Diagnostics & Imaging Week Correspondent

And D&IWs

LONDON – Whether someone survives the multiple organ failure that can follow severe infection – a condition known as sepsis – might depend on whether they have a certain variant of DNA within their mitochondria, the energy-producing organelles of the cell.

New research out of the UK shows that people with one variant of mitochondrial DNA who were admitted to an intensive care unit with sepsis had much higher survival rates than those with other variants.

The genetic variant might alter the way in which the mitochondria convert food into energy, and might allow the body to reach a higher temperature in order to fight the infection. In the study, the average temperature of people who survived was significantly higher than that of people who died.

The researchers now want to elucidate the mechanism by which those with one genetic variant have a lower risk of dying from sepsis. They hope that will give them clues for new ways to treat sepsis.

Patrick Chinnery, professor of neurogenetics at the University of Newcastle (Newcastle-upon-Tyne, UK), told Diagnostic & Imaging Week's sister publication BioWorld International: "This finding is very important because 40% of people who are admitted to an intensive care unit with sepsis die, despite all treatment. We have now opened up a completely new avenue to investigate and understand the process of how the body deals with sepsis. Hopefully, this means we will one day be able to develop new treatments and reduce the death rate associated with this condition."

It will be possible to identify patients on the intensive care unit who are less likely to survive a severe infection. Clinicians will want to investigate whether providing more aggressive clinical care for this group will improve the outcome, he added.

The research first appeared in the Dec. 17, 2005, issue of The Lancet in a paper titled: "Mitochondrial DNA and survival after sepsis: a prospective study." The first author is Simon Baudouin.

Independent studies already had suggested that the mitochondria of people who succumbed to severe infections may not be working as they should. But no one knew whether that mitochondrial defect was the cause of the sepsis, or whether the sepsis was the cause of the defect. Chinnery, Baudouin and colleagues decided to investigate whether there was a link between the type of mitochondrial DNA and the outcome in sepsis.

The team recruited 150 patients with severe sepsis who were admitted sequentially to the intensive care unit at the Royal Victoria Infirmary (Newcastle-upon-Tyne) and, with permission, analyzed their mitochondrial DNA.

Looking for single nucleotide polymorphisms, the team divided the patients into the 10 most common haplotypes, or groups, of mitochondrial DNA.

Comparison with a control group showed no difference between the frequency of the different haplotypes in the general population and that in the study population. In other words, a person's mitochondrial DNA haplotype does not dictate his or her risk of developing sepsis and ending up in intensive care.

Once there, however, Chinnery and his team showed that those with mitochondrial DNA haplotype H were more than twice as likely to survive to six months than those with other haplotypes.

Chinnery concludes that mitochondria clearly play an important role in dealing with the severe insult of infection. "We need to look carefully at the mechanisms involved," he said. "It may be possible to develop treatments for use in intensive care."

IVD harmonization sought

In a move aimed at harmonizing diagnostics regulations, the European parliament last month amended the medical devices directive (MDD) of 1993 to bring in the IVD directive (98/79/EC) in 1998.

The directive is made up of a number of articles that outline definitions, standards and vigilance and, as of Dec. 7, 2003, has been enforced in the 25 European Union (EU) member states and the four European free trade association members, namely Iceland, Norway, Liechtenstein and Switzerland.

While many regulatory hurdles have been removed with the implementation of the CE mark, this multinational standardized mark further allows global manufacturers to distribute their products within the EU, eliminating the need for additional quality testing or approvals.

However, while the CE mark indicates that the product meets the relevant IVD directives, language compliance issues have arisen, increasing the costs for manufacturers. The requirement for translating usage instructions into local languages has been transposed into 15 EU countries' national laws, since these countries do not differentiate between lay products and those used by professionals. As a result, IVD companies have had to increase their translation activities from five to 15 European languages since 2000. Hence, depending on the market size, companies will now have to decide if it is beneficial to translate their products' instructions for use in order to continue serving a market in the future.

"This will affect smaller markets, and the health systems of small countries are likely to suffer as a consequence," said Dr. Fiona Rahman, research analyst with Frost & Sullivan. "Since Europe is now in an open market era, customers may be forced to buy IVDs from other neighboring countries, but at their own risk and outside the liability of the manufacturer."

Also posing challenges are substantial differences in the U.S. and European labeling requirements. While the IVD directive encourages that the information on labels are presented as harmonized symbols, these symbols do not need to be accompanied by text explanations required by the FDA.

Though few would disagree that symbols on labeling are beneficial, the reluctance of the FDA to accept their use is a barrier to their universal adoption. The primary concern of the FDA is the possibility of end users not being able to understand the symbols, resulting in unsafe use.

The disadvantages of regulations are that they increase the cost of the products and delay their introduction in the commercial market. In addition, along with the implementation of regulations comes more administrative works such as paperwork, registration and approvals.

However, companies complying with these regulations will gain better access to more geographic markets, thus gaining an increase in the production and market value of their compliant products. Also, harmonized regulations encourage the development of new technology and since only quality products are allowed to enter the market, there is bound to be an increased value for the eventual end users.

"While the market believes that the IVD directive has increased the level of regulation for IVD products in Europe, when applied together with the common technical specifications, will increase the uniformity and quality of higher-risk products," said Rahman. "By incorporating translation and labeling changes, manufacturers can cost-effectively market their products worldwide and hence what may now appear as a chaos of regulatory requirements could pave the way for a successful international product release."

CardioMag trades on AIM in London

CardioMag Imaging (Schenectady, New York), developer of a non-invasive Magnetocardiograph (MCG) heart function visualization product for the cardiology community, said that its common stock has been admitted to trading on the AIM Market of the London Stock Exchange.

In connection with its AIM admission, CardioMag raised about $9.3 million in gross proceeds, pursuant to a placing of its common shares through its advisor and broker, Williams de Broe. The proceeds of the placement will be used for working capital, including expansion of the company's international marketing efforts and U.S. manufacturing.

The market capitalization of CardioMag based on the issue price in the placement is about $50.9 million.

CardioMag's MCG system integrates superconducting quantum interference devices with advanced software and hardware to form a new diagnostic technology providing functional information on the status of a patient's heart. The MCG system measures the magnetic fields generated by the heart's electrical activity, allowing a physician to identify abnormal cardiac conduction disturbances, including those created by the presence of coronary artery disease.

The company's first marketed product is the CMI 2409 system, several of which already are installed in hospitals around the world. A more advanced system, the CMI 2436, is currently at the prototype stage. The company also is developing a CMI Research system for use by medical research laboratories for animal studies of heart disease.

bioMerieux exercises RNA option

Gen-Probe (San Diego) said bioMerieux SA (Marcy L'Etoile, France) has exercised a second option to develop diagnostic products for certain undisclosed disease targets using Gen-Probe's ribosomal RNA technologies, pursuant to a year-old agreement. In exchange, bioMerieux will pay Gen-Probe a $2.1 million license fee.

bioMerieux also retains an option to develop products for other disease targets by paying Gen-Probe up to an additional $900,000 by the end of 2006. Gen-Probe also would receive royalties.