Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DEXAMETHASONE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1981

Dexamethasone for prevention of respiratory distress syndrome: multiple perinatal factors.

Antepartum dexamethasone administration was associated with a significant lowering of the incidence of respiratory distress syndrome (RDS) and with marked reduction of early neonatal mortality in premature infants. Dexamethasone had its greatest effect in infants delivered between 28 and 32 weeks' gestation (P < .001), and the difference was still significant up to 34 weeks' gestation (P < .05). Although the effect of dexamethasone was more marked in patients with intact membranes, it was also effective in those with prolonged rupture of the membranes. Membrane condition before delivery was unrelated to the incidence of RDS. The effectiveness of dexamethasone was analyzed with respect to the condition of the infant at delivery, the mode of delivery, and multiple births. As compared to the controls, dexamethasone was most effective in singletons, infants delivered vaginally, and those with high Apgar scores. The effect of dexamethasone was not significant in twins, breech deliveries, cesarean section deliveries, or infants with low Apgar scores. The effects of dexamethasone appear to be modified by intrauterine asphyxia. Dexamethasone therapy cannot be substituted for optimal delivery conditions of the premature.

Dexamethasone↗
PubMed1982

Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation.

The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin-B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.

Cell Aggregation↗
PubMed1980

High performance liquid chromatographic assay of dexamethasone in plasma and tissue.

Dexamethasone in plasma and in tissue is specifically quantitated by high performance liquid chromatography (ultraviolet detection at 254 nm) with an octadecyl silane reversed-phase chromatographic column employing peak-height ratio determination (internal standard, cyheptamide). The sample is first washed with heptane under alkaline conditions. The dexamethasone is then extracted from the washed sample with dichloromethane containing the internal standard. Dichloromethane is evaporated to dryness, and the concentrated extract is dissolved in tetrahydrofuran and then injected into a high performance liquid chromatograph. Dexamethasone and internal standard are eluted with a mixture of acetic acid, methanol, butanol, and water (11/19/30/440 by volume). Sensitivity limit is 10 ng, with linear response to at least 1.000 mg/liter plasma. Analytical recovery of dexamethasone from plasma is almost complete, and approximately 87% dexamethasone is recovered from brain tissue. Intra-assay precision (CV) is 1.07% (N = 11), and interassay precision is 1.38% (N = 5). No interference occurred in plasmas from patients treated with various drugs other than dexamethasone. Dexamethasone was estimated in plasma and in tumor tissue from patients on dexamethasone therapy.

Administration, Oral↗
PubMed1980

Shock-induced cytoplasmic NADH fluorescence changes in the living cat brain cortex: effect of dexamethasone.

The effect of dexamethasone administration on cerebrocortical NADH fluorescence, blood flow and blood volume, intracellular oxygen tension and electrocorticogram (ECoG) was studied in anaesthetized cats in two sets of experiments. Haemorrhagic shock was induced by stepwise decrease of mean arterial blood pressure from the control level a to 80, 60 and 40 mmHg. The bleeding was followed by reinfusion of the shed blood. The method of producing shock was identical in the untreated and dexamethasone treated groups. Dexamethasone was administered in the control period. The results are summarized as follows: (a) Dexamethasone, given in pharmacological doses failed to alter blood flow or blood volume, NADH fluorescence and the intracellular oxygen tension in the cerebral cortex of the cat; (b) Haemorrhagic shock resulted in a marked increase of cytoplasmic NADH fluorescence in the untreated group, while these changes were much smaller in the dexamethasone pretreated animals; (c) Dexamethasone pretreatment significantly reduced the extent of shock-induced cortical vasodilatation. In some experiments the brain cortex became ischaemic at 40 mmHg MABP; (d) Dexamethasone pretreatment failed to eliminate the shock-induced decrease in cortical intracellular oxygen tension and the irreversible deterioration of ECoG. It is suggested that the decrease in cortical cytoplasmic NAD reduction and the concomitant lactate acidosis might be involved in the ability of dexamethasone to control oedema during shock and other pathological conditions.

Animals↗
PubMed1995

Use of dexamethasone in the outpatient management of acute laryngotracheitis.

