last month for monitoring patients with metal-on-metal hip implants, stated: “The majority of patients implanted with MoM hip replacements have well functioning hips and are thought to be at a low risk of developing serious problems.”

Metal Ion Levels:

The article states that DePuy had been aware since 2008 of raised metal ion levels in people with ULTAMET metal-on-metal implants and implies that DePuy concealed this information. This assertion is misleading as it has long been known that patients with metal-on-metal hip implants – and also occasionally hip implants with other bearing surfaces – have “raised levels of ions.” In fact, an article published by Antoniou et al. in a widely read orthpaedic journal and referred to in your article cited seven references on this subject, which date back as far as 1996. When metal-on-metal hip implants were introduced, it was recognized that one of the effects of having metal bearing surfaces would be that constituents of cobalt and chromium would be released locally and systemically. However, data for prior generations of metal implants did not indicate clinical problems from these releases in well functioning implants, some of which had been in place more than 15 years.
The article expresses considerable alarm about the levels of metal ions associated with the ULTAMET metal-on-metal implant, appearing to claim that 20% of patients with ‘DePuy’s flagship Pinnacle hip system’ had blood metal ions above the 7 parts per billion (ppb) level in the MHRA guidance. The three studies cited for this proposition do not support this. The one peer-reviewed publication amongst them found that 5% of patients with ULTAMET implants had levels above 7ppb, with mean cobalt levels at or below 2.3 ppb at all time points measured.

In addition, the article does not establish that the level of metal ion release has clinical significance. Indeed, the U.S. FDA recently stated that there is insufficient evidence to correlate the presence of localized lesions, clinical outcomes, and/or the need for revision with specific metal ion levels for individual patients.

Cancer:

Although the article focuses on the potential risk of cancer from metal-on-metal implants, the connection between metal-on-metal devices and any form of cancer remains unproven, as the article itself concedes. The British Orthopaedic Association/British Hip Society, in response to the media attention generated by the article’s reference to cancer risks, stated that “Currently there is no verified evidence that having a metal on metal hip replacement increases cancer risk.” The BOA/BHS went on to warn that “It would be unwise to suggest removing these joint replacements and taking additional risks of surgery just on the possible cancer risk.” The BOA/BHS statement also noted that while the media reports mentioned one study that found abnormalities in bladder cells of patients with metal-on-metal hip implant, those same reports failed to mention a larger, longer term study that did not show any increased risk of bladder cancer in metal-on-metal hip implant patients. Furthermore an article in the current volume of BMJ comprising 40,576 patients with metal-on-metal hip implants showed that “…there was no evidence that metal on metal bearing surfaces were associated with an increased risk of any cancer diagnosis in the seven years after surgery”.

Taper Corrosion:

Observations of taper corrosion have been reported over the years in modular total hip replacement systems, regardless of what bearing surface is used. The clinical significance of these observations has not been established. Contrary to the assertion in the article, DePuy’s most commonly used tapers (‘12/14’) have employed the same angles and surface finishes since they were first introduced. The article also mistakenly asserts that current taper lengths were first introduced in 2004. In fact, the current taper length was first used in 2001. Since 2001, DePuy has gradually adopted this taper length on other stems.

The company investigates any specific complaints it receives related to taper corrosion. For example, as noted in the article, DePuy received complaints about taper corrosion from some surgeons in Japan. However, the article fails to mention that the stems at issue used a particular taper first introduced in the mid 1980’s, which is referred to as a ‘9/10’ taper, and that those stems, when used with metal-on-metal implants, were only available in Japan. The article also omits that in connection with its investigation, DePuy communicated with doctors in Japan in June 2011 and advised them not to use those particular stems in combination with certain metal-on-metal implants.

Introduction of the current generation of metal-on-metal implants:

The article suggests that the current generation of metal-on-metal hip implants was introduced despite known risks and without a clear clinical need. This is not true. Early failures in the first generation of metal-on-metal implants, largely attributed to limitations in the manufacturing process, led to the widespread adoption of polyethylene as the bearing of choice. However a subsequent review of these early metal-on-metal implants showed that many of them exhibited long-term success with much lower wear than polyethylene systems. As a result, when concerns emerged over the damage caused by polyethylene debris, and since manufacturing techniques had advanced, the orthopaedic community had renewed interest in metal-on-metal bearings once again. The other alternatives at this stage were newer polyethylenes that did not yet have long term clinical track records, and ceramics which had also experienced early failures in prior generations. An additional benefit of metal-on-metal implants was that they allowed for larger femoral heads to be used which provide greater stability and lower risk of dislocation. Viewed in context, the re-introduction of metal-on-metal hip implants was a well-considered response to the patient safety concerns being voiced about traditional polyethylene bearing technology.

Revision rate data:

DePuy continues to monitor on a monthly basis data about the ULTAMET metal-on-metal implants from a variety of sources, including published and unpublished data from national joint registries, published literature, company-sponsored clinical trials and internal complaint data. The ULTAMET metal-on-metal implant is performing in a manner consistent with or better than other metal-on-metal products and consistent with benchmarks set by the UK National Institute of Health and Clinical Excellence (NICE). Further, DePuy has conducted four separate studies that include patients with ULTAMET metal-on-metal implants with a head size equal to or greater than 36mm. The pooled results from those studies comprising 1076 hips (779 with a greater than 2 year follow-up), which show a 5 year survival rate of 97%, are consistent with the data from the national joint registries. A femoral stem with a shortened taper was used in 59% of these cases.
* * *
As shown with the examples above, the article fails to provide a balanced presentation of the facts surrounding metal-on-metal implants in general, and DePuy’s ULTAMET metal-on-metal implants in particular. Given the serious nature of the issues raised by the article, and the potential, as noted by the BOA/BHS in their statement, that patients may be scared into having unnecessary surgical procedures, a more balanced presentation would have been appropriate and more in keeping with the BMJ’s stated aim of ‘helping doctors make better decisions’.
Competing interests:Employees of DePuy Orthopaedics Inc

xxxx

ok now look at Debbie Cohen's response to this commentary above:

http://www.mydepuyhiprecall.com/2012/05/how-safe-are-metal-on-metal-hip.html

Wednesday, May 30, 2012

Progress in Texas DePuy Pinnacle MDL (multidisctirct litigation)

