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Paediatric heart sounds assessed by computer
SCIENCE AND MEDICINE
Paediatric heart sounds assessed by computer n electronic stethoscope and a computer program trained to recognise complex patterns can accurately distinguish innocent heart murmurs from pathological murmurs in children, report US researchers. The technology has potential as a “low-cost, high-volume screening tool”, says lead author Curt DeGroff (University of Colorado Health Sciences Center, Denver, CO, USA). “This would assist—not replace—the clinician’s assessment”, he stresses, “and could help in decision making about the utility of additional, often costly, tests.” DeGroff, a former electrical engineer who is now a paediatric cardiologist, and co-workers used the stethoscope to record heart sounds of 37 children with abnormal heart murmurs and 32 with innocent heart murmurs. The sounds were fed into the computer program—technically, an artificial neural network—so that it “learned” to discriminate between the different types of murmurs, and eventually achieved 100% sensitivity (ability to identify an abnormal
A
sensitivity and specificity, then I’m going to feel good if I can also show that those 100 patients represent the entire spectrum of heart disease. That’s not the same as saying if you test the technology on x number of patients, then you have statistical ‘power.’” For now, the study stands as a proof of concept, says DeGroff, who adds that the clinical skills needed to discern heart sounds are “atrophying”. “People are not being trained the way they used to be. There’s something in the human psyche that says, ‘well, I don’t have to learn to listen to the heart because I can always get an echocardiogram’. Yes, you can fall back on that, but then you have to go through the whole referral process, and some children with abnormal conditions may receive delayed diagnoses, while families of children with innocent heart murmurs may go through weeks of anxiety and tests to rule out problems. We’re hoping to avoid that.”
murmur) and 100% specificity (ability to identify and innocent murmur). (Circulation 2001; 103: 2711–16.) The “biggest challenge” for the electronic device may be similar to that which confronts the clinician—a limited ability to recognise hypertrophic cardiomyopathy, the condition that causes athletes to die unexpectedly, and heart problems in neonates that don’t produce a detectable murmur until after the first 4 to 6 weeks of life, says DeGroff. “Ultimately, this may be a limitation, but we’ll have to see. If the microphone in our electronic stethoscope ends up being more sensitive than the human ear, then maybe this won’t be a problem.” The team must also overcome scepticism, acknowledges DeGroff. “Compared with standard statistical techniques, the artificial neural network is a kind of black box. There’s not a specific number of patients I can come up with to show that it’s ‘robust’. I would say that if I’m testing 100 patients and have 99%
Marilynn Larkin
VEGF implicated in degeneration of motor neurons cientists this month have provided an insight into a potential cause of the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Peter Carmeliet (University of Leuven, Belgium) and colleagues report that age-dependent selective degeneration of motor neurons, reminiscent of ALS in human beings, develops in mice with mutations in the vascular endothelial growth factor gene (VEGF). The researchers bred the mice to investigate the relationship between hypoxia and angiogenesis. Hypoxia stimulates VEGF expression by activating transcription factors that bind to the hypoxia-response element in the VEGF promoter, which upregulates VEGF and counters the hypoxia. A targeted insertion–deletion strategy was used to generate mice with a specific deletion of the hypoxia-response element. The mice had normal baseline expression of VEGF but they lacked the ability to induce VEGF in response to hypoxia (Nat Gen 2001; 28: 131–38). “The new results from Carmeliet and colleagues show that the ability of very active neurons to recruit a
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more chronic increase in blood flow may be critical for maintaining neuronal survival throughout adult life”, comments Pate Skane (Duke Medical Center, Durham, NC, USA). “The new findings suggest that disrupting the intimate link between neuronal activity and
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Stephen Hawking: defects in VEGF?
