Sunday, September 30, 2012

More on Nanoparticles causing DNA damage from MOM hips through oxidatve stress (5 of x in a series)

Prior posts in the sequence
1 of x
More on Nanoparticles causing DNA damage from MOM hips with oxidative stress ( 1 of x in a series)
2 of x
http://www.mydepuyhiprecall.com/2012/09/more-on-nanoparticles-causing-dna_9.html
3 of x
http://www.mydepuyhiprecall.com/2012/09/more-on-nanoparticles-causing-dan.html
4 of x
http://www.mydepuyhiprecall.com/2012/09/more-on-nanoparticles-causing-dan_23.html


Discussing the 2nd of 4 seminal works on the issues related to causing free radicals in the cell environment from MoM:  Nanonparticles can cause DNA damage across a cellular barrier.

The last post in this series established that the group of scientists demonstrated there is both cytotoxic and genotoxic  effects of nanoparticles of cobalt chrom alloy in a tissue culture using human fibroblasts.  /The research on that article was done in 2007.

This article was published in 2009 and goes a step further to show that the nanoparticles can damage human fibroblast cells across the cell barrier without having to cross the barrier.  these would be categorized as indirect effects when evaluating the safety of nanoparticles in the body. 

1.  Nanoparticles have led to increasing concerns about their potential toxicity in the body.

2.  the current lack of knowledge in this regard has led to an urgent call for the establishment of principles and test procedures to ensure the safe manufacturing  and use of nanoparticles [
which are by products of the metal on metal hips.]

3.  Humans are exposed internally to CoCr nanoparticle by wear mechanisms associated with MoM chromium and Cobalt particles which are known to have both genotoxic and cytotoxic effects in human tissue culture causing DNA damage, chromosome aberrations and cell death if they are applied above a certain threshold.

4.  This paper study has been undertaken to assess the cellular toxicity when located on the other side of a fully confluent cell barrier.

5.  This study used:
  •  BeWo cells which is a human placental choriocarcinoma cell line
  • Trophoblasts  which are specialised cells of the placenta that play an important role in embryo implantation and interaction with the decidualised maternal uterus
6.  Indirect exposure for 24 hours of human fibroblasts to Co and Cr nanoparticles were internalized by these BeWo cells and did not traverse the cell barrier as they were too large to pass through but nonetheless  caused significant DNA damage to the fibroblasts.

7.  Mass spectroscopic analyses revealed the presence of low concentrations of co and cr ions indicating that metal ions were able to cross the cell barrier after particle exposure

8.   Direct nanoparticle toxicity to DNA is thought to be caused by oxidative damage including that from free radicals generated from the reactive particle surfaces and by the creation of chemical DNA adducts.

9.  The outcome of the indirect exposure, increase in tatraploidy* and DNA damage without overall change in cell proliferation is different from that of the direct exposure to nanoparticles at the same dose.

*tetraploid /tet·ra·ploid/ (tet´rah-ploid). 1. characterized by tetraploidy. 2. an individual or cell having four sets of chromosomes.  tetraploidy  is observed in 1–2% of early miscarriages

10  They suggested that a mechanism for the indirect manner in which the top layer of the BeWo cell barrier is damaged  might be through:
  • nano particle damage to the mitochondria
  • hypoxic mimicking actions of the cobalt ions or 
  • mechanical stress to certain mechanosensitve channels which in turn triggers cell signalling and secondary messengers 
11.  This mechanism works in similar way to that proposed to radiation by stander effect.  ---that is, cells exposed to low-dose radiation send a signal to non-irradiated cells, causing an induction of chromosome and gene mutations in the mitochondrial DNA through this signal.

12.  In this context, it is feasible that a process of indirect DNA damage  might have relevance to the human placenta because  it is in the first trimester that the embryo may be particularly vulnerable to teratogenic effects.

[ I have published other journal articles on similar topics:
13.  Tetratploidy as seen in these experiments can be associated with malformation[ in the fetus]!

14.  Extra-embrionic pathways have been suggested to modulate reactive oxygen species (ROS).  Excess free iron in the fetus, as tranported across the placenta by transferrin also contributes to oxidative stress which may damage fetal organs as apart of oxygen free radical disease of neonatology.

Conclusion:  The investigators concluded that an evaluation of nanoparticle safety not be limited to whether they gain access to privileged sites.  Instead, there should be an evaluation of their genotoxic potential for both direct and indirect effects to avoid any potential toxic risks to targets on the distal side of the cell barrier.

xxxxx

Information in the brackets are added by Connie: []

FDA Panel Says Yes to Implanted Eye Device

 

[Interesting that the FDA is still approving devices with considerable problems associated with them.!  Sounds to me like the device they tested in this case, is not the device that is going to market!  sound familiar?]

 
WASHINGTON -- An FDA panel voted unanimously on Friday to recommend approval of the first retinal prosthesis device intended to help nearly blind patients regain a small part of their vision.
The 19-0 vote to recommend approval of the Argus II Retinal Prosthesis device came after study results showed previously blind patients had functional vision with the device. But members of the FDA's Ophthalmic Devices Panel of the Medical Devices Advisory Committee did express some concern about the device's safety.

A single-arm feasibility study of 30 patients showed the Argus II improved visual acuity and daily function including walking straight on a sidewalk (18 of 27 patients) and noticing the direction a person in front of them is walking (25 of 27 patients).

"In most cases the 'on' is consistently outperforming the 'off,' " said panelist Mae Gordon, PhD, of the Washington University School of Medicine in St. Louis. "The data are very clear."

The Argus II is designed for use by patients with severe to profound retinitis pigmentosa, who experience progressive vision loss often leading to blindness. Roughly 1,300 patients a year develop the condition.

The device, manufactured by Second Sight Medical Products, is a three-part system. It includes a video camera attached to a pair of eyeglasses, a processing unit, and an implanted retinal prosthesis.
The glasses capture images, which are sent to the processing unit worn on a belt. The processor transforms the images into an electrical stimulation pattern that's sent to the implanted retinal prosthesis. The Argus II gained approval in Europe last year.

In the study, 15 of 16 patients studied were able to localize a square a year after the device was implanted. Half of the 30 patients read 8.9-inch letters from 12 inches away.

Consumer representative Larry Leguire, PhD, and others expressed concern about the number of adverse events in the small number of patients. There were 140 nonserious adverse events in the 30 patients.

Eleven of the 30 reported a serious side effect, defined as permanent impairment or medical intervention to ameliorate the adverse event. Seven of those patients needed a "minor" intervention including an antibiotic injection and other procedures.

Nine of the 30 patients in the trial needed a follow-up surgery to treat adverse events, the FDA said.
Panelists also struggled to balance the Argus II's safety concerns with the fact that they're dealing with already blind or nearly blind patients.

"This is a patient group that has no other option," said Bill Swanson, PhD, from the Indiana University School of Optometry. "Even if it isn't reliable, they and their doctor may still take the risk."

During the public comment period of Friday's meeting, several patients implanted with the device were moved to tears when they spoke about how the Argus II helped them see fireworks for the first time or recognize the face of a loved one they hadn't seen in years.

Some panelists expressed concern that the device under consideration is slightly different from that implanted in the 30 patients studied. The FDA has determined the changes Second Sight submitted won't introduce any new safety concerns, but the agency can't predict how they will impact performance.