Tracy Ray | May 17th, 2012 | Posted in Depuy Hip Recall News

Preliminary procedures are on track in the pending DePuy Pinnacle hip MDL in the U.S. District Court for the Northern District of Texas. On April 25, 2012, the judge overseeing the MDL, U.S. District Judge Ed Kinkeade, held a meeting with each side’s Pinnacle hip lawyer regarding the most expedient way to manage the more than 1,000 lawsuits in the MDL. After the meeting, they stated that they expected to be able to announce a case management process within six weeks.
Once that process is established, the next step will be to choose representative lawsuits for bellwether trials. These are trials of typical lawsuits in the MDL to ascertain how a jury is likely to respond to evidence that is common to all the cases. A DePuy hip lawyer can then use that knowledge to negotiate a settlement or to plan strategy for future lawsuits. The verdicts in the bellwether trials can also be used as precedents for future cases.

Plaintiffs claim complications from Pinnacle hip

The plaintiffs who filed these lawsuits typically claim to have suffered complications common to metal hip implants: implant loosening, pain, stiffness, immobility, and metallosis. These side effects result when the friction of metal on metal causes metal debris to rub off. If metal debris gets into the bloodstream, metallosis can result, which can ultimately lead to kidney or liver damage. Meanwhile, as the metal joins wear down, they no longer fit properly and become loose, causing pain and difficulty moving. In many cases, revision surgery is required to repair or replace the implant.

Monday, May 28, 2012

My results from a 2nd metals test: FISH testing for T(14;18) Translocations

The second metal tests are in.  The first one can be found here which was to confirm that there were no metals found in the first tumor (Ovary): (all on the blog)  Metal Test result back from the research lab   The results were as we expected.

This  new test was the Cytogenitics test based on the research done on finding translocations in hip patients.

Background on this topic can be found here:

Summary of the Systemic issues dicussed from 7a-7n/14 articles considered by the committee on mutagenicity

Quantification of t(14;18) in the lymphocytes of healthy adult humans as a possible biomarker for environmental exposures to carcinogens.

Evidence for a possible need for Cytogenic testing with Depuy hips or MoM hips (3 of x)

Detection of T (14;18) translocations in pheripheral blood lymphcytes in patients with total hip ateroplasty

Test results:

Note:  I have to review this with someone who understands the research test.  I can give you the answer I got but I have to talk to someone about the test methodology.  We ran these tests on the Ovarian tissues that was removed not on a sample from blood lymphocytes so again, this is preliminary.

  •  The FISH analysis is negative for the ALK gene arrangement in all of teh cells analyzed.
  • The FISH analysis with the probe specific for the (14;18) translocation was performed on 400 interphase nuclei.  There was no t (14;18) rearrangement  detected.
  • There were signals detected on two hybridizations with the 3p14.2 detected.
I will follow up on this.

Connie

 



Sunday, May 27, 2012

"Weird" paths with my cancer....first appointment with one of the top three cancer hospitals

Hi All,

As you know, I have been visiting the top 3 cancer centers to try and understand three things with my recent diagnosis of stage 4 renal cell carcinoma:
  • How did this recurrence happen so quickly?
  • What treatment should I seek?
  • How do the metals play in this treatment, if at all given they all seemed to appear right after the revision hip surgery?
I met with the first of 3 cancer centers on Friday and will meet with the second one on Tuesday.

The first thing we discussed was the "weird/unusual" occurrences with my case (the resident did the medical history to confirm his understanding of my case):
  • The primary tumor was quite a bit smaller than the secondary tumor which I removed a few weeks ago.
  • The path these tumors took was highly unusual.
  • The rapidity with which these tumors became apparent post revision.
  • No symptoms whatsoever....(same was the case with the hip and the damages done with that....I was completely asymptomatic.)
  • The slow growing nature of these tumors was unusual.  This type of growth occurs in only 10% of the population of renal cell carcinoma.
    • Interesting but the renal oncologist counted the start date from 6 years ago not from the time the tumors reappeared and grew.  (I have to check that out because my team felt they were rapidly growing tumors.  This guy though they weren't  if you count the start date from 6 years ago when the first sign of the disease appeared.)   Who knows?  I have become accustom to the disagreement among physicians.
He knew absolutely nothing about the hip effects here.  Zero.  He had no idea how the treatment he recommended may or may not be affected by the metals.  I didn't pursue it with him given his lack of knowledge in this area.

In any event, he strongly suggested IL2 treatment (interleukin 2) which is the most violent of the chemical approaches in all of cancer.  It apparently has a 5% chance of cure and in this cancer, there is not chance for cure at this stage.  I am very cautious about this approach but if you make it through the regime, you have a better  chance of survival than I have now.

My current life expectancy is 2.6 years based on no treatment from the Sloan Kettering scale.  It moves up to 36-45  months with the standard of care treatment:  Sutent.  The survival rate with that drug is low.

I am hoping that someone can tell me there is no potential to do  additional harm over and above what I have endured with the metals with this IL2.  I will be investigating this more on my own.

The orthopedic surgeons know little about the metal problems.  Surely, the cancer guys don't seem to know anything so the last group of guys I will approach are the biochemists.  Someone has to understand the potential effects of combining the chemicals and the metals.  If my levels were back to normal, I would have minimal concerns.  They are not.  I have some leads of people with whom I can contact.

