Relationship between Tryptase and Hypotension in Anaphylaxis during Anesthesia.

INTRODUCTION: Hypotension is a cardiovascular symptom that appears at the onset of anaphylaxis. It is considered an important factor as it affects the severity of anaphylaxis; however, its details remain to be elucidated. In this study, we investigated the characteristics of hypotension at the onset of anaphylaxis during anesthesia, along with the relationship between hypotension, tryptase and histamine. MATERIALS AND METHODS: The minimum systolic blood pressures of patients diagnosed with anaphylaxis using the clinical diagnostic criteria of the World Allergy Organization guidelines were extracted from electronic anesthesia records. We analyzed changes in tryptase and histamine that were measured after the onset of anaphylaxis. We analyzed the relationship of tryptase and histamine with the minimum systolic blood pressure and the severity of anaphylaxis. RESULTS: Of 55,996 patients, 25 were diagnosed with anaphylaxis during anesthesia (0.045%). Among these patients, the minimum systolic blood pressure was less than 90 mmHg. Furthermore, the minimum systolic blood pressure was inversely correlated with tryptase levels immediately to 1 hour, and 2 to 4 hours after the onset of anaphylaxis. The minimum systolic blood pressure was inversely correlated with the severity of anaphylaxis. The severity of anaphylaxis was positively correlated with tryptase levels immediately to 1 hour, and 2 to 4 hours after the onset of anaphylaxis. CONCLUSION: Hypotension tended to reflect the severity of anaphylaxis. Tryptase is an adjunct in the diagnosis of hypotension and may be a useful indicator of the severity of anaphylaxis. A larger-scale study is needed to validate these results.

Predictive underestimation of difficult direct laryngoscopy in a patient with rheumatoid arthritis-associated immobilized craniocervical junction.

BACKGROUND: The upper cervical spine is a major focus of damage by rheumatoid arthritis (RA). Specific screening for mobility of the upper cervical spine, which is essential for direct laryngoscopy, is lacking. Herein, we present a case of RA with Cormack-Lehane grade IV, which was not predicted by preoperative examination. CASE PRESENTATION: A 66-year-old woman with RA was scheduled for a right total knee arthroplasty and right elbow synovectomy. She had a long history of RA without symptoms related to the cervical spine or spinal cord. Although physical examination suggested moderate risk of difficult intubation with preserved cervical retroflexion, her Cormack-Lehane classification was grade IV under muscle relaxation. Bony integration of the occiput to axis was considered to be the main cause of difficult direct laryngoscopy, and restricted neck rotation was found postoperatively. CONCLUSIONS: RA patients may have limited upper cervical spine motion despite normal cervical retroflexion.

Peripheral nerve-derived fibroblasts promote neurite outgrowth in adult dorsal root ganglion neurons more effectively than skin-derived fibroblasts.

NEW FINDINGS: What is the central question of this study? Although fibroblasts are involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. What is the main finding and its importance? Nerve-derived fibroblasts have a greater neurite-promoting effect than skin-derived fibroblasts, and epineurium-derived fibroblasts can promote neurite outgrowth more effectively than parenchyma-derived fibroblasts. The epineurium-derived fibroblasts and parenchyma-derived fibroblasts have distinctly different molecular profiles, including genes of soluble factors to promote axonal growth. Fibroblasts are molecularly and functionally different depending on their localization in nerve tissue, and epineurium-derived fibroblasts might be involved in axon regeneration after peripheral nerve injury more than previously thought. ABSTRACT: Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin-derived Fb. Although both soluble and cell-surface factors contributed evenly to the neurite-promoting effect of nerve-derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.

IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.

Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.

Efficacy and limitations of additional steroid pulse therapy in IgA nephropathy patients whose hematuria did not remit on tonsillectomy and protocol steroid pulse therapy.

