Mg Of Hydrocortisone Research Articles

Desensitization treatment for anaphylactoid reactions to desferrioxamine in a pediatric patient with thalassemia

Desensitization treatment for anaphylactoid reactions to desferrioxamine in a pediatric patient with thalassemia

Cardiovascular function and glucocorticoid replacement in patients with hypopituitarism.

Retrospective analysis suggests an increased mortality from cardiovascular disease in hypopituitary adults; GH deficiency has been postulated to account for this. However, glucocorticoid replacement doses of 30 mg/day of hydrocortisone (HC) may be excessive, and could therefore be implicated in the increased cardiovascular mortality in this group of patients. The aims of this study were to establish whether patients with hypopituitarism have any abnormalities of the cardiovascular system compared to a control group and whether any of these parameters might be improved by reducing the replacement dose of glucocorticoid. A prospective analysis of cardiovascular function was carried out in 13 patients with hypopituitarism on routine replacement therapy and 20 normal controls who were matched for age and body mass index (BMI). Twenty-four-hour ambulatory blood pressure (BP), erect and supine BP, echocardiography, forearm plethysmography and cardiovascular reflexes in response to tilt, Valsalva and isometric hand grip were performed on controls and on patients taking 30 mg/day of HC and repeated following a reduction in HC dose to 15 mg/day for 3 months. Weight, plasma and urinary electrolytes, 24-hour urinary cortisol excretion, glucose, HbA1C and pituitary function were also assessed on HC 30 mg/day and 15 mg/day. Mean 24-hour ambulatory BP, in addition to day and night time BP, was lower in patients than in controls (achieving statistical significance in the male subgroup) and did not change significantly with a reduction in HC dose. Erect and supine BP was also lower in patients compared to controls and there was no evidence of postural hypotension following a reduction in HC dose to 15 mg/day. Systolic and diastolic left ventricular dimensions, interventricular septal thickness, ejection fraction and fractional shortening were similar in controls and patients and did not alter with a reduction in HC dose. Systolic and diastolic BP and heart rate responded appropriately to all tests of cardiovascular reflexes (tilt, Valsalva and isometric handgrip) in hypopituitary patients though again measurements of systolic BP were significantly lower in patients during these tests, independent of HC dose. Forearm plethysmography was similar in patients receiving 30 mg of HC and controls but forearm blood flow increased significantly when the HC dose was reduced to 15 mg/day. There was no change in weight, plasma and urinary electrolytes, glucose and HbA1C or pituitary function in the patient group throughout the study. In contrast to other studies we have failed to confirm cardiovascular dysfunction in GH deficient hypopituitary adults. Indeed, cardiovascular protection may be conferred on this group by the lower BP levels. Although a reduction in hydrocortisone dose was well tolerated in all patients, it appeared to confer no additional clinical benefit over the 3-month study period. In view of the conflicting data on cardiovascular function in hypopituitary patients, further prospective mortality studies are required in patients with adult GH deficiency.

Anaphylactoid Reaction in a Surgeon to Surgical Rubber Gloves

Anaphylactoid Reaction in a Surgeon to Surgical Rubber Gloves

Quantifying systemic absorption of topical hydrocortisone in erythroderma.

The systemic absorption of topical hydrocortisone (HC) was quantified in seven patients with erythroderma, using the ratio of the areas under the curves for plasma concentration vs. time, following topical and intravenous administration. Over a period of 24 h, 19-93 mg of HC was absorbed systemically, corresponding to 4-19% of the total topical dose of 500 mg. Thus, topical HC therapy of erythroderma is accompanied by a pharmacologically significant systemic dose.

Low-dose aminoglutethimide in postmenopausal breast cancer: Effects on adrenal and thyroid hormone secretion

Aminoglutethimide is effective in the treatment of breast cancer in postmenopausal patients as a result of its inhibition of aromatase. Its use is complicated by a number of endocrine side-effects which include the inhibition of thyroxine synthesis and inhibition of 11-steroid and 21-steroid hydroxylases. When aminoglutethimide is used at the conventional daily dose of 1000 mg in combination with 40 mg of hydrocortisone these effects can result in clinically significant hypothyroidism and increases in the serum levels of oestrone in response to stimulation of adrenocorticotropic hormone (ACTH). In the current study it was found that with twice daily treatment at the low dose of 125 mg aminoglutethimide plus 20 mg hydrocortisone there was no significant increase in oestrone levels after ACTH stimulation. In addition there was little effect on thyroid function: serum levels of triiodothyronine and thyroxine were unaffected whilst there was a marginally significant ( P < 0.05) increase in thyroid-stimulating hormone (TSH) levels from a mean (S.E.) 2.37 (0.23) mU/l to 3.78 (1.23) mU/l. The increased TSH levels were confined to those patients with pretreatment values greater than 2.5 mU/L, the most marked effect being in 1 patient whose pretreatment level was already outside the normal range.