Tomorrow I will talk about the Research tests for translocations and the metals.  I got those tests back on Thursday nite but haven't had time to publish them.

Interleukin 2 is very harsh treatment and undergoing that with the uncertainty surrounding the metals is not something I am comfortable with.  I don;t know if the other consults will recommend this treatment but we'll see.

Connie

Friday, May 25, 2012

Don't rely on one single investigative tool to make clinical decisions.

 I so agree with this thesis:
 
J Arthroplasty. 2012 May 17. [Epub ahead of print]

Evidence-Based Understanding of Management Perils for Metal-on-Metal Hip Arthroplasty Patients.

Source

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Abstract

Adverse biological reactions causing failures of metal-on-metal (MoM) hip arthroplasty can be local or systemic. Both dose-dependent cytotoxicity of wear debris leading to subsequent necrosis of periprosthetic soft tissues and adaptive immunity may play an important role in pathogenesis in susceptible patients. There appears to be a spectrum of clinical presentations of adverse soft tissue reactions, reflecting a complex interplay of implant, surgical, and patient factors. A systematic treatment approach is helpful in optimizing evidence-based management of MoM patients. Although specialized tests such as metal ion levels are a useful diagnostic tool for evaluating MoM hip arthroplasty patients, overreliance on any single investigative tool in clinical decision-making process should be avoided. Future research focusing on diagnostic tools for detecting adverse periprosthetic soft tissue necrosis as well as optimization of MoM bearings and modular connections to further diminish wear and corrosion is warranted.

xxx

very important message for patients!  things to avoid in my opinion:

Cr and Co levels are high, remove the hip.  Maybe a mistake.
No pain, no action required.....big mistake
moderate pain, postpone a comprehensive look at the issue...big mistake

Your surgeon should have a comprehensive look at the issues in 100% of all cases.  like the authors say, over reliance on a single investigative too in clinical decision making process should be avoided.

What might constitute comprehensive testing:
MRI (Mavrik protocol)
Blood levels taken periodically
Sonogram

There are others but these are the most common and the results should be viewed in the totality of the patent's history.

Wednesday, May 23, 2012

4 Stocks Proving That Regulation Matters

Medical device manufacturers play fast and loose with product safety. 

By
updated 5/22/2012 5:53:05 AM ET2012-05-22T09:53:05   
 
   Medical devices can and do make life decidedly better for a whole lot of people. However, some device manufacturers have alarmingly put out products that either fail to improve patient outcomes or, in too many cases, actually cause more damage. It looks likely that the FDA is going to tighten up surveillance, which means that these companies are going to have to get their acts together. How could this happen?The basic problem here is that, unlike drugs, a whole lot of medical devices make it to market with no clinical testing. Once implanted, they receive precious little oversight. Regrettably, it seems we cannot rely on the companies themselves to ensure that their products are safe, and so begin our problems.
Many of these offenders come from the 501(k) process that lets device makers gain approval for new products by claiming they are not materially different from pre-existing approved ones. In one case, a company didn't seek approval at all, leading to an inquiry from Sen. Charles Grassley, as we'll see below. And in 2009, the Government Accountability Office went so far as to release a report on the FDA's oversight failures. All this has finally pushed the FDA to begin work on a national surveillance strategy, due for release by the end of this year.

And our offenders are...Let's take a closer look at four companies exhibiting bad behavior and responsible for some, in my opinion, egregious medical device troubles.

Johnson & Johnson's DePuy Orthopaedics unit makes total hip replacements. These ice-cream-cone-shaped devices used to be made of both plastic and metal, but when DePuy chose to switch to an all-metal design, the device slipped through the clearance process without testing because it was deemed "substantially equivalent" to the previous model.

Trouble is, it did not behave equivalently once implanted. Nearly half of all implant recipients needed a second surgery within six years to repair the damage. DePuy only recalled the device after almost 100,000 people had already served as unwitting test subjects. A recent Forbes estimate puts the cost of claims settlements for all-metal hips to J&J, Zimmer, and other manufacturers at about $5 billion.

Edwards Lifesciences makes annuloplasty rings, which literally hold a leaky heart valve together. The company had full FDA approval for an existing set of rings, but in 2006 it released the Myxo ring, a new product Edwards had reengineered on the basis of the old one.
 
The Myxo ring went into hundreds of people's chest cavities with no testing or approval of any kind. To be fair to Edwards, this was all perfectly legal, and was based on a gaping loophole in the FDA's regulations. But critics in the medical community say the process amounted to an aftermarket experiment on unwitting human guinea pigs. The process was so alarming that it prompted that previously mentioned Senate probe. Edwards ultimately came away largely unscathed, but had to pull the product from the market and rebrand it under a new name with FDA approval.

Boston Scientific makes surgical mesh that is designed to support internal organs. The company had a mesh product designed to repair internal hernias, and sought approval for that product's vaginal use to treat urinary incontinence. Never mind that this was a different body part and required a different implantation method. The ProteGen Sling sailed through to market, again without specific testing for this new application.

The complaint reports started to flood in. One study found that 15% of vaginal mesh recipients suffered complications, and that the mesh benefited them no more than alternative treatments. Boston Scientific has not budged on its assertion that the mesh is safe and effective, so the FDA finally got off the couch this January and ordered proper studies of the product. We'll have to wait for results, but I'm betting they won't look too good.

St. Jude Medical makes implantable defibrillator leads. Defibrillators are similar to pacemakers, and basically shock a struggling heart back to life. The leads are the wires that connect the defibrillator to the heart. High-profile malfunctions have plagued the entire heart device industry, but St. Jude's may take the cake.

The company's Riata lead -- wiring up about 79,000 fragile hearts in the U.S. alone -- started eroding through its protective coating in some patients, thereby jolting them unconscious with raw electric shocks. One study found the flaw in 15% of patients, but other studies show the actual number may be double that. All this culminated in a recall, but only a full year after St. Jude had stopped selling Riata and sent guidance to doctors about the known flaws.

