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PubMed1996

A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron Delayed Emesis Study Group.

BACKGROUND: The purpose of this study was to investigate the efficacy and safety of oral ondansetron, given alone or in combination with dexamethasone in the control of cisplatin-induced delayed emesis. PATIENTS AND METHODS: This was an international, multicentre, double-blind, randomised, placebo-controlled, parallel group study. A total of 640 chemotherapy-naïve patients received ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. for the control of acute emesis prior to cisplatin (> or = 70 mg/m2) on day 1. Patients who were not rescued or withdrawn on day 1 were to be randomised 24 hours after the start of cisplatin administration to one of four groups; group I placebo oral (p.o.), twice daily (bd) on days 2-6 (n = 125); group II ondansetron (8 mg p.o. bd) on days 2/3 followed by placebo (p.o. bd) on days 4-6 (n = 199); group III ondansetron (8 mg p.o. bd) on days 2-6 (n = 214); group IV ondansetron (8 mg p.o. bd) plus dexamethasone (4 mg p.o. bd) on days 2-6 (n = 66). RESULTS: On day 1, 81% of patients had complete control of acute emesis, with 68% having no emesis and no nausea. Over days 2/3 and over days 2-6, significantly more patients receiving ondansetron plus dexamethasone (group IV) reported no emesis and no nausea (49% and 45%, respectively) compared to ondansetron alone (32% and 27%, respectively) or placebo (group I; 33% and 27%, respectively; P < 0.05 for all pairwise comparisons). There were no significant differences in the control of emesis over days 2/3, where 61% of patients had complete emetic control (0 emetic episodes) with ondansetron plus dexamethasone (group IV), 54% with ondansetron (groups II + III) and 49% with placebo (group I). In the distribution of nausea grades, ondansetron plus dexamethasone (group IV) was significantly superior to ondansetron (groups II + III); P = 0.037) and placebo (group I; P = 0.013) over days 2/3. Over days 2-6 there were no significant differences in the control of emesis, however a comparison of the distribution of nausea grades over days 2-6 showed ondansetron plus dexamethasone (group IV) to be significantly superior to ondansetron (group III; P = 0.043) and placebo (group I; P = 0.024). All treatments were well tolerated and no unexpected drug-related adverse events were reported. There were no differences in the overall incidence of adverse events between the active treatment groups or placebo. Constipation and headache, recognised side effects of 5-HT3 receptor antagonists, were the most commonly reported adverse events with the incidence of constipation with ondansetron alone (group III) being significantly greater than with over days 2-6 (14% vs. 6%; P = 0.030). CONCLUSION: In contrast to some previous investigations, in this study, ondansetron alone appears to have a minor role in the control of cisplatin-induced delayed emesis and nausea. In conclusion, the combination of oral ondansetron plus dexamethasone is superior to ondansetron and to placebo.

Adult↗
PubMed1999

Early dexamethasone treatment in preterm infants treated with surfactant: a double blind controlled trial.

The objective of the study was to test the hypothesis that early postnatal dexamethasone administration (days 1-5) in preterm infants with respiratory distress syndrome would improve acute respiratory status and therefore decrease long-term neonatal morbidity. This was a prospective, blind randomized controlled trial. Eligible neonates were preterm infants with birthweight < or = 1500 g who developed respiratory distress syndrome requiring mechanical ventilation and surfactant. A 5-day course of dexamethasone or placebo was initiated within the first 6 h after birth. The starting dose of dexamethasone was 0.5 mg/kg/day and it was tapered progressively. Results were analysed with t-test chi 2, Wilcoxon test, and ANOVA. Twenty-nine infants (n = 15 of early dexamethasone and n = 14 of placebo group) fulfilled the inclusion criteria. The dexamethasone group exhibited a significant improvement in arterial to alveolar oxygen ratio only between postnatal days 2 and 5 (p = 0.02). This initial improvement was not associated with long-term benefits. Infants who received dexamethasone had increased systolic blood pressure (p = 0.0001), diastolic blood pressure (p = 0.001), blood sugar (p = 0.02, serum urea (p = 0.03), and creatinine level (p = 0.02). All these side-effects were resolved by postnatal day 7. We concluded that a 5-day course of early postnatal dexamethasone was associated with only a transient improvement in oxygenation with no long-term benefits. Side-effects were more common in the dexamethasone group.

