E-Cadherin Is Expressed in Epithelial Cells of the Choroid Plexus in Human and Mouse Brains.

Evidence showing the functional significance of the choroid plexus is accumulating. Epithelial cells with tight and adherens junctions of the choroid plexus play important roles in cerebrospinal fluid production and circadian rhythm formation. Although specific types of cadherin expressed in adherens junctions of choroid plexus epithelium (CPE) have been examined, they remained uncertain. Recent mass spectrometry and immunolocalization analysis revealed that non-epithelial cadherins, P- and N-cadherins, are expressed in the lateral membrane of CPE, whereas E-cadherin expression has not been confirmed in CPE of humans or mice. In this study, we examined E-cadherin expression in CPE of mice and humans by RT-PCR, immunohistochemical-, and Western blotting analyses. We confirmed, by using RT-PCR analysis, the mRNA expression of E-cadherin in the choroid plexus of mice. The immunohistochemical expression of E-cadherin was noted in the lateral membrane of CPE of mice and humans. We further confirmed, in Western blotting, the specific immunoreactivity for E-cadherin. Immunohistochemically, the expression of E- and N-cadherins or vimentin was unevenly distributed in some CPE, whereas that of E- and P-cadherins or ß-catenin frequently co-existed in other CPE. These findings indicate that E-cadherin is expressed in the lateral membrane of CPE, possibly correlated with the expression of other cadherins and cytoplasmic proteins.

The Association between Preoperative Blood Pressure Elevations and Postoperative Adverse Outcomes after Non-cardiac Surgery: A Single-center Retrospective Observational Study.

Blood pressure (BP) often rises before surgery. This study investigated whether BP elevation immediately before surgery was associated with adverse outcomes. Medical records of 11,732 patients (average age: 61 years; male: 47.4%) who underwent non-cardiac elective inpatient surgery under general anesthesia at Kagawa University Hospital between January 2011 and June 2019 were reviewed. Differences between the first BP values measured on the day before surgery and the first BP values in the operating room were defined as Δ systolic BP (ΔSBP) and Δ diastolic BP (ΔDBP). The relationships between ΔSBP/ΔDBP and 30-day mortality, 30-day readmission, and over-the-standard length of hospital stay (OSLOS) were assessed. OSLOS was defined as a hospital stay longer than mean+2 standard deviations and was calculated using the Japanese Diagnosis Procedure Combination data. In univariate analysis, the differences in ΔSBP and ΔDBP between the OSLOS and standard LOS groups were both 2 mmHg. In multivariate logistic regression analysis, only ΔDBP was associated with OSLOS. The adjusted odds ratio (95% confidence interval) for the largest quartile was 1.31 (1.02-1.69) (p<0.05). ΔDBP was associated with OSLOS; however, there may be little need to worry about large ΔSBPs and ΔDBPs in clinical practice.

Immunoreactivities for hepcidin, ferroportin, and hephaestin in astrocytes and choroid plexus epithelium of human brains.

Iron plays essential roles in the central nervous system. However, how the iron level is regulated in brain cells including glia and neurons remains to be fully clarified. In this study, the localizations of hepcidin, ferroportin, and hephaestin, which are known to be involved in iron efflux, were immunohistochemically examined in autopsied human brains. Immunoreactivities for hepcidin and ferroportin were observed in granular structures within the cytoplasm of reactive astrocytes and epithelial cells of the choroid plexus. Granular structures showing immunoreactivities for hepcidin and ferroportin were also stained with antibodies for early endosome antigen 1 (EEA1). In addition, immunoreactivity for hephaestin was observed in the cytoplasm of epithelial cells of the choroid plexus as well as reactive astrocytes. Immunoreactivity for hephaestin in the cytoplasm of reactive astrocytes was occasionally colocalized with immunoreactivity for EEA1, while that of hephaestin was frequently observed in the cytoplasm showing no immunoreactivity for EEA1. These findings suggest that immunoreactivities for hepcidin and ferroportin are localized in close proximity to granular structures showing immunoreactivity for EEA1 in the cytoplasm of human brain astrocytes. They also suggest that immunoreactivity of hephaestin is localized in the cytoplasm of the choroid plexus epithelium as well as reactive astrocytes of human brains.

Guanylyl Cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia Models.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. METHODS: Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy. RESULTS: Recombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg · h; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg · h; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg · h; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide. CONCLUSIONS: Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.

