The inciting factor for bradycardia in COVID-19 patients: a potential harm of steroid treatment.

Background: The coronavirus disease 2019 (COVID-19) is a condition caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Although several papers have reported the presence bradycardia in patients with COVID-19, the pathophysiology behind this remains unclear. Therefore, we investigated the presence of bradycardia in patients with COVID-19. Methods: We conducted a retrospective cohort study in a total of 153 patients with COVID-19 and 90 patients with influenza who were hospitalized in our hospital from January 1, 2020 to December 31, 2021 and from January 1, 2014 to December 31, 2021, respectively. Data were collected from patient medical records, which included sex, age, duration of hospitalization, pneumonia complications, supplemental oxygen therapy, antiviral treatment, past history, and vital signs. Results: After adjustment, the incidence of bradycardia and steroid use in patients with COVID-19 were significantly higher than those in patients with influenza (P=0.007 and P<0.001, respectively). We then compared the detailed characteristics of patients with COVID-19 to evaluate risk factors for bradycardia. Multivariate logistic regression analysis revealed that steroid use was significantly related to bradycardia [P=0.031; odds ratio (OR): 3.67; 95% confidence interval (CI): 1.12-11.96]. Overall, results showed a higher incidence of bradycardia in patients with COVID-19 who received steroid treatment. Conclusions: Our results showed that steroid treatment in patients with COVID-19 may be associated with the incidence of bradycardia.

Effect of cinacalcet hydrochloride, a new calcimimetic agent, on the pharmacokinetics of dextromethorphan: in vitro and clinical studies.

Cinacalcet hydrochloride (cinacalcet) is a positive allosteric modulator of the calcium-sensing receptor indicated for the treatment of secondary hyperparathyroidism in dialysis patients. In vitro study has demonstrated that cinacalcet is a potent inhibitor of cytochrome P450 (CYP) 2D6 with a K(i) value of 0.087 micromol/L, which is comparable to the well-known potent CYP2D6 inhibitor, quinidine (0.064 micromol/L). A clinical study was conducted to assess the inhibitory effect of cinacalcet on CYP2D6 substrates in healthy volunteers. Each subject received 50 mg of cinacalcet or a matched placebo orally once daily for 8 days with 30 mg of dextromethorphan coadministered on day 8. The mean AUC(0-infinity) and C(max) of dextromethorphan increased 11- and 7-fold, respectively, in extensive metabolizers when coadministered with cinacalcet versus placebo. Therefore, during concomitant treatment with cinacalcet, it may be necessary to consider making dose adjustments for drugs with a narrow therapeutic index that are mainly metabolized by CYP2D6.

[Case of chronic pigeon breeder's disease accompanied by pulmonary cysts].

We treated a case of chronic pigeon breeder's disease with pulmonary cysts. The patient was a 49-year-old woman whose husband had started to breed pigeons 23 years earlier. She was given a diagnosis of hypersensitivity pneumonitis due to pigeons 1 year previously, but since her husband refused to stop keeping the birds, she could not stay out of contact with them. A chest CT scan showed bilateral multiple pulmonary cysts and a diffuse groundglass appearance. The transbronchial lung biopsy (TBLB) specimens showed bronchioloalveolitis characterized by infiltration of lymphocytes and plasma cells into the walls of the bronchioles and the surrounding alveolar walls. Tests for antibodies to extracts of both pigeon droppings and budgerigar droppings were positive. After admission to our hospital and avoidance of contact with birds, the groundglass changes, dyspnea, and hypoxemia ameliorated. Multiple pulmonary cysts in a non-smoker is a rare manifestation of chronic pigeon breeder's disease.

[Recurrence of non-small cell lung cancer after successful treatment with gefitinib--report of three cases].

Gefitinib, a first epidermal growth factor receptor (EGFR) inhibitor has been reported to be effective in chemotherapy-resistant non-small cell lung cancer. Gefitinib was also reported, however, to produce severe adverse effects, such as interstitial lung disease. Thus, clinical evaluation of gefitinib is still controversial and further studies are needed. We present 3 cases of non-small cell lung cancer (stage IV adeno-carcinoma) that showed recurrence after successful gefitinib treatment. Symptoms of all patients ameliorated in a week after the therapy, and radiograph and laboratory data improved. However, all showed recurrence in 3 to 7 months. After recurrence, patient 1 was re-treated with gefitinib at the request of the patient. Patient 2 has been on gefitinib. Patient 3 was treated with gefitinib, which was later replaced by another chemotherapy agent. After recurrence, however, no effective response was obtained in any of the 3 cases. There have been several reports of good response to gefitinib therapy at the first time in patients with advanced non-small cell lung cancer, but few reports of recurrence in patients after successful therapy with this agent. This report is thought to be important for the clinical evaluation of gefitinib and useful in terms of information about the resistance of gefitinib.