Dexamethasone↗
PubMed2003

Dexamethasone inhibits transforming growth factor-beta receptor (Tbeta R) messenger RNA expression in hamster preantral follicles: possible association with NF-YA.

To evaluate the site(s) and mechanism(s) of glucocorticoid-inhibition of transforming growth factor (TGF) beta receptor (TbetaR) mRNA expression in ovarian cells, steady-state levels of TbetaR mRNA in hamster preantral follicles exposed to FSH or estradiol with or without dexamethasone were determined by reverse transcription polymerase chain reaction and Southern hybridization. The effect of dexamethasone on follicular DNA and steroid synthesis and the expression of NF-Y and Sp3 were also investigated. Dexamethasone differentially inhibited FSH- or estradiol-induced expression of TbetaR mRNA in preantral follicles at all stages. Dexamethasone also strongly inhibited FSH-induced but not TGFbeta2-induced follicular DNA synthesis, and the inhibition was completely reversed by TGFbeta2. However, TGFbeta2 markedly attenuated FSH + dexamethasone-stimulated progesterone and FSH-induced follicular estradiol synthesis. Both FSH and estradiol upregulated NF-YA expression, but the effect was significantly attenuated by dexamethasone. Our results suggest that suppression of NF-YA levels is one of the mechanisms whereby dexamethasone reduces hormone-induced TbetaRI and TbetaRII mRNA levels in hamster preantral follicles. Dexamethasone potentiates the effect of FSH on granulosa cell steroidogenesis, whereas TGFbeta counteracts the effect. These data indicate that glucocorticoid and TGFbeta may form an important regulatory loop to modulate FSH regulation of preantral follicular growth and differentiation.

Animals↗
PubMed1999

The prophylactic effect of dexamethasone on postoperative nausea and vomiting in women undergoing thyroidectomy: a comparison of droperidol with saline.

UNLABELLED: The aim of this study was to evaluate the prophylactic effect of dexamethasone on postoperative nausea and vomiting (PONV) in women undergoing thyroidectomy. Droperidol and saline served as controls. One hundred twenty women (n = 40 in each of three groups) undergoing thyroidectomy under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. Immediately before the induction of anesthesia, Group 1 received IV dexamethasone 10 mg, whereas Groups 2 and 3 received IV droperidol 1.25 mg and saline, respectively. We found that both dexamethasone and droperidol significantly decreased the total incidence of PONV compared with saline, with an incidence of 32%, 35%, and 76%, respectively (P<0.01; Group 1 versus Group 3, Group 2 versus Group 3). Patients who received droperidol, however, reported a higher intensity of sore throat and a more frequent incidence of restlessness than those who received dexamethasone. We conclude that, although both dexamethasone and droperidol are effective as prophylactic antiemetics in women undergoing thyroidectomy, droperidol produces more side effects. IMPLICATIONS: We compared the prophylactic administration of dexamethasone to prevent nausea and vomiting with droperidol and saline in women undergoing thyroidectomy. Both dexamethasone and droperidol significantly reduced postoperative nausea and vomiting, but droperidol produced more side effects, which suggests that dexamethasone is a useful treatment in these patients.

Adult↗
PubMed2001

Dexamethasone for preventing nausea and vomiting associated with epidural morphine: a dose-ranging study.

