Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats

The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3–1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.     

Limited value of the international staging system for predicting long-term outcome of transplant-ineligible,newly diagnosed,symptomatic multiple myeloma in the era of novel agents

We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents.     

The Priority of Non-HDL-C Assessment to Predict New Lesions among Stable Angina Patients with Strong Statins

Aim: In this study, we aim to examine the clinical meaning of low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL as assessed by Friedewald equation [LDL-C (F)] and Martin method [LDL-C (M)] and non-high-density lipoprotein cholesterol (HDL-C) ＜100 mg/dL on the occurrence of new lesions among Japanese patients with stable angina who underwent percutaneous coronary intervention (PCI) and were prescribed with strong statins. Methods: Among the 537 consecutive stable angina patients who had underwent PCI and had been prescribed with strong statins, the association between the occurrence of new lesions with myocardial ischemia at the 9-month follow-up coronary angiography and ≤ 2 years after PCI and baseline characteristics were assessed. Results: New lesions appeared 9 months and ≤ 2 years after PCI in 31 and 90 patients, respectively. Multivariate logistic regression analysis revealed diabetes mellitus (DM) was significantly associated with the occurrence of new lesions ≤ 2 years after PCI [odds ratio (OR) 1.71, 95 % confidence interval (CI) 1.06–2.83,p=0.031], and only non-HDL-C ≥ 100 mg/dL was associated with the occurrence of new lesions both at 9 months and ≤ 2 years after PCI [OR 1.80, 95 % CI 1.10–3.00,p=0.021 and OR 1.85, 95 % CI 1.13–3.07,p=0.016]. Conclusions: Non-HDL-C ≥ 100 mg/dL was determined to be the independent risk factor for the occurrence of new lesions 9 months and ≤ 2 years after PCI among stable angina patients with strong statins. Residual risk after PCI should be considered by assessing not only DM but also non-HDL-C beyond the scope of LDL-C-lowering therapy with strong statins.     

Feeding jejunostomy following esophagectomy may increase the occurrence of postoperative small bowel obstruction

This study aimed to clarify the characteristics and treatment of bowel obstruction associated with feeding jejunostomy in patients who underwent esophagectomy for esophageal cancer. In this single-center retrospective study, 363 patients underwent esophagectomy with mediastinal lymph node dissection for esophageal cancer at the Wakayama Medical University Hospital between January 2014 and June 2021. All patients who underwent esophagectomy routinely underwent feeding jejunostomy or gastrostomy. Feeding jejunostomy was used in the cases of gastric tube reconstruction through the posterior mediastinal route or colon reconstruction, while feeding gastrostomy was used in cases of retrosternal route gastric tube reconstruction. Nasogastric feeding tubes and round ligament technique were not used. Postoperative small bowel obstruction occurred in 19 of 197 cases of posterior mediastinal route reconstruction (9.6%), but in no cases of retrosternal route reconstruction because of the feeding gastrostomy (P < .0001). Of the 19 patients who had bowel obstruction after feeding jejunostomy, 10 patients underwent reoperation (53%) and the remaining 9 patients had conservative treatment (47%). The cumulative incidence of bowel obstruction after feeding jejunostomy was 6.7% at 1 year and 8.7% at 2 years. Feeding jejunostomy following esophagectomy is a risk factor for small bowel obstruction. We recommend feeding gastrostomy inserted from the antrum to the jejunum in the cases of gastric tube reconstruction through the retrosternal route or nasogastric feeding tube in the cases of reconstruction through the posterior mediastinal route.     