Gordon and other panelists said because the new device reflects improvements on the original's shortcomings, the one the panel voted on Friday should be free of concerns.

Panelists strongly agreed there should be a considerable post-approval study to track possible safety concerns.

Draft labeling language for the device warns of a "cascade" of adverse events following an initial minor side effect, the briefing document released in advance of the meeting stated. Four patients in the study experienced this, including the youngest patient studied, a 27-year-old woman, who ended up with a detached retina.

The FDA reminded panelists that the applicant hasn't submitted any details on a possible post-approval study should its device gain clearance. Second Sight said it would use the same post-approval study currently being used in Europe, a nonrandomized, controlled study for a 1-year follow-up.

But the long-term effectiveness of the device isn't in question, the applicant said Friday.
"Clinically, we have not seen a decline and we've followed some patients for 5 years," said Second Sight consultant Lyndon da Cruz, PhD, MBBS, of the Moorfields Eye Hospital and University College in London.

The FDA is not bound to follow the recommendation of its advisory committees, but it often does.


New Hip Replacement Registry Report: Increase In Hip Revision Surgeries Attributed to Problems with DePuy ASR Hip Implants

The recalled DePuy ASR hip implants were behind the increase in hip revision surgery rates reported in the recently released 2012 Australian Orthopaedic Association annual report, Bernstein Liebhard LLP reports

New York, NY (PRWEB) September 28, 2012

The high revision surgery rates attributed to the recalled DePuy ASR hip implant were a notable finding in the recently released Australian Orthopaedic Association National Joint Replacement Registry’s (“AOANJRR”) 2012 annual report. Bernstein Liebhard LLP reports on the increase in revision hip procedures. In 2010, revision procedures represented 11.3 percent of all hip replacements, while the number increased to 12.5 percent in 2011. According to the report summary, “The major reason for this increase was the high number of revisions being undertaken for the ASR, in particular the ASR XL used in primary total conventional hip replacement. Last year there were 573 revision procedures reported for this prosthesis, this accounted for almost all of the increase in revision hip procedures.” There were 38,022 hip replacements reported to the registry in 2011.

The AOANJRR raised concerns about the DePuy ASR hip implant even before DePuy Orthopaedics issued the worldwide recall. DePuy removed the ASR hip from the Australian market in 2009 after receiving reports from the AOANJRR about higher than anticipated revision rates, and a decline in use of the device in Australia. “This decline was the reason the company gave for removing the ASR from the Australian market, well ahead of the subsequent worldwide withdrawal in 2010.”

Registry Report Finds High Failure Rates Of Metal-On-Metal Hip Replacements

The AOANJRR report also found that metal-on-metal bearing surfaces in total hip replacements, especially those with large femoral heads of 32mm and above, have higher failure rates than other bearing surfaces. “This increased rate of revision is evident in most metal on metal prostheses. This has been identified by the Registry for a number of years and the use of large head metal on metal bearings has now almost completely ceased in Australia.”

Saturday, September 29, 2012

Primer on Hip replacements (for those who are new to the site.)

Drug Watch


Total Hip Replacement




Hip replacements — the surgical repair of an aged or injured natural hip joint by adding an artificial joint, or implant — date back three centuries. Reasons for these implants are the same now as then: a fracture or similar injury to the hip, arthritis or a wearing down of the joint over time. The goal is to reduce pain and increase mobility.

Although there are varied designs and models of hips built by several manufacturers, there are three basic components of an artificial hip — a stem that is inserted into the femur (thighbone); a ball that attaches to the top of the femur; and a cup that attaches to the pelvis.

Patients can undertake one of three types of surgeries — partial hip replacement, total hip replacement or hip resurfacing. Modern implants, increasingly popular since the 1970s, are made from a combination of materials, including plastics, ceramics and metals. Many of the most recent devices were metal-on-metal designs, created with the hope that hip replacements would last longer to give younger, active patients more pain-free mobility for more years.

However, metal-on-metal hip implants produced one significant complication: metal ions can rub off of the devices and enter a recipient’s bloodstream, creating a metal poisoning known as metallosis. Other complications with these implants and others include a loosening of the implant, joint dislocation and, in one case, a squeaky hip.

These complications may lead recipients to pursue corrective actions that are both physical and financial. Many people with problematic artificial hips opt for revision surgery, a corrective procedure that gives them a new hip implant. Many of those same patients — and others — opt for legal action by suing device manufacturers, claiming the companies knew their hip systems were defective.

All hip replacement systems must be approved by the U.S. Food and Drug Administration (FDA) before being used in the United States. Device companies use the FDA’s 510(k) program to gain approval. The program allows the companies to streamline the approval process instead of making them undergo much more rigorous testing. Some of the largest device manufacturers are DePuy Orthopaedics, Zimmer Holdings and Stryker Orthopaedics. All three companies are facing issues with faulty hip devices.

Hip Implant Devices

Hip replacement (hip arthroplasty) is the rebuilding or replacement of the hip joint. The hip joint is made up of the femoral head, the ball at the top of the femur, and the acetabulum, the cup-shaped socket of the pelvis. When a person walks or moves their legs, the femoral head moves within the acetabulum in a similar fashion as a ball-and-socket joint. Hip implants are designed to mimic this natural movement as closely as possible.

The primary differences among implants are their size and the material that components are made of. Hip implant components are made of polyethylene (plastic), metal, ceramic or a combination of materials.

Type of ImplantDefining Characteristics and Details
Metal Ball and Polyethylene (Plastic) Cup or Liner (MoP)These are the most common type of hip implants and have been around since the 1960s. Plastic has a smoother surface finish that allows for less friction while the ball moves within the socket. However, MoP implants produce a lot of plastic debris, which will eventually cause the implant to fail and could lead to a condition called osteolysis.
Metal Ball and Metal Cup (MoM)MoM implants are very durable and can withstand the active lifestyle of younger patients. They have less wear and can accept larger bearings than implants made of other materials. However, their durability comes at a price. MoM hip implants shed metal particles that have been linked to a number of serious health issues like metallosis. Metal-on-metal implants have recently come under fire due to design flaws and early failure rates. Several manufacturers – including DePuy and Stryker — have recalled one or more all-metal hip implant products.
Ceramic Ball and Plastic Cup or LinerUnlike the plastic used in the MoP device, the plastic used in these devices is very dense. Although these materials are reliable and provide for a very smooth surface, there is still the issue of wear debris and the potential for osteolysis.
Ceramic Ball and Ceramic LinerAll-ceramic hips are known for their durability and reliability. They have been around since the early 1980s, but they were only recently approved for use in the United States. Although the femoral ball is made from very hard clay that is wear-resistant, these devices have a history of producing a squeaking noise, and shattering.
Ceramic Ball and Metal SocketThe first ceramic-on-metal hip received FDA approval in 2011. The goal is to avoid the problems of metal-on-metal implants. Postmarket studies are underway.

Hip Implants and the FDA’s 510(k) Program

Metal-on-metal hip systems are classified as Class III (higher risk) devices but are regulated under the Food and Drug Administration (FDA) 510(k) premarket notification program. That means they are not required to undergo premarket testing or clinical trials before they are used in patients. Under the 510(k) program, manufacturers simply have to state that their products are similar to products already on the market.