OBJECTIVE: Recent studies have demonstrated that a single intramuscular injection of dexamethasone (0.6 mg/kg) shortens the duration and severity of illness in hospitalized patients with acute viral laryngotracheitis (croup). Our objective was to determine if dexamethasone has a role in the outpatient management of patients with acute viral croup of moderate severity. METHODS: Patients, 6 months to 5 years of age, who came to the emergency department (ED) with acute viral croup, a croup score of at least 2 (range 0 to 17), and a disposition of discharge were randomized in a double-blind fashion to receive a single intramuscular injection of dexamethasone, 0.6 mg/kg, or an equal volume of normal saline before discharge from the ED. Patients were excluded if they had any structural abnormalities, had received any steroids in the preceding 24 hours, or if they required beta-agonist therapy, more than one racemic epinephrine treatment, or hospitalization. Patients were followed up by telephone 24 hours and 7 to 10 days after discharge to determine whether additional medical attention was sought for perceived lack of improvement or worsening of symptoms. Secondary outcome included the parents' perception of how the child was doing at 24 hours, based on a 4-point ordinal scale: worse (1), same (2), improved (3), symptoms resolved (4), and the number of days it took for complete recovery. RESULTS: Of the 38 patients comprising the study group, 19 received dexamethasone. The median age was 19 months (range 6 to 66 months), and median pretreatment croup score was 3 (range 2 to 5) for both groups. The number of patients requiring racemic epinephrine was similar in both groups. Five patients sought additional medical attention within 48 hours. Four of the five patients had received placebo (21% of the placebo group) and one had received dexamethasone (5% of the steroid group) (not statistically significant). At the 24-hour telephone follow-up, significantly more patients in the dexamethasone group had a score consistent with improvement compared with placebo (84% vs 42%, P = .003). There was no difference in the number of days for symptoms to completely resolve between the two groups. CONCLUSION: The use of dexamethasone in the outpatient management of viral croup was associated with a reduction in severity of illness within 24 hours after treatment. Patients with viral croup of moderate severity should be considered as candidates for the use of dexamethasone before discharge from the ED.

Ambulatory Care↗
PubMed1994

Dexamethasone-induced haptoglobin release by calf liver parenchymal cells.

Parenchymal cells were isolated from the liver of male calves, and monolayer cultures formed were treated with glucocorticoids to examine whether haptoglobin, appearance of which is associated with hepatic lipidosis (fatty liver) in cattle, is induced by steroid hormones. Without addition of dexamethasone, only trace amounts of haptoglobin were detected in culture medium. With addition of dexamethasone (10(-12) to 10(-4) M), considerable amounts of haptoglobin were released into the medium. Maximal release was observed at concentrations of 10(-8) to 10(-6) M dexamethasone. Haptoglobin release was similarly induced by cortisol, although the effect was less potent than that of dexamethasone. Actinomycin D (a known protein synthesis inhibitor) dose-dependently reduced amounts of haptoglobin released in response to 10(-8) M dexamethasone. Dexamethasone also induced annexin I, which is known to be synthesized in response to glucocorticoids. Dexamethasone treatment resulted in reduced protein kinase C activity in the cell cytosol, which has been shown to be an early event in dexamethasone-treated cells. Other than glucocorticoids, estradiol induced haptoglobin release, whereas progesterone was less effective. The association of haptoglobin with hepatic lipidosis can be reasonably explained by the fact that haptoglobin production by the liver is induced by glucocorticoids and estradiol, and these steroid hormones are triggers for development of hepatic lipidosis in cattle.

Animals↗
PubMed1994

The sequential appearance of sperm abnormalities after scrotal insulation or dexamethasone treatment in bulls.