BACKGROUND: Hematuria is the essential symptom of IgA nephropathy that has been suggested to be associated with long-term renal prognosis, Tonsillectomy and steroid pulse therapy (TSP), which is widely practiced in Japan, is effective for achieving hematuria remission. However, some cases are refractory to TSP, and additional steroid pulse therapy (SP) administered to these cases to achieve remission of hematuria. Nonetheless, the clinical significance of additional SP is unknown. METHODS: In this retrospective study, we enrolled 99 patients from Okubo Hospital whose hematuria persisted following TSP. Patients were divided into the hematuria remission and non-remission groups. A multivariate regression analysis was performed on the factors that contributed to hematuria remission. RESULTS: Following TSP, 103 of 403 patients (32.3%) did not achieve hematuria remission. Additional SP were performed in 99 of these patients, and remission of hematuria was achieved in 57 (57.6%). Patients with a greater degree of improvement in hematuria with TSP were significantly more likely to have remission of hematuria with additional SP (p = 0.0084*). Even in the hematuria non-remission group, both hematuria and proteinuria improved after additional SP. CONCLUSION: In IgA nephropathy, additional SP could induce hematuria remission and reduce proteinuria.

Feasibility of underwater microvascular decompression for hemifacial spasm: a technical note.

BACKGROUND: We present a case series of underwater microvascular decompression (MVD) for hemifacial spasm (HFS) and an evaluation of its feasibility and safety. METHODS: This retrospective study was conducted at a single institution and included 20 patients with HFS who underwent underwater MVD between September 2019 and January 2021. Surgery was performed in 3 steps, as follows: exoscopic wound opening (soft tissue, bone, dura, and arachnoid around the cerebellomedullary cistern), underwater endoscopic surgery (decompression of the facial nerve), and exoscopic wound closure. In underwater endoscopic surgery, the surgical field was continuously irrigated with artificial cerebrospinal fluid. Abnormal muscle response and brainstem auditory evoked potentials (BAEPs) were monitored. RESULTS: Neurovascular conflicts were clearly observed in all patients without fogging and soiling of the endoscope lens. HFS was completely relieved in 19 patients (95%). An amplitude reduction of wave V of BAEPs of more than 50% was not observed in any of the cases. In 5 cases (25%), the latency of wave V of BAEPs was prolonged for more than 1.0 ms; these changes completely or near completely returned to baseline values at dural closure in all 5 cases. A postoperative complication of transient facial palsy was observed in 1 patient (5%) during postoperative days 10-30. There were no other complications. CONCLUSIONS: Our findings suggest that underwater MVD is a safe and feasible option for the treatment of HFS. However, it did not show advantages over conventional endoscopic MVD when the protective effect on the eighth cranial nerve was evaluated.

Massive obstetric hemorrhage during cesarean section in a patient after conception by frozen-thawed embryo transfer: a case report.

BACKGROUND: Placenta accreta is a major cause of massive obstetric hemorrhage during cesarean section. In recent years, pregnancy by in vitro fertilization-embryo transfer has been reported as a risk factor for placenta accreta. CASE PRESENTATION: A 36-year-old G1P0 woman with systemic lupus erythematosus became pregnant by frozen-thawed embryo transfer. Emergency cesarean section was performed under general anesthesia due to the diagnosis of non-reassuring fetal status. The placenta invaded the myometrium and completely covered the entire anterior uterine wall. Following birth, 3000 mL of blood loss required rapid fluid infusion and blood transfusion. Total hysterectomy was performed because the placenta could not be separated from the uterine wall. Histological examination revealed placenta accreta/increta. CONCLUSIONS: When performing cesarean section on patients who have undergone frozen-thawed embryo transfer, preoperative examinations to assess for placenta accreta should be performed, and the anesthetic management should include sufficient planning for massive obstetric hemorrhage.

α2-Adrenergic Receptor and Isoflurane Modulation of Presynaptic Ca2+ Influx and Exocytosis in Hippocampal Neurons.

