Dexamethasone Infusion Research Articles

160 Steers inoculated with Salmonella exhibit dissimilar hematology and body temperature profiles based on their exposure to a synthetic glucocorticoid

Abstract The objective of this study was to determine the effects of daily dexamethasone (DEX) infusions on hematology and body temperature in response to experimental, oral inoculation with Salmonella typhimurium. Weaned Holstein steer calves (n = 20; BW=102±2.7 kg) received DEX (n = 10; 0.5mg/kg BW) or saline (CON; n = 10; 0.5mg/kg BW) for 4 d (from d -1 to d 2) while simultaneously receiving an oral inoculation of a naldixic acid resistant Salmonella typhimurium (3.4x106 CFU/animal) via milk replacer on d 0. Fecal swabs for SAL shedding were obtained daily and samples were confirmed positive starting 24 h post inoculation (d 1) to harvest (d 5). Dexamethasone (DEX) administration was achieved via indwelling jugular catheters which were fitted simultaneously with rectal temperature (RT) recording devices on d −2 relative to inoculation and placed in individual pens in an environmentally controlled facility. Whole blood was collected at -24, -12, and 0 h; and at 8-h intervals from 8 to 120 h for hematology. There was a time x treatment (There should be) for RT such that the DEX treatment resulted in a decreased RT on d -1 to 2. A treatment × time interaction (P < 0.05) was observed for total white blood cells (WBC), neutrophils, lymphocytes, eosinophils, and monocytes. Specifically, DEX increased WBC and neutrophils in DEX steers (P < 0.0001) yet lymphocytes increased following DEX administration (P < 0.05 at 24 and 48 h, respectively). Monocytes initially increased (P < 0.001) in response to the -24 h DEX treatment but slowly decreased beyond CON group levels following the 48 h DEX treatment. These data may be interpreted as either mimicking multiple acute stressors with respect to daily DEX injections, mild immunosuppression due to multiple DEX exposures, or a combination of both scenarios when juxtaposing DEX and Salmonella inoculation.

SAT-240 Type B Insulin Resistance Resulting in Hyperthecosis in a Postmenopausal Woman

Type B insulin resistance is characterized by autoantibodies to the insulin receptor, inducing severe insulin resistance requiring administration of suprapharmacologic doses of exogenous insulin for treatment. A case report by Declue, Shah, Marchese and Malone (1) described a young woman who carried a presumptive diagnosis of ovarian hyperthecosis and was subsequently found to have type B insulin resistance. However, once she was treated with antibody depletion therapy and circulating insulin levels normalized, the serum testosterone level normalized, indicating that the presumed diagnosis of hyperthecosis was incorrect. We present the case of a 49 year old African American woman who developed type B insulin resistance at the age of 45, requiring upwards of 1800 units of insulin daily. Simultaneously, she developed oligomenorrhea; excessive hair growth on the chin, chest, upper abdomen and upper thighs; and biochemical androgen excess with a serum total testosterone level of 275 ng/dL. At the age of 46, the type B insulin resistance was treated with two infusions of rituximab, dexamethasone, and cyclophosphamide. Her insulin requirements dropped precipitously, to the point where she currently requires only oral metformin; her current HbA1c is 6.1%. Her serum testosterone level, however, has remained elevated at 67 ng/dL, indicating a persistent hyperandrogenic state. Symptoms of a postmenopausal state were confirmed by a highly elevated serum FSH level of 44.1 mIu/mL; she is presently amenorrheic. A transvaginal ultrasound revealed a right ovarian volume of 19.3 mL and a left ovarian volume of 12.4 mL; 3 anechoic follicles were noted on the left, the largest of which measured 14.5 x 14.0 x 15.0 mm; 2 anechoic follicles were noted on the right, the largest of which measured 18.9 x 21.5 x 16.8 mm; bilateral hydrosalpinges were identified. A CT scan of the adrenals was normal. A presumptive diagnosis of hyperthecosis has been made, and the patient has been referred for bilateral oophorectomy. We postulate that, in this patient, the exposure of the ovaries to extremely high circulating insulin resulted in stimulation of the ovarian thecal cells and, ultimately, in autonomous function, yielding a clinical state of hyperthecosis. Reference: (1) Brown RJ, Joseph J, Cochran E, Gewert C, Semple R, Gorden P. Type B Insulin Resistance Masquerading as Ovarian Hyperthecosis. J Clin Endocrinol Metab. 2016;102(6):1789-1791.

Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model.

Spinal cord injury (SCI)-initiated inflammation was treated with anti-inflammatory reagents. We compared local spinal cord or intraperitoneal infusion of two Myxoma virus derived immune modulating proteins, Serp-1 and M-T7, with dexamethasone (DEX). Hemorrhage and necrosis after SCI initiate acomplex pathogenesis dominated by early, severe and highly destructive inflammatory macrophage infiltration. We examined sustained, 7-day, subdural infusion of either M-T7, achemokine modulator or Serp-1, aplasminogen activator and factor inhibitor. Mature male rats had epidural balloon crush SCI and sustained subdural infusion of Serp-1, M-T7, DEX or saline for 7 days via the osmotic pump. Aseparate group of rats with SCI had intra-peritoneal infusion. Clinical evaluation included endpoint monitoring with body weight, hemorrhagic cystitis and bilateral toe pinch response. Sections of the spinal cord were analyzed histologically and macrophage numbers counted by standardized protocol in the cavity of injury (COI). While the rats administered DEX demonstrated substantial body weight loss, dehydration and dermal atrophy consistent with steroid toxicity, rats infused with Serp-1 and M-T7 had no toxicity. Serp-1 improved withdrawal responses. Subdural infusion of Serp-1, M-T7 and DEX significantly reduced numbers of phagocytic, CD68-positive macrophages. With intraperitoneal infusion only M-T7 reduced macrophage counts, Serp-1 showed only atrend. Local infusion of highly active immune modulating proteins; Serp-1 and M-T7, targeting serine protease and chemokine pathways demonstrated excellent potential for neuroprotection after severe SCI in arat model, without adverse side effects. Sustained subdural infusion offers an alternative route of administration for treatment of SCI.

Potency of Dexamethasone in Labor Induction

Induction of labor is one of the most common interventions practiced in modern obstetrics. In the developed world, the ability to induce labor has contributed to the reduction in maternal and perinatal mortality and morbidity.

Preoperative dexamethasone for acute post-thoracotomy analgesia: a randomized, double-blind, placebo-controlled study

BackgroundThe analgesic effects of dexamethasone have been reported previously, and the present study determined the effects of preoperative dexamethasone on postoperative pain in patients who received thoracotomy.MethodsForty patients participated in this randomized, double-blind study. All patients received either dexamethasone via a 0.1 mg/kg intravenous bolus before anesthetic induction or an equal volume of saline. Postoperative analgesia was provided to both groups via epidural patient-controlled analgesia (PCA), which consisted of 250 μg of sufentanil in 250 mL of ropivacaine (0.18%) for 72 h. The primary outcome was the cumulative consumption of epidural PCA at postoperative 24 and 72 h. The secondary outcomes were the pain intensity scores during resting and coughing at postoperative 24 and 72 h, quality of recovery, total amount of rescue analgesics required, and length of hospital stay.ResultsNo significant differences was observed in the consumption of epidural PCA between the control and dexamethasone infusion groups at 24 h (63.6 [55.9–72.7] vs. 68.5 [60.2–89.0] ml, P = 0.281) and 72 h (199.4 [172.4–225.1] vs. 194.7 [169.1–252.2] ml, P = 0.890). Moreover, there was no significant difference in the pain intensity scores during resting and coughing at postoperative 24 and 72 h, quality of recovery, total amount of rescue analgesics required, and length of hospital stay.ConclusionA single intravenous administration of dexamethasone during the preoperative period does not reduce opioid consumption and post-thoracotomy pain.Trial registrationThe study was registered at http://cris.nih.go.kr (KCT0000359) and was conducted from December 2011 to October 2012.

