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PubMed1984

Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone.

Approximately 50% of depressed patients are resistant to the cortisol-suppressing effect of dexamethasone. To determine if glucocorticoid resistance could be a more generalized phenomenon in depressed patients, mitogen stimulation tests were performed on lymphocytes from 12 depressed patients and 12 control subjects before and after dexamethasone administration. Suppression of serum cortisol following administration of 1 mg of dexamethasone in four depressed patients and 11 control subjects was associated with a decreased lymphoproliferative response, but no such change occurred in the eight depressed patients and the single control subject who did not suppress cortisol. The dexamethasone-induced changes in the mitogen responses were positively correlated with the highest postdexamethasone serum cortisol values.

Adult↗
PubMed2006

Comparison of the dexamethasone-suppressed corticotropin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing's syndrome.

CONTEXT: The low-dose dexamethasone suppression test (LDDST) is widely used in confirming a diagnosis of Cushing's syndrome. CRH administration at the end of an LDDST has been reported to improve the diagnostic accuracy of this test. OBJECTIVE: Our objective was to assess whether CRH administration after a standard LDDST (LDDST-CRH test) improves diagnostic accuracy in Cushing's syndrome. DESIGN, SETTING, AND PARTICIPANTS: Thirty-six individuals with a clinical suspicion of Cushing's syndrome each completed a standard LDDST and an LDDST-CRH test at Hammersmith Hospitals NHS Trust, London. The LDDST involved administration of 0.5 mg oral dexamethasone given 6-hourly for 48 h. Serum cortisol was measured 6 h after the last dose of dexamethasone, with a value of 50 nmol/liter or below excluding Cushing's syndrome. Immediately after this, the LDDST-CRH test commenced with administration of a ninth dose of 0.5 mg dexamethasone. Exactly 2 h later, 100 mug human-sequence CRH was administered. Serum cortisol was measured 15 min after the CRH injection, with a value of less than 38 nmol/liter also excluding Cushing's syndrome. MAIN OUTCOME MEASURE: Diagnosis or exclusion of Cushing's syndrome was the main outcome measure. RESULTS: Twelve subjects were diagnosed with Cushing's syndrome (eight Cushing's disease and four primary adrenal). The sensitivity of the LDDST in diagnosing Cushing's syndrome was 100%, with a specificity of 88%. In contrast, although the sensitivity of the LDDST-CRH test was also 100%, specificity was reduced at 67%. These results give a positive predictive value of 80% for the LDDST and 60% for the LDDST-CRH test. CONCLUSION: This small study suggests that the addition of CRH to the LDDST does not improve the diagnostic accuracy of the standard LDDST in Cushing's syndrome.

Cohort Studies↗
PubMed2002

Comparative study of low-dose oral granisetron plus dexamethasone and high-dose metoclopramide plus dexamethasone in prevention of nausea and vomiting induced by CHOP-therapy in young patients with non-Hodgkin's lymphoma.

Standard-dose (2 mg/day) oral granisetron seems to have more antiemetic efficacy than that of high-dose (0.5-1 mg/kg/dose) metoclopramide in moderately emetogenic chemotherapy. However, the cost of oral granisetron is much higher than that of metoclopramide so the authors tried to overcome this disadvantage by dose reduction and adding dexamethasone to enhance the antiemetic effect of oral granisetron. Twenty four young patients (aged < 50 years), with non-Hodgkin's lymphoma receiving CHOP-therapy were enrolled and evaluated in a randomized, double-blind, crossover study comparing the antiemetic efficacy, toxicity and patients' preference of a combination of low-dose oral granisetron plus intravenous dexamethasone (gran/dex) with a combination of high-dose metoclopramide plus intravenous dexamethasone (met/dex) on days 1-5 after chemotherapy. The acute, delayed (day 2-5) and 5-day total control of nausea and vomiting in the gran/dex group were significantly higher than those of the met/dex group (75.0% vs 25.0%; p-value = 0.004, 79.2% vs 33.3%; p-value = 0.007 and 75.0% vs 25.0%; p-value = 0.004, respectively). Except for extrapyramidal reactions in the met/dex group, the side effects in both groups were comparable. The mean total score of antiemetic preference in the gran/dex group was also significantly higher than that of the met/dex group (9.0 vs 7.5; p-value = 0.004). In conclusion, low-dose oral granisetron combined with intravenous dexamethasone had significantly higher protective effects against both acute and delayed nausea and vomiting induced by CHOP-therapy. Thus, this regimen may be considered as an alternative outpatient antiemetic treatment for young patients with non-Hodgkin's lymphoma.

Administration, Oral↗
PubMed1994

"Ultrahigh" dexamethasone in acute brain injury. Results from a prospective randomized double-blind multicenter trial (GUDHIS). German Ultrahigh Dexamethasone Head Injury Study Group.