blood flow can, over a lifetime, lead to the onset of progressive neuronal degeneration.” The authors also showed that VEGF directly affects the survival of motor neurons—indicating another potential means by which alterations in VEGF may give rise to ALS. Carmeliet hopes that the findings can be extrapolated to man, but says that “we will first need to examine whether VEGF is
PA Photos
S
abnormally expressed in ALS patients and whether VEGF can be considered for chronic treatment”. The group is currently testing whether VEGF gene therapy can be used for ALS, using various animal models and treatment strategies. “The most promising route might be to deliver VEGF intrathecally, not only because VEGF might not be able to cross the blood–brain barrier when administered systemically, but also to avoid systemic side-effects, such as increased tumour growth”, says Carmeliet. The findings may have adverse neurological implications for patients currently receiving antiVEGF therapy for cancer, arthritis, or diabetic retinopathy. “The extent to which lifelong, genetic disruption of the VEGF promoter in mice models more acute blockade of VEGF receptors in humans—let alone other forms of angiostatic therapy—is unclear, but it would be prudent to bear this possibility in mind as such treatments are developed”, comments David Greenberg (Buck Institute for Age Research, Novato, CA, USA). Helen Frankish
THE LANCET • Vol 357 • June 9, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Paediatric heart sounds assessed by computer n electronic stethoscope and a computer program trained to recognise complex patterns can accurately distinguish innocent heart murmurs from pathological murmurs in children, report US researchers. The technology has potential as a “low-cost, high-volume screening tool”, says lead author Curt DeGroff (University of Colorado Health Sciences Center, Denver, CO, USA). “This would assist—not replace—the clinician’s assessment”, he stresses, “and could help in decision making about the utility of additional, often costly, tests.” DeGroff, a former electrical engineer who is now a paediatric cardiologist, and co-workers used the stethoscope to record heart sounds of 37 children with abnormal heart murmurs and 32 with innocent heart murmurs. The sounds were fed into the computer program—technically, an artificial neural network—so that it “learned” to discriminate between the different types of murmurs, and eventually achieved 100% sensitivity (ability to identify an abnormal
A
sensitivity and specificity, then I’m going to feel good if I can also show that those 100 patients represent the entire spectrum of heart disease. That’s not the same as saying if you test the technology on x number of patients, then you have statistical ‘power.’” For now, the study stands as a proof of concept, says DeGroff, who adds that the clinical skills needed to discern heart sounds are “atrophying”. “People are not being trained the way they used to be. There’s something in the human psyche that says, ‘well, I don’t have to learn to listen to the heart because I can always get an echocardiogram’. Yes, you can fall back on that, but then you have to go through the whole referral process, and some children with abnormal conditions may receive delayed diagnoses, while families of children with innocent heart murmurs may go through weeks of anxiety and tests to rule out problems. We’re hoping to avoid that.”
murmur) and 100% specificity (ability to identify and innocent murmur). (Circulation 2001; 103: 2711–16.) The “biggest challenge” for the electronic device may be similar to that which confronts the clinician—a limited ability to recognise hypertrophic cardiomyopathy, the condition that causes athletes to die unexpectedly, and heart problems in neonates that don’t produce a detectable murmur until after the first 4 to 6 weeks of life, says DeGroff. “Ultimately, this may be a limitation, but we’ll have to see. If the microphone in our electronic stethoscope ends up being more sensitive than the human ear, then maybe this won’t be a problem.” The team must also overcome scepticism, acknowledges DeGroff. “Compared with standard statistical techniques, the artificial neural network is a kind of black box. There’s not a specific number of patients I can come up with to show that it’s ‘robust’. I would say that if I’m testing 100 patients and have 99%
Marilynn Larkin
VEGF implicated in degeneration of motor neurons cientists this month have provided an insight into a potential cause of the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Peter Carmeliet (University of Leuven, Belgium) and colleagues report that age-dependent selective degeneration of motor neurons, reminiscent of ALS in human beings, develops in mice with mutations in the vascular endothelial growth factor gene (VEGF). The researchers bred the mice to investigate the relationship between hypoxia and angiogenesis. Hypoxia stimulates VEGF expression by activating transcription factors that bind to the hypoxia-response element in the VEGF promoter, which upregulates VEGF and counters the hypoxia. A targeted insertion–deletion strategy was used to generate mice with a specific deletion of the hypoxia-response element. The mice had normal baseline expression of VEGF but they lacked the ability to induce VEGF in response to hypoxia (Nat Gen 2001; 28: 131–38). “The new results from Carmeliet and colleagues show that the ability of very active neurons to recruit a
1856
more chronic increase in blood flow may be critical for maintaining neuronal survival throughout adult life”, comments Pate Skane (Duke Medical Center, Durham, NC, USA). “The new findings suggest that disrupting the intimate link between neuronal activity and
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Stephen Hawking: defects in VEGF?
blood flow can, over a lifetime, lead to the onset of progressive neuronal degeneration.” The authors also showed that VEGF directly affects the survival of motor neurons—indicating another potential means by which alterations in VEGF may give rise to ALS. Carmeliet hopes that the findings can be extrapolated to man, but says that “we will first need to examine whether VEGF is
PA Photos
S
abnormally expressed in ALS patients and whether VEGF can be considered for chronic treatment”. The group is currently testing whether VEGF gene therapy can be used for ALS, using various animal models and treatment strategies. “The most promising route might be to deliver VEGF intrathecally, not only because VEGF might not be able to cross the blood–brain barrier when administered systemically, but also to avoid systemic side-effects, such as increased tumour growth”, says Carmeliet. The findings may have adverse neurological implications for patients currently receiving antiVEGF therapy for cancer, arthritis, or diabetic retinopathy. “The extent to which lifelong, genetic disruption of the VEGF promoter in mice models more acute blockade of VEGF receptors in humans—let alone other forms of angiostatic therapy—is unclear, but it would be prudent to bear this possibility in mind as such treatments are developed”, comments David Greenberg (Buck Institute for Age Research, Novato, CA, USA). Helen Frankish
THE LANCET • Vol 357 • June 9, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.