In May 2011, the FDA ordered 21 manufacturers of metal-on-metal products to conduct postmarket studies. A year later, an FDA panel found that there is little reason for surgeons to continue to use metal-on-metal implant systems. The FDA states that “a decision on the proper classification of metal-on-metal hip systems is forthcoming.”

Hip Replacement Lawsuits

Even though the FDA does not require premarket testing of hip implants, device manufacturers are obligated to design and sell safe products, and warn consumers about any risks associated with their devices. When they fail to do so, patients have a right to seek justice in court. Through no fault of their own, they may have received a defective hip implant or one that has since been recalled.

Legal claims against hip implant manufacturers – including DePuy, Stryker and Zimmer — can help patients cover the high costs of ongoing medical care and any future surgeries that may be required. A legal settlement can also make up for some of the pain and suffering that patients must endure as they seek resolution to a painful hip problem. Punitive damages can discourage manufacturers from acting recklessly in the future.

Hip Replacement Surgery

If conservative treatments like physical therapy and pain medication fail to fix a hip problem, there are several surgical procedures that can provide a solution. Surgeons and patients will discuss the options before scheduling surgery. The decision is based on the age of the patient, as well as the unique problems with the hip joint. Technological developments and medical studies can also influence the decision. Every surgery comes with risks, but the risk can be minimized by choosing the safest, most appropriate procedure for each patient.
The three hip replacement procedures are total hip replacement, partial hip replacement and hip resurfacing.

Total Hip Replacement

A total hip replacement uses an artificial joint to replace the entire hip structure. During the procedure, a stem is inserted into the patient’s femur for stability, and a ball replaces the head of the femur. The socket is also replaced with an artificial cup. Hip implants are usually cemented in place, but some surgeons use a cementless approach instead. A hybrid total hip replacement uses a combination of both, implanting the cup without cement and setting the stem in place with cement.

Partial Hip Replacement

Partial hip replacements (hemiarthroplasty) are recommended when only one part of a hip needs treatment. In most cases, the acetabulum (also known as the socket or cup) is left intact and the head of the femur is replaced with a ball. Some partial hip replacements only address the acetabulum. A partial hip replacement is commonly used to correct a hip fracture occurring at the neck of the femur.

Hip Resurfacing

The primary goal of hip resurfacing is to avoid bone loss. The procedure can delay a total hip replacement in younger recipients, who are likely to outlive the original implant and require a second surgery later. It replaces the socket with an artificial cup and resurfaces the head of the femur instead of removing it. This is accomplished by cementing a covering on top of the femur. This component has a short stem that is inserted into the neck of the femur. Hip resurfacing is often used to help with arthritis.

Complications

As with any surgery, complications can arise following hip replacement procedures. Some problems can be detected immediately, while others may not surface for years. Serious situations may require patients to undergo a second surgery, called revision surgery.
Some of the complications associated with hip replacements are tied to the materials used in the implants. Metal-on-metal implants can lead to metallosis, which is a serious condition that occurs when metallic debris builds up in the soft tissue of the body. Osteolysis, another serious complication that can occur following hip replacement surgery, is the loss of bone around the implant as the body works to “clean up” foreign particles that are produced by the device during normal movement. This can lead to loosening and failure of the implant.
Other serious complications include:
  • Implant dislocation
  • Infection
  • Heterotopic ossification (soft tissue becomes calcified)
  • Avascular necrosis (bone death)
  • Loosening of the implant
  • Fracture

Revision Surgery

Following up to 10 percent of hip replacement surgeries, patients require one or more revision surgeries for further repair. Younger patients will most often require revision surgery, because hip implants are not designed to last more than 15-20 years. Recently, a rash of defective implants has meant more repeat surgeries for more patients. Often, these surgeries are necessary just a few years after the original operation.

Revision surgery is performed to replace one or more artificial hip components that have loosened, worn out, become dislocated or caused other serious complications. These procedures are tougher for surgeons and patients alike, since typically more bone must be removed and new implant parts inserted. The mortality rate also rises: For original hip replacement procedures, the death rate is 1 percent; for revision surgeries, the rate is 2.5 percent.

Hip Implant Manufacturers

Dozens of medical device manufacturers sell hundreds of hip components, and they often advertise their products directly to the consumer. Orthopaedic surgeons, however, are the most qualified to make the decision about which implant components to use in surgery. Most hip implant systems come with several options for surgeons — including different materials, modular necks and stems and/or a variety of femoral ball sizes.

Several of the world’s largest hip implant manufacturers – including DePuy, Stryker and Zimmer — have been forced to recall some of their most popular products after early failure rates and other metal-on-metal complications. Smaller brands – including Smith & Nephew, Biomet and Wright – also are under fire for selling defective implants.

DePuy Orthopaedics

DePuy, a division of Johnson & Johnson, developed three hip replacement designs since 2000 with high failure rates: the Pinnacle Hip Replacement System, the ASR XL Acetabular System and the ASR Hip Resurfacing System. The problems with all three systems arise from their metal-on-metal components, and the two ASR systems have been recalled.

According to data gathered by DePuy, approximately 12 percent of patients who received an ASR Hip Resurfacing System required revision surgery within five years of having the device, and about 13 percent of patients needed revision surgery within five years of receiving an ASR XL Acetabular System.
DePuy is facing lawsuits from patients who experienced complications after receiving one of its problematic hip implants.

Stryker Orthopaedics

In July 2012, Stryker recalled two hip replacement systems: the Rejuvenate and the ABG II modular-neck hip stems. These two hip designs have been associated with complications such as loosening of the implant and metallosis. The first lawsuit against Stryker for its hip design was filed in New Jersey on August 7, 2012.
The recall came just a few months after Stryker issued warnings to surgeons about the hazards associated with these two products. Stryker listed metallosis, tissue death and a number of other complications that could require revision surgery.

Zimmer Holdings

Zimmer is facing lawsuits over its Durom Acetabular Component (Durom Cup), a hip socket made of metal. This one-piece socket is secured in place with a plasma coating instead of cement to promote bone growth, but the implant does not always properly attach to the bone and can cause excruciating pain if it comes loose.
Zimmer briefly recalled the Durom Cup in 2008 to revise the instructions, but it returned to the market. Thousands of U.S. patients received the component between its debut in 2006 and the recall.

Smith & Nephew

Smith & Nephew recalled the metal liner component of its modular R3 Acetabular System on June 1, 2012. About 3,000 to 4,000 Americans received the faulty metal liner between 2009 and 2012, and these patients may be at an increased risk for revision surgery. If a patient has undergone revision surgery or a doctor has recommended it, compensation for medical expenses and injuries may be available.

Biomet Inc.

Biomet manufactures a metal-on-metal hip implant called M2a. It’s a modular device with many options, including M2a-Magnum, M2a-38, M2a-Taper, M2a-28mm, Stanmore and Exceed ABT. The metal-on-metal design can result in high failure rates and patients who received a defective Biomet hip implant may suffer from metallosis or another complication.

Wright Medical Technology Inc.

Wright Medical manufactures two hip implant products that are similar to DePuy’s ASR hip replacement systems. One is the Conserve Plus Total Resurfacing Hip System, which features a metal-on-metal ball and socket. The other is the Profemur Z Hip Stem, which is a modular metal product. Since 2003, about 10,000 of these hip replacement products have been implanted in patients. Because of their similarities to DePuy hip implants, these products may be associated with higher failure rates.