EFFICIENCY OF INHALATION AND PARENTAL THERAPY OF ACUTE BRONCHIAL OBSTRUCTION SYNDROME BY INFECTIOUS OR ALLERGIC GENESIS IN CHILDREN. PRINCIPLES AND TECHNIQUE OF INHALATIONS

Relevance. Diseases of the respiratory organs occupy the first ranked place in the structure of the incidence of children, reaching 50-75 % in the regions of Ukraine. The prevalence of the syndrome of bronchial hyperactivity increases . Objective: to study the effectiveness of nebulizer therapy for relief of acute bronchial obstruction syndrome in children with exacerbation of recurrent bronchitis or bronchial asthma. Materials and methods. 52 children of school age with acute bronchial hyperactivity (recurrent bronchitis – 28, bronchial asthma – 24) were examined. Two groups were formed by randomization: the main group (27 children) and the control group (25 children). Both groups were representative by sex, age, nosological diagnosis and severity of the disease. All children received basic therapy with topical glucocorticosteroids by nebulization. Children of the main group received intensive treatment by salbutamol inhalation during the first treatment day, and on 2–5 days as in the control group only 3 times a day. Children of the control group received inhalations together with intravenous drip infusions of euphyllin and dexamethasone. Results. In both groups, there was a dynamic regression of cough and sputum excretion, but in the main group, the rate of disappearance of cough by the 5th day of treatment was 3 times, and by the 10th day – 2,3 times higher, than in the control (p < 0.05); the rate of disappearance of sputum within 10 days is 1,7 times higher, respectively (p <0.05). Positive changes were confirmed by an auscultative pattern, the normalization of which occurred earlier for 1 week in patients receiving intensive nebulization bronchodilator therapy during the first day of the treatment. Conclusions. Competent use of nebulizers allows to increase the effectiveness of treatment of children with acute bronchial obstructive syndrome. Early relief of bronchospasm promotes faster normalization of inspiratory flow and respiration recovery. As a result, the terms of recovery and length of stay of children in the hospital are shortened.

Combined intraoperative paracetamol and preoperative dexamethasone reduces postoperative sore throat: a prospective randomized study.

Postoperative sore throat (POST) after general anesthesia with endotracheal intubation is a common and undesirable complication. In this study, we evaluated the combined effects of paracetamol and dexamethasone on the prevention of POST in patients after general anesthesia. A total of 226 patients scheduled for urologic surgery under general anesthesia were randomly assigned to one of two groups. In the DexaPara group (n=113), dexamethasone (10mg) and paracetamol (1000mg) was infused. In the Dexa group (n=113), dexamethasone (10mg) alone was given. POST, hoarseness, and dysphagia were monitored. The postoperative wound pain score and perioperative opioid requirements were compared. In addition, complications related to opioids were compared between the groups. The overall incidence of POST was lower in the DexaPara group than in the Dexa group [42 (37%) vs. 72 (64%), p<0.001]. The incidence of POST while resting at postoperative 1 and 6h was lower in the DexaPara group than in the Dexa group (p=0.008 and p=0.004, respectively). The incidence of postoperative nausea, vomiting, drowsiness, shivering, and headache was comparable between the groups. Paracetamol and dexamethasone infusion reduced the incidence of POST without serious complications in patients for urologic surgery under general anesthesia.

Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress

Major depression is hypothesized to be associated with dysregulations of the hypothalamic–pituitary–adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis.

Effects of dexamethasone treatment and respiratory vaccination on rectal temperature, complete blood count, and functional capacities of neutrophils in beef steers.

