Exercise-induced anaphylaxis unrelated to food ingestion and with hyperleukotrieneuria during challenge testing

Background Exercise-induced anaphylaxis (EIA) is a rare and potentially life-threatening disorder that can develop independently without food ingestion. Cold drinks can also trigger symptoms in some patients with cold-induced anaphylaxis. We present a case of a patient with EIA that was diagnosed on the basis of positive exercise loading test with hyperleukotrieneuria. Case presentation A 12-year-old girl presented with acute flushing, cyanosis, swollen eyelids, and dyspnea after an endurance run in winter or swimming in a cold-water pool. She also developed dyspnea after having a cold drink. She had no history of food allergies, atopy, or asthma. No association was noted between anaphylaxis and food intake in her history. On the first day, she ingested 200 mL of 5 °C cold water in 30 s, which did not trigger symptomatic responses, but her urinary leukotriene E4 (LTE4) level increased (pre-challenge test: 295 pg/mg-creatinine (cr), post-challenge test: 400 pg/mg-cr). On the second day, she underwent the exercise loading test according to the Bruce protocol by using an ergometer to increase the power of exercise every 2 min. She had been fasting for > 15 h and did not have breakfast. Just after the exercise loading test, the plasma adrenaline and noradrenaline increased. At 15 min after the exercise loading test, her plasma adrenaline and histamine (pre-challenge test: 0.7 ng/mL, 15 min post-challenge test: 81 ng/mL) rose sharply with anaphylaxis symptoms accompanied by increasing urinary LTE4 (pre-challenge test: 579 pg/mg-cr, post-challenge test: 846 pg/mg-cr). After she was discharged, she was restricted from strenuous exercise especially in cold environments and prescribed an adrenaline autoinjector. Conclusion Cold stimulation can become a co-effector of EIA. Measurements of urinary LTE4 levels during challenge testing are useful for diagnosing EIA and capture the pre-anaphylaxis stage.

Study on Haemodynamic Response to Laryngoscopy and Intubation using McCOY and Macintosh Laryngoscopes: A Comparative Approach

Introduction: Laryngoscopy and endotracheal intubation are known to cause increase in arterial blood pressure, heart rate and may be associated with various dysarythmias. This study is done to compare the hemodynamic changes with McCOY laryngoscope and Macintosh laryngoscope in 120 patients who were divided into 2 groups. Methods: A positive correlation has been demonstrated between force exerted at laryngoscopy and patient's height, weight, body mass index (BMI) and presence of maxillary incisors but it was seen that effect of these factors on force exerted with the McCOY blade is not as important as with Macintosh blade. So this study was done to compare the hemodynamic response to laryngoscopy and intubation using McCOY and Macintosh laryngoscope in stress attenuation. Results: Maximum increase in heart rate from the baseline after laryngoscopy in group 2 and a least rise in heart rate from base line in group 1.Group 1 has 9 % increase in heart rate from basal value. Group 2 has 22 % increases in heart rate from basal value. Group 1 has 6 % increase in Systolic BP from basal value Group 2 has 27 % increase in Systolic BP from basal value. Rise in Plasma adrenaline after laryngoscopy was not observed in Laryngoscopy with McCOY blade. Conclusion: McCOY laryngoscope produces significantly less in Hemodynamic parameters when compared with Macintosh blade.So this non­pharmacological intervention of McCOY blade can be utilized as a tool for obtunding hemodynamic responses to laryngoscopy and intubation

Mixed Corticomedullary Tumors of the Adrenal Gland Harboring Both Medullary and Cortical Properties