BACKGROUND: Evidence indicates that the anesthetic-sparing effects of α2-adrenergic receptor (AR) agonists involve α2A-AR heteroreceptors on nonadrenergic neurons. Since volatile anesthetics inhibit neurotransmitter release by reducing synaptic vesicle (SV) exocytosis, the authors hypothesized that α2-AR agonists inhibit nonadrenergic SV exocytosis and thereby potentiate presynaptic inhibition of exocytosis by isoflurane. METHODS: Quantitative imaging of fluorescent biosensors of action potential-evoked SV exocytosis (synaptophysin-pHluorin) and Ca influx (GCaMP6) were used to characterize presynaptic actions of the clinically used α2-AR agonists dexmedetomidine and clonidine, and their interaction with isoflurane, in cultured rat hippocampal neurons. RESULTS: Dexmedetomidine (0.1 µM, n = 10) or clonidine (0.5 µM, n = 8) inhibited action potential-evoked exocytosis (54 ± 5% and 59 ± 8% of control, respectively; P < 0.001). Effects on exocytosis were blocked by the subtype-nonselective α2-AR antagonist atipamezole or the α2A-AR-selective antagonist BRL 44408 but not by the α2C-AR-selective antagonist JP 1302. Dexmedetomidine inhibited exocytosis and presynaptic Ca influx without affecting Ca coupling to exocytosis, consistent with an effect upstream of Ca-exocytosis coupling. Exocytosis coupled to both N-type and P/Q-type Ca channels was inhibited by dexmedetomidine or clonidine. Dexmedetomidine potentiated inhibition of exocytosis by 0.7 mM isoflurane (to 42 ± 5%, compared to 63 ± 8% for isoflurane alone; P < 0.05). CONCLUSIONS: Hippocampal SV exocytosis is inhibited by α2A-AR activation in proportion to reduced Ca entry. These effects are additive with those of isoflurane, consistent with a role for α2A-AR presynaptic heteroreceptor inhibition of nonadrenergic synaptic transmission in the anesthetic-sparing effects of α2A-AR agonists.

Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling.

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) influx without significantly altering the Ca(2+) sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca(2+)]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca(2+) ([Ca(2+)]e). Lowering external Ca(2+) to match the isoflurane-induced reduction in Ca(2+) entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca(2+) entry without significant direct effects on Ca(2+)-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca(2+) influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system.

Prognostic factors associated with mortality in patients undergoing emergency surgery for abdominal aortic aneurysms.

PURPOSE: Surgical mortality rates following emergency surgery for ruptured abdominal aortic aneurysms (AAAs) remain high. This study investigated the mortality rate and identified prognostic factors affecting mortality in patients undergoing emergency repair of AAAs in our hospital. METHODS: Between January 2005 and June 2010, a total of 42 patients underwent emergency surgery for AAAs and were included in this retrospective study. The following variables concerning each patient were collected by chart review and compared between survivors and nonsurvivors: age; gender; preoperative levels of hemoglobin (Hb), hematocrit (Ht), platelets (Plts), base excess (BE), and serum glucose and lactate; presence of preoperative shock defined as hypotension (systolic blood pressure of less than 80 mmHg); incidence of blood transfusion, whether AAA was ruptured or impending; interval from admission to the hospital or arrival in the operating room until aortic cross-clamping; surgical duration; and volume of intraoperative blood loss and transfusion, total fluid infusion, and urine output. RESULTS: Nine patients died within 30 days postoperatively, a 30-day mortality rate of 21.4%. Among these nine nonsurvivors, eight had shown persistent preoperative shock (P = 0.0004 vs. survivors). Compared with the survivors, nonsurvivors were significantly older (P = 0.0052) and had lower preoperative levels of Hb/Ht (P < 0.0001), Plts (P = 0.0003), and BE (P < 0.0001), an elevated lactate level (P = 0.0048), shorter interval from admission (P = 0.0459) or arrival in the operating room (P = 0.0288) until aortic clamping, and intraoperatively more hemorrhage (P = 0.0038) associated with larger amounts of blood transfusion (P = 0.0083) and less urine output (P = 0.0004). CONCLUSIONS: The authors clarified that certain features such as age, persistent preoperative shock, and greater amounts of transfusion associated with greater blood loss and anemia were factors affecting the mortality in patients undergoing emergency surgery for AAAs. It might be of great importance to correct preoperative shock and anemia caused by massive bleeding before the onset of hemodynamic deterioration.

[Factors that affect the mortality in patients receiving emergency surgery for ruptured abdominal aortic aneurysms].