The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers ( = 32; 209 ± 8 kg) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute stress (ACU), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h only on d 0; 2) chronic stress (CHR), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h on d -3 to 0; or 3) control (CON), in which no DEX was administered. Steers were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices on d -4 relative to vaccination and placed in individual stanchions in an environmentally controlled facility. Blood samples were collected and serum was isolated at -74, -50, and -26 h; at 0.5-h intervals from -4 to 6 h; and at 12, 24, 36, 48, and 72 h relative to multivalent respiratory vaccination at 1200 h on d 0. Additional blood samples were used to analyze complete blood cell count (CBC) and functional capacities of neutrophils. There was a treatment × time interaction ( < 0.01) for RT such that DEX treatment in CHR and ACU steers decreased RT on d -3 and 0, respectively. A treatment × time interaction ( < 0.01) was observed for total white blood cells (WBC), neutrophils, lymphocytes, and monocytes. Specifically, DEX increased WBC and neutrophils in CHR and ACU steers ( < 0.001) yet decreased lymphocytes in CHR steers ( = 0.02) compared with CON steers. Neutrophil concentration increased rapidly, within 2 h of the DEX infusion, in ACU steers. Monocytes transiently increased ( < 0.001) in response to DEX treatment in CHR and ACU steers. In contrast, eosinophils were greater ( < 0.01) in CON steers than in ACU and CHR steers. A treatment × time interaction ( = 0.004) was observed for interferon-γ, with CON cattle exhibiting greater concentrations than the ACU and CHR cattle at 5 h after vaccination, through d 3. Treatment also influenced ( ≤ 0.001) the expression of L-selectin on the surface of neutrophils. The percentage of neutrophils engaging in phagocytosis and the oxidative burst were suppressed ( ≤ 0.001) among only the CHR steers, whereas the intensity of the oxidative burst was suppressed ( ≤ 0.001) for both ACU and CHR steers. These data suggest that our model induced acute and chronic immunosuppression and defined the acute response to a multivalent vaccine in CON steers.

Effects of dexamethasone treatment and respiratory vaccination on rectal temperature, complete blood count, and functional capacities of neutrophils in beef steers

The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers ( = 32; 209 ± 8 kg) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute stress (ACU), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h only on d 0; 2) chronic stress (CHR), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h on d -3 to 0; or 3) control (CON), in which no DEX was administered. Steers were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices on d -4 relative to vaccination and placed in individual stanchions in an environmentally controlled facility. Blood samples were collected and serum was isolated at -74, -50, and -26 h; at 0.5-h intervals from -4 to 6 h; and at 12, 24, 36, 48, and 72 h relative to multivalent respiratory vaccination at 1200 h on d 0. Additional blood samples were used to analyze complete blood cell count (CBC) and functional capacities of neutrophils. There was a treatment × time interaction ( < 0.01) for RT such that DEX treatment in CHR and ACU steers decreased RT on d -3 and 0, respectively. A treatment × time interaction ( < 0.01) was observed for total white blood cells (WBC), neutrophils, lymphocytes, and monocytes. Specifically, DEX increased WBC and neutrophils in CHR and ACU steers ( < 0.001) yet decreased lymphocytes in CHR steers ( = 0.02) compared with CON steers. Neutrophil concentration increased rapidly, within 2 h of the DEX infusion, in ACU steers. Monocytes transiently increased ( < 0.001) in response to DEX treatment in CHR and ACU steers. In contrast, eosinophils were greater ( < 0.01) in CON steers than in ACU and CHR steers. A treatment × time interaction ( = 0.004) was observed for interferon-γ, with CON cattle exhibiting greater concentrations than the ACU and CHR cattle at 5 h after vaccination, through d 3. Treatment also influenced ( ≤ 0.001) the expression of L-selectin on the surface of neutrophils. The percentage of neutrophils engaging in phagocytosis and the oxidative burst were suppressed ( ≤ 0.001) among only the CHR steers, whereas the intensity of the oxidative burst was suppressed ( ≤ 0.001) for both ACU and CHR steers. These data suggest that our model induced acute and chronic immunosuppression and defined the acute response to a multivalent vaccine in CON steers.

SY 15-4 ROLE OF HISTONE DEACETYLASES IN REGULATING ENDOTHELIAL AND VASCULAR FUNCTION

Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors. Corticoid-induced hypertensive animal model was established by infusion of adrenocorticotropic hormone (40 ng/kg/day), deoxycorticosterone acetate (40 mg/kg), and dexamethasone (100 μg/kg/day) with osmotic mini-pump. Valproic acid (VPA), a class I and IIa HDAC inhibitor administration significantly decreased corticoid-induced hypertension. VPA administration increased acetylation level of Mineralocorticoid receptor (MR), which was closely related with decreased binding affinity with hormone response element in the promoters of target genes such as glucocorticoid induced leucine zipper (Gilz) and serum glucocorticoid regulated kinase-1 (Sgk-1). HDAC3 and HDAC4 were interacted with MR after stimulation of aldosterone (10 nmol/L) for 30 min. HDAC4 inhibitor showed no effect on acetylation level and promoter binding affinity of MR. HDAC4 played a role as a scaffold between MR and HDAC3. In conclusion, HDAC inhibitors increased acetylation of corticoid receptor, resulted in decreased transcriptional activity of it and blocked corticoid induced-hypertension.