Comparison of general anesthesia and monitored anesthesia care in patients undergoing breast cancer surgery using a combination of ultrasound-guided thoracic paravertebral block and local infiltration anesthesia: a retrospective study.

PURPOSE: The aim of this study was to compare post-anesthesia recovery time and the incidence of hypotension episodes during anesthesia in breast cancer surgery between general anesthesia (GA) and monitored anesthesia care (MAC) retrospectively. Both techniques were combined with ultrasound-guided paravertebral block (US-PVB) and local infiltration anesthesia (LIA). METHODS: We reviewed the medical records of patients who received US-PVB for breast cancer surgery retrospectively and divided them into two groups based on the method of anesthetic management. In the GA group, anesthesia was induced using propofol and maintained by sevoflurane inhalation via a laryngeal mask airway after US-PVB was performed under sedation with midazolam. In the MAC group, US-PVB and surgery were carried out under sedation with propofol and remifentanil and supplemental oxygen through a facemask. All patients in both groups breathed spontaneously and received US-PVB and LIA with 0.5 % ropivacaine and diclofenac suppository for pain relief. RESULTS: Times from post-anesthesia care unit admission to fluid intake (mean ± SD; 79 ± 34 vs. 99 ± 33 min, P = 0.034) and gait (77 ± 45 vs. 109 ± 45 min, P = 0.013) were significantly shorter in the MAC group (n = 29) than in the GA group (n = 29). Average systolic blood pressure (SBP) was significantly lower (89 ± 11 vs. 99 ± 16 mmHg, P = 0.011) and the incidence of hypotension (SBP < 70 mmHg) was higher (52 vs. 21 %, P = 0.014) in the GA group than in the MAC group during anesthesia. CONCLUSION: MAC with US-PVB and LIA exhibited faster post-anesthesia recovery and a lower incidence of hypotension episodes during anesthesia than GA with US-PVB and LIA in breast cancer surgery.

Case of vascular air embolism during holmium laser enucleation of the prostate.

Vascular air embolism is a rare complication during transurethral surgery. A case of air embolism during holmium laser enucleation of the prostate in a 76-year-old man is presented. During the step of morcellation, the patient's blood pressure suddenly oscillated up and down, and end-tidal CO2 and arterial saturation decreased. Transesophageal and transthoracic echocardiography showed air collection in the right atrium. It was also discovered that incorrect assembly of the tube from the morcellator caused rapid entrainment of air into the vein. Computed tomography and abdominal X-ray showed niveau formation in the femoral vein and air collection in the pelvic retroperitoneal space. The patient recovered with careful observation and was discharged 7 days after the operation with no sequelae. This report is presented to remind urologists of this unusual complication that can occur during holmium laser enucleation of the prostate procedures.

[Monitored Anesthesia Care for Respiratory Endoscopy].

Sedation and/or analgesia are required during respiratory endoscopy procedure to reduce the patient's anxiety, unpleasantness and pain. At present most of diagnostic respiratory endoscopy cases are carried out outside the operating room without the involvement of anesthesiologists in Japan. Inadequate anesthesia/sedation may cause patient's discomfort and/or serious injury. Anesthesiologists are expected to play a part in the sedation and analgesia education/training for nonanesthesiologists to ameliorate patient satisfaction and safety. Interventional endoscopy procedures are more invasive and painful than simple diagnostic ones for patients, and sometimes result in a crisis such as respiratory tract bleeding and airway obstruction. Since the number of interventional cases and high-risk patients will increase with the society aging, peri-procedure management by anesthesiologists or monitored anesthesia care will become popular in the future.

[Transient Femoral Nerve Palsy after Ilioinguinal-Iliohypogastric Nerve Block: Comparison of Ultrasound-guided and Landmark-based Techniques in Adult Inguinal Hernia Surgery].

BACKGROUND: Transient femoral nerve palsy (TFNP) is a well-known complication associated with ilioinguinal-iliohypogastric nerve block (IINB). We compared the incidence of TFNP after ultrasound-guided IINB and that after anatomical landmark-based IINB. METHODS: We reviewed medical records of adult patients (ASA-PS 1-3, Age 21-87) who had received inguinal hernia surgery under general anesthesia and LINB retrospectively. IINB was performed using 0.5% ropivacaine either by ultrasound-guidance (US group, n = 16) or by landmark-based technique (LM group, n =17). TFNP was defined as sensory loss in the anterior aspect of the thigh or weakness of quadriceps femoris muscle in the nerve-blocked side. RESULTS: The frequency of TFNP in US group (6%) was lower than that in LM group (41%) in the post-anesthesia care unit (P = 0.019). TFNP symptom was resolved completely on the morning after surgery. The incidence of severe-intermediate postoperative pain and analgesic requirement were not different between the two groups. CONCLUSIONS: This study revealed that ultrasound-guided technique is effective to lower the incidence of TFNP after IINB in adult inguinal hernia surgery.