Adrenal cortex and medulla are derived from mesoderm and ectoderm, respectively. Mixed corticomedullary tumors (MCMTs), comprising an intimately admixed population of both adrenal cortical cells and pheochromocytes in a single adrenal tumor, are extremely rare and its pathogenesis has remained unknown. Here, we report a case of MCMT whose cells co-expressed cortical and medullary antigens in the same tumor cells.[Case description]A 40-year-old woman was referred to our hospital for investigating Takotsubo cardiomyopathy following resection of uterine fibroids. An abdominal CT scan depicted a 24 mm tumor on her left adrenal gland. Her basal serum ACTH, cortisol levels and urinary cortisol were 13.8 pg/mL, 9.5 μg/dL, and 26.5 μg/day respectively. The cortisol level was normally suppressed by an administration of 1 mg dexamethasone (1.4 μg/dL). Plasma renin activity, aldosterone levels and urinary aldosterone were 15.0 ng/mL/h, 122 pg/mL, and 5.0 μg/day, respectively (with administration history of azosemide). On the other hand, her plasma adrenaline and noradrenaline levels were elevated as high as 177 pg/mL and 536 pg/mL, and urinary metanephrine and normetanephrine were 2.12 mg/day and 1.10 mg/day. A 123I-metaiodobenzylguanidine scan revealed high uptake in the tumor. After adequate adrenergic α-receptor blockage, left adrenalectomy was performed. Her postoperative endocrine and clinical findings were normalized without any further complications.[Pathology] Immunohistochemistry (IHC) revealed the presence of MCMT. Cells morphologically consistent with pheochromocytoma and adrenocortical cells were confirmed by immunostaining of chromogranin A and SF-1, respectively. Chromogranin A-positive medullary-derived and SF-1-positive cortical-derived tumor cells were intermixed in the chimeric fashion. In addition, some tumor cells were positive for both proteins, indicating hybrid nature of the cells. Tumor cells of cortical origin expressed CYP11β1, 3β-HSD, p450c21, and p450c17, but not CYP11β2. Non neoplastic adrenal cortex were atrophic, whereas the glomerulosa was hyperplastic positive for CYP11β2, consistent with diffuse hyperplasia and adrenal medullar unremarkable. [Conclusions:]The adrenal tumor was clinically diagnosed as pheochromocytoma, but the pathological findings did reveal cortisol production in the tumor and aldosterone overproduction in the accompanying cortex. This is the first case of MCMT co-expressing adrenal medullary and cortical antigens in the same tumor cells as hybrid cells.

The Effects of Acute Glucoprivation on Adrenomedullary Function in SHR and WKY Rats

We have shown previously, acute intraperitoneal administration of 2-deoxy-d-glucose (2DG) into Sprague-Dawley rats led to activation of the adrenal medulla chromaffin cells, indicated with increased protein kinase activity and increased tyrosine hydroxylase (TH) phosphorylation, as well as increased plasma adrenaline and glucose levels. Here we have used spontaneous hypertensive (SHR) and Wistar Kyoto (WKY) rats to investigate whether hypertension alters basal adrenal chromaffin cell function, or the response of these cells to acute 2DG treatment. At basal level, we found no differences in adrenal medulla TH protein, TH phosphorylation, TH activity or catecholamine levels between SHR and WKY despite a significant difference in the level of systolic blood pressure; nor were there differences in plasma catecholamine levels or blood glucose (BG). Furthermore, the vehicle animals evoked no significant changes in any parameter measured in SHR, but evoked significant increases in pSer19TH, plasma adrenaline and BG in WKY. Single episode of glucoprivation evoked increases in PKA and CDK/MAPK, pSer40TH, pSer31TH, TH activity, and plasma adrenaline and BG in SHR, and in addition evoked increases in PKC, CAMKII, and pSer19TH in WKY. These findings are significant which indicates hypertension does not impact catecholamine function in the adrenal gland. It also appears that hypertension does not alter the adrenal response to glucoprivation. The findings are also significant as WKY showed greater adrenal activation of protein kinases and TH phosphorylation in response to saline and 2DG when compared to SHR and possible reasons for these findings are further discussed.

Anaphylaxis Induced by Exercise or Cold Stimulation with Hyperleukotrieneuria During a Challenge Testing Not Containing Food Ingestion

Background: Exercise-induced anaphylaxis (EIA) is rare and a potentially life-threatening disorder that can develop independently without food ingestion. Cold drinks can also trigger symptoms in some patients with cold-induced anaphylaxis. We present the case of a patient with exercise and cold-induced anaphylaxis that was diagnosed based on hyperleukotrieneuria in exercise loading and cold-drink challenge testing.Case presentation: A 12-year-old girl presented with acute flushing, cyanosis, swollen eyelids, and dyspnea after an endurance run in winter or swimming in a cold-water pool. She also developed dyspnea after having a cold drink. She had no history of food allergies or atopy. No association was noted between anaphylaxis and food intake in her history. On the 1st day, she ingested 200 mL cold water at a temperature of 5°C in 30 s, which did not trigger any symptomatic responses, but urinary LTE4 level increased (pre-challenge test 295 pg/mg.cr, post-challenge test 400 pg/mg.cr). On the 2nd day, she underwent the exercise loading test according to the Bruce protocol by increasing the power of exercise every 2 min using an ergometer. She had been fasting for >15 h and did not have breakfast. Just after the exercise loading test, the plasma adrenaline and noradrenaline increased. At 15min. after the exercise loading test, the plasma adrenaline and histamine (pre-challenge test 0.7 ng/mL, 15min.post-challenge test 81 ng/mL) rised sharply with anaphylaxis symptom accompaneid by increasing of urinary LTE4 (pre-challenge test 579 pg/mg.cr, post-challenge test 846 pg/mg.cr). After she was discharged, she was restricted from strenuous exercise especially in cold environments and prescribed an adrenaline autoinjector.Conclusion: To our knowledge, cold stimulation becomes a co-effector for EIA. Measurements of urinary LTE4 levels during challenge testing are useful to diagnose anaphylaxis induced by exercise or cold stimulation.