Thursday, September 27, 2012

Sintering Your Way To Dental Implants And Hip Replacements

Forbes


TJ McCue, Contributor

Additive manufacturing (AM) touches or will touch many aspects of our lives. From 3D printers that can quickly print prototypes to advanced metal laser sintering processes, everything from hip implants to that dental bridge or crown, are being “printed” from 3D modeling tools and software. The medical “parts” industry is a subset of AM industry which will hit $2.1 Billion this year and forecasted to be $3.7 Billion by 2015.

Creating a new hip takes an amazingly precise machine. Tens of thousands of acetabular hip cups (titanium implants) have been produced to date by AM advances. According to Dr. Michele Pressacco of Lima Corporate, Lima alone has produced 40,000 hip cups over the past five years.
To be accurate, Lima is using a technique known as Electron Beam Melting (EBM) which is more advanced than your basic laser sintering method. You can read about Selective Laser Melting here on Wikipedia, which includes EBM. This technique allows them to produce precise hip, shoulder, and knee protheses.

If you thought some guy in a lab was hand crafting your dental crown, think again. An estimated 50 million dental copings gave been produced to date by additive manufacturing. That’s right, 50 million. A coping is the main metal structure of a dental crown or bridge. Increasingly, dental labs are transitioning to digitally-driven processes for dental restorations.

Many of these labs, if not most, are small businesses. Often started by maker types who like to tinker and fix and create. Often, one or two people operate 1, 2, or 4 rapid prototyping machines and produce thousands of parts, test models, or finished products.

Jumping up a bit bigger than one or two machines, Morris Technologies (Cincinnati, Ohio), for example, owns and operates 20 direct metal laser sintering machines, in addition to other rapid prototyping technologies, to manufacture and prototype products for a range of industries including aerospace and medical. CEO Greg Morris is one of the speakers at this year’s EuroMold event.
At the end of November, EuroMold will take place in Germany. This additive manufacturing conference is one of the biggest around and last year hosted 1,324 exhibitors from 38 countries and 57,955 designers, engineers, managers, and executives from 97 countries. These individuals and organizations represent many industries, including automotive, consumer electronics, medical, aerospace, packaging, household appliances, furniture, sporting goods, and toys. I’m willing to bet that many of the attendees are entrepreneurs and makers getting a new company off the ground.

Wohlers Associates, a consulting firm that tracks additive manufacturing, provided me with a media copy of their 2012 State of the Industry report this past spring, will run its own conference alongside EuroMold, focused on metal additive manufacturing, with experts from around the world. I profiled Mr. Wohlers and his data in a couple of earlier posts: 3D Printing Industry Will Reach $3.1 Billion Worldwide by 2016 and Additive Manufacturing Will Change in the Next 5-10 Years.

Orthopedic startup in Indiana aims to sell cheaper, more durable total hip implant

September 27, 2012 8:35 am by | 1 Comments



Steering clear of the metal-on-metal hip implant controversy that has embroiled the likes of Zimmer and Johnson & Johnson, a Warsaw, Indiana startup will soon be introducing a total hip implant that aims to be a better, cheaper alternative to those produced by larger players in the field.

Iconacy recently won clearance for the Food and Drug Administration to market the i-Hip. The product was designed by four orthopedic surgeons who will be clinically testing the product before a full market launch, said Tom Allen, Iconacy’s president and CEO.

The product uses a Vitamin E infused polyethlene licensed from Mass General Hospital and the Cambridge Polymer Group, Allen said and has several clinical benefits such as a better interlocking mechanism.

The vitamin-infused polyethlene is very durable and is stable even as people age, according to the Cambridge Polymer Group. And the design is such that surgeons find it easy to maneuver the implant, especially removing the liner if it has worn out or whether an adjustment needs to be made. In designing the i-Hip like traditional implants instead of the metal-on-metal implants that have now become a major liability to some orthopedics manufacturers, Iconacy has been prescient.

One of the surgeons who designed i-Hip said “absolutely not” to developing a metal-on-metal device.

“He said it over three years ago – he knew something that we didn’t,” Allen said.
Yet, he frankly admits that Iconacy is not trying to reinvent the wheel. Instead it is combining clinically proven technologies with advanced material technologies. Add to that a lean, state-of-the-art manufacturing process – and where else to produce orthopedic implants than Warsaw, also known as the orthopedic capital of the world – and you have a product that aims to be both clinically effective and financially viable.

Allen said the company is currently discussing how to price the i-Hip but said that it will be lower than $7,000 to $9,000 charged by competing devices made by Zimmer, Johnson & Johnson’s DePuy, Stryker and others.

“We are going to de able to deliver our product cheaper because of our lean operations and (because we are) taking advantage of modern technology as far as machine operations go,” Allen said.

The company has raised $3 million in seed capital to get the regulatory nod, but will need to raise money again by January. In this same time period, the i-Hip will be clinically tested. Once the money is raised and the tests completed, he expects the company to do a full commercial launch.

Allen declined to say how much money Iconacy is seeking as well as what he is telling investors regarding the exact size of the market Iconacy is chasing.
“Baby boomers are entering the (age) when our joints wear out,” Allen said. “The market is increasing and we are playing in a big market – several billions of dollars. We have (revenue) forecasts that we have shared with investors but are not at liberty to share with anybody.”

A 2010 report forecast that the U.S. hip and knee replacement markets would grow to be $14.8 billion by 2015, with the knee market claiming majority of that share.

xxx

Hey, I hope you guys put more money into testing than you do trying to get government approval to go-to -market.  Do it right this time around!

European Union Proposes New Rules On Medical Devices

istock anaylist

[Yet again, the Europeans beat us to the  punch in terms of proposing reforms!]

(By Balachander) The European Commission has proposed new rules on medical devices and in vitro diagnostic medical devices after recent scandals about faulty silicone breast implants and problems with some metal-on-metal hip replacements highlighted the need for greater transparency.
The EU is adopting proposals on medical devices in a move to further strengthen patient safety after the existing regulatory framework has come under harsh criticism, in particular after the French health authorities found that a French manufacturer (Poly Implant Prothèse, PIP) had for several years apparently used industrial silicone instead of medical-grade silicone to make breast implants contrary to the approval issued by the notified body, causing harm to thousands of women around the world.

The commission proposes important changes regarding various aspects relevant for the life-cycle of medical devices, such as the scope of the legislation, the pre-market assessment of devices, their control once on the market, the transparency of data concerning marketed devices and the management of the regulatory system by the authorities.

The EU plans will affect a huge range of medical devices including: home-use items like sticking plasters, pregnancy tests and contact lenses to x-ray machines, pacemakers, breast implants, hip replacements and HIV blood tests.

Health and Consumer Policy Commissioner John Dalli said the proposals adopted significantly tighten the controls so as to ensure that only safe devices are placed on the European Union's market at the same time, they foster innovation and contribute to maintaining the competitiveness of the medical device sector, which has an estimated market value of around 95 billion euros.

The new proposals include wider and clearer scope of EU legislation, extended to include, for example, implants for aesthetic purposes, and clarified for instance, as regards medical software. This will ensure that the safety and performance of these products are correctly assessed before they are placed on the European market, the commission said.