This retrospective study was performed to identify the perioperative factors affecting the mortality rate in 28 patients, who had received emergency surgery for ruptured abdominal aortic aneurysms from January, 2005 to June, 2008. Five (17.9%) of these 28 patients died of massive bleeding, sepsis, or multiple organ failure during or within 11 days after surgery. Various factors which might influence the outcomes were compared between the survivors and non-survivors. Preoperative hypotension defined as a systolic blood pressure < or = 80 mmHg associated with hemorrhagic shock was the only significant factor affecting the mortality. There were no significant differences in age, gender, the time from the admittance to the hospital to aortic cross clamping, duration of surgery, and the amount of blood products transfused and intraoperative blood loss, between the two groups. Of great importance is that preoperative hypotension should be corrected before the onset of hemodynamic deterioration.

Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons.

Studies in animal models of Parkinson's disease have revealed that degeneration of noradrenaline neurons is involved in the motor deficits. Several types of adrenoceptors are highly expressed in neostriatal neurons. However, the selective actions of these receptors on striatal signaling pathways have not been characterized. In this study, we investigated the role of adrenoceptors in the regulation of dopamine/dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) signaling by analyzing DARPP-32 phosphorylation at Thr34 [protein kinase A (PKA)-site] in mouse neostriatal slices. Activation of beta(1)-adrenoceptors induced a rapid and transient increase in DARPP-32 phosphorylation. Activation of alpha(2)-adrenoceptors also induced a rapid and transient increase in DARPP-32 phosphorylation, which subsequently decreased below basal levels. In addition, activation of alpha(2)-adrenoceptors attenuated, and blockade of alpha(2)-adrenoceptors enhanced dopamine D(1) and adenosine A(2A) receptor/DARPP-32 signaling. Chemical lesioning of noradrenergic neurons mimicked the effects of alpha(2)-adrenoceptor blockade. Under conditions of alpha(2)-adrenoceptor blockade, the dopamine D(2) receptor-induced decrease in DARPP-32 phosphorylation was attenuated. Our data demonstrate that beta(1)- and alpha(2)-adrenoceptors regulate DARPP-32 phosphorylation in neostriatal neurons. G(i) activation by alpha(2)-adrenoceptors antagonizes G(s)/PKA signaling mediated by D(1) and A(2A) receptors in striatonigral and striatopallidal neurons, respectively, and thereby enhances D(2) receptor/G(i) signaling in striatopallidal neurons. alpha(2)-Adrenoceptors may therefore be a therapeutic target for the treatment of Parkinson's disease.

[Comparison of urinary output during general anesthesia, between patients administered with remifentanil and those without remifentanil administration].

BACKGROUND: Transient renal failure during surgery is caused by increasing secretion of stress hormone such as ADH and renin. We suspected that urinary output varies according to administration of remifentanil with potent analgesic effects. Consequently, we studied intraoperative urinary output of two groups, patients administered with remifentanil and those without remifentanil administration. METHODS: We compared urinary output during general anesthesia, of 327 patients administered with remifentanil (Group R) and 314 patients without remifentanil administration (Group NR) retrospectively. Patients were excluded if they were under the age of eighteen, receiving epidural anesthesia, or having medicine with diuretic effect. RESULTS: There were no significant difference in background of the patients in each group, in particular, age, sex, body weight, and ASA grade. We found no significant difference in intraoperative factors; operation time, total blood loss, volume of infusion, anesthesia time, and given dose of fentanyl. Urinary output of Group R was estimated as 512 +/- 435 ml, and that of Group NR was 409 +/- 405 ml (P value was 0.02). CONCLUSIONS: We found a significance difference in urinary output during anesthesia, between patients administered with remifentanil and those without remifentanil administration. We suspect that remifentanil decreases urinary output in the perioperative period.

Cerebrospinal fluid following cerebral ischemia accelerates the proliferation of bone marrow stromal cells in vitro.