Accountability returns?There is clearly a thread through these stories: If medical device manufacturers were high school kids in the basement with a keg, the FDA was the parent who went upstairs and trusted the teens to holler if there was a problem. But these companies are not children, and I expect better from them. I cannot see clear to investing my money in companies that do not take the safety and efficacy of their products more seriously. It's only going to get harder for them now that the FDA is finally rousting itself to action.

Tuesday, May 22, 2012

Low Molecular weight antioxidants are capable of chelating metal ions like Chromium and cobalt

This was found in an abstract on oxidative stress that I published a few days ago:http://www.mydepuyhiprecall.com/2012/05/advances-in-metal-induced-oxidative.html

"Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, and other antioxidants) are capable of chelating metal ions reducing thus their catalytic activity to form ROS. A novel therapeutic approach to suppress oxidative stress is based on the development of dual function antioxidants comprising not only chelating, but also scavenging components. Parodoxically, two major antioxidant enzymes, superoxide dismutase (SOD) and catalase contain as an integral part of their active sites metal ions to battle against toxic effects of metal-induced free radicals."

xxxxx

Definition:

Chelation therapy (noun) is the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology. Poison centers around the world are using this form of metal detoxification

Chelation therapy is the use of chelating agents to detoxify poisonous metal agents  such as chromium and cobalt by converting them to a chemically inert form that can be excreted without further interaction with the body, and was approved by the U.S. Food and Drug Administration in 1991

Chelation is the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central atom.[

xxxx

I was in to see my Internist last week and she and I spoke about using some alternative therapies to deal with the metal levels possibly starting pre chemo.... I was curious to see her recommendations and then compared them to the recent abstract reference to other antioxidants.  I wondered what dose levels they would be looking at?

Anyone ever try this or hear of it?  I'm sure that they are megadoses of vitamins.  I found a reference to  a physician who was giving IV megadoses of Vitamin C for this purpose  but it was not well received by the medical community.

Interesting how many options are available albeit, all not well regarded by the medical community.  If anyone has been given high does vitamins therapy for this, I would surely be interested in your story.

Monday, May 21, 2012

Measuring Cr and Cobalt levels in the organs.

    J Biomed Mater Res A. 2012 Jun;100(6):1529-38. doi: 10.1002/jbm.a.34091. Epub 2012 Mar 15.

    Distribution of metal released from cobalt-chromium alloy orthopaedic wear particles implanted into air pouches in mice.

    Source

    Bioengineering Unit, University of Strathclyde, Wolfson Center, Glasgow G4 0NW, United Kingdom.

    Abstract

    Metal-on-metal hip replacement implants generate wear debris and release ions both locally and systemically in patients. To investigate dissemination of metal, we determined blood and organ levels of cobalt (Co), chromium (Cr), and molybdenum (Mo) following the implantation of Co-Cr alloy wear debris in mice using skin pouches as a model system. We observed increased metal levels in blood for up to 72 h; the levels of Co were highest and remained elevated for 7 days. Co levels were elevated in all organs studied (liver, kidney, spleen, lung, heart, brain, and testes), with the peak at 48 h; highest levels were measured in liver and kidney (838.9 ± 223.7 ng/g in liver, and 938.8 ± 131.6 ng/g in kidney). Organ Cr levels were considerably lower than Co levels, for example, Cr in kidney was 117.2 ± 12.6 ng/g tissue at 48 h. Co is more mobile than Cr, reaching higher levels at earlier time points. This could be due to local tissue binding of Cr. Exposure to Co-Cr particles in vivo altered antioxidant enzyme expression and activities. We observed induction of catalase protein in the liver and glutathione reductase (GR) and peroxidase (GPx) proteins in the spleen. Activities of catalase and GPx in the liver were significantly increased while that of GR was decreased in the kidney. Organs of mice with Co-Cr particle implantation were exposed to increased metal levels capable of inducing reactive oxygen species scavenging enzymes, suggesting the tissue may be subjected to oxidative stress; however, the overall antioxidant defence system was not markedly disturbed.
    xxxxxxxxxx

    Definitions


    Redox (reduction-oxidation) reactions include all chemical reactions in which atoms have their oxidation state changed
    In
    chemistry, the oxidation state is an indicator of the degree of oxidation of an atom in a chemical compound.
    Oxidative stress represents an imbalance between the systemic manifestation of
    reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause dispruptions in normal mechanisms of cellular signaling

    Carcinogenesis or oncogenesis or tumorigenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes on cellular and genetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.

    Sunday, May 20, 2012

    Litigation involving the recalled DePuy ASR hip will be underway in early November or December 2012, pending a plaintiff's motion filed Monday, May 14.

    Sacramento, CA (PRWEB) May 18, 2012

    Monday, attorneys at Kershaw, Cutter & Ratinoff initiated an early trial date for a lawsuit* involving the DePuy ASR hip replacement recall. It will likely be one of the first of more than 7,000 DePuy ASR cases in the country to be tried before a jury.

    KCR's lawyers report that they are seeking an expedited trial date on behalf of a client who alleges she is currently suffering from an incurable staph infection she acquired during a surgery to remove her recalled DePuy ASR hip.* Under California law, anyone over the age of 70 who is suffering from a life threatening health condition may obtain an expedited trial date.

    "“We have now been litigating these cases for almost two years and I think everyone involved is anxious to see how a jury will evaluate these claims,"” said plaintiff’'s attorney Stuart Talley. "If the plaintiff’'s motion is granted, it is likely that the DePuy lawsuit trial date will be set in early November or December 2012."

