Siemens Healthcare Diagnostics and Illumina have entered into a partnership aimed at setting new standards in the use of next-generation sequencing for the rapid, accurate identification of patients’ infectious disease states and potential treatment paths. Through this agreement, the companies plan to make existing Siemens molecular HIV tests compatible with the recently launched Illumina MiSeq next-generation sequencing platform, with the ultimate goal of introducing breakthrough sequencing-based infectious disease assays for the clinical diagnostics market.
Ten years ago the TRUGENE HIV-1 Genotyping Assay, the first DNA sequencing-based test for HIV to be cleared by the FDA, was launched to a worldwide market. This laid the foundation for Siemens to become a leader in infectious disease testing solutions that employ DNA sequencing technology. Since then, TRUGENE has become one of the market’s leading DNA sequencing tests for infectious disease testing. By making this test compatible with Illumina’s MiSeq analyser, Siemens expects to be well positioned to help even more clinical laboratories leverage next-generation sequencing for their infectious disease testing with the fastest turnaround time and highest accuracy possible.

Roche sets up co –marketing agreement with private laboratory to support greater access to HPV testing

In an innovative commercial agreement, leading healthcare company Roche and foremost private cellular pathology laboratory Unilabs-IHS, are collaborating to help make state-of-the art testing for signs of cervical cancer more accessible to thousands of women in London and throughout the UK.

Roche’s leading-edge and fully automated cobas® HPV test which runs on the acclaimed cobas 4800 system, will provide a fast turn-around of cervical smear samples from potentially thousands of women per year, sent to the London based laboratory from clinicians from all over the country.  The testing at Unilabs-IHS, will not only be conducted as a follow up  to the traditional “Pap” cervical smear method to check ambiguous results, it will also be used upon request in primary screening for cervical pre cancer, giving a greater chance to avoid disease progression.

The ultra-high reliability of the cobas HPV test will be of huge benefit for clinicians and patients alike, due to the test’s unique genotyping that individually identifies genotypes 16 and 18, the highest risk types associated with the development of cervical cancer and its precursor lesions, while simultaneously identifying 12 other high risk HPV types.  Such technology provides better risk stratification of patients enabling a more sensitive and efficient approach to cervical screening. 

Dr Glen Dixon,  Medical Director of Cytopathology at Unilabs-IHS   from Unilabs-IHS said “We are delighted to have come to this agreement with Roche.  Using the cobas HPV test on the cobas 4800 platform for our HPV testing work load, means that clinicians will not only have the fastest ever turnaround times, but will also have enhanced and incontrovertible HPV results, with no need to re-test – and all at no extra cost.”

Paul Eros, Director of Molecular Diagnostics at Roche said: “HPV testing provides earlier identification of those women at risk of developing cervical cancer.  The agreement that we have struck with Unilabs-IHS for cervical screening with the cobas HPV test, is a significant step forward towards spreading access to HPV testing at the primary screening stage.  Given the clear benefits of this technology to patients as well as the NHS, we look forward to seeing the technology’s timely introduction at the primary screening stage, across the country via the national cervical screening programme – promising a better deal for women and a more efficient approach to cervical screening.”

Researchers at Winship Cancer Institute have identified a new function for a gene that normally prevents the development of cancer.
Scientists had known that the gene, which encodes a protein called p14 ARF, works inside the cell to control proliferation and division. A team led by Erwin Van Meir, PhD, discovered that p14 ARF also regulates tumour-induced angiogenesis, the process by which growing cancers attract new blood vessels.
The findings provide insight into how cancers form and progress, communicate with surrounding vascular cells and could guide the development of new therapies to fight tumours whose growth is driven by loss of p14 ARF.
Van Meir is professor of neurosurgery and haematology & medical oncology at Emory University School of Medicine, and director of the Laboratory for Molecular Neuro-Oncology at Winship Cancer Institute. Abdessamad Zerrouqi, PhD, research associate, is the first author of the paper.
Pinning down the new function for p14 ARF was a several-year detective investigation for Zerrouqi. The gene was a slippery target because growing cells in culture tend to lose or silence it, he says. P14 ARF is not turned on in most tissues of the body, but is activated in response to aberrant growth signals.
The gene encoding p14 ARF is mutated or silenced in many types of cancers, including most gliomas, the most common brain cancer in adults. People who inherit mutations affecting this gene develop ‘melanoma-astrocytoma syndrome,’ with increased occurrence of both types of tumours. ARF stands for ‘alternate reading frame’ because the DNA sequence overlaps with another protein that is read out of step in comparison to ARF. Previous research had linked the function of p14 ARF to another gene, p53, which is also frequently mutated in cancers. P53 is known as ‘guardian of the genome’ because it shuts down cell division in response to DNA damage.
Zerrouqi says several clues pointed to a separate function for p14 ARF. P14 ARF is often lost when astrocytoma progresses to glioblastoma, a more deadly form of brain cancer.
‘These tumours are bigger, more infiltrative and more vascularised,’ he says. ‘Yet p53 is usually lost at an early stage, before this transition takes place. This suggested that p14 ARF has a function that is independent of p53.’
Zerrouqi could show that restoring p14 ARF in cells from a tumour that had lost it interfered with the tumour’s ability to stimulate blood vessel growth. P14 ARF induces brain cancer cells to secrete a protein called TIMP3, which inhibits vascular cell migration, he found.
Zerrouqi and Van Meir’s findings are applicable to brain cancers as well as several other cancer types. TIMP3 itself has been found to be silenced in brain, kidney, colon, breast and lung cancers, suggesting that it is an obstacle to their growth. Emory University School of Medicine