Extensive Peculiar Cutaneous Form of Neurofibromatosis Type I as a New Mutation - a Case Report

Abstract Neurofibromatosis-1 (NF1) is one of the most common hereditary multisystemic disorders. The disease manifests a variety of characteristic features that include: hyperpigmentary abnormalities of the skin (café-au-lait macules, freckles in the axillae, and iris Lisch nodules) and growth of benign peripheral nerve sheath tumors (neurofibromas) in the skin. Associated extracutaneous clinical features include: skeletal abnormalities, neurological, cardiovascular, endocrine and other malformations. NF1 is caused by mutation in the neurofibromatosis-1 gene, which codes for the protein neurofibromin. The inheritance of NF1 follows an autosomal dominant trait, although about 50% of patients present with new („de novo“) mutations, and represent the first member of their family. No difference in the severity of the disease can be found in patients with familial mutations versus those with new mutations. We present a 78-year-old female patient with an extreme cutaneous form of neurofibromatosis who reported no affected family member. Apart from skin problems, she had no major health issues in childhood and adolescence, but in recent decades she had frequent headaches, occasional abdominal pain, and vision and hearing impairment. About 10 to 14 days before admission, she developed a severe cough, shortness of breath, and chest and abdominal pain. On examination, the patient of short stature (hight: 152 cm, weight: 49 kg) presented with thousands of soft nodules dispersed over the whole body, except on extensor sides of thighs and lower legs; the nodules varied in color from skin-colored, livid erythematous, to brown-grey; the nodules on the abdomen were moist, partly bleeding from the base, and accompanied by an unpleasant odor. Her feet were also densely covered by dark purple lumps, with dystrophic changes of the toe nails that were thickened, frayed, and yellowish. The skeletal abnormalities included: short stature, severe osteoporosis and osteosclerosis of the head bone structure; degenerative arthropathc-spondylotic changes of the thoracolumbar spine segment with signs of diffuse skeletal hyperostosis; pronounced degenerative changes of the lumbar spine. CT scans of the head, chest and abdomen showed the following abnormalities: flattening of the paraventricular gyri and reduction of brain parenchyma with hypodensity of the white matter in terms of cortical atrophy; periventricular bilateral small post-ischemic microvascular brain lesions of varying chronicity; in the parenchyma of the upper left lung lobe the apical presence of small areas of pleural effusion with consequent subatelectic region; distended stomach and a small inner wall herniation; hypotrophic right kidney; atherosclerotic lesions of the abdominal aorta; low grade infrarenal kinking of the abdominal aorta. Pathohistological analysis of biopsy specimen taken from the nodule corresponded with cutaneous neurofibroma. Consultative examinations of various specialists pointed to the existence of the following comorbidities: obstructive respiratory syndrome and right lobe pneumonia that were treated by antibiotics, aminophylline and dexamethasone infusions; psycho-organic syndrome without focal neurological deficit; Lisch nodules in each eye, and senile cataract. Considering the age and medical presentation of the patient, no other treatment was considered. In conclusion, this is a sporadic case of cutaneous neurofibromatosis 1 in a 78-year-old female patient who presented with extremely severe cutaneous neurofibromas, making this case at least rather peculiar.