    According to the complaint, the DePuy ASR hip was touted as being a revolutionary new hip replacement that incorporated a more durable “metal on metal” design. However, after several years on the market, doctors discovered that this revolutionary design was anything but durable. The complaint alleges that a flaw in the design causes excessive wear and tear in the ASR hip, releasing metal wear debris into the patients’ hip joints and blood stream, which can cause severe tissue damage, pain, potential long term health issues and a host of other related problems.




    The complaint also states that after the DePuy ASR recall was announced, thousands of DePuy ASR hips had to be surgically removed from patients through what is commonly referred to as “revision surgery.” In many cases, these revisions surgeries occurred only months after the original ASR was implanted in their hip.



    "“These hips were supposed to last up to 20 years and instead many had to be removed just a year or two later," Talley explained. "What many people do not understand is that hip revision surgeries are extensive and are fraught with potential complications. In older individuals these complications can shorten their life by years."

    The medical device lawyers at Kershaw, Cutter & Ratinoff encourage anyone with a DePuy ASR hip to contact a lawyer as soon as possible to protect their legal rights. Because the statute of limitations varies from state to state, patients who do not act fast may lose their right to claim damages if they occur in the future.

    *DePUY ASR™ HIP SYSTEM CASES, JCCP No. 4649, San Francisco Court

    Saturday, May 19, 2012

    Hip companies report first quarter results from thier business

    Orthopedic Device Company Q1 Financial Report Updates   (excerpts)                    Written by Laura Miller | May 16, 2012 

    Biomet. During the third quarter of the 2012 fiscal year, Biomet reported $709 million net sales worldwide, a 5 percent increase over the same period last year. Biomet reported growth in the large joint reconstructive business, including 4 percent growth in knees and 6 percent growth in hips. Total net sales for the large joint reconstructive business were $422.7 million. Sports medicine sales jumped 16 percent to $92.7 million while the company's trauma business only grew 1 percent in the third quarter. Despite the positive sports medicine and joint replacement growth, Biomet's spine and bone healing business took a hit. The overall business line sales dropped 5 percent to $76.5 million, while just spine products dropped 3 percent.

    Johnson & Johnson. Johnson & Johnson's first quarter orthopedics sales were flat overall and dropped 3.5 percent in the United States. The company reported $1.4 million in worldwide orthopedics sales, which was slightly below the $1.5 million reported in the first quarter of 2011. The company's international orthopedics sales increased 2.6 percent, which offset a decrease in the U.S. market. During the first quarter, the company reported $271 million in expenses related to litigation and the DePuy ASR Hip recall costs.

    Smith & Nephew. Smith & Nephew reported $1 billion in revenue for the first quarter of 2012, a 3 percent increase over the same period last year. The company's knee implant business was up 6 percent over the first quarter last year, driven by Legion Revision Knee System sales. The company's hip implant business dropped 2 percent in connection with the continuing controversy surrounding metal-on-metal total hip implants. Sales of the company's Birmingham Hip Resurfacing system particularly suffered. Its sports medicine joint repair business grew by 7 percent, and the arthroscopy enabling technologies business was up 1 percent.

    Stryker. Orthopedic and spine device company Stryker reported $2.2 billion in first quarter net sales, a 7.2 percent increase over the same period last year. The increase was driven by similar jumps in the company's reconstructive, MedSurg, neurotechnology and spine business lines. Acquisitions in the spine and neurotechnology businesses drove a 12.4 percent net sales increase, while increased unit volume and changes in product mix also contributed to the business line's success. The company's knee and hip business lines also reported a net sales increase of 3.3 percent and 5.1 percent, respectively. During the first quarter, the company incurred $17 million in acquisition- and integration-related charges for Neurovascular, Orthovita, Memometal and Concetric acquisitions

    Wright Medical Group. hips and knees business lines dropped 9.6 percent and 5.3 percent respectively. The upper extremities business line saw a 13.3 percent decrease in revenues and the biologics line dropped 21.3 percent.

    Zimmer. Zimmer's hip and knee sales were up 2 percent during the first quarter while spine sales dropped 7 percent. Total knee and hip sales reached $471 million and $344 million, respectively. Overall, the company $1.4 billion in first quarter net sales, a 2.2 percent increase over the same period last year. Net earnings for the first quarter were $209.6 million, a slight increase over the first period of 2011. Operating cash flow during the first quarter was $207.4 million. The company reported 1 percent growth in both the American and European markets, along with a 10 percent growth in the Asia Pacific market.

    Friday, May 18, 2012

    Statue of Limitations comming up for claims filing re the Depuy hip case!

    Will Broadspire continue to pay a patient’s out of pocket medical expenses after their statute of limitations (“SOL”) runs in August of 2012 (for most 2 year SOL states)?


    The two year anniversary date of the recall is approaching and will serve as a bar to claimants that have statutes of limitations that expire prior to filing a civil claim with a Court of competent jurisdiction. A quick look at the statute of limitations that are at issue reveal approximately 28 States have statutes of limitation that are 2 years or less. In those States, the statute of limitations could expire as soon as July 16, 2012. (Less than 90 days from right now!)

    Here is a list of states with  these deadlines (findlaw.com)

    A plaintiff in each state must bring an action within a certain period of time prescribed in the state's statute of limitations. In most states, the time period begins when the plaintiff discovered or should have discovered his or her injury, under what is known as the discovery rule. A few states begin this time period when the injury actually occurred. Some states have also enacted statutes of repose, which bar actions that are not brought within a specified period of time after some event has occurred, such as the initial sale of a product. (From Find.law.com)