In a prospective randomized double-blind multicenter trial, the efficacy and safety of a 51-hour ultra-high intravenous dexamethasone dosing regimen was investigated in patients with moderate and severe head injury. 300 patients between 15 and 55 years of age were randomized to receive either placebo or dexamethasone: 500 mg intravenous infusion within 3 h after trauma initially, followed by 200 mg after 3 h, thereafter 8 times 200 mg at 6 hourly intervals, resulting in a total administered dose of 2,3 g in 51 hours. Primary end points for assessment of efficacy were: Modified Glasgow Coma Scale (grading 3-16) on Day 5, modified Glasgow Outcome Scale (grading 1-6) 10-14 months after injury, and the time interval until consciousness improved above a level of modified GCS > or = 8. Secondary endpoints were CT results and neurological and laboratory data. The two groups were well matched with respect to important prognostic variables, such as age, severity of trauma, and interval between trauma and application of the drug. 269 patients (89.7%) were available for final examination after 10-14 months. Results were surprisingly favourable in both groups: Lethality in the dexamethasone and placebo group was 14.3 and 15.4%, respectively, and 61.7 and 57.4%, respectively, achieved social and professional rehabilitation after 10-14 months (outcome scale 6). No statistical difference was seen between the dexamethasone and the placebo group in any of the primary end points of efficacy and safety (incidence of upper gastrointestinal bleeding, infection, and thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids.

A combined LC/RIA procedure is described for the selective determination of dexamethasone (DEX) and its prodrug dexamethasone-21-isonicotinate (DIN) in plasma. The low affinity of the employed dexamethasone antiserum for DIN (cross-reactivity less than 0.5%) allowed the direct determination of DEX in plasma extracts. For the determination of DIN, both substances of interest were separated by LC, the DIN containing fraction was collected, hydrolysed and the generated DEX was consequently assayed by radioimmunoassay. The assay detection limits were 0.1 ng ml-1 for DEX and 0.75 ng ml-1 for DIN. For both substances, inter- and intra-day variabilities (RSDs) were 6 and 12%, respectively.

Binding Sites↗
PubMedDate not supplied

A selective HPLC/RIA for dexamethasone and its prodrug dexamethasone-21-sulphobenzoate sodium in biological fluids.

A combined high performance liquid chromatography/radioimmunoassay procedure is described for the simultaneous determination of dexamethasone (DEX) and its prodrug dexamethasone-21-sulphobenzoate sodium (DSS) in plasma. After precipitation of the plasma proteins by acetonitrile, the protein-free supernatant was injected onto a C18 reversed phase liquid chromatographic system and DSS- and DEX-containing fractions were collected. Hydrolysis of DSS by 0.01 N NaOH, followed by fractions extraction of both hydrolysed DSS and DEX fractions with ethyl acetate allowed the use of a dexamethasone-specific radioimmunoassay for the selective determination of both compounds. The method is accurate and reproducible (intraday variability for DSS and DEX < 6%, interday variability for DEX 14%), allowing quantification of DEX and DSS as low as 0.3 ng/mL and 0.7 ng/mL, respectively.

Chromatography, High Pressure Liquid↗
PubMed2002

Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia.

Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.

Adult↗
PubMed1986

Investigations on the effects of long-term administration of a methionine-enkephalin analogue on the adrenal zona fasciculata of rats treated with dexamethasone or dexamethasone and ACTH.

Prolonged (7 days) methionine-enkephalin (DALA) treatment provoked a dose-dependent increase in the volume of zona fasciculata cells of dexamethasone-administered rats, along with a notable rise in the plasma concentration of corticosterone and the activity of 11 beta-hydroxylase. Comparable dose-dependent effects were observed after chronic administration of ACTH to dexamethasone-suppressed rats. The chronic administration of the maximum dose of DALA (500 micrograms/kg/day) was found to significantly further the trophic action of ACTH on the zona fasciculata of dexamethasone-treated animals. It is suggested that enkephalins act independently of and synergistically with ACTH in stimulating the growth and steroidogenic capacity of the rat adrenal zona fasciculata.

Adrenal Cortex↗
PubMed1988

The dexamethasone suppression test in relation to symptomatology: preliminary findings controlling for serum dexamethasone concentrations.

A diagnostically heterogeneous sample of psychiatric inpatients (n = 52) was administered the 1 mg dexamethasone suppression test (DST) shortly after hospital admission. Each was also assessed using the Hamilton Rating Scale for Depression (HRSD) and selected items of the Present State Examination (PSE) representing psychomotor retardation and anxiety. A potent determinant of postdexamethasone serum cortisol concentrations was found to be the level of serum dexamethasone concentration achieved following the oral dose. No relationship was found between postdexamethasone cortisol concentration and the scores on either the HRSD or an anxiety scale derived from selected PSE items. However, symptoms of psychomotor retardation were significantly related to postdexamethasone serum cortisol concentration, particularly when the serum dexamethasone concentrations were taken into account. It may be that DST nonsuppression in psychiatric patients is in part a reflection of the presence of psychomotor retardation, a phenomenon that cuts across diagnostic categories.