Oxidative stress and protein catabolism following dexamethasone and isoflupredone administration in Holstein calves

Background: Glucocorticoids have several benefits in large animal medicine but apart from their benefits, there are several disadvantages attributed to the use of these drugs. Among the disadvantages, disturbance in protein metabolism is one of the side effects of glucocorticoids which has been investigated in human and laboratory animals. OBJECTIVES: There are no information regarding the effects of glucocorticoids on protein metabolism in large animals. Hence, the present experimental study was performed to evaluate the protein metabolism following glucocorticoids administration in Holstein calves. METHODS: Ten clinically healthy Holstein calves (6 to 8 months old) were assigned into 2 equal groups (n=5), containing Dexa and Iso. Dexamethasone (1 mg/kg, intramuscularly) and isoflupredone(1 mg/kg, intramuscularly) were administered in Dexa and Iso groups, respectively, on two consecutive days. Blood samples were taken at days 0 (1st drug administration), 1 (2nd drug dministration), 2, 3, 5 and 7, from all studied animals. Sera were assayed for total protein, albumin, globulin, serum amyloid A and haptoglobin. RESULTS: Serum amyloid A and haptoglobinexperience significant increase after administration of both drugs. Isoflupredone induced the synthesis of serum amyloid A and haptoglobin more than dexamethasone (p<0.05). Serum concentrations of total protein, albumin and globulin experienced significant decrease after infusion of dexamethasone and isoflupredone (p<0.05). Circulating levels of these proteins in Iso group were lower than Dexa one, significantly. CONCLUSIONS: Isoflupredone and dexamethasone can induce the protein catabolism. Furthermore, the concentrations of serum amyloid A and haptoglobin, as oxidative stress biomarkers, increased following both drugs administrations due to their oxidation effects on proteins. Finally, the effects of isoflupredone on the metabolism of proteins are significantly higher than dexamethasone in Holstein calves.

Performance of the 4-mg intravenous dexamethasone suppression test in differentiating Cushing disease from pseudo-Cushing syndrome

ContextDiscriminating Cushing disease (CD) from pseudo-Cushing syndrome (PCS) is a challenging task that may be overcome with the 4-mg intravenous (IV) dexamethasone suppression test (DST). ObjectiveAssess the performance of the 4-mg IV DST in the differential diagnosis between CD and PCS in well-characterized patients. DesignRetrospective comparative study of subjects seen in a tertiary care unit (November 2008 to July 2011). MethodsThirty-six patients with PCS and 32 patients with CD underwent 4-mg IV dexamethasone infusions from 11 am to 3 pm. Areas Under ROC Curves (AUCs) were estimated and compared for ACTH and cortisol measured at 4 pm the same day (day 1) and 8 am the next day (day 2). The ROC curve of the marker with the highest AUC was used to determine the threshold with the highest specificity for 100% sensitivity. ResultsThe AUC of ACTH at 8 am on day 2 was estimated at 98.4% (95% CI: [92.1–100]), which is significantly greater than that of ACTH at 4 pm on day 1 (P=0.04) and that of cortisol at 8 am on day 2 (P=0.05). For ACTH at 8 am on day 2, the threshold with the highest specificity for 100% sensitivity was estimated at 14.8ng/L. At this threshold, the sensitivity was estimated at 100% [89–100] and the specificity at 83.3% [67–94]. ConclusionThe 4-mg IV DST is an easy and accurate tool in distinguishing CD from PCS. It deserves thus a better place in establishing the diagnosis of CD.

Treatments and outcomes of subglottic stenosis in children after surgical repairing congenital heart disease