    ALABAMA An action must be brought within one year from the time when the injury is or should have been discovered.
    ALASKA An action must be brought within two years from the time when the injury is or should have been discovered.
    ARIZONA An action must be brought within two years from the time when the injury is or should have been discovered. The state has enacted a 12-year statute of repose that begins to run once the product is first sold. The statute of repose does not apply to actions based on negligence or breach of warranty.
    ARKANSAS An action must be brought within three years from the time when the injury is or should have been discovered.
    CALIFORNIA An action must be brought within two years from the time when the injury is or should have been discovered.
    COLORADO An action must be brought within two years from the time when the injury is or should have been discovered.
    CONNECTICUT An action must be brought within two three years from the time when the injury is or should have been discovered. The state has enacted a 10-year statute of repose that begins to run once the manufacturer or seller has last parted with the product.
    DELAWARE An action must be brought within two years from the time when the injury is or should have been discovered.
    DISTRICT OF COLUMBIA An action must be brought within three years from the time when the injury is or should have been discovered.
    FLORIDA An action must be brought within two years from the time when the injury is or should have been discovered. The state has enacted a 12-year statute of repose, subject to various exceptions.
    GEORGIA An action must be brought within two years from the time when the injury is or should have been discovered or one year from the date on which death has occurred. The state has enacted a 10-year statute of repose, subject to various exceptions.
    HAWAII An action must be brought within two years from the time when the injury is or should have been discovered.
    IDAHO An action must be brought within two years of the date on which the injury occurred. The state has enacted a 10-year statute of repose, subject to various exceptions.
    ILLINOIS An action must be brought within two years of the date on which the injury occurred. The state has enacted a 12-year statute of repose that begins to run once the product is sold and a 10-year statute of repose that begins to run once the product is delivered to the first owner.
    INDIANA An action must be brought within two years of the date on which the injury occurred. The state has enacted a 10-year statute of repose.
    IOWA An action must be brought within two years of the date on which the injury occurred.
    KANSAS An action must be brought within two years of the date on which the injury occurred.
    KENTUCKY An action must be brought within one year of the date on which the injury occurred. If injury, death, or property damage does not occur within eight years of the product's use, then this creates a rebuttable presumption that the product does not contain a defect.
    LOUISIANA An action must be brought within one year of the date on which the injury occurred. This statute does not apply to minors.
    MAINE An action must be brought within six years of the date on which the injury occurred.
    MARYLAND An action must be brought within three years of the date on which the injury occurred.
    MASSACHUSETTS An action must be brought within three years of the date on which the injury occurred.
    MICHIGAN An action must be brought within two years of the date on which the injury occurred. If a product is in use for more than 10 years, then liability cannot be based on strict liability.
    MINNESOTA An action must be brought within four years of the date on which the injury occurred.
    MISSISSIPPI An action must be brought within two years of the date on which the injury occurred.
    MISSOURI An action must be brought within five years of the date on which the injury occurred.
    MONTANA An action must be brought within three years of the date on which the injury occurred.
    NEBRASKA An action must be brought within four years of the date on which the injury occurred. The state has enacted a 10-year statute of repose, which begins to run from the date in which a product is first sold.
    NEVADA An action must be brought within four years of the date on which the injury occurred.
    NEW HAMPSHIRE An action must be brought within three years of the date on which the injury occurred, except where a legal duty has been imposed by the government, in which case the action must be brought within six years. The state has enacted a 12-year statute of repose, which begins to run once the product is manufactured and sold.
    NEW JERSEY An action must be brought within two years of the date on which the injury occurred.
    NEW MEXICO An action must be brought within three years of the date on which the injury occurred.
    NEW YORK An action must be brought within three years of the date on which the injury occurred.
    NORTH CAROLINA An action must be brought within six years from the date of the initial purchase.
    NORTH DAKOTA An action must be brought within 10 years from the date of the initial purchase or within 11 years of the date of manufacture.
    OHIO An action must be brought within two years of the date on which the injury occurred.
    OKLAHOMA An action must be brought within two years of the date on which the injury occurred.
    OREGON An action must be brought within two years of the date on which the injury occurred. The state has enacted an eight-year statute of repose.
    PENNSYLVANIA An action must be brought within two years of the date on which the injury occurred.
    RHODE ISLAND An action must be brought within three years of the date on which the injury occurred.
    SOUTH CAROLINA An action must be brought within three years of the date on which the injury occurred.
    SOUTH DAKOTA An action must be brought within three years of the date on which the injury occurred. The state has enacted a six-year statute of repose, which begins to run after purchase.
    TENNESSEE An action must be brought within four years of the date on which the injury occurred. The state has enacted a statute of repose that runs six years after an injury and 10 years after the initial purchase of a product.
    TEXAS An action must be brought within two years of the date on which the injury occurred.
    UTAH An action must be brought within two years of the date on which the injury occurred.
    VERMONT An action must be brought within three years of the date on which the injury occurred.
    VIRGINIA An action must be brought within two years of the date on which the injury occurred.
    WASHINGTON An action must be brought within two years of the date on which the injury occurred. The state has enacted a 12-year statute of repose.
    WEST VIRGINIA An action must be brought within two years of the date on which the injury occurred.
    WISCONSIN An action must be brought within three years of the date on which the injury occurred.
    WYOMING An action must be brought within four years of the date on which the injury occurred.

    Thursday, May 17, 2012

    Metal Test result back from the research lab

    I finally got my results back from the research lab specializing in metal analysis.

    Due to the recurrence of my cancer after complete discharge from the surgeon a year ago, there were three things that we were interesting in reviewing post revision when we noticed that tumors began growing and the in situ renal cell carcinoma metastasized. :
    (1) I am very pleased that the chromium and cobalt levels are dropping considerably.  They have certainly dropped in half since the revision.  Still concerned though about these metal levels mixed with chemical levels from the cancer treatment which I have not yet started.

    (2)  I am relieved with  results from the tests to  detect any metals in the organ which was removed from the recent surgery showed no metal particles:







    (3) I  haven't seen the results from the cytogenetic test yet.