Deaths in early phase of acute myocardial infarction and approaches for reducing the in-hospital and out-hospital case-fatality rates of the disease

Shiritsu Asahikawa Hospital received a total of 922 patients with acute myocardial infarction (AMI) from 1961 through 1985. The numbers of AMI patients and deaths during 1981-1985 were 2.8 times and 2.3 times, respectively, those observed during 1971-1975. However, decreasing trends were noted in the overall and age-adjusted mortality due to ischemic heart disease (IHD) per population of 100,000 Asahikawa residents between 1975 and 1984, suggesting a discrepancy between our CCU data and the city's records. We investigated the prehospital condition, out-of-hospital cardiac arrest, and the mechanism of early deaths in patients hospitalized with AMI. It was found that the increase of AMI patients admitted to our hospital was due to an increase in the hospitalization rate of AMI patients and the establishment of the coronary care unit (CCU) which allowed the admittance of patients who might have been declared dead out-of-hospital in the past. On the other hand, the declining trends in IHD mortality in the entire city of Asahikawa were attributable to reductions in the in-hospital and out-of-hospital fatality rates of patients with AMI, to improved hospital fatality rates of patients with AMI, and to improved survival rates in AMI patients who developed ventricular fibrillation (Vf) or who experienced out-of-hospital cardiac arrest episode. In order to further decrease the case-fatality rate of patients with AMI, it is essential to continuously educate residents on emergency treatment to be given at the onset of AMI.     

Mantle cell lymphoma with EBV-positive Hodgkin and Reed–Sternberg-like cells in a patient after autologous PBSCT: Phenotypically distinct but genetically related tumors

The case of 70-year-old man with mantle cell lymphoma (MCL) carrying t(11;14) translocation that relapsed as nodal lymphoma combining MCL and classic Hodgkin lymphoma (cHL) 9 years after autologous peripheral blood stem cell transplant (auto-PBSCT) is reported. Lymph nodes contained two separate areas of MCL and cHL-like components. Hodgkin and Reed–Sternberg (HRS)-like cells were accompanied by a prominent histiocyte background. HRS-like cells were CD5⁻, CD15⁺, CD20⁻, CD30⁺, PAX5⁺, Bob.1⁻, Oct2⁻ and EBER⁺. The MCL component expressed cyclin D1 and SOX11, whereas cyclin D1 and SOX11 expressions were reduced and lost, respectively, in HRS-like cells. Polymerase chain reaction results showed a single clonal rearrangement of the IGH gene in MCL and cHL-like components. CCND1 break apart fluorescence in situ hybridization showed split signals in both MCL and HRS-like cells, suggesting that MCL and cHL-like components were clonally related. Acquisition of p53 expression and Epstein–Barr virus (EBV)-positivity was seen in HRS-like cells. The patient died of disease progression with elevated hepatobiliary enzymes. The autopsy showed both MCL and cHL-like components around the bile ducts, splenic white pulp and bone marrow. The two components were phenotypically distinct, but genetically related, suggesting that transformation of MCL to HRS-like cells during the course of MCL in association with EBV infection.     

Effects of movement duration on error compensation in periodic bimanual isometric force production

Recent studies using bimanual force production have examined how factors influence redundancy in the nervous system. The present study examined effects of different movement durations on bimanual force control strategies. Ten healthy male participants produced periodic isometric forces such that the sum of two finger forces was a target cycling between 5 and 10 % of maximum voluntary contraction during five movement durations (500, 750, 1,000, 1,250, and 1,500 ms). Correlations between the two finger forces changed from positive to negative with an increase in duration. The polynomial regression analysis indicates that while the correlations between two finger forces were most negative at the target duration of 1,250 ms, they became more positive as the durations deviated from 1,250 ms. Similarly, while force variability was smallest at the target duration of 1,250 ms, it increased as the durations deviated from 1,250 ms. These findings suggested that while the duration of 1,250 ms might be a natural frequency of both fingers, bimanual force strategies changed from force error compensation to force coupling as the durations deviated from 1,250 ms. In addition, while the variance in the sum of two finger forces (the task-relevant variance) decreased with movement duration, the difference between both the finger forces (the task-irrelevant variance) did not change with the duration. Thus, a decrease in the task-relevant variance with movement duration resulted in the negative correlation between the two finger forces and the small force variability.