The European industry association Eucomed welcomes most of the recommended measures in the EU proposal but voices strong concern with regards to the 'scrutiny procedure', saying it will ultimately harm patients and will negatively impact European governments and industry.
Eucomed said the proposed scrutiny procedure will "fundamentally change the current system and will not lead to the desired outcome of increased safety for patients."

The measure would address some political calls to move the system towards a centralised pre-market authorisation system as found in the United States but will ultimately result in harming European patients and negatively impact mostly European small and medium sized enterprises (SME), said the industry body.






[ by Connie: Gee, what gives these people the Europeans that we have a centralized pre -market authorization system?????  We had the same recalls they did!!]





BEUC, The European Consumer Organisation, said it welcomes the intention to improve post-marketing monitoring, but regrets that the plans fall short of increasing quality and safety standards before these products reach consumers.

"Consumers must be given more and better information on medical devices while having the backup of redress if things go wrong such as in the case of the PIP breast implants scandal," Monique Goyens, Director General of BEUC, commented.

The Commission expects that the proposals will be adopted in 2014 and would then gradually come into effect from 2015 to 2019.

Mortality and implant revision rates of hip arthroplasty in patients with osteoarthritis: registry based cohort study

 

 
BMJ2012;344doi: 10.1136/bmj.e3319(Published 14 June 2012)
Cite this as:BMJ2012;344:e3319
 
 

Abstract

Objectives To examine mortality and revision rates among patients with osteoarthritis undergoing hip arthroplasty and to compare these rates between patients undergoing cemented or uncemented procedures and to compare outcomes between men undergoing stemmed total hip replacements and Birmingham hip resurfacing.

Design Cohort study.

Setting National Joint Registry.

Population About 275 000 patient records.

Main outcome measures Hip arthroplasty procedures were linked to the time to any subsequent mortality or revision (implant failure). Flexible parametric survival analysis methods were used to analyse time to mortality and also time to revision. Comparisons between procedure groups were adjusted for age, sex, American Society of Anesthesiologists (ASA) grade, and complexity.

Results As there were large baseline differences in the characteristics of patients receiving cemented, uncemented, or resurfacing procedures, unadjusted comparisons are inappropriate. Multivariable survival analyses identified a higher mortality rate for patients undergoing cemented compared with uncemented total hip replacement (adjusted hazard ratio 1.11, 95% confidence interval 1.07 to 1.16); conversely, there was a lower revision rate with cemented procedures (0.53, 0.50 to 0.57). These translate to small predicted differences in population averaged absolute survival probability at all time points. For example, compared with the uncemented group, at eight years after surgery the predicted probability of death in the cemented group was 0.013 higher (0.007 to 0.019) and the predicted probability of revision was 0.015 lower (0.012 to 0.017). In multivariable analyses restricted to men, there was a higher mortality rate in the cemented group and the uncemented group compared with the Birmingham hip resurfacing group. In terms of revision, the Birmingham hip resurfacings had a similar revision rate to uncemented total hip replacements. Both uncemented total hip replacements and Birmingham hip resurfacings had a higher revision rate than cemented total hip replacements.

Conclusions There is a small but significant increased risk of revision with uncemented rather than cemented total hip replacement, and a small but significant increased risk of death with cemented procedures. It is not known whether these are causal relations or caused by residual confounding. Compared with uncemented and cemented total hip replacements, Birmingham hip resurfacing has a significantly lower risk of death in men of all ages. Previously, only adjusted analyses of hip implant revision rates have been used to recommend and justify use of cheaper cemented total hip implants. Our investigations additionally consider mortality rates and suggest a potentially higher mortality rate with cemented total hip replacements, which merits further investigation.

Wednesday, September 26, 2012

Metal implant to fix Jaw Joint?

THE PATIENT

'My jaw would pop out of its socket several times a day,' said Lauren Reed

'My jaw would pop out of its socket several times a day,' said Lauren Reed
From my earliest memories, my jaw has been a real problem.

I was born with temporomandibular joint disorder, which meant my jaw joint did not sit in the socket properly.

It was constantly painful and I often woke up with blinding headaches that had been caused by it.

I’ve taken painkillers every day of my life.

They worked a bit, but I still couldn’t sleep or eat properly so I was constantly exhausted.

It was like seeing the world through a grey fog.
My jaw would pop out of its socket several times a day.

It made such a loud crack people nearby would ask what on earth had made the noise.

Doctors said there was nothing they could do, so I tried to get on with my life.
But it got worse and worse so when I was 21 I found an orthodontist, who offered me an operation that involved breaking and realigning my lower jawbone.

After recovering from the surgery, I knew something wasn’t right.
On opening my mouth, my jaw swung to the right by two centimetres.
The operation had basically gone wrong and left my jaw even more badly dislocated, and more painful than ever.

I started taking painkillers like they were sweets, but the pain got worse.
I’m a violin teacher and sometimes it was even painful to talk, which obviously affected my ability to do my job. So two years ago I was referred to Shaun Matthews, a surgeon at King’s College Hospital in London.

He told me about a new operation that could give me a completely new jaw joint made of metal.

The metal joint would be held in place with screws, but he said no one would be able to tell or see the scars.
'For the first time ever I didn't have any pain. It felt like a miracle,' said Lauren
'For the first time ever I didn't have any pain. It felt like a miracle,' said Lauren
I did feel pretty terrified, but he said if I didn’t have it the pain would probably get worse and at some point in the next few years I might not even be able to open my mouth.

So I went ahead, in November 2010.
The operation took nine hours and I was under general anaesthetic.
 
Afterwards I was on morphine for the first 12 hours, but then just regular painkillers.
My jaw was very swollen, which took three days to start going down. But for the first time ever I didn’t have any pain. It felt like a miracle.
I was allowed home after four days’ observation and given jaw exercises that would stop the muscles seizing up.

I could eat only soft foods such as scrambled eggs for two months, but four weeks after the op I could fully open my mouth.

A few weeks later I went back to teaching — now, I’ve got so much energy that I’m bouncing around like a 20-year-old.

The only restriction is that my new jaw cannot move from side to side, but it doesn’t stop me from doing anything such as chewing, talking, yawning and so on.
It will need to be replaced in 15 to 20 years due to wear and tear, but that’s fine.
This operation has transformed my life and I’m ridiculously happy.

THE SURGEON

Shaun Matthews is an oral and maxillofacial surgeon at King’s College Hospital in London. He says:
We have two jaw joints, one on each side of the face, sitting just in front of the ears and connecting the jawbone to the skull.
The jaw is a ball and socket joint — the head of the jawbone fits into a hollow, close to the ear.

The jaw joint is a complex joint and probably the most used in the human body, in activities such as eating and talking, so problems are common, with around one in four people affected at some point.

Temporomandibular joint disorder, which Lauren has, is an umbrella term for jaw dysfunction — some people are born with it, but it can be triggered by an injury or dental work.

It can also be caused by overworking the jaw muscles through frequent chewing or clenching or grinding the teeth.

Jaw problems can also be caused by rheumatoid arthritis, osteoarthritis and tumours.
Jaw replacement can help with all of these conditions.
This type of surgery has been available since the Eighties, but previous metal jaw joint implants were poorly engineered.

