This study describes the first reliable synthesis of N-alkynyl imides (ynimides). This was accomplished with a copper-catalyzed coupling reaction between alkynyl(triaryl)bismuthonium salts and five-membered imides. We also found that it was possible to utilize N-ethynyl phthalimide as a variant of the highly labile ethynamine. 4-Amino-1,2,3-triazole was successfully obtained via the CuAAC reaction of N-ethynyl phthalimide with azide followed by hydrazinolysis of the phthaloyl protecting group.

Infective endocarditis (IE) caused by Serratia liquefaciens has been reported in only 2 adults. We experienced the first pediatric (neonatal) case of IE caused by S. liquefaciens, with mitral valve vegetation 4 days after a palliative heart surgery. This report underscores the importance of treating for both gram-positive and gram-negative bacteria in IE cases until the blood cultures elucidate the details.

Background Although indomethacin and ibuprofen are the standard treatments for hemodynamically significant patent ductus arteriosus (hsPDA), they are associated with renal impairment and gastrointestinal complications. Paracetamol for hsPDA closure does not provoke a peripheral vasoconstrictive effect and seems to have effects similar to those of indomethacin and ibuprofen. We have previously reported the safety of low-dose (7.5 mg/kg) intravenous paracetamol for preterm infants with hsPDA, who were indomethacin-resistant or -contraindicated but did not affect the need for surgical PDA ligation. However, reports considering the use of higher-dose (15 mg/kg) paracetamol for hsPDA have not been published in Japan. Cases In 16 premature infants in whom indomethacin or ibuprofen was contraindicated or ineffective, 15 mg/kg of paracetamol was intravenously administered every 6 hours for 3 days after obtaining parental consent. hsPDA closure or narrowing was observed in 14 infants (88%), with the need for surgical closure totally avoided in nine cases (56%). High plasma paracetamol levels were observed in three cases. No paracetamol-related side effects or adverse events were reported. Conclusion The intravenous administration of higher dose paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials to explore the optimized dose and timing of administration are needed.

Maintaining the patency of ductus arteriosus (DA) is essential for fetal circulation and normal development of the fetus. In almost-term infants, the DA constricts and causes intraluminal ischemic hypoxia, which eventually leads to the closure and remodeling of the DA a few days after birth. The occurrence of patent DA (PDA) is inversely related to gestational age and weight, with a higher incidence in preterm infants. 1 PDA is a significant cause of morbidity and mortality in preterm infants, including bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and acute renal failure due to increased pulmonary blood flow and focal organ ischemia. [2][3][4] In Japan, the AbstractBackground Although indomethacin (IND) is the standard treatment for hemodynamically significant patent ductus arteriosus (hsPDA) in Japan, it may be associated with renal impairment and gastrointestinal complications. The use of paracetamol for hsPDA closure has recently increased. Unlike IND, paracetamol does not have a peripheral vasoconstrictive effect and can be given to infants with contraindications to IND. Based on limited data available from randomized trials, paracetamol and IND seem to have similar effects. However, there have been no reports of the use of paracetamol for hsPDA in Japan. Cases Our drug administration protocol was approved by the institutional ethics committee after purchasing a clinical trial insurance. In three premature infants in whom IND was contraindicated or ineffective, a 7.5 mg/kg of paracetamol was intravenously administered every 6 hour for 3 days after obtaining parental consents. A temporary hsPDA closure was observed in two of the three infants. However, all three infants eventually needed surgical closure. No side effects, such as hepatic and renal dysfunctions, and adverse events were reported. Conclusion The intravenous administration of paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials with optimized dose and timing of administration are needed.

For the first time, we report about two extremely low birth weight infants who were born at 25 and 22 weeks' gestation and who survived functional pulmonary atresia (fPA) with normal intracardiac anatomy. A slow, reflected, and bimodal blood flow pattern in the pulmonary artery (both cases) and the presence of pulmonary regurgitation (1 case) were useful for diagnosing fPA. Timely use of lipo-prostaglandin E1 to maintain adequate pulmonary flow and reduce pulmonary arterial resistance and sodium bicarbonate to improve acidosis were effective treatments to attain forward flow. As optimal management is essential for the intact survival of extremely early preterm infants and the accurate diagnosis of fPA is difficult without the awareness of the disease entity, our cases underline the importance of recognizing that fPA can occur even in extremely low birth weight infants with normal intracardiac anatomy.

We have evaluated the sensitivity of the classical blood subinoculation method, modified through cyclophosphamide treatment of transferred mice, for the detection of occult parasitaemias in Trypanosoma cruzi chronically infected mice. Besides its simplicity, the method was shown to be highly sensitive for both the "chronic" phase parasites (99% of chronic cases were shown to harbour occult parasitaemias) and for the acute phase parasites (T. cruzi could be detected in 53.8% of animals transferred with one Y strain parasite and in 20% of animals transferred with one CL strain parasite). Using acute phase bloodforms, the assay proved to be more sensitive than conventional subinoculation when dealing with the CL, but not the Y strain of the parasite. With the help of this parasite detection tool, we have studied during a one year period, the evolution of subpatent parasitaemias in a group of mice which survived through chemotherapy from lethal acute phase of T. cruzi infection. Cyclophosphamide transfer assay revealed occult parasitaemias in 100% of the chronic animals, nevertheless, continuous and discontinuous patterns of positivity were observed.

M-mode echocardiography has been playing an important role in the diagnosis of fetal tachyarrhythmia. We recently encountered a neonatal case of atrial flutter with 2:1 atrioventricular conduction. However, M-mode erroneously indicated 1:1 atrioventricular movement. While the movement of the atrial wall far from the atrioventricular valve was much faster than that of the ventricular wall, the atrial wall adjacent to the atrioventricular valve fully synchronized to that of the ventricular wall. Thus, to avoid this novel pitfall, it would be important to add an additional assessment focusing on the movement of the atrial wall far from the ventricle.

To investigate functional changes in Trypanosoma cruzi parasites induced during their interaction with the vertebrate host, we compared the blood clearance profiles of blood forms isolated from infected normal mice (Reg-Tc) or from infected mice immunodepressed after treatment with cyclophosphamide (Cy-Tc). Parasite blood numbers were measured at various time intervals in animals injected intravenously (i.v.) with 1-2 x 10(6) T. cruzi of either isolate. In the absence of added immune sera (spontaneous clearance), Reg-Tc and Cy-Tc were cleared from blood at similar rates. However, when acute immune mouse serum (Ac-IMS) was injected i.v. 2 min after inoculation of parasites, a significant proportion of Cy-Tc only was cleared from the blood an hour later, whereas Reg-Tc were not, their clearance profile being identical to that observed in mice injected with normal mouse serum. Cy-Tc susceptibility to Ac-IMS was not the result of a toxic effect of cyclophosphamide over T. cruzi as parasites recovered from animals immunodepressed by irradiation before infection were cleared similarly by acute serum. Contrary to Ac-IMS, chronic immune mouse serum induced similar rates of disappearance of Reg-Tc and Cy-Tc from blood. Our results suggest the occurrence of T. cruzi selection or modification during the acute phase, which leads to an increased parasite resistance to the clearance properties of acute-phase antibodies.