UNLABELLED: We conducted a dose-ranging study of dexamethasone for preventing nausea and vomiting within the first 24 h after the administration of epidural morphine. Two hundred twenty-five women (n = 45 in each of the five groups) undergoing simple abdominal total hysterectomy under epidural anesthesia were enrolled in this randomized, double-blind, placebo-controlled study. When the incision closure was completed, patients received IV dexamethasone, 10 mg, 5 mg, or 2.5 mg; IV droperidol 1.25 mg; or saline 2 mL. All patients received epidural morphine 3 mg for postoperative analgesia. We found that patients who received dexamethasone 5 mg or 10 mg or droperidol 1.25 mg were significantly different from those who received saline alone in the following variables: the total incidence of nausea and vomiting, the incidence of more than four vomiting episodes, the number of patients requiring rescue antiemetics, the total number of patients with no vomiting and/or no antiemetic medication (P < 0.05 to P < 0.01). The differences among dexamethasone 10 mg and 5 mg and droperidol 1.25 mg were not significant. Dexamethasone 2.5 mg was ineffective. In conclusion, because dexamethasone 5 mg was as effective as 10 mg as an antiemetic, we recommend the smaller dose for preventing nausea and vomiting associated with epidural morphine. IMPLICATIONS: We conducted a dose-ranging study of dexamethasone for preventing nausea and vomiting within the first 24 h after the administration of epidural morphine. We found that dexamethasone 5 mg was as effective as 10 mg. We recommend the smaller dose for this purpose.

Adult↗
PubMed1999

Dexamethasone changes brain monoamine metabolism and aggravates ischemic neuronal damage in rats.

BACKGROUND: Glucocorticoids have been reported to aggravate ischemic brain damage. Because changes in the activities of various neuronal systems are closely related to the outcome of ischemic damage, the authors evaluated the effects of dexamethasone on the monoaminergic systems and ischemic neuronal damage. METHODS: The right middle cerebral artery was occluded for 2 h, and the tissue concentrations of monoamines and their metabolites were determined in the cerebral cortex and the striatum of rats. The turnover of 5-hydroxytryptamine was compared in animals injected with saline and those injected with dexamethasone twice (2 mg/kg in each injection) by evaluating the probenecid-induced accumulation of 5-hydroxyindoleacetic acid. The turnovers of norepinephrine and dopamine were estimated from the alpha-methyl-p-tyrosine-induced depletion of norepinephrine and dopamine, respectively. The effect of dexamethasone on the infarct volume was evaluated by triphenyltetrazolium chloride stain in rats subjected to 2 h of occlusion. RESULTS: Dexamethasone did not affect the cortical 5-hydroxytryptamine or 5-hydroxyindoleacetic acid contents. However, it suppressed the turnover of the cortical 5-hydroxytryptamine on both sides. Dexamethasone reduced the turnover of the striatal 5-hydroxytryptamine and facilitated the dopamine turnover. In rats subjected to 2 h of occlusion and 2 h of reperfusion, the infarct volume was 10.5 times greater in the group that received dexamethasone than in the animals that received saline. CONCLUSIONS: Dexamethasone suppresses the inhibitory serotonergic system and facilitates the excitatory dopaminergic system in the rat telencephalon. This may be a mechanism by which dexamethasone aggravates ischemic neuronal injury.

Animals↗
PubMed2002

Dexamethasone changes the composition of insulin-like growth factor binding proteins in the newborn mouse ileum.

BACKGROUND: Early postnatal glucocorticoid exposure accelerates the maturation of the bowel mucosa but results in bowel wall thinning in the newborn mouse ileum and increases the risk of focal ileal perforation in extremely premature infants. We have previously demonstrated a redistribution of insulin-like growth factor-I (IGF-I) from the submucosa in control animals to the distal villi of those treated with early postnatal dexamethasone, implicating IGF-I as an important mediator of dexamethasone's capacity to alter tissue growth. To investigate the possibility that IGF binding proteins (IGFBPs) might contribute to this process, we characterized the localization and abundance of IGFBP peptides and mRNAs in the same model. METHODS: Newborn mice received daily intraperitoneal injections of dexamethasone (l microg/g) or phosphate-buffered saline and then were euthanized on day 3 of life. Their ileums were harvested and prepared for microscopy. Tissue sections of ileum from both treatment conditions were processed in parallel for immunolocalization of each of the six IGFBP peptides and for in situ hybridization of each of the six IGFBP transcripts. RESULTS: Transcripts for IGFBP-1, -2, and -3 were highly abundant and ubiquitous the ileal mucosa, whereas transcripts for IGFBP-4, -5, and -6 were less abundant in epithelial cells. There were no differences in abundance between control and dexamethasone-treated ileum with regard to mRNA localization or abundance for IGFBP-1, -2, -3, and -6. In contrast, mRNA transcripts for IGFBP-4 and -5 were modestly increased with dexamethasone treatment (although only IGFBP-4 was significant). Strikingly different patterns of IGFBP immunolocalization were observed between control and dexamethasone-treated animals. IGFBP-1, -2, -3, and -5 were not detected in control ileum, whereas IGFBP-4 and -6 were both present in the mucosa. In contrast, dexamethasone treatment resulted in dramatic mucosal increases in IGFBP-2, -3, -4, and -5, paralleling the changing distribution of IGF-I that we previously reported. CONCLUSION: Taken together, these findings further implicate the IGF system as an important participant in dexamethasone-induced maturation in the newborn mouse ileum.

