Pulmonary Toxicity Induced by Pepleomycin 3-[(S)-l'-Phenylethylamino] Propylamino-Bleomycin

Chemotherapy regimens containing pepleomycin, a derivative ofbleomycin, were used for 81 patients with advanced primary lungcancer and 32 patients with metastatic pulmonary tumors. Amongthe patients with non-small cell carcinoma of the lung, partialresponses were observed in three of 27 patients treated withpepleomycin + carbazilquinone and four of 26 patients treatedwith pepleomycin + mitomycin C (published in Cancer TreatmentReports, 1983). Five partial responses (primary organ: larynx,esophagus, lung, pancreas and uterus; one patient each) in 23evaluable patients with metastatic pulmonary tumors were observedduring treatment, for an overall response rate of 21.7%. Inpatients with primary lung cancer, no correlation between theincidence of the decrease in partial arterial oxygen tension(PaO₂) during treatment and age was observed. Decrease in PaO₂during treatment was found more frequently in patients withabnormal pulmonary function before treatment than in patientswith normal pulmonary function, but the mean lowest values ofPaO₂, in the two groups were the same. Intravenous weekly injectionof pepleomycin is less likely to result in a decrease in PaO₂,than two daily intramuscular injections. Definite pulmonarytoxicity occurred in seven of the 113 patients (6.2%). Eachof the seven received a total dose of over 60 mg and their ageswere over 60 yr, although no correlation between the incidenceof pulmonary fibrosis and total cumulative dose of pepleomycinwas observed. Six of the seven patients died of pulmonary fibrosisin spite of prednisone treatment. Clinical, radiologic and histopathologicfindings associated with pepleomycin were the same as thoseof bleomycin pulmonary toxicity. Further studies are neededto determine the appropriate dose schedule and route of administrationof pepleomycin with regard to its benefit and toxicity.     

Elimination of Ventricular Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia by Targeting “Catecholamine‐Sensitive Area”: A Dominant‐Subordinate Relationship between Origin Sites of Bidirectional Ventricular Premature Contractions

We report on a patient diagnosed with catechoaminergic polymorphic ventricular tachycardia (CPVT) who underwent catheter ablation of ventricular premature contractions (VPCs) induced by epinephrine. VPCs were classified roughly into three types. Type 1 and Type 2 VPCs (right bundle branch block [RBBB] configuration and inferior axis) were eliminated by radiofrequency applications at the left aortic sinus of Valsalva and the anterolateral papillary muscle (APM), respectively. Although no spontaneous VPCs were seen after the elimination of Type 1 and 2 VPCs, pacing resulting in capture at the APM induced Type 3 VPC (RBBB configuration and superior axis) reproducibly. The electrophysiological findings observed in our representative case have important implications both for understanding the pathophysiology of CPVT and for considering therapeutic strategies.     

Association between work-related changes caused by the COVID-19 pandemic and severe psychological distress among Japanese workers

This study aimed to evaluate the association between work-related changes caused by COVID-19 and psychological distress among Japanese workers. The cross-sectional study was conducted from August 25 to September 30, 2020. The participants were 15,454 employees who were registered as panelists with an online survey company. The Kessler psychological distress scale with a 13-point cutoff was used to measure psychological distress. Multiple logistic regression was performed. Of the respondents, 8.9% were evaluated as having severe psychological distress. Among five examined work-related changes, being laid off and changing jobs (adjusted odds ratio [aOR] = 5.43; 95% confidence interval [CI]: 4.18–7.05), experiencing temporary workplace closure (aOR = 1.94; 95% CI: 1.67–2.25), being forced to visit the workplace for paperwork (aOR = 1.84; 95% CI: 1.58–2.15), and starting telework from home (aOR = 1.18; 95% CI: 1.01–1.37) were associated with increased psychological distress; no significant association was found for participation in work-related online meetings. The impact on psychological distress was greater among men, especially for being laid off and changing jobs because of COVID-19. It is important to assess and reduce negative mental health effects among workers experiencing work-related changes caused by the COVID-19 pandemic, taking gender differences into account.     