[Safety in general anesthesia for ambulatory electroconvulsive therapy].

BACKGROUND: Ambulatory electroconvulsive therapy (ECT) is prevailing nowadays because of its lower cost and less disruption of the patient's social activity. We evaluated the safety and recovery profiles of general anesthesia for acute-phase or continuation/maintenance ambulatory ECT. METHODS: Forty outpatients with a mean age of 56 years for the management of mental disorders were reviewed. A total of 762 bilateral ECT procedures were performed under general anesthesia using propofol/ thiopental/sevoflurane and suxamethonium. RESULTS: During anesthesia, hypertension and tachycardia occurred in 281 (37%) and 214 procedures (28%), respectively. During post-anesthesia care unit stay, the medication most used was oxygen in 161 procedures (21%), and confusion and headache occurred in 54 procedures (7%) and 39 procedures (5%), respectively. No patients required unplanned hospital admission. Mean stay time in the day surgery unit was 172 min. Two ECT treatments (0.3%) in 2 patients needed unplanned return to our hospital within 24 hr after ECT due to worsening of their psychiatric conditions. CONCLUSIONS: General anesthesia for ambulatory ECT with our protocol was proven to be safe without causing serious complications.

D-allose ameliorates cisplatin-induced nephrotoxicity in mice.

Cisplatin (cis-diamminedichloroplatinum II) is a potent antineoplastic agent widely used to treat various forms of cancer. However, its therapeutic use is limited because of dose-dependent nephrotoxicity. Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. D-allose is an aldo-hexose present in nature that recently has been demonstrated to inhibit production of inflammatory mediators in septic kidneys. The purpose of this study was to determine the protective effects of D-allose on cisplatin-induced nephrotoxicity. Cisplatin (20 mg/kg) was administered by intraperitoneal injection to mice in the cisplatin group and the cisplatin plus D-allose group, as was normal saline to control group mice. D-allose was intraperitoneally administered immediately after cisplatin injection. Serum and renal tumor necrosis factor (TNF)-alpha concentrations, renal monocyte chemoattractant protein-1 (MCP-1; a chemotactic factor for monocytes), renal function, histological changes and renal cortex neutrophil infiltration were determined 72 h after cisplatin injection. The serum TNF-alpha concentration in the cisplatin plus D-allose (400 mg/kg body weight) group significantly decreased in comparison with that in the cisplatin group. The renal TNF-alpha and MCP-1 concentrations in the cisplatin plus D-allose group significantly decreased in comparison with those in the cisplatin group. Neutrophil infiltration in the cisplatin plus D-allose group was significantly lower than that in the cisplatin group. Cisplatin-induced renal dysfunction and renal tubular injury scores were attenuated by D-allose treatment. These results reveal that D-allose attenuates cisplatin-induced nephrotoxicity by suppressing renal inflammation. Hence, D-allose may become a new therapeutic candidate for treatment of cisplatin-induced nephrotoxicity.

The number of physicians is related to the number of nighttime emergency surgeries in Japan: An ecological study.

PURPOSE: Increasing the number of physicians per population may improve the quality of medical services, but there are few reports on this aspect in the field of surgery. This study aimed to examine whether the number of physicians is associated with the number of nighttime emergency surgeries, which may be one of the indicators of the quality of medical services in the field of surgery. METHODS: This was a prefecture-based ecological study utilizing open data from Japanese government surveys conducted between 2015 and 2019. The relationship between the number of physicians and the number of nighttime emergency surgeries in 47 prefectures of Japan was evaluated by correlation analysis and panel data regression analysis. The correlation analysis was conducted between the number of physicians per 100,000 population and the number of nighttime emergency surgeries per 100,000 population per year in each prefecture in Japan. In the panel data regression analysis, panel data of the prefectures in Japan from 2015 to 2019 were created. We evaluated whether the number of physicians was related to the number of nighttime emergency surgeries, independent of the number of acute care beds per 100,000 population, population density, and the elderly population ratio. RESULTS: From the correlation analysis, the correlation coefficient between the number of physicians per 100,000 population and the number of nighttime emergency surgeries per 100,000 population was 0.533 (P < 0.001). In the panel data regression analysis, there was a significant association between the number of physicians per 100,000 population and the number of nighttime emergency surgeries per 100,000 population (P < 0.001). The regression coefficient (95% confidence interval) for the number of physicians per 100,000 population was 0.246 (0.113-0.378). CONCLUSION: The number of physicians is associated with the number of nighttime emergency surgeries.