Objective To explore the treatments and outcomes of children complicated with subglottic stenosis after surgical repairing congenital heart disease(CHD). Methods A total of 34 cases complicated with subglottic stenosis after CHD surgery from July 1, 2010 to June 30, 2013 were retrospectively analyzed. There were 19 boys and 15 girls with an average age of 7.8±1.6 months and an average weight of 5.5±3.0 kilogram. According to the Cotton's subglottic stenosis grading system, the degrees were Ⅰ(n=5), Ⅱ(n=12), Ⅲ(n=17) and Ⅳ(n=0). They were divided into two groups of A(intubation, n=8) and B(non-intubation, n=26) according to treatment plan. Group A had endotracheal intubation implanted for over 24 h after endotracheal tube dilatation or subglottic stenosis surgery. Systemic infusion of dexamethasone was used for 1 week. Group B had an immediate extubation after dilatation. Dexamethasone infusion and budesonide atomization were administered for 1 week. Chi-square or Fisher's exact test was used to compare the profiles of readmission, re-stenosis rate and mortality for two groups. Statistical analysis was performed with 16.0 SPSS software. P<0.05 was considered statistically significant. Results All patients completed treatment. The median follow-up period was 15 months. The readmission rate(11.5% vs 75.0%), re-stenosis rate(11.5% vs 87.5%)and mortality(3.8% vs 37.5%) of group B were significantly lower than those of group A. And the differences were statistically significant(P<0.05). Conclusions Subglottic stenosis is a rare postoperative complication of congenital heart disease. Early diagnosis and proper interventions yield a good prognosis. Tracheal extubation immediately after dilatation with endotracheal tube to treat subglottic stenosis is both simple and suitable for wider popularization at primary hospitals. Key words: Subglottic stenosis; Heart diseases, congenital; Follow-up studies

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Atrial fibrillation (AF) occurs frequently after cardiac surgery and is mostly self-limiting. It relates to direct surgical effects on the atria, atrial ischaemia during surgery, adrenergic activation and a general state of inflammation. Although most postoperative AF is transient, it may lead to a prolonged hospital stay and increased mortality [1]. Treatment strategies include the use of beta blockers, several antiarrhythmic drugs such as propafenone, sotalol and amiodarone, antioxidants to reduce ischaemia-reperfusion damage, angiotensin inhibition and anti-inflammatory medication such as N-acetylcysteine, naproxen, colchicine and glucocorticosteroids. In this edition of the Netherlands Heart Journal, Jacob et al. [2] report a substudy of the DECS study [3], which aims to describe the influence of a single high-dose infusion of the glucocorticoid dexamethasone during cardiac surgery on the perioperative function of the left atrium and the development of postoperative AF. The authors have put much effort into the sophisticated analysis of transoesophageal echocardiography recordings (TEE). We commend the investigators for their focus on atrial function rather than atrial size only, especially since atrial function may better reflect atrial pathophysiology than merely looking at atrial anatomy. Their methodology should be followed when evaluating atrial performance in order to understand atrial remodelling processes much more efficiently. In the original DECS study [3], dexamethasone did not reduce the incidence of postoperative AF, suggesting that a single dose of dexamethasone cannot effectively ameliorate atrial inflammation, which is one of the presumed arrhythmogenic mechanisms. In line with that previous observation in the main DECS study, the present substudy shows that dexamethasone is not associated with preservation of atrial function at the very end of the operation. We again commend the investigators for having performed such extensive TEE analyses. We understand that collecting data immediately after surgery was most appropriate considering the complex logistics and limited acceptance of TEE in the awake patient. On the other hand, atrial inflammation may not be at its peak right after surgery and therefore the investigators may have missed the beneficial effects of dexamethasone on atrial function. This notion is fed by the fact that postoperative AF reaches its highest incidence on day two after cardiac surgery [4]. Comparing preoperative and postoperative left atrial (LA) function within the dexamethasone and placebo groups (rather than the presented comparison between dexamethasone and placebo before and after surgery) suggests that the LA total emptying fraction is stable in the placebo group, while it seems to decrease in the dexamethasone group. Whilst correction of the LA function parameters for fluid status may appear explanatory one cannot exclude an early unexpected deleterious effect of dexamethasone potentially precluding a net positive effect during the next few days after surgery. Future studies on postoperative atrial inflammation may shed more light on these notions. The present study shows the feasibility of assessing perioperative atrial function using TEE. However, it also illustrates the limitations of fitting methodology to standard care which precluded observing atrial inflammation when it—expectedly—was at its peak. To paraphrase the present Dean and Vice Chairman of the Board of the University Medical Centre Utrecht, it is time for a ‘transition in science’ [5]. Among others, this may be taken by clinical scientists as a call for always creating the most optimal methodologies whilst respecting clinical routines. This certainly will contribute to producing high-quality papers with impact, which can be used to guide important clinical decisions and thus improve the quality and length of patients’ lives [5].