Animals↗
PubMed2002

Efficacy of single-dose dexamethasone as adjuvant therapy for acute pharyngitis.

HYPOTHESIS: Pharyngeal inflammatory pain is reduced by a single dose of dexamethasone. STUDY DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. METHODS: From August 1998 to July 2000, a total of 118 patients were enrolled. We compared placebo (n = 37), a 10-mg single dose of intramuscular injection of dexamethasone (n = 39), and a 10-mg single dose of oral dexamethasone (n = 42). All patients were given oral antibiotics and had bacterial throat cultures. RESULTS: Complete telephone follow-up 12 hours after treatment was available in 111 patients, and 24-hour follow-up data were available in 116. The change in pain visual analogue scale scores (pretreatment score minus 12-h follow-up score) reported by patients who were given either intramuscular (median score, 4; mean score +/- SD, 4.2 +/- 2.3) or oral dexamethasone (median score, 3; mean score +/- SD, 3.8 +/- 2.3) was significantly greater than that of the patients who were given placebo (median score, 2; mean score +/- SD, 2.1 +/- 2.0) (P <.001 and P =.002, respectively). This difference in improvement was also evident when the percentage of change was compared in the three treatment arms at 12-hour and 24-hour follow-up. Patients who were given dexamethasone had the onset of pain relief a median of 4 hours earlier than those who were given oral and intramuscular placebo (P =.029). Statistically significant differences among the three treatment arms were confirmed when a bacterial pathogen was identified (n = 47) but not in a subset that did not have a pathogen identified. CONCLUSIONS: Single-dose dexamethasone appears to be a safe, effective, and inexpensive adjunctive treatment for acute pharyngitis in patients 15 years of age and older. Patients treated with intramuscular or oral dexamethasone had significant relief of pain (relative to baseline) compared with patients who were given placebo. Identification of a bacterial pathogen had a significant impact on the response to dexamethasone.

Acute Disease↗
PubMed1994

Site-specific dexamethasone delivery for the prevention of neointimal thickening after vascular stent implantation.

BACKGROUND: Site-directed pharmacologic therapy using drug-impregnated polymers may achieve high local tissue levels at sites of arterial injury without systemic side effects. The aim of this study was to determine whether sustained, local administration of the synthetic glucocorticoid dexamethasone reduces the severity of intimal hyperplasia induced by arterial stenting in a porcine model of restenosis. METHODS: Dexamethasone-impregnated silicone polymers (20% loading by weight) were formulated and tested in vitro to determine the time course of drug release. Oversized metallic stents were implanted in both carotid arteries of 14 juvenile Yorkshire farm pigs. A dexamethasone-impregnated polymer matrix was then placed around the external surface of the stented artery on one side, and a control polymer was placed contralaterally in an identical manner. Two animals were killed 5 days after stent implantation and the remainder after 35 +/- 1 days. RESULTS: Ex-vivo dexamethasone release from the silicone polymers was estimated to be 5 mg/day for the first 3 days and 0.3 mg/day thereafter. The arterial tissue dexamethasone levels after 5 days were 1307 +/- 498 ng/g of tissue on the treated side and 7.5 +/- 1.0 ng/g of tissue on the control side. The plasma dexamethasone level was 1.6 +/- 0.3 ng/ml, with no step-up in concentration across the segment surrounded by the drug-impregnated polymer. After 35 days, macroscopic examination and computerized morphometric analysis showed a substantial difference in the extent of polymer-induced adventitial and perivascular scarring but no difference in the extent of neointimal thickening. The adventitia:media ratio was 2.99 +/- 0.33 on the dexamethasone-treated side but 4.29 +/- 0.36 on the control side (P < 0.02). The intima:media ratios were 0.48 +/- 0.09 and 0.52 +/- 0.07, respectively. CONCLUSION: Sustained, local dexamethasone therapy has potent anti-inflammatory and anti-fibrotic effects but, with the dose and route of administration used in this study, does not reduce the intimal hyperplastic response to injury in this model.