General anesthesia with remimazolam for a pediatric patient with MELAS and recurrent epilepsy: a case report.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease. We report here the safe use of remimazolam in a pediatric MELAS patient. CASE PRESENTATION: A 10-year-old girl (118 cm, 16 kg) was scheduled for an open gastrostomy to improve nutrition and epileptic seizure control. We induced and maintained general anesthesia with remimazolam, remifentanil, fentanyl, and rocuronium. We also performed a bilateral subcostal transversus abdominis plane block before the surgery. The surgery finished uneventfully. After we discontinued remimazolam administration, the patient woke up immediately but calmly without flumazenil. Epileptic seizures did not occur during intra- and early post-operative periods. CONCLUSION: Remimazolam enabled us to provide a pediatric MELAS patient with general anesthesia without causing delayed emergence or epileptic seizures.

Income Change One Year after Confirmed Cancer Diagnosis and Its Associated Factors in Japanese Patients.

The number of patients who survive for a long time after cancer diagnosis is rapidly increasing; however, such patients experience major problems such as returning to work and changes in their income. This study aimed to determine the extent of income changes of cancer patients during the first year after cancer diagnosis and identify the influencing factors. From November 2019 through January 2020, we conducted a multicenter, self-administered anonymous survey of cancer patients in Kagawa Prefecture, Japan. The number of questionnaires collected was 483 (recovery rate 60.4%), and the number of participants who met the inclusion criteria was 72. Mean year-on-year income level one year since cancer diagnosis was 66% (SD: 32%; median: 70%). Cancer stage (p = 0.016), employment status at diagnosis (p = 0.006), and continued employment at the same workplace (p = 0.001) were associated with income change. Findings from this study showed that cancer patients lost one-thirds of their income one year after their diagnosis. It was related to the stage of their illness, employment status, and continued employment at their workplace just before the diagnosis. Employers should provide cancer patients with the support they need to keep them employed.

Difference in abundance of blood and lymphatic capillaries in the murine epididymis.

It is well known that the epididymis is responsible for the transportation, storage, and maturation of spermatozoa, and that it has four segments: i.e., initial segment, caput, corpus, and cauda. Previous studies revealed the presence of a very dense network of blood capillaries only in the initial segment; however, the relative distribution of blood and lymphatic capillaries has remained unknown. In the present study, we investigated the distribution of intraepididymal blood and lymphatic capillaries in mice by use of monoclonal antibodies against CD31 and lymph vessel endothelium HA-receptor 1, respectively. The results showed that lymphatic networks were quite scarce in the initial segment and strikingly abundant in the cauda compared with the other two regions. In sharp contrast, blood capillaries were abundant in both the initial segment and cauda but sparse in the other two regions. This observation suggests that the characteristic distribution of blood and lymphatic capillaries in the epididymis contributes to the different roles of each epididymal region.

Effect of single-dose dexmedetomidine on emergence agitation and recovery profiles after sevoflurane anesthesia in pediatric ambulatory surgery.

PURPOSE: To study the effects of dexmedetomidine (DEX), a selective α(2)-adrenoreceptor agonist, on emergence agitation (EA), recovery profiles, and parents' satisfaction after sevoflurane anesthesia in pediatric ambulatory surgery. METHODS: In a double-blind trial, 81 children (ASA PS 1 or 2, 1-9 years) undergoing same-day or overnight-stay surgery were randomly assigned to receive intravenous DEX 0.3 µg kg⁻¹ (n = 39) or saline (n = 42) over 10 min after induction of anesthesia. Anesthesia was induced and maintained with sevoflurane using a facemask or laryngeal mask airway with spontaneous respiration. Agitation was assessed with a 1-4 point scale and pain with a 0-10 point scale. The patients' parents were interviewed 24 h after surgery, and adverse events and the parents' level of satisfaction with perioperative care were recorded. RESULTS: The incidence of EA (agitation scale score 3 or 4) was significantly lower in the DEX group (28%) than in the saline group (64%) (P = 0.0011). The mean pain scales in the DEX group were significantly lower than in the saline group during the stay in the post-anesthesia care unit (PACU) (P < 0.01). The incidence of adverse events, times to the first drinking and voiding in the PACU, time spent in the PACU, and parents' satisfaction level were not different between the two groups. CONCLUSION: Intravenous DEX at a dose of 0.3 µg kg⁻¹ after induction of anesthesia reduced sevoflurane-associated EA and postoperative pain in pediatric ambulatory surgery, with no increase in the incidence of adverse events and with no change in parents' satisfaction level.