Scrotal insulation and dexamethasone treatment were used as a model to compare the effect of testicular heating and stress on spermatogenesis. Insulation was applied to the scrotum of eight bulls (insulated) for a period of four days, eight bulls were treated daily for seven days with 20 mg dexamethasone injected intramuscularly, and four bulls were untreated controls. Semen from four bulls in each group was collected and evaluated over a six-week period after treatment. Blood samples for testosterone analysis were taken hourly for eight hours at the beginning and the end of the six-week period from the control bulls and before and after treatment from the four insulated and four dexamethasone-treated bulls that were not used for semen collection. At the end of the last blood sampling period, the four bulls in each group were castrated for the collection of testicular tissue for the determination of testosterone concentrations. Basal, peak episodic, and mean serum testosterone concentrations among control bulls, pre and postinsulated bulls, and pretreatment samples of dexamethasone-treated bulls were not different (p > 0.05); however, bulls that had received dexamethasone treatments had significantly lower basal, peak episodic, and mean testosterone concentrations (p < 0.05). Tissue concentrations of testosterone in control, insulated, and dexamethasone-treated bulls were not significantly different but tended to be lower in dexamethasone-treated bulls (p > 0.13). The spermiograms of the control bulls varied insignificantly over the six-week sampling period; however, there was a marked increase in sperm defects in insulated and dexamethasone-treated bulls. The types of sperm defects and the temporal relationships of rises and declines of sperm defects were quite similar for both treatments. All bulls recovered to approximately pretreatment levels of sperm defects by six weeks after the initiation of treatment. Results indicate that two of the most common types of insults to spermatogenesis in bulls, heat and stress, result in similar spermiograms.

Animals↗
PubMed1993

C3 synthesis by A549 alveolar epithelial cells is increased by interferon-gamma and dexamethasone.

The third component of complement, C3, is produced in the lung by several cell types including alveolar epithelial cells. Since interferon-gamma (IFN-gamma) and dexamethasone regulate C3 gene expression in non-pulmonary cells, and because IFN-gamma and dexamethasone interact to regulate the functional activity of alveolar epithelial cells, we investigated the effects of IFN-gamma and dexamethasone on C3 production by A549 human alveolar epithelial cells. Treatment of A549 cells with IFN-gamma alone increased C3 production in a time-and dose-dependent manner. Maximal increase in C3 production occurred after stimulation of A549 cells with 500 IU/ml IFN-gamma for 3 days and was 3.4-fold greater than control. Dexamethasone (0.1 microM) stimulation of A549 cells increased C3 production 6.7-fold over controls on day 3. Treatment of A549 cells with IFN-gamma plus dexamethasone resulted in an 11-to 13-fold increase in C3 synthesis. C3 mRNA levels were increased in A549 cells treated with IFN-gamma and dexamethasone individually and in combination suggesting that IFN-gamma and dexamethasone increase C3 synthesis by a pre-translational mechanism. IFN-gamma and dexamethasone did not alter the two-chain structure of the C3 molecule produced by A549 cells, as assessed by Western blotting. We speculate that IFN-gamma and glucocorticoids may be important in the local regulation of C3 synthesis in the lung.

Blotting, Northern↗
PubMedDate not supplied

Renal calcification: a complication of dexamethasone therapy in preterm infants with bronchopulmonary dysplasia.

We have previously reported a case study in which renal calcification formation may have been a complication of dexamethasone exposure in an infant with bronchopulmonary dsyplasia. To determine whether dexamethasone is associated with renal calcification formation, we conducted a prospective, nonrandomized study of 36 infants < 30 weeks' gestation and weighing < 1250 gm treated with dexamethasone because of bronchopulmonary dysplasia and compared them with a group not receiving dexamethasone. We identified seven infants in the dexamethasone group (n = 19) but no infant in the comparison group (n = 17) with renal calcifications at 2 months of age (p = 0.008). The urinary calcium excretion tended to be increased (15.5 +/- 16.6 vs 6.9 +/- 6.7 mg/kg/day ¿p = 0.05¿) and the calcium/creatinine ratio was significantly greater in the dexamethasone group (1.2 +/- 1.0 vs 0.6 +/- 0.4 ¿p = 0.02¿). Infants who received dexamethasone were significantly smaller 819.1 +/- 141.1 vs 954.6 +/- 141 gm ¿p = 0.008¿), were younger (26.2 +/- 1.7 vs 27.7 +/- 1.2 weeks ¿p = 0.004¿), received ventilator support longer (33.3 +/- 14.7 vs 12.1 +/- 14.7 days ¿p = 0.0001¿), and required more days of supplemental oxygen (54.3 +/- 9.7 vs 36.4 +/- 23.8 days ¿p = 0.009¿). We conclude that smaller, younger, and sicker infants are at the highest risk for the development of renal calcifications and that dexamethasone may be associated with increased urinary calcium excretion, which contributes to renal calcification formation.