Animals↗
PubMed2004

Dexamethasone effects on group B streptococcal infection in newborn rats.

BACKGROUND: We previously published that human neutrophil-mediated bacterial killing of group B Streptococcus (GBS) in vitro was dependent on the timing and concentration of dexamethasone exposure. HYPOTHESIS: Dexamethasone treatment would affect neutrophil mediated killing of GBS in an animal model. METHODS: Wistar rat pups were randomly allocated to receive placebo or dexamethasone before, early or late after GBS infection. Suckling rats were infected with 104 or 105 colony-forming units of GBS or nothing. Pups were followed for survival, quantitative bacteremia, growth and neutrophil-mediated bacterial killing. Neutrophils for bacterial killing were obtained via cardiac puncture before infection. Statistics included chi square for survival, Mann-Whitney U test for bacteremia, analysis of variance for growth and paired Student's t test for bacterial killing analyses. RESULTS: Dexamethasone treatment before invasive GBS infection decreases quantitative bacteremia, improves survival and improves neonatal neutrophil-mediated bacterial killing in suckling rats, whereas dexamethasone treatment after infection increases bacteremia and decreases survival. Regardless of timing of dexamethasone treatment, before or after invasive GBS infection, growth was significantly impaired in all suckling rats receiving dexamethasone compared with controls. CONCLUSION: Treatment with dexamethasone before invasive GBS infection improves survival and decreases bacteremia in suckling rats; this appears in part to be mediated by improved neonatal neutrophil-mediated bacterial killing. We speculate that this improvement in outcome may be a result of improved number or function of neutrophil cell surface receptors.

Animals↗
PubMed1994

Dexamethasone promotes ulcer plugging in experimental enteritis.

AIM: We investigated the effect of dexamethasone on indomethacin-induced ulceration in the rat. METHODS: Groups of four rats received oral indomethacin (15 mg/kg) and the jejunal mucosa was examined 24 h later for mucosal ulceration. Three of the groups received oral dexamethasone (1, 3 and 6 mg/kg) 0.5 h prior to indomethacin, while the fourth received vehicle. Haematological evaluation was performed and ulcers were assessed both histologically and immunohistochemically. RESULTS: Indomethacin caused multifocal jejunal ulceration that was reduced only by the highest dose of dexamethasone (6 mg/kg). Indomethacin caused a significant fall in the blood haemoglobin concentration that was prevented by dexamethasone at all doses. The ulcers induced by indomethacin alone were deep, punched-out and haemorrhagic while the ulcers arising in rats pre-treated with dexamethasone (all doses) were 'plugged' by a white fibrino-purulent exudate. Histologically, the dexamethasone ulcer exudate was composed of bacteria, fibrin, mucus and a significant increase in the numbers of neutrophils. Dexamethasone alone had no significant pathological effect on the small intestine. CONCLUSIONS: We report the observation that dexamethasone at high doses inhibits indomethacin-induced jejunal ulceration in the rat while at low doses it promotes 'plugging' of ulcers with bacteria, fibrin, mucus and neutrophils that probably reduces haemorrhage from the ulcer base.

Animals↗
PubMed2007

The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing's states.

