A 50-year-old male spray paint worker was admitted with non-productive cough and dyspnea on exertion. Chest X-ray and chest CT showed diffuse interstitial shadows in the bilateral lung fields. After admission, the symptoms and chest X-ray findings improved over several days, and he was followed as an outpatient. He then developed nocturnal dyspnea with wheezing and dry cough every day. About two months later, chest X-ray showed more severe diffuse interstitial shadows which did not disappear after admission. Bronchoalveolar lavage and transbronchial lung biopsy revealed allergic exudative interstitial pneumonia, and he was treated with steroid therapy. Paint contains toluene diisocyanate, and challenge test to toluene diisocyanate was positive. In the early course, this case presented with bronchoconstriction; bronchial reversibility and bronchial hyperresponsiveness to methacholine were positive. Bronchoconstriction may cause worsening of respiratory symptoms in patients with hypersensitivity pneumonitis induced by isocyanates.
To elucidate the mechanisms of acquired resistance to mitomycin C (MMC) in non‐small cell lung cancer (NSCLC), we established two MMC‐resistant NSCLC sublines by continuous exposure to MMC, using PC‐9 as a parent cell line. The sublines, PC‐9/MC2 and PC‐9/MC4, were 6.4‐ and 10‐fold more resistant to MMC than their parent cell line, respectively, at the IC 50 value as determined by MTT assay. They exhibited cross‐resistance to EO9, but were not resistant to cisplatin, vindesine, etoposide, carboquone, or KW‐2149, a novel MMC derivative. They were collaterally sensitive to adriamycin and menadione. Accumulation of the drug was decreased in the resistant sublines to about 60% of that in the parent cells. Cytosolic DT‐diaphorase (DTD) activities were decreased to 13.5±3.2 in PC9/MC2 and 1.3±0.6 in PC‐9/MC4 from 261.5±92.7 nmol/min/mg protein in the parent PC‐9. NADH:cytochrome b 5 reductase activities in both of the resistant cell lines were significantly decreased as compared to that in the parent cell line. Addition of dicumarol resulted in a two‐fold increase in IC 50 value in PC‐9, whereas the IC 50 value showed no change in PC‐9/MC4. Moreover, dicumarol did not affect the sensitivities to KW‐2149 but decreased the sensitivities to EO9 in both the parent and the resistant cell lines. Formation of an alkylating metabolite was significantly decreased in the resistant cells, in parallel to the degree of resistance. We concluded that deficient drug activation due to decreased DTD activity was important as a mechanism of resistance to MMC in PC‐9, a relatively DTD‐rich NSCLC cell line.
A 70-year-old woman was hospitalized for status asthmaticus. The level of CRP was high and chest roentgenogram showed infiltrative shadows in the left middle lung field. Artificial respiration and continuous infusion of methylprednisolone and aminophylline 750 mg/24 hr were performed. Eight hours after admission, seizures suddenly occurred. At this time, brain CT showed no abnormal findings. The seizures were thought to be induced by theophylline toxicity, since serum theophylline concentration was high at 69.9 micrograms/ml. Because theophylline clearance of the patient in a clinically stable condition was normal, it was speculated that theophylline clearance was reduced during status asthmaticus. It is thought that this rare case of theophylline toxicity occurred due to reduction of theophylline clearance during status asthmaticus associated with pneumonia.