So though short-term results were encouraging, longer-term results were less impressive and many of the joints failed and had to be removed.
However, recent developments have hugely improved outcomes.
The new jaw implants have been designed and modelled on technology used in the manufacture of artificial hip and knee joints — so they are a lot stronger and better made.

Web-based technology and virtual surgery also means we can plan more complex surgical procedures and construct bespoke implants that precisely fit the patient’s anatomy.

Lauren’s implants were created specially in the U.S. using three-dimensional scans of her head and jaw.

Her scans were performed three months before the operation.
These allow for the mapping of important nerves and blood vessels, so these can be avoided during surgery, making it safer.
The new joint implants work like a hinge.
There are two parts — a plastic socket, which we attach to the cheekbone, and a metal implant, which is secured into the jaw below.

This metal section has a ball at one end, which sits inside the plastic socket so the joint can open and close.

The replacement is small, about the size of a matchbox, but flat.
The operation involves making incisions in front of the ear and behind the lower jaw line, to allow access to the jaw joint and lower jaw.

First, we remove the damaged part of the jaw joint.

We secure the hinge on to the patient’s cheekbone using titanium screws, then wire the jaw together so the new joint fits precisely in the correct bite.
We then secure the metal implant to the lower jaw, stitch the incisions and remove the wire.

Lauren’s operation took nine hours because of its complexity.
Similar but more straightforward procedures usually take five to six hours.
Patients have jaw exercises to do from the day after surgery and full recovery takes six to eight weeks.

Not everyone having this type of operation needs to have custom-made implants — some can have a generic version, which comes in various sizes and shapes.
Because it is such new technology, few dentists and GPs are aware that people with these problems can be helped.

It’s an excellent operation that will allow many patients to get their quality of life back — or as in Lauren’s case, actually know some quality of life for the first time.
The implants cost £5,000 to £16,000. This procedure is available on the NHS, with a referral from a GP, and privately, though there are only a limited number of surgeons in the UK, Europe and worldwide who perform it.


MOM hip controversy finally hits Smith and Nephew

September 25, 2012 by Arezu Sarvestani

The metal-on-metal hip implant failure controversy finally claims Smith & Nephew, maker of the first MoM hip to hit the market.
Updated September 25, 2012, at 5:45 p.m. with comment from Smith & Nephew.
hips xray illustration
 
 
Smith & Nephew (FTSE:SN, NYSE:SNN) issued an "Urgent Field Safety Notice" for its Birmingham Hip Modular Head implants, part of the suite of devices that pioneered the metal-on-metal hip field when they 1st hit the market in 1997.

The orthopedic giant warned the Hong Kong department of health that new data on the implants, gathered since 2010, suggests a 1.29% failure rate based on the National Joint Registry of England and Wales and a 1.12% failure rate based on the Australian Orthopaedic Association's National Joint Replacement Registry.

On their own the rates exceed the 1% benchmark established by the U.K.'s National Institute for Health and Clinical Excellence. Prior to 2010 registry data showed a 1% revision rate for the devices, according to the company.

"Smith & Nephew’s highest priority is to deliver safe and effective medical technology to benefit patients," Smith & Nephew spokesman Joe Metzger told MassDevice.com today. "As such, we have notified customers and regulatory bodies of a change to the indications for use for the Birmingham Hip Modular Head used during total hip replacement and revision.

Benefits of Less invasive hip surgery

I liked this summary.  First time around, I had this type of surgery done.  I hear that many patients experience a very invasive surgery in thier first implant.  You should always ask about the laproscopic approach for your first surgery.  The benefits are obvious.

Why use a  laproscopic approach to  Total Hip Replacement?

 
The technique causes less surgical trauma than other techniques because NO MUSCLES ARE CUT, which aids in rapid recovery.

This approach can potentially provide you with the following benefits:


  1. DECREASED POST-OPERATIVE PAIN 
       In comparison with "conventional" surgical techniques, this  approach can reduce the post-operative pain as muscles are not cut.
  2. SHORTER REHABILITATION 
       Rehabilitation can usually start the day of the operation or the day after, subject to your doctor's approval, based on your post-operative conditions. Standing up and walking with arm crutches may start immediately, with your doctor's authorization as well.
  3. SHORTER HOSPITAL STAY 
     This  technique may significantly reduce the duration of your hospital stay. Your surgeon may still recommend a longer stay depending on your post-operative condition.
  4. REDUCED SCAR SIZE
    The skin incision is often shorter than with “conventional” surgery and therefore scar size is reduced.
  5. FASTER RETURN TO DAILY ACTIVITIES 
       This technique may allow you to return to daily activities in a shorter time frame.
  6. LESS BLOOD LOSS
       Preservation of muscles and vessels potentially reduces blood loss. Transfusions are rare, blood clots in the legs (deep venous thrombosis) are potentially less likely.
  7. REDUCED RISK OF DISLOCATION 
       As a result of  this technique the preservation of muscles significantly improves the stability of the hip. The risk of dislocation is minimal and the post-operative limitation of movements, usually prescribed in other techniques, may not be necessary. The risk of dislocation is reduced because the anterior approach is performed from the front of your body and dislocation is mainly related to posterior hip structure damage.
  8. REDUCED RISK OF LIMPING
    This  is characterized by a surgical technique that protects the various muscles, blood vessels and nerves encountered during exposure of the hip joint. Minimizing muscle and nerve damage reduces the chances of limping.
Because of the this  technique, some doctors allow their patients to drive when they are able to get in and out of the car comfortably, have excellent control of their legs and are not taking pain medication.

  Depending on your general condition and with the approval from a surgeon, some  patients may be driving in 8 -10 days.

xxx

I actually experienced all of these in my first surgery.  Very different though than the revision.  Long time to recovery in the revision.

Lifetime Warranty on Knee replacements?

 

 MarketWatch

Biomet Announces Lifetime Limited Implant Replacement Warranty on Oxford(R) Partial Knee When Implanted with Signature(TM)* Personalized Patient Care System


WARSAW, Ind., Sep 24, 2012 (BUSINESS WIRE) -- Biomet announced today a Lifetime Knee Implant Replacement warranty in the U.S., covering the Oxford(R) Partial Knee utilizing Signature(TM) technology. With the Lifetime Implant Replacement Warranty, Biomet will cover the cost of a Biomet replacement implant for U.S. patients who received the Oxford(R) Partial Knee implanted utilizing Signature(TM) technology and need revision surgery for any reason, subject to the terms and conditions of the written warranty. The warranty is effective for the replacement of Oxford(R) Partial Knees implanted utilizing Signature(TM) personalized positioning guides in the United States on or after September 10, 2012. Any additional costs associated with a replacement surgery beyond the Biomet replacement implant will not be covered by Biomet.

Biomet President and CEO Jeff Binder stated: "Since our founding 35 years ago, Biomet has established a heritage of offering innovative technologies and services that contribute to the delivery of high-quality, high-value personalized patient care. We believe that this is the only warranty of its type in the U.S., and we plan to assess the value of the program to our customers in a dynamically changing healthcare environment."