[A case of bronchostenosis in the allograft after lung transplantation in pulmonary lymphangioleiomyomatosis].

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease characterized by hamartomatous proliferation of abnormal smooth muscle cells in the lungs. Recently, severe LAM has been listed as an indicated disease for lung transplantation. A 34-yr-old woman with severe pulmonary cystic changes in a chest CT scan was diagnosed as having an isolated form of pulmonary LAM without genetic disorders. Despite intensive progesterone treatment, her pulmonary functions deteriorated rapidly. In January 2001, a left single-lung transplantation was performed from a cadaveric donor. The total operating time was 8 hours and 47 minutes. Total ischemic time was 5 hours and 59 minutes, which was within the permitted time limit. Except for right pneumothorax, the postoperative course was fairly good without any sign of rejection or infection in the allograft. For about two months after transplantation, bronchostenosis occurred in the left lower lobe bronchus, and necessitated a stent placement. During the following three months, stenosis of the bronchi in the anastomotic and peripheral sites occurred repeatedly, which also necessitated stent placement or balloon dilations on each occasion. Despite all the intensive treatment, the bronchostenosis of the peripheral sites still remains and improvement of her pulmonary functions has been poor. Moreover, a recent chest CT scan revealed a progression of the disease in the native lung. Consequently, we registered her as a candidate for transplantation of the right lung. Bronchostenosis should be kept in mind as a complication of lung transplantation.

Malignant mesothelioma associated with chronic empyema with elevation of serum CYFRA19: A case report.

Malignant neoplasms are reported to occur with long-standing tuberculous pleuritis or chronic empyema. During the clinical course of chronic empyema, subjective symptoms such as chest pain and deterioration of dyspnea and abnormal clinical signs such as increased abnormal chest shadows have frequently been found. Though difficult, differentiating the occurrence of malignant tumors from worsening chronic inflammation is crucial. We report here a case of malignant mesothelioma associated with chronic empyema with elevation of serum CYFRA19.

Protein C deficiency in a family with thromboembolism and identified gene mutations.

Protein C is the central component of the major anti-thrombotic regulatory system, and individuals with hereditary protein C deficiency tend to have an increased risk of thromboembolism. During the last several years, mutations causing protein C deficiency have been identified. In the present study, we report familial cases with three nucleotide substitutions: One is a missense mutation Arg169Trp, which was previously reported. The other two are C-154T promoter polymorphism (rs1799808 on dbSNP database), the function of which is unknown and Ser99Ser synonymous polymorphism (rs5936). All three mutations were found in a 24-year-old patient with pulmonary thromboembolism and his 54-year-old father who also had pulmonary thromboembolism. C-154T promoter polymorphism (rs1799808 on dbSNP database) and Ser99Ser synonymous polymorphism (rs5936) were found in the patient's mother.

Silico-asbestosis that responded to steroid therapy.

A 73-year-old man with silico-asbestosis responded to steroid therapy. Chest CT scans showed diffuse micronodular opacities and ground glass opacities bilaterally throughout the entire lung fields, as well as progressive massive fibrosis in the bilateral upper lung fields. Diagnostic thoracoscopic biopsy revealed mixed dust pneumoconiosis with silicotic nodules, as well as fibrosis similar to that of Usual Interstitial Pneumonia (UIP) with many fibroblastic foci and alveolitis. Many asbestos bodies were also detected by iron staining.

cis-Elements involved in expression of unspliced RNA in Moloney murine leukemia virus.

Murine leukemia virus (MLV) produces the unspliced RNA and the singly spliced RNA at a proper ratio at a time. To identify cis-elements involved in the production of the unspliced RNA, we examined the level of unspliced RNA in a series of mutants derived from a prototype Moloney MLV mutant gag-encoding G3.6. Our present data indicated that nt 1560-1906 region in the CA-encoding region in gag was the negative cis-element and nt 5119-5355 region, which was immediately upstream of the splice acceptor site, was the positive cis-element for expression of the unspliced RNA. It was found that the former element made expression of the unspliced RNA dependent upon the latter. These two elements were functional as discrete elements and their activities were relatively position-independent.