Study findings indicate that lipid-binding proteins are better markers for acute myocardial infarction than cholesterol.
The international study, published recently, investigated the accuracy of using concentrations of lipoproteins and lipids to determine the risk of acute myocardial infarction.
The standardized case–control study of acute myocardial function involved 12,461 cases and 14,637 age-matched and sex-matched controls in 52 countries. Non-fasting blood samples were available from 9345 cases and 12,120 controls. From these samples, concentrations of plasma lipids, lipoproteins and apolipoproteins were measured, and cholesterol and apolipoprotein ratios were calculated. The study indicated that the apolipoprotein B100 (ApoB)/apolipoprotein A1 (ApoA1) ratio had the highest population-attributable risk (PAR) at 54%. The total cholesterol/high-density lipoprotein (HDL) cholesterol ratio had a PAR of 32%, significantly lower than that of the ApoB/ApoA1 ratio (p = 0.0001). Encouragingly, the results were reported to be consistent in all ethnic groups, men and women, and for all ages.
The authors conclude that, out of the cholesterol ratios investigated, the non-fasting ApoB/ApoA1 ratio best estimates the risk of acute myocardial infarction and should therefore be introduced into worldwide clinical practice.
The results are in contrast to those found the previous year in the Framingham Heart study, which concluded that ApoB/ApoA1 ratios are not better markers than cholesterol. The two major studies had different protocols. The recent study involved a variety of ethnic groups in many countries and was based on more than 10,000 cases. Whereas the Framingham study involved only 3300 cases, however, the smaller cohort potentially means it was standardized better. Another difference between the studies is that the recent one only recruited participants who already had suffered a heart attack.
Corresponding author of the study Matthew McQueen from McMaster University (ON, Canada) comments, “Automated apolipoprotein tests now are available and I use them to add information to what is shown by conventional cholesterol testing.”
Source: McQueen MJ, Hawken S, Wang X et al. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case–control study. Lancet 372(9634), 224–233 (2008).
New screening test for sepsis
A 5-h test for 64 sepsis-causing pathogens has been developed by Seegene.
A novel and fast-acting sceening test for sepsis, Seeplex® has from announced by Seegene at the 2008 Annual Meeting and Clinical Lab Expo of the American Association for Clinical Chemistry (AACC). Sepsis is the primary cause of death in non-coronary intensive care units worldwide. Sepsis is hard to diagnose and treat as it can be caused by Gram-positive bacteria, Gram-negative bacteria or one of eight fungi, none of which leave a clear indication of their origin.
The cost of the wide-impacting disease is over $35 billion, with 18 million cases of severe sepsis reported each year. An unwelcome feature of the condition is that it often affects patients who were admitted to hospital for unrelated reasons. Furthermore, clinicians are not able to confidently determine the most suitable treatment for the first days of the disease. They are limited to a choice of several tests which are not guaranteed to determine if the disease is present or not. Another option is to perform a multiple-phase blood culture test covering a range of specific targets; however, this is an expensive and lengthy process. As a solution to the lack of efficient diagnosis, Seegene have developed the Seeplex Sepsis Test. The single lab test quickly determines levels of suspected targets in a patient’s blood sample, allowing the most appropriate treatment to be administered and is significantly cheaper than other currently available methods.
The sensitivity of the diagnostic assay has been compared with blood culture test methodology in a clinical study in Korea. Out of 370 hospital patients suspected of having sepsis, 53 patients tested positive using the Seeplex Sepsis Test while 32 patients tested positive using the blood culture method. The Seeplex test was completed on the same day the blood samples were taken, whereas the blood culture took 3–4 days to generate test results.
Within 5 h, the Seeplex Sepsis test screens for 64 sepsis-causing pathogens; 48 Gram-positive bacteria, ten Gram-negative bacteria and six fungi. Four drug resistant genes (vanA, vanB, mecA and blaSHV) can also be discriminated. “The Seeplex Sepsis DNA test is a fundamental breakthrough for accurate, rapid and cost-effective sepsis diagnostics,” said Jong-Yoon Chun, chief executive officer of Seegene. “We believe the Seeplex testing system opens a new window for not only saving lives but also furthering understanding of this complex disease by providing precise information of infected pathogens at the earliest possible stage.”
Through diagnosing sepsis at an early stage, the test will reduce the unnecessary use of antibiotics.
Source: www.seegene.com
Microscopic microscope developed
New microscope may allow on-spot blood, urine and stem cell screening.
A potentially revolutionary cell-imaging technology has enabled the development of the ‘microscopic microscope’. Scientists from California have developed a super-compact, high-resolution microscope with potential applications in blood fraction analysis, urine screening for infection, stem cell screening and sorting, tumor cell counting and drug screening. The approximate cost of mass-producing the mini microscope is thought to be $10 and only requires sunlight for illumination, making its use in developing countries feasible. The authors write, “In a Third World, environment, a complete, low-cost and compact microscope system suitable for malaria diagnosis can be a boon for a health worker who needs to travel from village to village.”
The microscope employs computer chip technology with microfluidics, the channeling of fluid flow at extremely small scales, and is dubbed an optofluidic microscope.