Big gaps in basic knowledge about the numbers and causes of apparently inexplicable heart attacks among young sportsmen and women are seriously hampering our ability to prevent them, says a sport and exercise medicine specialist in the British Journal of Sports Medicine.
At the very least, we need to start building reliable databases of all such events across sport, in a bid to start plugging these knowledge gaps, say Dr Richard Weiler and colleagues.
His comments come in the wake of the recent high profile case of premier league footballer, Fabrice Muamba, who collapsed on pitch, in front of a stadium packed with spectators, after sustaining a sudden heart attack.
Fortunately, Mr Muamba recovered, but cases like these, although rare, are still likely to occur despite screening programmes, and they are poorly understood, emphasises Dr Weiler.
These cases have prompted improvements in pitch-side and acute sports medicine, including emergency life support, defibrillation and the development of practical education courses and emergency care guidelines, says Dr Weiler.
None the less, he says: ‘We still lack many answers to basic questions about these afflictions. We do not know the exact numbers and trends in prevalence or incidence, and do not understand the [multiple causes] that trigger sudden cardiac death in previously healthy athletes.’
Issues that still need further investigation are the roles of gender and ethnicity, geography and genes, he says.
For example, Sub-Saharan Africa may be a ‘cardiac hotspot,’ with recent research linking sudden heart attacks to sickle cell trait.
Other research suggests that African Americans are three times more prone to sudden cardiac death/arrest than white athletes, although the rates vary considerably depending on the type of sport played.
And another study found that heart (ECG) tracing patterns differ between white and black athletes, although whether this is normal or indicates a higher risk for sudden cardiac death is not known, says Dr Weiler.
Screening programmes throw up a considerable number of false positive results, and it is still far from clear whether screening actually cuts the number of deaths, whether it is cost effective, and how to manage any abnormal findings, he says.
‘It is vital that we start to answer these questions based on reliable science and evidence,’ he insists. ‘To achieve this, we propose the collection and recording of reliable data across sport of every sudden cardiac death/arrest,’ he writes.
But for this to happen, co-operation and collaboration will be needed among sporting organisations, federations, and clubs, in addition to the establishment of sport specific and national registries for these incidents, he suggests.
Dr Weiler cites a FIFA (International Football Federation) initiative. This requires a medical assessment before a match for all FIFA competitions, and includes a recently established database for all its 208 member associations in a bid to build up an evidence base and better understand the condition.
‘This is one of many efforts needed to fill knowledge gaps and enable us to mitigate the risks of sudden cardiac arrest/death,’ concludes Dr Weiler, adding that minimum standards of pitch-side medical care across all sports are essential. EurekAlert

French researchers have found a way to identify quickly the 5-10% of patients in whom the commonly used painkiller, tramadol, does not work effectively. A simple blood test can produce a result within a few hours, enabling doctors to switch a non-responding patient on to another painkiller, such as morphine, which will be able to work in these patients.
Dr Laurent Varin, an anaesthesiologist at the Caen Teaching Hospital (Caen, France), presented the findings.
Tramadol is a synthetic opioid that is metabolised in the liver via an enzyme called cytochrome P450 2D6 (CYP2D6) to produce a small molecule (or ‘metabolite’) called O-demethyltramadol (ODT). ODT is between two and four times better at inducing analgesia than tramadol that is not metabolised successfully. This is because ODT has a 200-fold higher affinity to the opioid receptors in humans than un-metabolised tramadol, meaning that it binds to the receptors more successfully, blocking out the signals for pain.
Dr Varin said: ‘In our hospital we frequently use tramadol after surgery – about 50-60% of patients are treated with it, while the rest are treated with nefopam, which is a non-opioid painkiller. However, in about 5-10% of Caucasian patients the CYP2D6 enzyme is inefficient and does not produce enough ODT to bind effectively to the opioid receptors; these patients are known as ‘poor metabolisers’ and will have poorly controlled pain unless the problem is identified quickly and they are switched to morphine or nefopam.’
In order to identify the ‘poor metabolisers’, Dr Varin and his colleagues decided to investigate the ratio between tramadol and ODT in patients’ blood to see if this would give an indication of how efficiently CYP2D6 was working. They recruited 294 Caucasian patients who were receiving tramadol after surgery for a number of digestive conditions such as stomach, bowel and liver cancer, or for surgery on the spleen, gall bladder or pancreas. They collected blood samples after 24 and 48 hours post-surgery, and tested them for concentrations of tramadol and ODT using ‘high performance liquid chromatography tandem mass spectrometry’, which separates out the different components in the blood.
The researchers also used genotyping to analyse and identify the DNA make-up of the patients to discover which of them had inefficient CYP2D6. This revealed that eight per cent (23) of the patients were ‘poor metabolisers’. Then the researchers assessed the ratio of tramadol to ODT in the blood samples of the ‘poor metabolisers’ and the other patients.
‘We found that, after 24 hours, an ODT/tramadol ratio of less than 0.1 indicated a deficient CYP2D6 activity with an accuracy of 87% sensitivity – the test’s ability to correctly identify positive results – and 85% specificity – the test’s ability to correctly identify negative results,’ said Dr Varin. ‘This means that this ratio is highly accurate at detecting ‘poor metabolisers’ who need to be switched to another painkiller.’
Dr Varin and his colleagues believe that the ODT/tramadol ratio gives doctors a new tool to identify ‘poor metabolisers’ in the clinic. ‘This test is simple and cheap, costing only about 30 Euros. It can be performed quickly in just a few hours, instead of many days when the genotyping method is used, and will enable clinicians to make the best treatment choices for their patients. If a patient is suffering unrelieved postoperative pain and the blood test reveals an ODT/tramadol ratio of less than 0.1, then the clinicians can switch quickly to morphine, rather than trying to increase the dose of tramadol and risk adverse drug effects by overdosing. EurekAlert