Bronchopulmonary Dysplasia↗
PubMed1996

Cardiac effects of dexamethasone in very low birth weight infants.

OBJECTIVE: To characterize the cardiac effects of dexamethasone in very low birth weight infants. DESIGN: Prospective, randomized, placebo-controlled, double-blind trial. Enrolled subjects were randomized to receive either a 42-day tapering course of dexamethasone or a saline placebo. Echocardiographic measurements were obtained on days 0, 7, 14, 28, and 42. SUBJECTS: Thirteen infants received dexamethasone and 13 a saline placebo. The two groups were similar in birth weight, gestational age, age at enrollment, and sex/ race composition. RESULTS: Patients receiving dexamethasone had a significantly larger increase in septal thickness on days 7, 14, and 28 and left ventricle (LV) posterior wall thickness on day 14. A significantly lower left ventricular end-diastolic dimension in the dexamethasone group was initially noted on day 7 and persisted until day 42. With the reduced left ventricular end-diastolic dimension, no significant differences in LV mass were noted, despite the increased wall thickness. No differences in LV systolic function, as assessed by area shortening, were seen. Assessment of diastolic function showed a significant increase in the atrial portion of mitral inflow in dexamethasone patients on day 14, as well as a significant prolongation in isovolumic relaxation time on days 7, 14, and 28. CONCLUSIONS: Infants receiving dexamethasone developed evidence for impaired LV filling with a lager increase in wall thickness but no increase in LV mass, asymmetric septal hypertrophy, or augmented systolic function. This suggests that alterations in left ventricular filling play an important role in the development of hypertrophy seen with dexamethasone administration.

Anti-Inflammatory Agents↗
PubMed1996

Activation of the mitogen-activated protein kinase cascade is suppressed by low concentrations of dexamethasone in mast cells.

Antigen stimulation of mast cells via the IgE receptor, Fc epsilon RI, results in recruitment of the cytosolic tyrosine kinases, Lyn and Syk, and the phosphorylation of proteins. We examined the effects of the glucocorticoid dexamethasone on these events in a cultured (RBL-2H3) mast cell line. Nanomolar concentrations of dexamethasone suppressed phosphorylation of proteins that were associated with the activation of the mitogen-activated protein (MAP) kinase/phospholipase A2 pathway without inhibiting initial events. For example, tyrosine phosphorylation of the subunits of Fc epsilon RI, Lyn, or Syk or of the Ras-guanine nucleotide exchange factor, Vav, was not suppressed in cells treated with up to 1 microM dexamethasone. In contrast, phosphorylation of Raf1, MEK1, p42mapk, and cytosolic phospholipase A2, as well as the associated increase in MAP kinase activity and release of arachidonic acid, were markedly inhibited in cells treated with as little as 10 nM dexamethasone--a concentration that only partially inhibited hydrolysis of inositol phospholipids or release of secretory granules. Prolonged exposure to dexamethasone also resulted in a partial decrease in expression of MEK1, p42mapk, and cytosolic phospholipase A2, which may contribute further to the effects of dexamethasone on this pathway. Activation of the MAP kinase/phospholipase A2 pathway by the calcium-mobilizing agent thapsigargin was similarly suppressed in dexamethasone-treated cells. These findings suggested that an early step in the pathway, possibly a step immediately before the activation of Raf1, was suppressed by low concentrations of dexamethasone.

Animals↗
PubMed1996

[Dexamethasone's effect on glutamate receptor in experimental hypoxic-ischemic cerebral injury].