While clinical trials have illuminated both the virological and clinical efficacy of baloxavir for influenza and post-treatment viral resistance, these aspects warrant further study in real-world settings. In response, we executed a prospective, observational study of the Japanese 2022–2023 influenza season. A cohort of 73 A(H3N2)-diagnosed outpatients—36 treated with baloxavir, 20 with oseltamivir, and 17 with other neuraminidase inhibitors (NAIs)—were analyzed. Viral samples were collected before and after administering an antiviral on days 1, 5, and 10, respectively. Cultured viruses were amplified using RT-PCR and sequenced to detect mutations. Fever and other symptoms were tracked via self-reporting diaries. In the baloxavir cohort, viral detection was 11.1% (4/36) and 0% (0/36) on day 5 and day 10, respectively. Two isolates from day 5 (5.6%, 2/36) manifested I38T/M-substitutions in the polymerase acidic protein (PA). For oseltamivir and other NAIs, viral detection rates were 60.0% (12/20) and 52.9% (9/17) on day 5, and 16.7% (3/18) and 6.3% (1/16) on day 10, respectively. No oseltamivir-resistant neuraminidase mutations were identified after treatment. Median fever durations for the baloxavir, oseltamivir, and other NAI cohorts were 27.0, 38.0, and 36.0 hours, respectively, with no significant difference. Two patients harboring PA I38T/M-substitutions did not exhibit prolonged fever or other symptoms. These findings affirm baloxavir's virological and clinical effectiveness against A(H3N2) in the 2022–2023 season and suggest limited clinical influence of post-treatment resistance emergence.
A 49-year-old man was admitted with non-productive cough and left chest discomfort. About one month prior to the admission, he suffered a non-penetrating injury to the left anterior chest. Although rib fracture or pleural effusion was not reported, left chest discomfort and non-productive cough progressed gradually. Chest X-ray film and chest CT scan on admission showed left massive pleural effusion. Close examination revealed a marked increase of eosinophils in the pleural effusion (77% of total cell counts). Because malignancy, parasitic disease, and collagen disease were differentiated, we diagnosed this case as post-traumatic eosinophilic pleural effusion, and decided to administers corticosteroid therapy; hydrocortisone 300 mg was infused into the left pleural space. Seven days after the treatment, the pleural effusion and peripheral eosinophilia had completely disappeared. This case suggests that direct infusion of corticosteroid into the pleural space provides greater drug availability in the treatment of post-traumatic eosinophilic pleural effusion related to immunological reaction of the pleura. The indication and dosage of corticosteroids should be established, however, because there have been some reports of cases of improvement without any special treatment.
We propose an optimization system for motion planning of robot arms using Petri Nets. The proposed optimization system consists of four sub-systems consisting of automatic generation of Petri Nets from event log data, optimization system of firing sequence of derived Petri Net model, verification system using Petri Net simulation, and an automatic program generation system. The model generation system automatically generates the Petri Net model from the event logs using process mining. The Petri Net verification system is used to check the consistency of the generated Petri Nets to obtain the optimal firing sequence for robot motion. The motion planning algorithm generates motion programs for robots based on optimal firing sequences. The proposed optimization model is applied to a 6-DOF (Degree of Freedom) robot manipulator (Niryo Ned). Experimental results show that the proposed method achieves motion plan optimization for the pick-and-place operation with different robot configurations.
To assess the susceptibility of epidemic influenza viruses to the four most used neuraminidase inhibitors (NAIs) during the 2023-24 influenza season in Japan, we measured the 50 % inhibitory concentration (IC50) of oseltamivir, peramivir, zanamivir, and laninamivir in virus isolates from the sample of 100 patients. Viral isolation was done using specimens obtained before and after treatment, with the type/subtype determined by RT-PCR using type- and subtype-specific primers. IC50 values were determined by a neuraminidase inhibition assay using a fluorescent substrate. The virus isolates included 16 A(H1N1)pdm09, 19 A(H3N2), and 65 B/Victoria-lineage. The geometric mean (GM) IC50 values of pre-treatment samples for oseltamivir, peramivir, zanamivir, and laninamivir were 0.90 nM, 0.62 nM, 1.09 nM, and 2.77 nM for A(H1N1)pdm09; 0.86 nM, 0.67 nM, 1.64 nM, and 3.61 nM for A(H3N2); and 16.12 nM, 1.84 nM, 3.87 nM, and 11.35 nM for B/Victoria, respectively. These values were comparable to those from the previous eleven seasons, and no virus with significantly reduced susceptibility to any of the NAIs was found either before or after drug administration in the 2023-24 season. These results indicate that susceptibility to these four NAIs has been maintained across the three influenza types/subtypes over the past fourteen seasons in Japan.
