In April 2000, Francois Cornelis of the rheumatoid polyarthritis laboratory at the Genopole (Evry, France) started a new project aimed at identifying the genetic factors involved in the disease, which affects 200,000 to 400,000 people in France alone.
The initial work of analyzing DNA from 10,000 rheumatoid arthritis (RA) patients has resulted in identification of the first predisposition gene, which was identified in 75% of the patients tested. The next target is to discover the other genes implicated and, above all, their many combinations, which are the true risk factors of the disease, according to Cornelis.
He said that this next stage, which started in January, will be carried out by a consortium of laboratories from seven European countries, but that in addition, they were inviting researchers from all over the world to come to test their own hypotheses in identifying the risk factors involved. More than 200,000 RA patients have offered to provide blood samples, and 120,000 have already been signed up, Cornelis said.
The results will be fed into a database which will be accessible on Internet to allow each research team to test out its own theories, with the results available to all groups. In France, the project is being supported by the Fondation pour la Recherche Medicale in partnership with the French Society of Rheumatology.
Genmab (Copenhagen, Denmark) has reported positive results from a Phase I/II clinical trial on 35 patients with severe rheumatoid arthritis. Fifty per cent of patients in the highest-dose cohort showed favorable responses to a single dose of HuMax-CD4, a fully humanized antibody for the treatment of RA, as measured by the criteria defined by the American College of Rheumatology.
British Biotech (Oxford, England) and Serono (Geneva, Switzerland) have signed a cooperation agreement on the development and commercialization of metalloenzyme inhibitors (MEIs) for treating inflammatory disease. The collaboration, which could be worth $ 30 million to $80 million to British Biotech, will aim at identifying new compounds under the company's proprietary MEI platform technology.
Serono has the option to exclusively develop BB-2827, a collagenase inhibitor that British Biotech has just taken into clinical trials as a treatment for rheumatoid arthritis.
PVC or PVC-free dialysis: The choice
The controversy over the use of soft polyvinyl chloride (PVC) in medical devices has mounted in Europe as pressure groups have continued to seek a ban on the use of PVC in products such as blood bags, dialysis and plasmapheresis systems. EUCOMED (Brussels, Belgium), the European medical device industry association, published a revised position paper in December which said that "scientific studies into medical PVC have produced no significant adverse findings" and that "PVC, using di(2-ethylhexyl) phalate as a plasticizer, has a well-documented history of safe and effective use in a variety of medical products."
The medical device industry has responded to the challenge to the use of PVC in different ways. Some companies – especially in the end-stage renal disease sector, which features extracorporeal blood-purification technology such as hemodialysis and peritoneal dialysis, as well as in plasmapheresis – are offering alternative non-PVC materials, especially for dialysis procedures.
Baxter Healthcare (Deerfield, Illinois) has developed Clear-Flex hemofiltration systems, Braun Schiwa (Glandorf, Germany) now offers Perfuflac and Fresenius Medical Care (Bad Homburg, Germany) has introduced Biofine for peritoneal dialysis applications. Jorg Vienken, director of science services at Fresenius, pointed out that dialysis is a long-term application, in some cases for more than 20 years, and for hemodialysis patients long-term continuous exposure to plasticizers has been linked to an increase in liver size, elevation of hepatic enzymes and acute hepatitis, but without outward signs of infections. These signs vanished when PVC systems were replaced by PVC-free alternatives.
A frequently overlooked aspect identified by Vienken was that of disposal. Incineration of 1 kilo of soft PVC produces 1 liter of hydrochloric acid (HCl) released into the atmosphere. He said, "In this respect, 100,000 peritoneal dialysis patients will generate 25,000 tons of PVC waste per year and combustion of this will burden the environment with 10,000 tons of HCl."
The European Commission published a "green paper" on PVC in July 2000 that was generally regarded as unsatisfactory, since it concentrated on the disposal aspects, rather than the whole life cycle, and therefore ignored its usefulness.
Discussions are under way between the PVC industry and the European Commission, which is committed to issuing a final definitive communication on the subject this year. If a decision is made to phase out PVC use generally, and in the medical device industry in particular, polyolefines and other materials certainly offer practical alternatives for medical applications.
Therapy and analgesia infusion systems
New to the infusion pump sector is Aitecs (Vilnius, Lithuania), which produces a full line of syringe pumps. The SP-145 patient-controlled analgesia (PCA) syringe pump can accommodate syringes from 10 ml to 100 ml capacity and operates in either programmed dose or key activated bolus modes.
