Although intravascular lithotripsy (IVL) has been an emerging novel option to treat vascular calcification, the specific effects on histology have not been systematically examined.The authors examined the histologic effects of IVL on coronary calcified lesions from human autopsy hearts and evaluated the diagnostic ability of optical coherence tomography (OCT) and micro-computed tomography (CT) to detect calcium fracture as identified by the gold standard histology.Eight coronary lesions were treated with IVL, and 7 lesions were treated with 10 atm inflation using an IVL catheter balloon without lithotripsy pulses (plain old balloon angioplasty [POBA]). OCT and micro-CT imaging were performed before and after treatment, and the presence of calcium fracture was assessed. The frequency and size of fractures were measured and compared with the corresponding histology.All 15 treated lesions were diagnosed as sheet calcium by histology. Histological evidence of calcium fracture was significantly greater in the IVL group compared with the POBA group (62.5% vs 0.0%; P = 0.01). Calcified lesions with fracture had a larger maximum arc degree of calcification (median 145.6 [IQR: 134.4-300.4] degrees vs 107.0 [IQR: 88.9-129.1] degrees; P = 0.01). Micro-CT and histology showed an excellent correlation for fracture depth (R2 = 0.83; P < 0.0001), whereas OCT showed less correlation (R2 = 0.37; P = 0.11). The depth of fractures measured by OCT were significantly shorter than with those measured by histology (0.49 [IQR: 0.29-0.77] mm vs 0.88 [IQR: 0.64-1.07] mm; P = 0.008).IVL demonstrated a histologically superior fracturing effect on coronary calcified lesions compared with POBA. OCT failed to identify the presence of some calcium fractures and underestimated the depth of fracture when compared with micro-CT.
We have been focusing on fabricating a photodetector that consists of a diamond cold cathode and an amorphous selenium (a-Se) photoconductor, which is one of the practical applications of a cold cathode. We have previously succeeded in achieving a proto-type photodetector of which a heavily nitrogen (N)-doped diamond was used as the cold cathode, and the results indeed showed a low operation voltage. This heavily N-doped diamond was fabricated using urea as a dopant and the saturated solution of urea and methanol was diluted with acetone and used as a reactant gas. Although this diamond cathode exhibited low extraction voltage, the reproducibility of obtaining low threshold cathode was not as high as expected and the improvement should be considered for wider extensive application. In order to solve this problem, dimethylurea was introduced due to its structure more similar to diamond and soluble in acetone, where urea is insoluble without the use of methanol. Dimethylurea-saturated solutions of acetone diluted at a ratio of 1:100, 1:1000, and 1:10000 with acetone is vaporized and used as the reactant gas and diamond is grown on a silicon substrate by hot filament CVD method. The N/C ratio in the CVD apparatus is 1000 ppm, 100 ppm and 10 ppm respectively. The electron emission characteristics of N-doped diamond doped with dimethylurea are then measured. The experiment was performed under a base pressure of 4 x 10 -6 Pa. Anode-cathode distance is fixed to 50mum and the current versus voltage (I-V) characteristics are measured.
Hypophosphatasia (HPP) is an autosomal recessive metabolic disorder with impaired bone mineralization due to mutations in the ALPL gene. The genotype‐phenotype correlation of this disorder has been widely described. Here, we present two affected siblings, whose fetal phenotypes were discordant. A 31‐year‐old Japanese woman, G0P0, was referred to our institution because of fetal micromelia. After obstetric counseling, the pregnancy was terminated at 21 weeks’ gestation. Post‐mortem radiographs demonstrated severely defective mineralization of the skeleton. The calvarial, spinal, and tubular bones were mostly missing. Only the occipital bones, mandible, clavicles, ribs, one thoracic vertebra, ilia, and tibia were relatively well ossified. The radiological findings suggested lethal HPP. Genetic testing for genomic DNA extracted from the umbilical cord identified compound heterozygous mutations in the ALPL gene (c.532T>C, p.Y178H; c.1559delT, p.Leu520Argfs*86). c.532T>C was a novel variant showing no residual activity of the protein by the functional analysis. The parents were heterozygous carriers. In the next pregnancy, biometric values on fetal ultrasonography at 20 and 26 weeks’ gestation were normal. At 34 weeks, however, a small chest and shortening of distal long bones came to attention. The neonate delivered at 41 weeks showed serum ALP of <5U/L. Radiological examination showed only mild thoracic hypoplasia and metaphyseal mineralization defects of the long bones. ALP replacement therapy was introduced shortly after birth, and the neonate was discharged at day 22 without respiratory distress. Awareness of discordant fetal phenotypes in siblings with HPP precludes a diagnostic error, and enables early medical intervention to mildly affected neonates.