The central nervous system in the embryo develops around the cerebrospinal fluid (CSF), which regulates cell proliferation and differentiation. Neurogenesis has been also reported in the subventricular zone (SVZ), which is close to CSF, after stroke in rats. In this study, CSF extracted following stroke in rats was added to bone marrow stromal cell (MSC) culture in vitro, and the proliferation and differentiation of MSCs were studied. Primary cultures of MSCs were obtained from 7-week-old Lewis rats and incubated in a plastic tissue culture flask. CSF was retrieved from other rats 48 hrs after 0, 15 and 75 min after middle cerebral artery occlusion (MCAO). CSF from these three groups were added to respective MSC culture solutions, and the cells were then incubated for 72 hrs. Western blots of the extracellular signal-regulated kinase-1 and -2 (Erk1/2) were obtained just after the CSF induction. The expressions of CD34, CD45, CD90 and CD108 were assessed by flow cytometric analysis. The proliferation of MSCs was accelerated by the addition of post-stroke CSF, especially in the 15-min MCAO, in a dose-dependent manner. The morphology and surface antigens of the cells were maintained in all groups. Phosphorylated-Erk1/2 was elevated in all the CSF-treated groups, although this effect was more enhanced in the 15-min MCAO group. Our data indicate that the addition of post-stroke CSF to the primary medium stimulated the proliferation of MSCs, and that these MSCs maintained their characteristics through the p-Erk1/2 pathway. These results suggest that use of post-stroke CSF as a component of culture media could facilitate the autologous transplantation of MSCs.

[Anesthetic management of a child with an esophageal foreign body which was misdiagnosed as asthma attack].

We have experienced anesthesia of a child with airway stenosis caused by esophageal foreign body (coin-type lithium battery), which was misdiagnosed as asthma. The case is an 18-month-old boy who had asthma-like symptoms since 2 months before, and visited our hospital because these symptom had started to worsen 3 days before visit. His stridor was significant and we noted a coin-shaped foreign body on chest X-ray taken for admission. Therefore we removed the foreign body using upper gastrointestinal endoscope under general anesthesia. The airway management was very difficult because airway stenosis had been aggravated for delayed diagnosis, diagnosing.

[A case report of anesthesia for a child with Pompe's disease (glycogen storage disease type II)].

A case report of a child with Pompe's disease (glycogen storage disease type II), who underwent two general anesthetics, is presented. The progressive infiltration of heart and skeletal muscle with glycogen results in a severe form of cardiomyopathy and respiratory muscle weakness. Death usually occurs by 1 year of age from respiratory insufficiency or end-stage cardiomyopathy. Consequently, there are significant problems in the anesthetic management of these patients. The patient, a female child of 6 months presented signs of cardiac failure and took treatment with olprinone and diuretic. The initial surgical procedure was placement of a subcutaneous central venous catheter. Anesthesia was induced with ketamine and midazolam intravenously, and was maintained with nitrous oxide (50%) and intravenous ketamine. The dosage of the dopamine and olprinone was necessary to maintain circulation. For tracheotomy, the second procedure, anesthesia was induced and maintained with sevoflurane and dopamine. Recently a promising enzyme replacement therapy has resulted in improved clinical outcomes, and the number of anesthesia for infants of with Pompe's disease will increase in future.

[Anesthetic management of the ex-utero intrapartum treatment (EXIT) procedure for giant epignathus and of the tumor excision].

We report an anesthetic management of the ex-utero intrapartum treatment (EXIT) procedure performed in a fetus with giant epignathus due to laryngeal atresia at 28 weeks' gestation. Anesthesia of the mother was induced with thiamylal and vecuronium, and maintained with 4% sevoflurane in 100% oxygen before delivery. Sevoflurane provided excellent uterine relaxation. To maintain the arterial pressure, the patient received acetate Ringer and ephedrine 4mg. After hysterotomy, a pulse oxymeter and an ultrasound transducer were applied to monitor fetal Sp(O2) and heart rate. No anesthetic agents were injected into the fetus in addition to transplacental sevoflurane. Tracheostomy was performed on the fetus by pediatric surgeons on placental support. The uterine tone improved soon after discontinuing sevoflurane, intramyometrial injection of oxytocin and ergometrine infusion after delivery. Excision of the tumor was performed on day 2 of life. Pediatric surgeons tried to excise it totally, but it was hard to differentiate the tumor from the normal tissue, and partial excision was performed. After the excision, the neonate weighed 944 g and excised specimen weighed 253 g. Though the neonate was immature and the tumor was very large, no perioperative complications were associated with EXIT and the tumor excision.