    Remember, I am taking two paths to dismiss the metals as being contributory to this occurrence.  I do not think the metals caused the renal cell cancer because I had it before and it reoccurred.  I have not ruled out the fact that the revision might have precipitated the recurrence by flooding my body with yet more metals which would increase the activity of the immune system by trying to fight the foreign material thereby providing an opportunity  for dormant or orphan cells to flourish.    That process might be termed "onconogenic stiumulation".  That discussion will be left to the cancer specialists I am seeing.

    I am concerned about how, if at all, this activity effects the treatment paradigm for my current cancer therapy when and if it begins.  

    Also, the association between the metals and cancer from a causative perspective are a bit more long term (so I have been lead to believe).  I do want to see the T 14-18 translocation results from the cytogenetic tests however.  I will share those with you when I have them.

    Tuesday, May 15, 2012

    A great pictorial to illustrate the metal on metal oxidation process (5 of 5 in a series)

    This is the final post on a 5 part series on DNA damage from metals:
    Oxidative Stress process associated with Metal on metal hips (series 4 of x)
    Oxidative Stress process associated with Metal on metal hips (series 3 of x)
    Advances in metal-induced oxidative stress and human disease. (2 of x in a series)
    Advances in carcinogenic metal toxicity and potential molecular markers. (1 of x in a series)

    This is a great summary diagram of what can happen when metal particles (Chromium and cobalt) enter into the cell.

    1.  Metal particles are outside of the cell
    2.  Chromium 6 crosses the cell barrier and is oxidized to chromium 3. 
    3.  Chromium 6 is the MORE toxic chromium. 
    4.  That is not to say that Chromium 3 is not. 
    5.  That is also not to say that because Chromium 6 is immediately oxidized to chromium 3, there is no issue. (Follow the green highlights in this illustration to see the end point.)
    6.  Even if Chromium 6 is oxidized to chromium 3, Chromium 3 seems to have as one of 3 end points, DNA damage which is the first step in a cancer process.
    7.  That doesn't mean that it gets to cancer but it is a great illustration of the path options which chromium 3 can take.
    8.  If you read yesterday's post, this diagram is an explination of the steps discussed  in that post and the diagram was taken from the same journal article (link is above).

    this was all quite complicated to me  but this picture simplifies this greately.  If there is a conflict between what I said above and what is written below listen to the experts below.  I tried my best to boil this down so we can understand the issue.

     (incase you had not read yesterday's post.)

    "Different pathways are used by metal ions to enter into the cells. Cr (chromium) 6 can cross the cytoplasmic membrane through the non-specific phosphate/sulfate anionic transporters. Within the cell, Cr6 undergoes rapid metabolic reduction to form Cr 5, then Cr4 and finally Cr 3.

    At each step, of Cr reduction from Cr6, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated. Whether or not Cr 3 is able to cross the cell membrane on its own without a carrier remains controversial. Co (cobalt)2 can cross the cell membrane using the non-specific ion transporter and it is oxidized in the cytosol to Co 3. Co-oxidation leads to the generation of ROS and TNS. Co 2 and CR 6-3 can also bind some metal-binding proteins such as transferrin or ferritin. In the endosome, Co 2 and Cr 6-3 are unbound from their protein carrier via the DMT1 transporter. They are released in the cytosol where they can be reduced or oxidized and result in the generation of ROS/RNS. ROS and RNS are known to be involved in the oxidation, leading to their degradation,lipid perodixation and DNA damage. Cr 3 can also cross the nuclear membrane and particpate in alteration of DNA.

    Metal particles released from the articulating surface of the MoM prosthesis can be phagocytosed by the cells. Inside the phago-lysosome, particles become corroded and release metal ions in the cystol.

    Oxidative Stress process associated with Metal on metal hips (series 4 of x)

    This is a series of articles on Oxidative Stress which results in DNA changes and potentially cancer

    Oxidative Stress process associated with Metal on metal hips (series 3 of x)
    Advances in metal-induced oxidative stress and human disease. (2 of x in a series)
    Advances in carcinogenic metal toxicity and potential molecular markers. (1 of x in a series)

    "Different pathways are used by metal ions to enter into the cells. Cr (chromium) 6 can cross the cytoplasmic membrane through the non-specific phosphate/sulfate anionic transporters.  Within the cell, Cr6 undergoes rapid metabolic reduction to form Cr 5, then Cr4 and finally  Cr 3.

    At each step, of Cr reduction from Cr6, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated.  Whether or not Cr 3 is able to cross the cell membrane on its own without a carrier remains controversial.  Co (cobalt)2 can cross the cell membrane using the non-specific ion transporter and it is oxidized in the cytosol to Co 3.  Co-oxidation leads to the generation of ROS and TNS.  Co 2 and CR 6-3 can also bind some metal-binding proteins such as transferrin or ferritin.  In the endosome, Co 2 and Cr 6-3 are unbound from their protein carrier via the DMT1 transporter.  They are released in the cytosol where they can be reduced or oxidized and result in the generation of ROS/RNS. ROS and RNS are known to be involved in the oxidation, leading to their degradation,lipid perodixation and DNA damage. Cr 3 can also cross the nuclear membrane and particpate in alteration of DNA.

    Metal particles  released from the articulating surface of the MoM prosthesis can be phagocytosed by the cells.  Inside the phago-lysosome, particles become corroded and release metal ions in the cystol."

    Reference source: page 743

    Acta Orthop. 2008 Dec;79(6):734-47.

    Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions.



    Source

    Nuffield Department of Orthopaedic Surgery, Institute of Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford, UK. guillaume.mabilleau@ndos.ox.ac.uk
     
    [All of this matters in terms of trying to get to the bottom of whether these metals can cause cancer.  The more research done in this area, the better.  I hope this series helps you see the possible connections between metals being able to cross the cell barrier resulting in changes in DNA which can potentially result in cancer.
     
    I have a recurrent cancer that was arrested and seemed to come back mysteriously after this revision surgery.  I am investigating the links and will be seeing the top Oncologists in the world over the next two weeks before I start any kind of treatment and will share any information I have.)