Fresenius Vial (Brezins, France) has launched its Orchestra infusion work station, which handles up to eight syringe pumps or infusion pumps. The system provides the first interactive and centralized infusion data management system (IDMS), according to the company. The IDMS operates without any added software or hardware units on a stand-alone basis with advanced protocol capabilities.
B. Braun Melsungen's (Melsungen, Germany) fluid management (fm) workstation can be operated through an fm controller, with a central monitor to perform remote operation. Up to 18 infusion pumps (five different types) can be controlled with a single selector knob. Both volumetric infusion and precision syringe pumps can be included in the workstation.
Medex (Annecy-le-Vieux, France) has developed two soft-bag injectors for use in computed tomography and magnetic resonance (MR) environments. Capable of delivering pressures of up to 300 psi and using bags ranging in size from 100 ml to 500 ml, the Medex Soft Bag Injector (SBI) provides the same capabilities as conventional syringe injectors. The new SBI 2500-MR unit is compatible with non-magnetic conditions and intended for MR imaging injections. The bag contains two partitions for gadolinium and saline.
Bladder cancer diagnosis by MRI
MRI-based virtual endoscopy offers many advantages over conventional cytoscopy as a methodology for diagnosing bladder cancer, according to Markus L mmle and his group at University Hospital (Munich, Germany).
L mmle noted that traditional cystocopy can be painful and that there also are risks of infection, perforation, scarring and stricture of the urethra. He admitted, however, that sensitivity was slightly better than with using MRI-based virtual endoscopy.
In their trials on 24 patients with bladder tumors, diagnosed by cystocopy, L mmle's group detected 30 of 33 tumors with no false-positives, using a Philips (Best, the Netherlands) Gyroscan ACS-NT 1.5 Tesla scanner with synergy body coil. Philips' Easy Vision software was used to generate 3-D images of the urinary bladder. L mmle plans to increase the sensitivity in future trials using a 4.0 Tesla MRI scanner with better image resolution.
Interestingly, L mmle's team detected two tumors undetected in initial cystocopy but picked up by virtual endoscopy. "This was because one of the tumors was located on the anterior bladder wall, and the other tumor was obscured by blood in the urine (hematuria), which does not affect MRI," L mmle said.
MRI in CJD diagnosis
Hopes raised 18 months ago at the Royal Victoria Infirmary (Newcastle, England) that MRI could help diagnose new variant Creutzfeldt-Jakob Disease (nvCJD) have been dashed by the latest results from the UK's National CJD Surveillance Unit (Edinburgh, Scotland).
The earlier results reported by Alan Coulthard and colleagues used a standardized method of reading MRI scans to detect scarring deep in the brain' posterior thalamus, with positive results but on only a small sample.
Researchers at Edinburgh now have been able to investigate 108 brain samples from patients who may have died from CJD, in a blinded study using MRI and standard pathological analysis. They have found that lesions in the corpus striatum and in the posterior thalamus produced a highly specific increased signal (94% to 98% and 100%, respectively) for CJD.
Unfortunately, sensitivities at 8.6% and 18.4% were inadequate, and the group has reluctantly decided that MRI did not provide high enough specificity and sensitivity in response to be used for diagnosing CJD. Andrew Crean, who led the Edinburgh study, has emphasized, nevertheless, that more work needs to be done in this area before MRI brain imaging for CJD can be completely ruled out.
MRI-compatible anesthesia system
The Datex-Ohmeda division of Instrumentarium (Helsinki, Finland) has adapted its Aestiva/5 anesthesia machine into the Aestiva/5 MRI for use in an MRI environment. The configuration is planned to make it suitable also for general anesthesia use in conventional surgical settings. User interfaces have not changed between the two versions, so that only a very short learning curve is necessary.
The availability of anesthesia is important for MRI clinicians when dealing, for example, with critically ill or disabled patients. This MRI-compatible anesthesia machine would also be a valuable adjunct in MRI-guided surgery, a rapidly developing surgical sector.
MRI-compatible patient monitor
InVivo Research (Orlando, Florida) has supplied its first Magnitude MRI patient monitor at the Royal Brompton Hospital (London) in the newly opened cardiovascular MR unit, which has a Siemens (Erlangen, Germany) Magnetom MR unit.
