Molecular diagnosis in a child with sudden infant death syndrome.

Although sudden infant death syndrome (SIDS) has been associated with long QT syndrome-a genetic disorder that causes arrhythmia-a causal link has not been shown. We screened genomic DNA from a child who died of SIDS and identified a de-novo mutation in KVLQT1, the gene most frequently associated with long QT syndrome. This mutation (C350T) had already been identified in an unrelated family that was affected by long QT syndrome. These results confirm the hypothesis that some deaths from SIDS are caused by long QT syndrome and support implementation of neonatal electrocardiographic screening.

Comparison between low-dose dobutamine echocardiography and thallium-201 scintigraphy in the detection of myocardial viability in patients with recent myocardial infarction.

AIM: To compare the predictive value of thallium-201 single photon emission computed tomography (SPECT) scintigraphy (Sci) and low-dose dobutamine echocardiography (Dob) in predicting late recovery of dysfunctioning myocardium in patients with recent, uncomplicated myocardial infarction (MI). METHODS AND RESULTS: 19 patients (18 male, aged 58+/-8 years) with recent MI and ejection fraction <50% (35.5+/-8.3%) underwent 5-15 microg/kg per min Dob, rest-redistribution Sci and coronary angiography, respectively, 14+/-6, 16+/-7 and 17+/-5 days after MI. On an eleven-segment ventricular model devised to compare Dob and Sci segment by segment, each dysfunctioning ventricular segment was considered viable if it showed recovery of mechanical function at the echocardiographic follow-up, performed 6.3+/-1.5 months after revascularization (five PTCA, five GABG) or medical therapy. Among the 104 dysfunctioning segments, of which 26 (25%) showed recovery at follow-up, Dob and Sci gave a concordant response in 50 (48%, k = 0.13), correctly predicting the recovery (or not) of function in 42. Forty-two of 54 discordant responses were due to segments judged viable only by Sci and which had no recovery at follow-up (of these 37 were akinetic or severely hypokinetic at baseline). At the segment-by-segment analysis, the sensitivity, specificity, and accuracy in predicting recovery of function at follow-up were, respectively, 69, 88 and 84% for Dob as against 88, 36 and 49% for Sci (P<0.001 for both specificity and accuracy, P=NS for sensitivity). CONCLUSION: In patients with recent MI, the specificity of Dob in the detection of myocardium capable of late mechanical recovery is significantly higher with respect to Sci, whereas sensitivity is slightly, not significantly higher for the latter. It is conceivable that Sci detects viable myocardium even if it is transmurally limited to epicardial layers in segments with severely impaired mechanical function in which viability will not affect late recovery of function.

Interaction of neuromelanin and iron in substantia nigra and other areas of human brain.

Nine areas of the brain were studied by electron paramagnetic resonance spectroscopy and total reflection X-ray fluorescence spectroscopy to measure paramagnetic metal ions, free radicals (neuromelanin), and total metal content. We also determined the extent of accumulation of metal ions by melanins incubated in homogenates of a region of the brain (putamen). The electron paramagnetic resonance spectra of metal ions varied considerably among areas of the brain. There was no correlation between total content of particular metal ions (iron was especially pertinent) and the observed electron paramagnetic resonance spectra, except that the substantia nigra appeared more consistently to have a prominent g = 4 electron paramagnetic resonance signal characteristic of ferric iron in a rhombic state. Only the substantia nigra, and to a lesser extent the locus coeruleus, had a free radical signal consistent with that of neuromelanin. This signal was much more prominent in the unprocessed substantia nigra but when metal ions were removed (reducing the amount of suppression of the electron paramagnetic resonance signal of neuromelanin due to dipole-dipole broadening from nearby metal ions), the electron paramagnetic resonance spectrum of neuromelanin of the locus coeruleus increased much more than that of the substantia nigra. This suggests that the structure of the pigment may differ in these two regions. Incubating synthetic melanins with homogenates of putamen resulted in accumulation of metal ions on the melanins with the concentrations of the three metal ions, relative to their values in the putamen, increasing by factors of 20-30, 3-4, and 25-30, for iron, copper, and zinc, respectively. This suggests that the metal content of isolated neuromelanin may include metal ions which became bound to the neuromelanin during the isolation procedure.

Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain.

Radiochemical neutron activation analysis has been used to determine the concentration of 36 elements in neuromelanin, 22 elements in substantia nigra, and 32 elements in putamen of healthy subjects without signs of neurological disorders. Substantia nigra and putamen tissues were carefully dissected from the brain using special surgical instruments and tools as well as an adequate sampling procedure to avoid the risk of metal contamination during sampling. Neuromelanin was isolated from putamen by a multiple-step procedure (extraction with phosphate buffer, lipid and protein elimination by methanol extraction, and sodium dodecyl sulfate-proteinase). The isolated pigment as well as substantia nigra and putamen underwent neutron activation analysis involving irradiation in a high-neutron-flux reactor, radiochemical separations, and counting of the induced radionuclides by computer-based gamma-ray spectrometry. Iron was the element present in the highest concentration in all analyzed samples. The amount of iron was similar in substantia nigra and putamen (3,000 and 3,830 ng/mg wet weight, respectively) and 10 times higher in neuromelanin (30,800 ng/mg dry weight). Zinc was also present at high levels in three samples, ranging from 16.8 (substantia nigra) to 1,500 ng/mg (neuromelanin). Elements such as Zn, Cr, Se, Sr, Co, Sb, Ni, Hg, Ce, Au, Ag, Ta, and Sc were present in neuromelanin at much higher concentrations than in substantia nigra and putamen. These findings indicate that substantia nigra and putamen contain metals at higher concentrations than observed in blood and that neuromelanin has a particular affinity for metals.