Hemodynamic impact of ephedrine on hypotension during general anesthesia : a prospective cohort study on middle-aged and older patients

Background Ephedrine is a mixed α- and β-agonist vasopressor that is frequently used for the correction of hypotension during general anesthesia. β-responsiveness has been shown to decrease with age; therefore, this study aimed to determine whether aging would reduce the pressor effect of ephedrine on hypotension during general anesthesia. Methods Seventy-five patients aged ≥ 45 years were included in this study, with 25 patients allocated to each of the three age groups: 45–64 years, 65–74 years, and ≥ 75 years. All patients received propofol, remifentanil, and rocuronium for the induction of general anesthesia, followed by desflurane and remifentanil. Cardiac output (CO) was estimated using esCCO technology. Ephedrine (0.1 mg/kg) was administered for the correction of hypotension. The primary and secondary outcome measures were changes in the mean arterial pressure (MAP) and CO, respectively, at 5 min after the administration of ephedrine. Results The administration of ephedrine significantly increased MAP (p < 0.001, mean difference: 8.34 [95% confidence interval (CI), 5.95–10.75] mmHg) and CO (p < 0.001, mean difference: 7.43 [95% CI, 5.20–9.65] %) across all groups. However, analysis of variance revealed that the degree of elevation of MAP (F [2, 72] = 0.546, p = 0.581, η2 = 0.015 [95% CI, 0.000–0.089]) and CO (F [2, 72] = 2.023, p = 0.140, η2 = 0.053 [95% CI, 0.000–0.162]) did not differ significantly among the groups. Similarly, Spearman’s rank correlation and multiple regression analysis revealed no significant relation between age and the changes in MAP or CO after the administration of ephedrine. Conclusion The administration of ephedrine significantly increased MAP and CO; however, no significant correlation with age was observed in patients aged > 45 years. These findings suggest that ephedrine is effective for the correction of hypotension during general anesthesia, even in elderly patients

Hepatocyte Growth Factor

Hepatocyte growth factor (HGF) exerts biological activity through the Met receptor tyrosine kinase. HGF plays essential roles in the embryonic development of the liver and placenta, and in the migration of myogenic precursor cells. In mature tissues, HGF plays roles in tissue protection and regeneration, including in the liver and kidney. HGF participates in invasion, metastasis, and drug resistance. Drug development targeting HGF-Met has been challenging. One focus has been the use of recombinant HGF as a biological drug and another has been the use of HGF-Met inhibitors for cancer treatment. Clinical trials using HGF or HGF-Met inhibitors are ongoing. © 2014 Elsevier Inc. All rights reserved.[Book Chapter

脳卒中片麻痺患者の足関節背屈機能障害に対する視覚性運動錯覚の効果：ABABシングルケースデザイン

ABSTRACT The purpose of this study was to investigate the effect of simultaneous intervention with the kinesthetic illusion induced by visual stimulation (KiNvis) and voluntary exercise on ankle dorsiflexion dysfunction in a patient with right-sided stroke hemiparesis. Within an ABAB single-case design, we conducted two phases each lasting five days. Phase A represented the baseline during which only voluntary ankle dorsiflexion (VAD) was performed. Phase B involved simultaneous performance of VAD and KiNvis. We measured the angle of ankle joint dorsiflexion (AJD), and the 10 m maximum walking speed (10MWS). AJD and 10MWS were significantly improved in phase B.東京都立大学学位論文甲第1066号副論

Hepatocyte growth factor and Met in drug discovery

Activation of the hepatocyte growth factor (HGF)-Met pathway evokes dynamic biological responses that support the morphogenesis, regeneration and survival of cells and tissues. A characterization of conditional Met knockout mice indicates that the HGF-Met pathway plays important roles in the regeneration, protection and homeostasis of cells such as hepatocytes, renal tubular cells and neurons. Preclinical studies in disease models have indicated that recombinant HGF protein and expression plasmid for HGF are biological drug candidates for the treatment of patients with diseases or injuries that involve impaired tissue function. The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing. Biological actions of HGF that promote the dynamic movement, morphogenesis and survival of cells also closely participate in invasion-metastasis and resistance to the molecular-targeted drugs in tumour cells. Different types of HGF-Met pathway inhibitors are now in clinical trials for treatment of malignant tumours. Basic research on HGF and Met has lead to drug discoveries in regenerative medicine and tumour biology. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately

肺高血圧症に対するトロンボキサン合成阻害作用をもった新規長期作用型プロスタサイクリンアゴニストの経口投与

BACKGROUND: Continuous administration of prostacyclin has improved the survival of patients with pulmonary arterial hypertension (PAH). However, this treatment has some problems, including its short duration of activity and difficult delivery. Therefore, we developed ONO-1301, an orally active, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. METHODS AND RESULTS: We investigated whether oral administration of ONO-1301 can both prevent and reverse monocrotaline (MCT)-induced PAH in rats. Rats were randomly assigned to receive repeated oral administration of ONO-1301 twice daily beginning either 1 or 8 days after subcutaneous injection of MCT. A control group received oral saline, and a sham group received a subcutaneous injection of saline instead of MCT. MCT-treated controls developed significant pulmonary hypertension. Treatment with ONO-1301 from day 1 or 8 significantly attenuated the increases in right ventricular systolic pressure and the increase in medial wall thickness of pulmonary arterioles. Kaplan-Meier survival curves demonstrated that the effect of ONO-1301 was equivalent to that of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. A single oral dose of ONO-1301 increased plasma cAMP levels for up to 6h. Treatment with ONO-1301 significantly decreased urinary 11-dehydro-thromboxane B2 and increased the plasma hepatocyte growth factor concentration. CONCLUSIONS: Oral administration of ONO-1301 ameliorated PAH in rats, an effect that may occur through cAMP and hepatocyte growth factor.博士（医学）・乙1326号・平成26年3月17日日本循環器学会の許諾を得て登録（2014年6月6日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients : a single-center, randomized, controlled trial

Background Remimazolam confers a lower risk of hypotension than propofol. However, no studies have compared the efficacy of remimazolam and propofol administered using target-controlled infusion (TCI). This study aimed to investigate hemodynamic effects of remimazolam and target-controlled propofol in middle-aged and elderly patients during the induction of anesthesia. Methods Forty adults aged 45–80 years with the American Society of Anesthesiologists Physical Status 1–2 were randomly assigned to remimazolam or propofol group (n = 20 each). Patients received either remimazolam (12 mg/kg/h) or propofol (3 μg/mL, TCI), along with remifentanil for inducing anesthesia. We recorded the blood pressure, heart rate (HR), and estimated continuous cardiac output (esCCO) using the pulse wave transit time. The primary outcome was the maximum change in mean arterial pressure (MAP) after induction. Secondary outcomes included changes in HR, cardiac output (CO), and stroke volume (SV). Results MAP decreased after induction of anesthesia in both groups, without significant differences between the groups (− 41.1 [16.4] mmHg and − 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: − 8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Seven (35%) and 11 (55%) patients in the remimazolam and propofol groups, respectively, experienced hypotension (MAP < 65 mmHg over 2.5 min), without significant differences between the groups (p = 0.341). Conclusions Hemodynamics were not significantly different between remimazolam and target-controlled propofol groups during induction of anesthesia. Thus, not only the choice but also the dose and usage of anesthetics are important for hemodynamic stability while inducing anesthesia. Clinicians should monitor hypotension while inducing anesthesia with remimazolam as well as propofol

Magnetic characterization change by solvents of magnetic nanoparticles in liquid-phase magnetic immunoassay

Liquid-phase magnetic immunoassay (MIA) using magnetic nano-particles (MNPs) has been studied as a more rapid method compared to optical methods for inspecting proteins and viruses. MIA can estimate the number of conjugated antibodies without being washed differently from conventional optical immunoassay. However, in the case of the liquid phase, it is considered that the magnetic properties of MNPs are affected by physical properties such as viscosity and impurity substances such as biological substances contained in the blood. In this study, the effect of sodium chloride (NaCl) in buffer and serum solution was evaluated to reveal the effect of serum because the sodium (Na+) and chloride (Cl-) ions in the serum dominate ion balance of blood. The measurement results of AC magnetic susceptibility and a dynamic light scattering (DLS) showed that the aggregation of MNPs was largely affected by the concentration of NaCl. This effect of the NaCl could be explained by shielding of the surface charge of MNPs by ions in the solution. Although the concentrations of NaCl in the buffer and serum solution were almost same, we found that MNPs were aggregated more in their size for those in the serum solution because of other impurities, such as proteins. These results suggest evaluation of effects of the contaminants in serum and optimization of polymer coatings of MNPs could be important factors to realize measurements of magnetic immunoassay with high accuracy. (C) 2019 Author(s)