The Lifetime Implant Warranty builds on the proven track record of the Oxford(R) Partial Knee. One published long-term clinical study on the Oxford(R) Partial Knee demonstrated a 91% survivorship at 20 years.(1)

Biomet's Oxford(R) Partial Knee System is designed to help surgeons preserve and restore normal knee function and movement by replacing only the medial, diseased compartment of the knee. The Oxford(R) Partial Knee procedure removes approximately 75% less bone** than a total knee replacement and has been shown to allow for a more rapid recovery(2) when compared to a total knee replacement. The Signature(TM) Personalized Patient Care System complements the Oxford(R) Partial Knee by providing surgeons with a technique to perform knee replacement surgery specific to a patient's anatomy.

Partial knee replacement is intended to preserve healthy knee structures in patients with limited knee arthritis by replacing only one side of the knee, and to provide more natural motion when compared to a total knee replacement.(3,4) Partial knee replacement may also provide for less pain(5) and shorter recovery periods(2) than total knee replacement.

Patient Risk Information

The Oxford(R) Partial Knee is intended for use in individuals with osteoarthritis or avascular necrosis limited to the medial compartment of the knee and is intended to be implanted with bone cement. The Oxford(R) Knee is not indicated for use in the lateral compartment. Potential risks include, but are not limited to, loosening, dislocation, fracture, wear and infection, any of which can require additional surgery. For additional information about the Signature(TM) system and the Oxford(R) Knee, including risks and warnings, talk to your surgeon and see the full patient risk information on http://oxfordknee.com .

About Biomet

Biomet, Inc. and its subsidiaries design, manufacture and market products used primarily by musculoskeletal medical specialists in both surgical and non-surgical therapy. Biomet's product portfolio encompasses large joint reconstructive products, including orthopedic joint replacement devices, and bone cements and accessories; sports medicine, extremities and trauma products, including internal and external orthopedic fixation devices; spine and bone healing products, including spine hardware, spinal stimulation devices, and orthobiologics, as well as electrical bone growth stimulators and softgoods and bracing; dental reconstructive products; and other products, including microfixation products and autologous therapies. Headquartered in Warsaw, Indiana, Biomet and its subsidiaries currently distribute products in approximately 90 countries.

Tuesday, September 25, 2012

Metal-on-Metal hip Implants Can Corrode

FDA Reports

At the Food and Drug Administration (FDA) meeting about hip implant devices in July, Dr. Jeremy L. Gilbert presented information about dangerous corrosion that may occur in metal-on-metal implants.

Corrosion happens when a chemical reaction gradually destructs a metal. This is currently happening inside patients’ bodies and leading to hip replacement complications and life-threatening health issues.

The metal components of a metal-on-metal hip corrode when they rub together and become “stressed, abraded, worn or fretted.” As soon as the components wear through the surface of the metal, the corrosion is rapid and unstoppable. The ions released by the worn-down metal can cause serious problems in the body, such as metal poisoning, tissue necrosis and a bone dissolving process called osteolysis.

Stainless steel, cobalt, chromium and titanium – the metals used in metal-on-metal hip implants – are all susceptible to corrosion. Researchers have known about modular implant corrosion since the 1980s, and all current metal combinations in metal-on-metal implants are known to have this reaction, according to Dr. Gilbert. Hip implant failure will continue to happen as long as these metal hip implants are on the market.

When batteries corrode, we buy new ones and replace them. That’s not so easy with a hip implant. Hip replacement failure leads to painful revision surgery and more recovery time. Patients who are suffering from complications due to a defective hip implant are urged to speak to a hip recall lawyer immediately.

Consolidation Of Federal Biomet Hip Lawsuits?

An attorney for the Rottenstein Law Group attended the conference of the Judicial Panel on Multidistrict Litigation held on Thursday in lower Manhattan to address the merits of consolidation of federal lawsuits by claimants alleging harm caused by metal-on-metal hip implants manufactured by Biomet, Inc.

Several lawyers representing plaintiffs argued in favor of consolidation of the various suits for pretrial proceedings. One lawyer for Biomet argued against consolidation, suggesting that the creation of an MDL case would lead to a greater number of suits filed against the company than there would be otherwise. The judges on the JPML asked each lawyer questions, but gave no indication of how the panel might rule on consolidation.

In 2001, Biomet voluntarily recalled hip prostheses that included a potentially defective component manufactured by another company beginning in 1998. The hip replacement system that Biomet recalled in 2001 uses a zirconia ceramic femoral (thigh bone) head manufactured by St. Gobain Desmarquest, a French company. Several months before Biomet’s recall, the U.S. Food and Drug Administration had mandated a recall of St. Gobain Desmarquest’s femoral heads because they were fracturing at a higher rate than expected in some patients 13 to 27 months after being implanted. Biomet was one of eight U.S. artificial joint manufacturers that voluntarily recalled their hip replacement systems in response to the recall of St. Gobain Desmarquest’s ceramic femoral heads. The events surrounding the FDA’s recall of St. Gobain Desmarquest’s femoral heads, and Biomet’s voluntary recall of the hip implant devices that incorporated those femoral heads, can be found under the “Orthopaedic” section on this page of the FDA’s web site.

Hip replacement surgery is one of the most common joint replacement procedures performed in the United States, according to the FDA. Many who suffer from osteoarthritis and other conditions find relief after surgery; some, however, have suffered debilitating side effects. Metal-on-metal hip implants have been particularly problematic for patients. Once deemed a technological breakthrough that would extend the lifespan of artificial hip joints, metal-on-metal hip implants often fail at a much higher-than-expected rate. Moreover, the all-metal construction sometimes leads to metallosis, a condition that results when microscopic metal particles shed from the joint become embedded in a recipient’s tissue. These dangers have led recently to numerous hip replacement lawsuits.

The One Orthopedic Stock to Own for 2013

Barrons

Brean Murray says Zimmer Holdings shares have upside based on the pipeline.

Brean Murray, Carret & Co.

We are initiating coverage of key names in the orthopedic group, with a generally favorable view. Our thesis is predicated on several assumptions: 1) the market has absorbed the "new norm" on pricing -- down 2%-3% for hips and knees; 2) volumes (low-single digits) are stabilizing, but continued improvements in uninsured rates create upside opportunities for stocks; and 3) mix remains the swing factor, and still the least appreciated by investors.

Our contention on mix is that the absence of compelling new products, combined with impact of metal-on-metal hip recalls (which was a negative-mix driver.......subscription article

Where are the Transvaginal Mesh Studies Requested by the FDA?

Posted on by Brenda Fulmer (Searcy Denney)

Last January 3, the U.S. Food and Drug Administration (FDA) decided to get tough on transvaginal mesh manufacturers. After noting a five-fold increase in complications among women implanted with the polypropylene mesh to treat pelvic organ prolapse (POP) and stress urinary incontinence (SUI), the FDA asked the mesh makers to find out why.
The FDA flexed its little-used muscle. Under Section 522 of the Federal Food, Drug and Cosmetic Act, the agency can request postmarket studies if a device is implanted and if the complications are serious enough.

Transvaginal mesh fit the bill and the order went out 33 manufacturers of surgical mesh for pelvic organ prolapse (POP) and seven manufacturers of single-incision mini-slings for SUI. They were to spend money and a lot of it, to come up with three years worth of monitoring to look for and report rates of mesh erosion, vaginal shortening and scarring, neuromuscular pain, revision surgeries, all of the complications that are ruining the lives of thousands of women.
Women were to be followed for three years and adverse events reported at 6 months, 12, 18, 24 and 36.
That was January; this is the end of September. What has happened? Absolutely nothing.