Adolescent↗
PubMed1993

Dexamethasone abolishes the activation by nerve growth factor of protein kinase N: effects of nerve growth factor and dexamethasone on protein kinase N.

Protein kinase N (PKN) is a basic 45-47 kDa serine/threonine protein kinase activated by NGF and several other factors in PC12 cells and other cell types. It is inhibited in vitro by purine analogs. In this work, we further characterize the modulation of PKN activity following exposure of PC12 cells to dexamethasone or NGF, which respectively direct these cells towards the chromaffin- or neuron-like phenotype. We show here that the two factors elicit opposite effects on the activation of the kinase: dexamethasone inhibits while NGF stimulates the basal level of PKN activity. Simultaneous addition to the cells of the factors causes no variation from basal kinase activity. Addition of dexamethasone not to the cells, but to partially purified PKN during the kinase assay, causes no modulation of the enzyme.

Animals↗
PubMed1987

Dexamethasone suppression test in severe schizophrenic illness: effects of plasma dexamethasone and caffeine levels.

A dexamethasone suppression test (DST) was administered to 31 inpatients with a severe acute schizophrenic exacerbation 4 or 5 days following admission and repeated after 4 weeks or prior to discharge. We identified 15 patients (48%) who were nonsuppressors on the DST at the first test. To exclude major confounders of DST results we monitored weight constancy and plasma concentrations of dexamethasone. In a subgroup of patients also plasma caffeine contents were determined. Our results indicate that DST nonsuppression occurs frequently among patients with schizophrenic crisis. Since caffeine plasma levels were indistinguishable between suppressors and nonsuppressors we reject that excessive caffeine intake accounts for DST nonsuppression among individuals with schizophrenia. Nonsuppressors had lower plasma dexamethasone levels than suppressors and reversal of the DST status from nonsuppression to suppression was associated with an increase of plasma concentrations of the test drug.

Adult↗
PubMedDate not supplied

A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy.

A double-blind, parallel-group study in 189 ovarian cancer patients compared the efficacy of ondansetron 8 mg i.v. (OND) and metoclopramide 60 mg i.v. (MET) both in combination with dexamethasone 20 mg i.v. in the prevention of carboplatin-induced emesis. On day 1, complete or major control of emesis (0-2 emetic episodes) was observed in 97% patients from the OND group compared with 74% patients from the MET group (p < 0.001). Similarly, a worst-day analysis over days 1-3 showed complete or major control of emesis in 87% patients (OND) compared wth 66% patients (MET) (p < 0.001). Similar findings in favour of the OND group were observed for nausea grade on day 1 and the worst-day grade during days 1-3. OND was better tolerated than MET. Fewer patients from the OND group (13%) reported adverse events compared with the MET group (21%). Extrapyramidal type symptoms were observed in 6 (6%) patients from the MET group (paraesthesia, involuntary movement of the jaw and tongue, and restlessness), compared with none from the OND group. Ondansetron plus dexamethasone is a highly effective and well-tolerated treatment and is significantly superior to metoclopramide plus dexamethasone in the prevention of carboplatin-induced emesis.

Adult↗
PubMed1989

Topical dexamethasone lowers rabbit ocular tension, as does topical mifepristone (RU 486), a peripheral blocker of dexamethasone and progesterone.

The variability of the response of the rabbit eye to topical 1% dexamethasone has been shown in two groups of 20 young albino rabbits each (total 40) tested in succession. The pressure anomalously fell significantly (but by only 1 mm Hg) in both groups in the first 4 weeks of administration, but not in subsequent weeks. Mifepristone (RU 486), a peripheral antagonist of dexamethasone and progesterone, reduced the pressure significantly, again by only 1 mm Hg, in the first group of 20 rabbits, not the second. Accordingly, no conclusion was possible on the originating question: does pre-treatment with mifepristone prevent the dexamethasone-induced rise in rabbit intra-ocular pressure?

Administration, Topical↗
PubMed1986

Dexamethasone concentrations and the dexamethasone suppression test in psychiatric disorders.

The dexamethasone suppression test (DST) has been widely used in psychiatry as a laboratory aid for the diagnosis of endogenous depression; failure to suppress serum cortisol levels is interpreted as confirming a clinical diagnosis of endogenous depression. We found that serum dexamethasone concentrations in this test vary widely and are determinants of the DST response: non-suppression of serum cortisol levels is associated with low serum dexamethasone concentrations, and suppression is associated with high concentrations.