The combination of cold exposure training and a breathing exercise attenuates the inflammatory response in humans

Background - We previously showed that a training intervention encompassing two breathing exercises and exposure to cold enables for voluntary activation of the sympathetic nervous system, reflected by profoundly increased plasma adrenaline levels, and subsequent attenuation of the endotoxin-induced inflammatory response. Herein, we determined the contribution of the different elements of the training, assessed if the training duration is of importance, and whether it can be provided by an independent trainer instead of the well-known individual who devised it. Methods – Forty healthy male volunteers were randomized to either a short or extensive training in both breathing exercises (i.e. cyclic hyperventilation with or without prolonged breath retention) by either the creator of the intervention or an independent trainer. In a subsequent study, 48 healthy male volunteers were randomized to cold exposure training, training in the established optimal breathing exercise, a combination of both, or no training. All 48 subjects were subsequently intravenously challenged with 2 ng/kg lipopolysaccharide to induce endotoxaemia. Results - Both breathing exercises were equally effective in enhancing plasma adrenaline concentrations and this response was also independent from the length of the training or the individual who provided it. Cold exposure training alone did not result in relevant modulation of the endotoxin-induced cytokine response, although flu-like symptoms were markedly reduced compared with the untrained group. Whereas subjects who received training in the breathing exercise alone displayed attenuated plasma levels of pro-inflammatory cytokines IL-6, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β (-34%, -14%, -48%, -37%, and -28%, respectively) during endotoxemia, combined training resulted in enhanced concentrations of anti-inflammatory IL-10 (+44%) and reduced concentrations of TNF-α, IL-6, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β (-32%, -35%, -30%, -48%, -29%, -35%, -30%, respectively) compared with untrained individuals. Conclusions - The combination of cold exposure training and a hyperventilation breathing exercise attenuates the in vivo inflammatory response most potently. Our study demonstrates that the immunomodulatory effects of the intervention can be reproduced in a standardized manner, thereby paving the way for clinical trials. Trial registration - Both studies described in this manuscript are registered at www.clinicaltrials.gov (breathing exercises study: NCT02417155; experimental human endotoxaemia study: NCT03240497).

Discovering Pain in Newborn Infants

Randomised Trial of Fentanyl Anesthesia in Preterm Babies Undergoing Surgery: Effects on the Stress Response. By Anand KJ, Sippell WG, and Aynsley-Green A. Lancet 1987; 1:243–8. Reprinted with permission. In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 μg/kg intravenously) to the anesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the nonfentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the nonfentanyl group on the second and third postoperative days. Compared with the fentanyl group, the nonfentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anesthesia may be associated with an improved postoperative outcome.

Abstract P169: Dipeptidyl Peptidase-4 Regulates Hematopoietic Stem Cell Activation in Response to Chronic Stress

Background: Dipeptidyl peptidase-4 (DPP4) inhibition exhibits multiple pleotrophic effects. Hematopoietic stem cell (HSC) activation has been implicated in the pathogenesis of stress-related metabolic disorder and cardiovascular disease. Given that interaction between β3-adrenergic receptor (Adrβ3) signaling and the immune system may link stress and the initiation and progression of disorders, we investigated whether DPP4 regulates immune over-reactions in a chronic stress mouse model, focusing on HSC activation. Methods and Results: Male 8-week-old mice fed a normal diet underwent chronic stress were randomly assigned to one of three groups and administered vehicle or a low or high dose of the DPP4 inhibitor anagliptin. Control mice were left undisturbed. The stress increased the blood and brain DPP4 activity, the levels of plasma adrenaline and noradrenaline, and the bone marrow (BM) niche cell adrenergic receptor (Adrβ3) expression, and it decreased the levels of plasma glucagon-like peptide (GLP-1) as well as brain GLP-1 receptor (GLP-1R) and BM Cxcl12 expressions. These changes were reversed by DPP4 inhibition. The stress activated the BM sca-1 high c-Kit high CD48 low CD150 high HSC proliferation, giving rise to high levels of blood leukocytes and monocytes. These DPP4 inhibition-related benefits were mimicked by DPP4 depletion and by GLP-1R activation. Adrβ3 inhibition mitigated BM Cxcl12 expressions and HSC activation. Conclusions: DPP4 activity appears to regulate chronic stress-induced BM HSC activation and inflammatory cell production via an Adrβ3-CXCLl12-dependent mechanism that is mediated by the GLP-1-GLP-1R axis, suggesting that the inhibition of DPP4 or the stimulation of GLP-1R may have applications in the treatment of inflammatory diseases.