The manufacturers were given 30 days to respond initially to the 522 orders. Nothing. Now when you look at the FDA’s own website for 522 studies you see that the plans are “pending”, or the study is pending” or “other” – in other words the follow-up that was so important to give mesh sufferers some answers just has not begun as if this were not a crisis.
Clearly the medical device industry understands that the FDA is a lapdog watchdog agency. Has there been any action for noncompliance? Not yet. The agency has the authority to seize products off store shelves or demand a recall. Again a paper tiger.

As if the January 3, 2012 orders for mesh studies were not enough, in May 2011, many makers of metal-on-metal (MoM) hips were required to also begin the expensive and arduous postmarketing follow-ups on people living today with metal hip implants.

These too have devastating life-altering injuries as emerging science shows that metal debris can and does get into the blood stream of many hip implant patients, with the potential to create metallosis and necrotic tissue around the hip. The revision rate is unacceptably high, so much so that the DePuy MoM hip (Johnson & Johnson) had to be pulled from the market leaving 93,000 patients wondering when their number will be up.

Still no postmarketing plans have gotten underway. At least with metal hips, the agency’s website acknowledges the plan is “overdue”!

They certainly are, and so is a federal agency that has some teeth.

Sunday, September 23, 2012

More on Nanoparticles causing DNA damage from MOM hips throught oxidatve stress (4 of x in a series)

Next in the series (4 of x) I will discuss the the key systemic processes in these journal articles:

Cancer
Redox chemistry,
Free Radicals and
ROS (Reactive oxygen species)
Oxidative stress

Prior posts in the sequence
1 of x
More on Nanoparticles causing DNA damage from MOM hips with oxidative stress ( 1 of x in a series)
2 of x
http://www.mydepuyhiprecall.com/2012/09/more-on-nanoparticles-causing-dna_9.html
3 of x
http://www.mydepuyhiprecall.com/2012/09/more-on-nanoparticles-causing-dan.html


Discussing the first of 4 seminal works on the issues related to causing free radicals in the cell environment from MoM.

This article was published in 2007.  Effect of nano-and micron-sized particles of cobalt-chromium alloy on the human fibroblasts in vitro.  (see the prior posts for definitions.)

1.  Nano particles induce more DNA damage than Micron particles.

2. Nano particles disintegrate within the cells faster than micro particles  that crease electron dense deposits in the cell that were enriched in cobalt.

3.  The concept of Nanotoxicology is a key concept for understanding what materials should go into the further design of hips.

4.  Nanotoxicology is the study of the internal exposure to particles from surgical implants

5.  Metal on metal produce smaller particles than metal on poly and in fact there are more metal on metal particles generated than poly.

6.  Both implants may cause an increase of chromosome aberrations in patients.

7.  The wear debris from implants may cause  DNA and chromosome damage, cytokine release and cytoxicity in human cells.

In 2007, this study by the top scientists in the field  decided to compare the biologic effects of the same Co and CR alloy used in the hip implants when presented to human fibroblasts in tissue cultures.  so the investigators wanted to know what happens when you subject metal on metal to  cells in the  body.

[A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen,[1] the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals]

Here is what they found:

(1) They found the generation of free radicals by the particles such that they could see the presence of hydrogen peroxide suggesting that a fenton driven reaction was taking place actually generating these free radicals. 

(The hydroxyl radical can damage virtually all types of macromolecules: carbohydrates, nucleic acids (mutations), lipids (lipid peroxidation) and amino acids  The hydroxyl radical has a very short in vivo half-life of approximately 10−9 seconds and a high reactivity.[3] This makes it a very dangerous compound to the organism.[4][5]

Unlike superoxide, which can be detoxified by superoxide dismutase, the hydroxyl radical cannot be eliminated by an enzymatic reaction. Mechanisms for scavenging peroxyl radicals for the protection of cellular structures includes endogenous antioxidants such as melatonin and glutathione, and dietary antioxidants such as mannitol and vitamin E.

(2)  ROS was measured so see the prior posts for that definition

(3)  Genotoxcity/ test results showed DNA damage to the DNA via a break in single and double strands in a dose dependent manner.

(4)  Cytoxicity/ The cellular integrity was measured and after 3 days of exposure and the level of LDH was measured and was found to be significant.

(5)  Cytokine release (Adverse effects of cytokines have been linked to many disease states and conditions ranging from major depression[12] and Alzheimer's disease[13] to cancer[14] with levels either being elevated or changed.)

(6)  This increased biological reactivity could be due to one or more  of the following:
  • increased release of free radicals within the cell with subsequent oxidative DNA damage
  • increased release of metals from the nanoparticles
(7)  Exposure of the cells to nanoparticles and micron sized particles cause different types and amount of cell damage.

(8)  There was a faster and shorter release of metal from the nanoparticles.

(9)  The nanoparticles caused more mitorchodrial damage, more DNA damage and more subsequent cell death than the microparticles (poly)

(10)  The oxidative damage to DNA by Hydroxly free radicals occurred.

(11)  There may have been additional and secondary damage in the nanoparticle exposed cells from increased damage to mitochondria proteins or from lipid peroxidation which could have generated a number of secondary DNA damaging agents in the cells.

There may be a number of fundamentally different biological responsies of human cells to surgical implant materials which depend on particle size.

Next in the series, we will look at DNA damage across the cell barrier. (5 of x)



DNA Damage to Embrioys in Zebrafish from Cobalt exposure

[Seems as though I published this before but I guess not.  This is an important article and relates to the oxidative stress articles I have published previously and that is:  these surgeries cause oxidatve stress which can lead to damage in the DNA...this goes a step further and demonsrtate what that oxidatives stress does to embryos]

2012 Sep 16. [Epub ahead of print]

The Effects of Cobalt on the Development, Oxidative Stress, and Apoptosis in Zebrafish Embryos.

Source

Department of Orthopaedics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kong-Jiang Road, Shanghai, 200092, China.

Abstract

Metal-on-metal hip arthroplasty has been performed with increasing frequency throughout the world, particularly in younger and more active patients, including women of childbearing age. The potential toxicity of cobalt exposure on fetus is concerned since cobalt ions generated by metal-on-metal bearings can traverse the placenta and be detected in fetal blood and amniotic fluid. This study examined the effects of cobalt exposure on early embryonic development and the mechanisms underlying its toxicity. Zebrafish embryos were exposed to a range of cobalt concentrations (0-100 mg/L) between 1 and 144 h postfertilization. The survival and early development of embryos were not significantly affected by cobalt at concentrations <100 μg/L. However, embryos exposed to higher concentrations (>100 μg/L) displayed reduced survival rates and abnormal development, including delayed hatching, aberrant morphology, retarded growth, and bradycardia. Furthermore, this study examined oxidative stress and apoptosis in embryos exposed to cobalt at concentrations of 0-500 μg/L. Lipid peroxidation levels were increased in cobalt-treated embryos at concentrations of 100 and 500 μg/L. The mRNA levels of catalase, superoxide dismutase 2, p53, caspase-3, and caspase-9 genes were upregulated in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays also revealed abnormal apoptotic signals in the brain, trunk, and tail when treated with 500 μg/L cobalt. These data suggest that oxidative stress and apoptosis are associated with cobalt toxicity in zebrafish embryos.