OBJECTIVE: Cushing's syndrome (CS), when fully expressed, is easily diagnosed. Mild cases, however, may require careful distinction from pseudo-Cushing's states as may occur in depression, alcoholism, polycystic ovary disease and visceral obesity. The aim of the present study is a reappraisal of the diagnostic accuracy of the two tests most commonly used to differentiate CS from pseudo-Cushing's: corticotropin-releasing hormone (CRH) stimulation after low dose dexamethasone administration and desmopressin stimulation. DESIGN: The study population comprised 32 patients with CS and 23 with pseudo-Cushing's evaluated retrospectively. METHODS: Urinary free cortisol (UFC), serum cortisol at midnight and after low dose dexamethasone (1 mg overnight and 2 mg over two days) were measured. Further, patients were tested with dexamethasone + CRH and desmopressin and the diagnostic performances of the two tests were compared in the entire series as well as in patients with mild hypercortisolism only (i.e. UFC < 690 nmol/24 h). RESULTS: As expected, measurement of UFC, assessment of cortisol rhythmicity and inhibition after 1 mg/2 mg dexamethasone failed to clearly classify patients with pseudo-Cushing's. Administration of CRH following 2-mg dexamethasone achieved 100% sensitivity but 62.5% specificity. Conversely, desmopressin testing correctly classified all but two patients with pseudo-Cushing's (90% specificity) with 81.5% sensitivity. Diagnostic accuracy was comparable in the subgroup with mild hypercortisolism (21 CS, all 23 pseudo-Cushing's patients). Desmopressin offered an incremental diagnostic effectiveness of 35.8/million inhabitants compared with dexamethasone + CRH as a second-line test. CONCLUSIONS: Neither of the two tests guarantees absolute diagnostic accuracy. The specificity of dexamethasone + CRH is less brilliant than previously reported and appears to be inferior to desmopressin stimulation. The greatest diagnostic effectiveness results from the low-dose dexamethasone test combined with the desmopressin test. Skilful use of dynamic testing and balanced clinical judgement are necessary to distinguish between Cushing's syndrome and pseudo-Cushing's.

Adolescent↗
PubMed1981

Induction of metallothionein in HeLa cells by dexamethasone and zinc.

Metallothioneins are induced by both Zn2+ and dexamethasone in HeLa cells grown in serum-free medium. Dexamethasone is able to induce metallothionein synthesis in HeLa cells in virtually zinc-free medium ([Zn2+] = .01 microM). The presence of dexamethasone does not shift the dose/response curve for metallothionein induction by Zn2+, further indicating that the two inducers work through independent mechanisms. Dexamethasone stimulates Zn2+ uptake 1.7-fold over 24 h. However, there is no increase in Zn2+ uptake during the first 4 h. In contrast, metallothionein synthesis in response to either Zn2+ or dexamethasone is clearly observable within 4 h of exposure to either inducer. The increased intracellular 65Zn2+ content observed at 24 h is completely accounted for by the increased level of metal bound to metallothionein. In a continuous labeling experiment the rate of synthesis of metallothionein reached a steady state after about 4 h, in response to either inducer. The lag period was identical for both dexamethasone and Zn2+, with similarly shaped induction curves. Induction by dexamethasone, but not by Zn2+, was inhibited by progesterone. Zn2+ and dexamethasone appear to induce metallothionein synthesis in HeLa cells by mechanisms independent of one another.

Dexamethasone↗
PubMedDate not supplied

A randomized trial of two dexamethasone regimens to reduce side-effects in infants treated for chronic lung disease of prematurity.

OBJECTIVE: Dexamethasone has been widely used to reduce the incidence of chronic lung disease in preterm infants. However side-effects are common, and the ideal dose of dexamethasone has not been identified. We aimed to determine whether an individualized course of dexamethasone given to preterm babies at risk of chronic lung disease reduced the total dose of dexamethasone administered and reduced side-effects compared with a standard 42-day course. METHODS: Thirty-three infants in a regional neonatal unit with a birthweight of < or =1250 g who required mechanical ventilation at 7 days of age were randomly assigned to a 42-day course of dexamethasone or an individualized course tailored to their respiratory status. The primary outcome was linear growth at 36 weeks corrected gestational age. RESULTS: Infants in the individualized course received a 40% lower total dose of dexamethasone. However, there was no difference between the two groups in linear growth or in the incidence of any other side-effects of treatment. There was also no difference in respiratory status or neurodevelopmental outcome. CONCLUSION: The individualized course of dexamethasone used in this study reduced the total dose of dexamethasone administered but did not significantly reduce side-effects of treatment or alter outcome in infants at risk of chronic lung disease.