In order to probe into dexamethasone's effect on glutamate receptor (Glu R) in hypoxic-ischemic encephalopathy (HIE) of newborn, we established newborn pigs' model of HIE to investigate Glu R in their forebrain crude synaptic membrane and the effect of dexamethasone in different HIE times and different dosages on the changes of Glu R. This study included five groups: HIE group (no medication); dexamethasone treatment group (10 mg/kg before HIE); dexamethasone treatment group (10 mg/kg after HIE); dexamethasone treatment group (5 mg/kg before HIE); dexamethasone treatment group (5 mg/kg after HIE). The results showed that the mean receptor density (Bmax) of dexamethasone treatment group (10 mg/kg before HIE) was significantly lower than that of the other groups (P < 0.05), but there was no statistic difference in the affinity of Glu R between all the experimental groups. These findings suggested that the preventive use of dexamethasone in large dosage would reduce the binding of Glu, and could possibly protect the brain tissues from damage in HIE.

Animals↗
PubMed1998

[Effect of concurrent use of ondansetron hydrochloride and dexamethasone against nausea and vomiting in lung cancer patients receiving cisplatin].

We examined the efficacy of concurrent use of ondansetron hydrochloride and dexamethasone, and the effective dose of dexamethasone against nausea and vomiting in lung cancer patients receiving chemotherapy including single high dose cisplatin. The study was carried out on total of 44 courses of chemotherapy in either initial onset or recurrence of lung cancer. The patients were given 4 mg of ondansetron injection on the day of cisplatin injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 4. These patients were randomly allocated into 2 groups, i.e., those who, on Day 2, concomitantly received 10 mg of dexamethasone (D10 Group, 22 courses) or 20 mg (D20 Group, 22 courses), for comparing the antiemetic effects in a different concomitant dose of dexamethasone. An efficacy rate of 70% or more was achieved in each group for acute emesis on Day 1. The efficacy rate was 80% or above for emesis on Day 2 when dexamethasone was concurrently administered, and Days 3 and 4 in both groups. No significant difference was observed between the groups. A higher complete suppression rate against nausea was seen in D20 Group even though the difference from D10 Group was not significant. Furthermore, food intake rate on Day 2 was significantly better in D20 Group. However, in the cases that were graded effective or markedly effective for acute emesis on Day 1, the efficacy rate was also high in both groups through Days 2-4. It was notable that the efficacy rate of Days 2-4 was 100% in D2 Group. The high efficacy rate was shown in male patients regardless of which dose of dexamethasone was used. However, control of emesis was unfavorable in female patients on Day 1 and was still unfavorable even though dexamethasone was combined from Day 2. We considered from the above results that 10 mg/day of concurrent dexamethasone is sufficient in suppression of delayed emesis on Day 2. However, in order to improve nausea or food intake, or to suppress emesis in patients who are highly likely to show unfavorable control for Day 2 and onward, 20 mg/day should also be effective.

Aged↗
PubMed2006

Dexamethasone diminishes the pro-inflammatory and cytotoxic effects of amyloid beta-protein in cerebrovascular smooth muscle cells.

BACKGROUND: Cerebrovascular deposition of fibrillar amyloid beta-protein (Abeta), a condition known as cerebral amyloid angiopathy (CAA), is a prominent pathological feature of Alzheimer's disease (AD) and related disorders. Accumulation of cerebral vascular fibrillar Abeta is implicated in promoting local neuroinflammation, causes marked degeneration of smooth muscle cells, and can lead to loss of vessel wall integrity with hemorrhage. However, the relationship between cerebral vascular fibrillar Abeta-induced inflammatory responses and localized cytotoxicity in the vessel wall remains unclear.Steroidal-based anti-inflammatory agents, such as dexamethasone, have been reported to reduce neuroinflammation and hemorrhage associated with CAA. Nevertheless, the basis for the beneficial effects of steroidal anti-inflammatory drug treatment with respect to local inflammation and hemorrhage in CAA is unknown. The cultured human cerebrovascular smooth muscle (HCSM) cell system is a useful in vitro model to study the pathogenic effects of Abeta in CAA. To examine the possibility that dexamethasone may influence CAA-induced cellular pathology, we investigated the effect of this anti-inflammatory agent on inflammatory and cytotoxic responses to Abeta by HCSM cells. METHODS: Primary cultures of HCSM cells were treated with or without pathogenic Abeta in the presence or absence of the steroidal anti-inflammatory agent dexamethasone or the non-steroidal anti-inflammatory drugs indomethacin or ibuprofen. Cell viability was measured using a fluorescent live cell/dead cell assay. Quantitative immunoblotting was performed to determine the amount of cell surface Abeta and amyloid beta-protein precursor (AbetaPP) accumulation and loss of vascular smooth cell alpha actin. To assess the extent of inflammation secreted interleukin-6 (IL-6) levels were measured by ELISA and active matrix metalloproteinase-2 (MMP-2) levels were evaluated by gelatin zymography. RESULTS: Pathogenic Abeta-induced HCSM cell death was markedly reduced by dexamethasone but was unaffected by ibuprofen or indomethacin. Dexamethasone had no effect on the initial pathogenic effects of Abeta including HCSM cell surface binding, cell surface fibril-like assembly, and accumulation of cell surface AbetaPP. However, later stage pathological consequences of Abeta treatment associated with inflammation and cell degeneration including increased levels of IL-6, activation of MMP-2, and loss of HCSM alpha actin were significantly diminished by dexamethasone but not by indomethacin or ibuprofen. CONCLUSION: Our results suggest that although dexamethasone has no appreciable consequence on HCSM cell surface fibrillar Abeta accumulation it effectively reduces the subsequent pathologic responses including elevated levels of IL-6, MMP-2 activation, and depletion of HCSM alpha actin. Dexamethasone, unlike indomethacin or ibuprofen, may diminish these pathological processes that likely contribute to inflammation and loss of vessel wall integrity leading to hemorrhage in CAA.