Association between preventive measures against workplace infection and preventive behavior against personal infection

To prevent the spread of infection, it is necessary for each individual to adopt infection prevention behavior. We investigated the effect of infection control measures implemented in the workplace on personal infection prevention behavior. We conducted a self-administered questionnaire survey through the Internet from December 22 to 25, 2020, during which period coronavirus disease 2019 (COVID-19) was spreading. Among respondents aged 20 to 65 years (n=27,036), 21,915 workers were included in the analysis. The results showed that as the number of infection control measures in the workplace increased, implementation of infection prevention behavior by individuals also significantly increased. However, the relationship differed depending on the type of personal infection prevention behavior. Specifically, infection control measures against COVID-19 in the workplace may affect personal infection prevention behavior. Implementation of infection control measures in the workplace increases awareness of the importance of individual infection prevention behavior and its implementation by all individuals. These findings may be applicable not only to COVID-19 measures but also to responses to other emerging infections and seasonal influenza.     

Fas-mediated apoptosis is involved in the elimination of gene-transduced hepatocytes with E1/E3-deleted adenoviral vectors

Gene-transduced hepatocytes with E1/E3-deleted adenoviral vectors are eliminated immediately and the expression of transduced genes disappears rapidly following the vector administration. In this report, we analysed the involvement of apoptotic cell death in the elimination of hepatocytes infected with adenoviral vectors. An E1/E3-deleted adenoviral vector expressing Escherichia coli β-galactosidase (LacZ) was injected via the portal vein into congenitally Fas-deficient mice (lpr), Fas ligand-deficient mice (gld) and their control mice, MRL and C3H. 5-Bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) staining of the liver specimens showed that 80–100% of hepatocytes were LacZ positive at 7 days after virus administration, suggesting that most of the hepatocytes received the injected adenoviral vectors. In normal mice, the number of LacZ-positive cells decreased dramatically at 14 and 21 days after transduction and few positive cells were observed at day 28. β-Galactosidase activity, quantified by the O-nitrophenyl-beta-D-galactopyranoside assay, gave comparable results to X-gal staining. At days 14 or 21, many apoptotic hepatocytes and apoptotic infiltrating cells were detected with the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) in situ apoptosis detection method. This observation suggested that the apoptotic process was associated with the elimination of adenovirus-infected hepatocytes. To test the involvement of the Fas—Fas ligand interaction in this apoptotic process, the period of transgene expression was measured in 1pr and gld mice, which had received the same amount of AxCALacZ. X-Gal histochemical analysis detected many LacZ-positive cells in 1pr or gld mice liver even at 21 or 28 days after AxCALacZ injection. There were significant differences in the reduction rates of β-galactosidase activity of liver homogenates between lpr and MRL, or gld and C3H mice. Based on these observations, we conclude that the Fas-mediated apoptotic process is involved in the elimination of hepatocytes infected with E1/E3-deleted adenoviral vectors.     

Defibrillation Effects of Intravenous Nifekalant in Patients with Out-of-Hospital Ventricular Fibrillation

Nifekalant (NF), a pure K⁺ channel blocker developed in Japan, has been reported to be effective in the treatment of life-threatening ventricular arrhythmias. We studied its efficacy in 18 men and 4 women with out-of-hospital ventricular fibrillation (VF) admitted to our emergency department between August 2001 and March 2004. The number of DC shocks delivered for out-of-hospital VF, serum Na⁺ and K⁺, arterial blood pH, and base excess were compared in 8 patients treated with NF, 0.3 mg/kg i.v. followed by a continuous intravenous (group N) versus 14 patients treated with lidocaine, 2 mg/kg, i.v. (group C). The two groups were similar with respect to their baseline characteristics. Sinus rhythm returned in 5 of 8 patients in group N versus 2 of 14 patients in group C (P < 0.05). These seven patients were admitted to the intensive care unit, though all died within 1 month. The results of this study suggest that NF may be effective in defibrillation of out-of-hospital VF, though controlled studies are needed to confirm our observations.