The mechanics of the optofluidic microscope is not vastly complicated. A layer of metal is coated onto a grid of charge-coupled device sensor. A line of holes, less than 1 millionth of a meter diameter, and spaced 5 µm apart is punched into the metal. Each hole corresponds to one pixel on the sensor. Finally, a microfluidic channel is placed on top of the metal and sensor, through which the liquid containing the sample to be analyzed will flow. As the sample flows across the line of holes, the passage of light is blocked and this is detected by the sensor. The series of images are then put together to create a 2D image of the object. Changhuei Yang, assistant professor of electrical engineering and bioengineering at the California Institute of Technology speculates on a further future use of the microscope chips, “An implantable microscope analysis system can autonomously screen for and isolate rogue cancer cells in blood circulation, thus, providing important diagnostic information and helping arrest the spread of cancer.”
Source: Cui X, Lee LM, Heng X et al. Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging. Proc. Natl Acad. Sci. USA 105(31), 10670–10675 (2008).
Genetic test that helps determine cancer cell type is cleared by the US FDA
The Pathwork Tissue of Origin test has been cleared for marketing by the US FDA. The test compares the genetic material of a patient’s tumor with a database of genetic information. The test can analyze 15 tumor types, including bladder, breast and colorectal tumors. Daniel Schultz, director of the FDA’s Center for Devices and Radiological Health comments, “In the past, scientists have classified different types of cancers based on the organs in which the tumors develop. With the help of microarray technology, they will be able to classify these types of cancers in a standardized non-reader dependent manner based on the patterns of gene activity in the tumor cells.” The accuracy of the test in affirming the existing tissue of origin of 15 common tumor types is similar to that of expert pathologists using current standards of practice.
Source: www.pathworkdx.com
Hepcidin-binding domain assay for diagnosing anemia and iron overload
A new assay for the diagnosis of anemia related to chronic illness and diseases of iron overload has been developed by scientists in the USA.
The distribution of iron within the body is controlled by the peptide hormone hepcidin and the iron transporting receptor ferroportin. The peptide, produced in the liver, binds to ferroportin. This binding inhibits the transportation of iron out of storage cells. In a healthy individual, hepcidin is therefore released when iron levels are sufficient. However, an excess of hepcidin in the blood can cause anemia and a deficiency of hepcidin leads to a build-up of iron that is detrimental to cell function.
The ability to test for hepcidin would be valuable in the diagnosis of iron balance disorders. This may become a reality following a study by researchers at the University of Utah (UT, USA) and the University of California (CA, USA). The group have identified the specific site where the hepcidin binds to ferroportin, the hepcidin-binding domain. This permits the creation of a synthetic binding site which can be placed on agarose beads. This allows the concentration of active hepcidin in the blood to be measured. The test is called the HBD assay and is reported to be rapid and sensitive.
The assay may be particularly useful in the diagnosis of anemia of chronic disease, or anemia of inflammation, as recent studies suggest this syndrome is due to excessive production of hepcidin. The assay will also be valuable in the diagnosis of hemochromatosis, as it can be caused by insufficient levels of hepcidin. Hemochromatosis is the most common human disorder of iron overload and leads to the abnormal accumulation of iron in the liver, heart, skin and other organs.
Source: De Domenico I, Nemeth E, Nelson JM et al. The hepcidin-binding site on ferroportin is evolutionary conserved. Cell Metab. 8(2), 146–156 (2008).
Kidney disease marker test to be developed
A study has indicated neutrophil gelatinase-associated lipocalin to be a suitable marker for acute kidney injury.
Acute kidney injury (AKI) may be distinguished from other forms of kidney dysfunction via the urine-based diagnostic marker neutrophil gelatinase-associated lipocalin (NGAL). Data on this marker was presented at the 2008 American Association for Clinical Chemistry Annual Meeting (DC, USA).
NGAL is produced by the kidney tubules and appears in urine within 2–4 h following AKI. In clinical tests, NGAL correctly identified 90% of children who developed AKI following cardiopulmonary bypass surgery for congenital heart defects. The detection of high NGAL levels is important as, in the study, children with higher NGAL levels were more likely to die or need dialysis.
“The urine NGAL marker has the potential to represent a major advance in identifying patients at risk for developing AKI after surgery or trauma and in other situations commonly seen in critically ill patients,” said Prasad Devarajan, director of nephrology and hypertension at the Cincinnati Children’s Hospital Medical Center and presenter of the data. “From the single drop of urine, we obtain essential information when time is critical to help prevent kidney failure and save lives.”
A urine NGAL test is currently being developed and international clinical trials are planned.
Source: www.labnews.com/en
A study finds plasma fibronectin associated with venous thromboembolism
A US study has indicated that elevated plasma fibronectin levels are associated with venous thromboembolism (VTE). Fibronectin has a role in blood coagulation, cell adhesion and platelet thrombus initiation. Fibronectin is associated with ischemic heart disease and coronary artery disease. The study was designed to assess the hypothesis that plasma fibronectin levels are also linked with VTE. The researchers compared plasma fibronectin levels in the Scripps Venous Thrombosis Registry for 113 VTE cases with those of age- and sex-matched control subjects. The VTE cases had significantly higher mean fibronectin concentration compared with the controls. Idiopathic VTC cases were associated with higher levels of fibronectin than the controls. Interestingly, elevated fibronectin was only significant in male patients. Only 25% of female VTE patients had idiopathic VTE compared with 80% of male patients. The authors comment, “Our study confirms previous reports that suggested plasma fibronectin levels are significantly influenced by age and sex and that males have higher levels than females.” It is not known if evlevated fibronectin is a causative risk factor for VTE or just a biomarker for events.
Source: Pecheniuk NM, Elias DJ, Deguchi H, Averell PM, Griffin JH. Elevated plasma fibronectin levels associated with venous thromboembolism. Thromb. Haemost. 100(2), 224–228 (2008).