Journal Article↗
PubMed1990

Transient inhibition of RU 486 antiglucocorticoid action by dexamethasone.

RU 486 antagonizes both progesterone and glucocorticoids at the receptor level. To study the duration of RU 486 antiglucocorticoid activity on corticotropic function and to establish the means of overcoming it with dexamethasone, plasma corticolipotropic hormones and cortisol were measured in 10 healthy male patients during the 3 days after intake, at 2200 h, of a single 400-mg dose of RU 486, alone or combined with a single dexamethasone dose (1, 2, or 4 mg) given at 2400 h. On the first day after RU 486 alone, ACTH, lipotropin, and cortisol plasma levels were significantly higher than basal values. The 1-mg dose of dexamethasone totally abolished the stimulatory effect of RU 486, and higher doses of dexamethasone (2 and 4 mg) further depressed hormone levels. During the succeeding days, antiglucocorticoid activity of RU 486 alone was still present 34 h after administration, while on the third day all hormone levels returned to normal. After the combined administration, the RU 486 effect reappeared as early as the first day with the 1-mg dose of dexamethasone, while it was delayed until the third day with the higher doses. These results showed that a single 400-mg dose of RU 486 induced a response that lasted at least 34 h. Thus, a dose-dependent competition between RU 486 and dexamethasone was demonstrated. However, the suppressive effect of dexamethasone was only transient, after which the antiglucocorticoid activity of RU 486 reappeared.

Adrenocorticotropic Hormone↗
PubMed1989

Collagen shield enhancement of topical dexamethasone penetration.

Collagen corneal shields were investigated as a vehicle for enhancing the ocular penetration of topical 0.1% dexamethasone alcohol in rabbit eyes. Four protocols were compared: a single dexamethasone drop, hourly drops, a 24-hour collagen shield presoaked in 0.1% dexamethasone, and a presoaked collagen shield followed by hourly drops. Dexamethasone concentrations in the cornea, aqueous, iris, and vitreous were measured by radioassay at six time intervals, and cumulative drug delivery over 6 hours was calculated for each tissue. Treatment with a presoaked collagen shield plus hourly drops resulted in peak and cumulative drug delivery to the cornea, aqueous, iris, and vitreous that was twofold to fourfold higher than delivery achieved with hourly drops alone. A presoaked shield by itself yielded equivalent or superior peak and cumulative drug delivery compared with a regimen of hourly drops. Collagen shields significantly enhance topical dexamethasone penetration and may be useful for maximizing the intraocular delivery of dexamethasone and for decreasing the required frequency of topical dexamethasone administration.

Animals↗
PubMed2000

Treatment of chronic suppurative otitis media with topical tobramycin and dexamethasone.