Adjustment Disorders↗
PubMed1988

A randomized comparison of haloperidol plus dexamethasone versus prochlorperazine plus dexamethasone in preventing nausea and vomiting in patients receiving chemotherapy for breast cancer.

The antiemetic effectiveness of haloperidol plus dexamethasone was compared with that of prochlorperazine plus dexamethasone in a prospective study of patients receiving chemotherapy for breast cancer. Chemotherapy consisted of cyclophosphamide, doxorubicin or methotrexate, and fluorouracil in all patients. Patients who received the doxorubicin-containing combination experience significantly more nausea and vomiting than those who received the chemotherapy combination containing methotrexate. There was no significant difference between the two antiemetic regimens in the overall incidence of post-chemotherapy nausea and vomiting, but patients who received haloperidol and dexamethasone did have a lower incidence of severe vomiting. Neither regimen is highly effective, especially for the combination containing doxorubicin, and cannot be recommended as standard antiemetic therapy for this population of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

A comparison of the standard high dose dexamethasone suppression test and the overnight 8-mg dexamethasone suppression test for the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome.

To improve the overnight 8-mg dexamethasone (DEX) suppression test (DST) for differential diagnosis of Cushing's syndrome and to develop optimal criteria for its interpretation, we increased the number of blood samples and measured the suppression of both plasma ACTH and cortisol. Forty-one patients who were subsequently proven at surgery to have Cushing's syndrome were studied (34 Cushing's disease and 7 ectopic ACTH secretion). DEX (8 mg, orally) was administered at 2300 h. Blood samples for ACTH and cortisol measurements were obtained at 0800, 0830, and 0900 h on the day before and at 0700, 0800, 0900, and 1000 h on the morning after DEX treatment. The conventional 6-day DST was also performed, with measurement of both urinary free cortisol and urinary 17-hydroxysteroids as indices of suppression. Optimal criteria for the diagnosis of Cushing's disease were developed for both the overnight 8-mg and the 6-day tests using receiver operating characteristic curves. The results were compared with those using the previously published criteria for diagnosis of Cushing's disease by the overnight 8-mg test (> 50% suppression of plasma cortisol at 0700-0800 h). In our patients, the previously published criterion for the overnight 8-mg test yielded high sensitivity (88%), but low specificity (57%), in making the diagnosis of Cushing's disease. When the time of cortisol measurement and the diagnostic criteria for Cushing's disease were revised to achieve 100% specificity, the sensitivity of the overnight 8-mg test was 71%, which was not significantly different from that of the 6-day test (79%; P = NS). Addition of plasma ACTH levels to the test did not improve diagnostic accuracy compared to that with measurement of plasma cortisol levels alone. When the revised 8-mg overnight dexamethasone suppression test was combined with the 6-day dexamethasone suppression test, sensitivity increased to 91%, with a specificity of 100%, which was significantly better than that of the overnight 8-mg test alone (P < 0.002). We conclude that the overnight 8-mg DST has low specificity for the diagnosis of Cushing's disease when performed as originally described. However, with revised sampling times and diagnostic criteria, the overnight test has sensitivity and specificity similar to those of the conventional 6-day DST. The diagnostic performance of a criterion that combines the results of both tests is better than the diagnostic performance of either test alone.

Administration, Oral↗
PubMed2005

A randomized, double-blind study of granisetron plus dexamethasone versus ondansetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing abdominal hysterectomy.

In this randomized, double-blind study, we evaluated whether small-dose granisetron (0.1 mg) plus dexamethasone 8 mg (G+D) was as effective as ondansetron 4 mg plus dexamethasone 8 mg (O+D) for preventing vomiting during the 0 to 2 h after tracheal extubation in patients undergoing abdominal hysterectomy requiring general anesthesia. Dexamethasone (D) was administered at induction of anesthesia, and granisetron (G) or ondansetron (O) was given approximately 15 min before tracheal extubation. Data on postoperative nausea and vomiting were collected at 0, 2, 6, and 24 h. For the primary efficacy endpoint, most patients in each group had no vomiting in the 0- to 2-h interval (82/87 [94%] for G+D versus 86/89 [97%] for O+D). Effectiveness of G+D was demonstrated versus O+D. Treatment groups were similar with regard to moderate or severe nausea, complete response, rescue medication use, and total control over 24 h. A descriptive assessment of adverse events showed that both combinations were well tolerated with infrequent and similar incidences of adverse events. The combination of small-dose G administered just before tracheal extubation plus D given at induction of anesthesia is an effective alternative to O+D in preventing vomiting during the 0- to 2-h interval after tracheal extubation.

Adult↗