Anti-Inflammatory Agents↗
PubMed1988

The dexamethasone suppression test for Japanese with eating disorders.

A one-mg oral overnight dexamethasone suppression test (DST) was conducted on 22 inpatients with eating disorders. To confirm that the dexamethasone tablets had been ingested, we measured the plasma concentrations of dexamethasone the next morning (at 0900 hr after DST). The diagnosis of anorexia nervosa and bulimia was made according to the criteria for DSM-III, respectively. Of the 22 patients with eating disorders, 16 satisfied the criteria for anorexia nervosa and 6 for bulimia. The DST was carried out within 2 weeks of hospitalization on each patient. The subjects were given 1 mg of dexamethasone in the evening (at 2300 hr) and blood samples were collected the following day (at 0900, 1600 and 2100 hr, respectively). The plasma cortisol and dexamethasone levels were concurrently determined by RIA. The criterion for non-suppression was a failure to suppress the plasma cortisol levels below 5.0 micrograms/dl in any one of the three samples. All but one patient with bulimia had ingested the dexamethasone. Thirteen (62%) of 21 patients with eating disorders were nonsuppressors. We found a significant positive correlation between the plasma cortisol levels at 1600 hr or 2100 hr and a decrease in ideal body weight (n = 16, r = 0.613, p less than 0.05; r = 0.75, p less than 0.01, respectively) and a significant inverse relationship between the plasma dexamethasone levels at 0900 hr and the plasma cortisol levels at 1600 hr was recognized (n = 21, r = 0.631, p less than 0.01). These results suggest that the blood dexamethasone levels as well as body weight might contribute to the abnormalities of DST seen in patients with eating disorders.

Anorexia Nervosa↗
PubMed1994

Dexamethasone and fetal heart rate variation.

OBJECTIVE: To determine the effect of maternal administration of dexamethasone on fetal heart rate and its variation. DESIGN: Retrospective analysis of computerised data derived from cases studied over three years. SETTING: High risk pregnancy unit, John Radcliffe Hospital, Oxford. SUBJECTS: Twenty-eight pregnant women, at 27 to 32 weeks of gestation, to whom dexamethasone was given to accelerate pulmonary maturation in the expectation of preterm delivery. METHODS: Dexamethasone (two doses of 12 mg intramuscularly, 12 h apart) was given on 51 occasions at weekly intervals (one to four occasions per patient). Complete data were available for cardiotocograph analysis from computerised measurement of fetal heart rate variables for two days before and four days after dexamethasone and, in 19 women, measurements of umbilical arterial flow velocity waveforms before and after dexamethasone. RESULTS: In 10 pregnancies without fetal distress there was a highly significant (P < 0.01) transient rise in short term fetal heart rate variation after dexamethasone administration, from means (SE) 6.4 (0.28) to 9.8 (0.4) ms. In 18 pregnancies with subsequent delivery for fetal distress (abnormal fetal heart rate pattern) and high umbilical arterial resistance index [mean 0.93 (0.06 SE)], the rise in short term fetal heart rate variation was less (P < 0.01), from mean (SE) 5.4 (0.26) to 6.1 (0.48) ms. In a further case of discordant twin pregnancy, the larger twin continued to respond to dexamethasone administrations with a rise in fetal heart rate variation for five weeks; the smaller twin, with maintained tachycardia and reduced umbilical arterial end-diastolic flow velocity, failed to respond after the first two weeks. CONCLUSION: The results show that maternal dexamethasone administration normally causes a rise in fetal heart rate variation for up to a day. This rise is reduced in pre-eclampsia or intrauterine growth retardation, associated with a reduction in umbilical flow, perhaps because of a consequential lower concentration of steroid in the fetus. The results contrast with those for betamethasone which has been reported to reduce fetal heart rate variation.