    Sunday, May 13, 2012

    Oxidative Stress process associated with Metal on metal hips (series 3 of x)

    This is  the 3rd in a series on Oxidative Stress and its relationship to cancer.  This is  follow on from the prior two articles:
    Advances in metal-induced oxidative stress and human disease. (2 of x in a series)
    Advances in carcinogenic metal toxicity and potential molecular markers. (1 of x in a series)

    I was reading these two prior articles on the oxidative stress process which results in carcinogens from Chromium and cobalt  and recalled reading this exact same process from this article done by the guys at Oxford University:

    Acta Orthop. 2008 Dec;79(6):734-47.

    Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions.

    Source

    Nuffield Department of Orthopaedic Surgery, Institute of Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford, UK. guillaume.mabilleau@ndos.ox.ac.uk

    Now this article reviewed the periprosthetic biological reactions of the metal on metal arthroplasty.

    Here is the section on  page 742 called :  metal induced intracellular effects.  Sounds very much like the prior two articles printed in 2011 but from a different perspective.

    "Reactions with metal ions can lead to generation of free radicals:  reactive oxygen species (ROS) and ractive nitrogen species (RNS) which can in turn, cause cellular dysfunction.  In side the cells, Cr6 is oxidized to Cr3." [Now remember, Cr 6 is the most toxic of the Chromiums however, it is in fact the metal that appears to first be introduced via the metal on metal hips.]......."Permanent modification of gentic material resulting from this oxidative damage represents the first step in mutagensis, carcinogensis and ageing... direct binding of Cr3 to DNA is well documented.  In cells, 2 main processes exist to correct DNA aberrations and to restore the integrity of the genome:  excision repair (BER) and neculeotide excision repair (NER).  Under stimulation by Co2 and Cr6, both of these mechanisms are inhibited."

    [It looks like the same process of the oxidative stress is present with the hip revisions.  it also sounds as though this oncogenic stimulation is present.  Unfortunately, this chemistry is way beyond me.  I have consults arranged with the top cancer centers to try and get some better insight into this material. 

    My concern is the following:

    (1) Should I be placed on Chemo like treatment when I have been exposed to the amount of metals that I have?
    (2) Is it possible that my tumors will shrink as the metal levels receded from the revision?
    (3) Is it possible that I had some orphan dormant cells that were activated during the revision with the amount of stress that my body was under with the exceedingly high levels of metals that get released during revisions?

    How does all of the effect my treatment for Stage 4 renal cell at this point?

    Tomorrow I will discuss the pathways used by metal ions to enter into the cells which is a really important point to understand if you have the questions that I do. 
     

    Saturday, May 12, 2012

    Advances in metal-induced oxidative stress and human disease. (2 of x in a series)

    I find these articles on oxidative stress and oncogenic stimulation fascinating because these same terms have been used in the technical journals to explain what may happen with the metal on metal implants.  I will deal with that next.

    xxxxxxx
    Toxicology. 2011 May 10;283(2-3):65-87. Epub 2011 Mar 23.
    Advances in metal-induced oxidative stress and human disease.

    Source

    Department of Chemistry, Faculty of Natural Sciences, Constantine The Philosopher University, SK-949 74 Nitra, Slovakia. kjomova@ukf.sk

    Abstract


    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione.

     Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties.

     The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, and other antioxidants) are capable of chelating metal ions reducing thus their catalytic activity to form ROS. A novel therapeutic approach to suppress oxidative stress is based on the development of dual function antioxidants comprising not only chelating, but also scavenging components. Parodoxically, two major antioxidant enzymes, superoxide dismutase (SOD) and catalase contain as an integral part of their active sites metal ions to battle against toxic effects of metal-induced free radicals. The aim of this review is to provide an overview of redox and non-redox metal-induced formation of free radicals and the role of oxidative stress in toxic action of metals.

    xxx

    Definitions:

    Redox (reduction-oxidation) reactions include all chemical reactions in which atoms have their oxidation state changed

    In chemistry, the oxidation state is an indicator of the degree of oxidation of an atom in a chemical compound.

    Oxidative stress represents an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause dispruptions in normal mechanisms of cellular signaling

    Carcinogenesis or oncogenesis or tumorigenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes on cellular and genetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.

    Alternative theories of Cancer:

    Several alternative theories of carcinogenesis, however, are based on scientific evidence and are increasingly being acknowledged. Some researchers believe that cancer may be caused by epigenetic alterations (heritable and reversible changes other than the DNA sequence)[5] or aneuploidy (numerical and structural abnormalities in chromosomes)[6] rather than by mutations. Cancer has also been considered as a metabolic disease in which the cellular metabolism of oxygen is diverted from the pathway that generates energy (oxidative phosphorylation) to the pathway that generates reactive oxygen species (figure). This causes an energy switch from oxidative phosphorylation to aerobic glycolysis (Warburg's hypothesis) and the accumulation of reactive oxygen species leading to oxidative stress (oxidative stress theory of cancer).[7] All these theories of carcinogenesis may be complementary rather than contradictory.

    Next post will deal with the metal on metal links to oxidative stress.

    Friday, May 11, 2012

    Advances in carcinogenic metal toxicity and potential molecular markers. (1 of x in a series)

    Well, this is a very interesting article indeed.  This weekend, i am going to re read and publish the oxidative stress issues that have been reviewed in a number of journal articles re the hip artheroplasties.  I will also present these articles to the oncologists I will be seeing over the next two weeks at the top 3 cancer centers for my own condition that has developed.
    xxxx
    Int J Mol Sci. 2011;12(12):9576-95. Epub 2011 Dec 20.

    Advances in carcinogenic metal toxicity and potential molecular markers.

    Source

    Department of Life Science, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea; E-Mail: pkoedrith@gmail.com.

    Abstract

    Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system's ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.