[Remifentanil is useful for cardiovascular stability during cesarean delivery in a parturient with Marfan's syndrome].

A 25-year-old parturient with Marfan's syndrome was scheduled for cesarean delivery. She suffered with severe scoliosis and asymptomatic aortic root dilatation. To establish a cardiovascular stability and prevent aortic dissection perioperatively, we selected the use of remifentanil, an ultra-short acting opioid analgesic with general anesthesia. General anesthesia was induced with remifentanil (0.2 microg x kg(-1) x min(-1)), propofol (100 mg), and vecuronium bromide (10 mg). Anesthesia was maintained with 100% O2, sevoflurane (1-1.5%), and remifentanil (0.2-0.25 microg x kg(-1) x min(-1)). She remained hemodynamically stable during surgery. A lively infant was delivered and Apgar scores were 8 and 9 at 1 and 5 min, respectively. Their post-delivery courses were uneventful. Remifentanil was useful for anesthetic management in a pregnant patient with Marfan's syndrome undergoing cesarean delivery, although attention to infant's respiratory condition should be paid because remifentanil can cross the placenta.

Physiological Modeling of Concentration-Effect Relationship for Nondepolarizing Neuromuscular Blocking Drugs.

This paper reports modeling of physiological processes of neuromuscular transmission considering effects of nondepolarizing neuromuscualr blocking drugs (NDNBs) used during general anesthesia. NDNBs are considered to act by interacting with acetylcohine receptors located at pre- and post-junctional sites. This paper proposes an extension of the standard model of synaptic depression used in the field of neuroscience to describe the pre-junctional effect of NDNBs. The extended model is then combined with a previously proposed model of the post-junctional effect to simulate the whole process of neuromuscular transmission. The derived model can be used to predict pharmacologic relationship between the drug concentration and its actual effect of NDNBs. Specifically, the model firstly enables the estimation of Post-tetanic Count (PTC), a clinically used monitoring measure for deep neuromuscular blockade (NMB). The effectiveness of the derived model is discussed by comparing simulation results with clinical data obtained from a patient undergoing a surgical operation.

A model-predictive hypnosis control system under total intravenous anesthesia.

In ambulatory surgery, anesthetic drugs must be administered at a suitable rate to prevent adverse reactions after discharge from the hospital. To realize more appropriate anesthesia, we have developed a hypnosis control system, which administers propofol as an anesthetic drug to regulate the bispectral index (BIS), an electroencephalography (EEG)-derived index reflecting the hypnosis of a patient. This system consists of three functions: 1) a feedback controller using a model-predictive control method, which can adequately accommodate the effects of time delays; 2) a parameter estimation function of individual differences; and 3) a risk control function for preventing undesirable states such as drug overinfusion or intraoperative arousal. With the approval of the ethics committee of our institute, 79 clinical trials took place since July 2002. The results show that our system can reduce the total amount of propofol infusion and maintain the BIS more accurately than anesthesiologist's manual adjustment.

[Ambulatory anesthesia for an adult patient with autism and epilepsy: sedation using oral and intravenous dexmedetomidine].

A 22-year-old male patient with autism and epilepsy was scheduled to undergo impacted third molar extractions at an outpatient setting. Oral preanesthetic medication with dexmedetomidine and subsequent midazolam with ketamine was acceptable and effective to place intravenous cannula. General anesthesia was maintained with intravenous propofol and dexmedetomidine and operation was performed uneventfully. Sedation with intravenous dexmedetomidine was continued after operation to attenuate and/or manage postoperative problems, such as emergence agitation, dysphoric reactions, pain, opioid-related nausea/vomiting and seizure. He recovered from postoperative sedation and was discharged home without significant problems. Oral and intravenous dexmedetomidine was useful for anesthetic care in the uncooperative patient.