Blood Flow Velocity↗
PubMed1996

An interaction of ondansetron and dexamethasone antagonizing cisplatin-induced acute and delayed emesis in the ferret.

1. Cisplatin, 5 mg kg-1, i.p., administered as a single treatment, induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of ondansetron and dexamethasone and their interaction over a three day period. 2. Ondansetron, 1 mg kg-1, i.p., administered three times per day in two experiments, antagonized significantly the retching and vomiting that occurred on days 1 and 2 by 60-76 and 73-84%. On the third day of treatment there was a trend for a 38% reduction in one experiment and a 74% reduction in the other. 3. There was a trend for dexamethasone, 1 mg kg-1, i.p., administered as a single daily injection for three days, to reduce by 37% the retching and vomiting response that occurred on day 1, the reduction of 77% on day 2 achieved significance and dexamethasone non-significantly increased the retching and vomiting response by 46% on day 3. However, dexamethasone 1 mg kg-1 i.p. administered three times per day for three days significantly reduced the retching + vomiting response by 85, 97 and 86% on days 1, 2 and 3 respectively. 4. The combination of dexamethasone, 1 mg kg-1, i.p., as single daily injections with ondansetron, 1 mg kg-1, i.p., administered three times per day improved the control of the retching and vomiting response, significantly reducing the total numbers of retches and vomits by more than 70% over a three day period. The combination of dexamethasone (1.0 mg kg-1) and ondansetron (1.0 mg kg-1), both administered three times daily, abolished cisplatin-induced emesis over the three day period. 5. The three times per day administration of ondansetron, 1 mg kg-1, i.p., plus dexamethasone, 1 mg kg-1, i.p., administered only on day 1 prevented day 1 emesis but did not modify the retching and vomiting that occurred on days 2 and 3. 6. The present results indicate that ondansetron and dexamethasone significantly reduce cisplatin-induced emesis in the ferret during both the acute and delayed phase; drug/co-treatment can exert an additive action to abolish cisplatin-induced emesis. The ferret model may be useful to detect anti-emetic drug action for treatment of chemotherapy-induced acute and delayed emesis in man.

Animals↗
PubMed1996

Regulation of histamine H1 receptor coupling by dexamethasone in human cultured airway smooth muscle.

1. The regulation of histamine-induced [3H]-inositol phosphate and intracellular calcium responses in human cultured airway smooth muscle cells was studied. 2. Histamine induced concentration-dependent [3H]-inositol phosphate formation (EC50 4 microM). This response was inhibited by a range of selective H1 receptor antagonists but not by the H2-selective antagonist, tiotidone or the H3 receptor-selective antagonist, thioperamide, indicating that an H1 receptor is involved in this response in human cultured airway smooth muscle cells. 3. Preincubation of human cultured airway smooth muscle cells with concentrations of dexamethasone > 10 nM for 22 h produced concentration-dependent inhibition of histamine-induced inositol phosphate formation. The maximum inhibition observed was 45% of the response in control cells. The inhibitory effect of dexamethasone was itself reversed by prior exposure to the glucocorticoid receptor antagonist, RU38486 (10 microM). Preincubation for 22 h with 1 microM dexamethasone produced inhibition of the inositol phosphate response to histamine to all concentrations of histamine inducing significant inositol phosphate formation in these cells. In contrast, the response to the G protein activator, NaF (0.1-20 mM) was unaltered by preincubation with dexamethasone. 4. Preincubation of human airway smooth muscle cells with 1 microM dexamethasone for time periods of < 6 h failed to inhibit histamine-induced inositol phosphate formation in human airway smooth muscle cells. 5. Histamine also induced concentration-dependent elevation of intracellular calcium levels in Fura 2-loaded human airway smooth muscle cells. This response was inhibited by preincubation with 1 microM dexamethasone. 6. We conclude that signal transduction through the H1 receptor in human airway smooth muscle is subject to regulation by dexamethasone and that this may in part account for the protective effect of dexamethasone against spasmogen-induced contractile responses in the airways.

Anti-Inflammatory Agents↗