OBJECTIVES: To investigate the safety and efficacy of a topical combination of tobramycin and dexamethasone in a primate model of chronic suppurative otitis media (CSOM) and to explore the contribution of the added topical steroid for the treatment of CSOM. DESIGN: Blinded, randomized, placebo-controlled trial. SUBJECTS: Sixty juvenile cynomolgus monkeys randomized into the following 6 treatment groups of 10 monkeys each: 0.3% tobramycin (group 1), combined 0.3% tobramycin-0.1% dexamethasone (group 2), combined 1.0% tobramycin-0.33% dexamethasone (group 3), 0.1% dexamethasone (group 4), vehicle (group 5), and phosphate-buffered saline solution (group 6). INTERVENTIONS: Chronic suppurative otitis media was established by inoculating the right ear with Pseudomonas aeruginosa. After 4 weeks of drainage, animals were treated according to the group assignment with 3 drops twice daily for 7 weeks. Hearing thresholds were monitored with repeated auditory brainstem response testing (ABR), and clinical response was monitored with repeated otoscopic examinations and cultures throughout the study. Cytocochleograms were evaluated for quantification of outer hair cell loss. RESULTS: Rapid resolution of otorrhea and eradication of P aeruginosa occurred in all groups receiving tobramycin. The inclusion of dexamethasone accelerated the resolution of otorrhea and negative yields of cultures compared with tobramycin alone. Otorrhea and positive culture findings persisted in the groups not treated with topical antibiotic. Results of ABRs at 4 and 8 weeks and cytocochleograms for outer cell hair loss were not affected by drug administration. Perilymph samples collected at the end of the study showed no detectable tobramycin. CONCLUSIONS: Combined tobramycin-dexamethasone ear drops were safe and effective in the monkey CSOM model. Dexamethasone enhanced the efficacy of tobramycin.

Administration, Topical↗
PubMed1999

Lipid intolerance in neonates receiving dexamethasone for bronchopulmonary dysplasia.

BACKGROUND: We hypothesized that dexamethasone induces hypertriglyceridemia (triglyceride levels >2.82 mmol/L [250 mg/dL]) and increases free fatty acid (FFA) levels and that steroid-induced hypertriglyceridemia is associated with hyperinsulinemia and elevated FFA levels. OBJECTIVE: To study the effect of dexamethasone sodium phosphate on lipid metabolism in neonates receiving intravenous lipids. DESIGN: A prospective cohort study with patients serving as their own controls. SETTING: Neonatal Intensive Care Unit, Children's Hospital at Strong, Rochester, NY. METHODS: All neonates younger than 29 weeks' gestational age at birth receiving 3 g/kg per day of intravenous lipids who were to start dexamethasone therapy for bronchopulmonary dysplasia were eligible. Exclusion criteria included neonates with active infection, prior hypertriglyceridemia, bleeding manifestations, recent surgery, thyroid medication, and human recombinant insulin intravenous infusion therapy. Ten neonates were studied. Blood was drawn for triglyceride, FFA, and insulin assays before initiating and at 1, 2, 3, and 5 days after starting dexamethasone therapy. On day 3, dexamethasone dosage was decreased as per protocol. Intravenous lipid intake was kept constant. Statistical analysis was done using a paired t test. RESULTS: Six of 10 neonates reached a state of hypertriglyceridemia (95% confidence interval, 26.2%-87.8%). The mean average increase in triglycerides, insulin, and FFA levels in neonates receiving 3 g/kg per day of intravenous lipids after initiation of dexamethasone therapy was 0.75 mmol/L (66.6 mg/dL) (P=.007), 127 pmol/L (P = .006), and 47.5 micromol/L (P = .65), respectively. Six neonates who developed hypertriglyceridemia had significantly elevated mean peak FFA levels (918.3 micromol/L) prior to developing hypertriglyceridemia compared with 4 neonates (mean peak FFA levels, 380.2 micromol/L) who had triglyceride levels lower than 2.82 mmol/L (250 mg/dL) (P = .002). CONCLUSION: We conclude that dexamethasone induces hypertriglyceridemia in the presence of hyperinsulinemia and increased FFA levels.

Bronchopulmonary Dysplasia↗