Multimodal perineural analgesia with combined bupivacaine-clonidine-buprenorphine-dexamethasone: safe in vivo and chemically compatible in solution.

The use of adjuvants in regional anesthesia has increased. However, there are knowledge gaps pertaining to 1) in vivo local tissue effects of these adjuvants; and 2) chemical compatibility and solubility of these drugs in solution with each other and with local anesthetics. This study addresses these gaps in knowledge. In vivo rat safety/toxicopathology study and analytical chemistry study. Collaborating Good Laboratory Practice laboratories under the direction of the university-based principal investigator. Single-injection formulations of clonidine, buprenorphine, and dexamethasone were combined with either bupivacaine or midazolam, and were administered to groups of rats. Post-injection behavior was monitored to assess changes related to the block. A continuous infusion of bupivacaine, clonidine, and dexamethasone was administered to another group of rats, and behavioral effects were recorded. After 15 days, rats were sacrificed and their nerves/dorsal root ganglia were examined by the pathologist. Samples of combined drug solutions were processed at an analytical chemistry laboratory for compatibility, solubility, and stability. Each of the single-injection formulations produced reversible sensory and/or motor block. None of the study drugs caused damage to any of the nerve segments or related tissue. The text describes the concentrations at which compatibility and solubility of the combined drug solutions were achieved. Four-drug single-injection formulations are described that 1) had compatible and stable concentrations in solution; and 2) produced reversible nerve block without causing long-term motor or sensory deficits or damage to sciatic nerves/dorsal root ganglia.

Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model.

Trauma in spinal cord injury often results in massive damage to the white matter and in damage to myelin that results in a severe phagocyte-rich infiltration apparently directed at removing immunologically toxic myelin debris. In the epidural balloon crush injury to the rat cranial thoracic spinal cord, the dorsal column was crushed, which at one week post-op resulted in its obliteration by a severe infiltration by a virtually pure population of macrophages that internalized all damaged myelin. A week-long subdural infusion of dexamethasone, a stable synthetic corticosteroid, resulted in remarkable inhibition of the macrophage infiltration of the crush cavity and in the lack of removal of myelin debris by phagocytosis. In this study we demonstrated that spinal cord injury results in a severe inflammatory response directed at massively damaged myelin, and we inhibited this response with a subdural infusion of a powerful anti-inflammatory drug, dexamethasone.

Histopathological and audiological effects of mechanical trauma associated with the placement of an intracochlear electrode, and the benefit of corticosteroid infusion: prospective animal study.

This study aimed to present the histopathological and audiological effects of mechanical trauma associated with the placement of a model electrode in the scala tympani in rats, and the effects of continuous topical corticosteroid application. The study comprised three groups of rats. The round window membrane was perforated in all three groups and a model electrode was inserted in the round window. Group one received no further treatments. Groups two and three also had an intrathecal microcatheter compatible with a mini-osmotic pump inserted; in group two this was used to release normal saline and in group three the pump released 400µg/ml dexamethasone. Dexamethasone infusion given after implantation of the intracochlear model electrode was more effective for preventing hearing loss than the administration of just one dose of dexamethasone. The findings suggest that continuous dexamethasone infusion is beneficial for preventing the loss of hair cells and neurons associated with early and late periods of intracochlear electrode trauma.

Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via recovery of BDNF signal cascades

Major depression is a complex disorder characterized by genetic and environmental interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat depression. Neurogenesis following chronic antidepressant treatment activates brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders depression-like behavior. Infusion of cDEX decreased body weight and produced a trend towards lower locomotor activity during darkness. In the forced-swim test, cDEX-mice exhibited increased immobility times compared with mice administered saline. Flu treatment reversed decreased locomotor activity and mitigated forced-swim test immobility. Real-time polymerase chain reactions using brain RNA samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1 (XBP1) gene expression was lower in cDEX-mice compared with the saline group. However, marked expression of the XBP1 gene was observed in cDEX-mice treated with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5-HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline group, and these decreases normalized to control levels upon Flu treatment. Our results indicate that the Flu moderates reductions in voluntary activity following chronic dexamethasone infusions in mice via recovery of BDNF signal cascades.