The Magnitude monitor incorporates a digital signal processing method and adaptive filters to provide artifact-free ECG signals in the presence of rapid and strong gradients. Used in combination with a wide range of cardiac and peripheral gating solutions, the system is particularly well suited for use during cardiovascular MRI, according to Dudley Pennell, director of the cardiovascular MR unit.
Insufficient children's vaccination levels
Vaccination against measles in France covers between 80% and 85% of all children, a level insufficient to effectively interrupt the transmission of the virus. As a result, there are between 18,000 and 20,000 childhood cases of measles each year in France, of which 40% are age 10 or more. Since measles becomes more serious as children get older, this statistic concerns French epidemiologists, and has arisen as a result of policies in place up to 1995 requiring a single vaccination at nine months of age, which gives a vaccinal efficacity of 90% to 95% at best.
Since 1997, a second vaccination at between 3 and 6 years of age has increased the efficacity level to 97% to 99%, using as standard a triple vaccine (measles, mumps and rubella). In September 1994, all teenagers and babies started to receive hepatitis B vaccinations, but while the level of infant vaccination is high, only an estimated 80% of teenagers receive their second vaccination. As a result, epidemiologists estimate that it will take 20 to 25 years to achieve a targeted reduction in hepatitis B cases by 90%. Because of the need, until recently, to program two separate vaccinations for hepatitis and for measles at different ages, effective coverage, especially of teenagers, has been problematic.
A pediatric hexavalent vaccine that covers measles, mumps and rubella, as well as diptheria, tetanus and hepatitis B, has been developed by GlaxoSmithKline (GSK) and is manufactured by the company's biologicals division in Rixensart, Belgium. Infanrix Hexa, the new GSK vaccine, has received EC authorization for use in all 15 European Union countries. It already is available in Germany.
The World Health Organization (Geneva, Switzerland) has set an objective of the global elimination of measles by 2007, but for hepatitis B, a major global infectious disease problem largely with sexual transmission, the situation is much less optimistic.
Needle-free injection from R sch
R sch (Berlin, Germany) launched the innovative Injex and Rojex needle-free injection devices made by Equidyne (San Diego, California) late in 1999 after receiving CE-mark approval for the European market. Since then, additional clinical trials on penetration depth and histologic dispersion of medications have been arranged with German universities for heparin anticoagulant, cytokines and several vaccines. R sch said that its own investigations, as well as independent studies, have shown no impairment of the molecular structure, immunoreactivity or resorption of medication such as insulin and a recent ex vivo study on penetration depth and dye dispersion, performed by Mediport (Berlin, Germany), has shown a strictly subcutaneous pattern and tissue-preserving properties compared with conventional needle injection methods.
Bracco gains license for Dyax phage imaging
Bracco (Milan, Italy) is to pay Dyax (Cambridge, Massachusetts) $3 million up front for a worldwide exclusive license to Dyax's proprietary phage display technology in imaging. Bracco will pay another $3 million a year for the next three to six years, as well as milestone and royalty payments.
The license covers existing Dyax products for inflammation, cardiovascular and oncology imaging applications. Dyax's phage display technology is a discovery method that can identify proteins, peptides and humanized monoclonal antibodies that bind to diagnostic and therapeutic targets.
Orphan drugs in Europe
Reports from the European Medicines Evaluation Agency (EMEA) indicate that Europe's orphan drug system for promoting medicines for rare diseases is at last beginning to show positive results.
At its last meeting, the Committee for Orphan Medicinal Products (COMP) voted in favor of another six positive opinions on the designation of orphan products, bringing the total since the program started last year to 14.
These opinions are forwarded to the European Commission for decision, and eight positive decisions already have been announced. They include two versions of alpha-galactosidase A for the treatment of Fabry disease – one from TKT Europe-5S of Sweden and the other from Genzyme (Cambridge, Massachusetts); arsenic trioxide for the treatment of promyelocytic leukemia from Voisin Consulting (Paris); fluorouracil for the treatment of glioblastoma from Ethypharm (Lyon, France); gemtuzumab ozogamicin for the treatment of acute myeloid leukaemia from Wyeth-Ayerst (St. Davids, Pennsylvania); and somatropin for AIDS-related wasting from Serono (Geneva, Switzerland).
The newly launched Giotto Image mammography unit from IMS (Pontecchio Marconi, Italy) is capable of performing two examinations in one: mammography in the vertical and stereotactic biopsy in the prone position. For digital biopsies, the system combines high image quality with ease of use, according to the company. The system can be upgraded to full digital mammography.