Quantitative 99 Tcm-HMPAO white blood cells and 67 Ga scanning in rheumatoid arthritis

This investigation assessed 99Tcm-HMPAO white blood cell (Tc-WBC) and 67Ga knee uptake indices before and after 90Y treatment in patients with intractable rheumatoid arthritis (RA) and correlated the uptake indices with the clinical score. Sixteen knee joints with RA were treated with intra-articular injection of 185 MBq of 90Y-silicate colloid (Amersham) flushed with 50 mg of hydrocortisone. Clinical score, quantitative 67Ga and Tc-WBC knee uptake indices were obtained before and three weeks after treatment. Our results showed that 9/16 (56%) had a good response and 7/16 (44%) had a poor response to 90Y injection. There was poor correlation between clinical improvement and changes in 67Ga and Tc-WBC knee uptake indices (r = 0.46 and 0.14, respectively). The correlation coefficient between changes in 67Ga and Tc-WBC knee uptake indices was 0.29.

Effects of Hydrocortisone on the Ultrastructure of the Thymic Cysts of the Chick Embryo

Thymi from 80 19-day chick embryos that were injected with 2.5 mg of hydrocortisone on the 15th day of incubation were examined by light and electron microscopy. Six thymic tissue blocks from each embryo were evaluated. Hydrocortisone caused a marked depression of thymic volume due mainly to the depletion of lymphocytes. Cystic structures, consisting of intercellular and intracellular cysts and individual cystic cells, were more numerous per unit area of medullary tissue intreated embryos than in the controls, hi the treated group, the shape of cystic cells varied from squamous to columnar, and hypertrophied columnar cells were also evident The luminal surface possessed well-developed microvilli with membrane invaginations at their bases. The terminal web was prominent and the lateral plasma membranes were highly interdigitated. The rough and smooth-surface endoplasmic reticula and the Golgi complex of thymi from treated embryos were more developed than those in the controls. Mitochondria and vesicles were increased in number following hydrocortisone treatment. Cysts lined partially by cystic and endothelial-like and smooth muscle cells were encountered in the treated group. These structural modifications probably reflect responses to increased absorptive or transport function. The data suggest that hydrocortisone may alter the structure of cystic cells in chick embryos.

Steroid treatment of laryngotracheitis: A meta-analysis of the evidence from randomized trials : Kairys, S.W., Olmstead, E.M. and O'Connor, G.T., Pediatrics (1989) 83/5 (683–693)

The use of adrenocorticoids to reduce the morbidity associated with laryngotracheitis (croup) remains controversial despite ten published reports of randomized trials involving 1,286 patients. To determine whether, viewed in aggregate, these studies demonstrate a significant benefit of steroid treatment for this disorder, a meta-analysis of the nine methodologically satisfactory trials was performed. Clinical improvement 12 and 24 hours posttreatment and incidence of endotracheal intubation were evaluated. For each end point, an estimate of the overall effect was obtained by calculating a typical odds ratio and 95% confidence interval. This analysis indicates that the use of steroids in children hospitalized with croup is associated with a significantly increased proportion of patients showing clinical improvement 12 hours (odds ratio = 2.25, 95% confidence interval = 1.66, 3.06) and 24 hours (odds ratio = 3.19, 95% confidence interval = 1.70, 5.99) posttreatment and a significantly reduced incidence of endotracheal intubation (odds ratio = 0.21, 95% confidence interval = 0.05, 0.84). Higher initial doses of steroid (greater than or equal to 125 mg of cortisone or greater than or equal to 100 mg of hydrocortisone) were associated with a larger proportion of patients improved 12 hours posttreatment than was seen with lower doses. These results support the use of steroids in the treatment of hospitalized children with croup and, in the absence of a randomized clinical trial of sufficient size, provide the most reliable estimate of the impact of steroid therapy on the morbidity associated with croup. In addition, the results of this meta-analysis may be used to estimate the number of subjects who would be required to conduct a randomized clinical trial of steroids for the treatment of croup.

Steroid Treatment of Laryngotracheitis: A Meta-Analysis of the Evidence From Randomized Trials

The use of adrenocorticoids to reduce the morbidity associated with laryngotracheitis (croup) remains controversial despite ten published reports of randomized trials involving 1,286 patients. To determine whether, viewed in aggregate, these studies demonstrate a significant benefit of steroid treatment for this disorder, a meta-analysis of the nine methodologically satisfactory trials was performed. Clinical improvement 12 and 24 hours posttreatment and incidence of endotracheal intubation were evaluated. For each end point, an estimate of the overall effect was obtained by calculating a typical odds ratio and 95% confidence interval. This analysis indicates that the use of steroids in children hospitalized with croup is associated with a significantly increased proportion of patients showing clinical improvement 12 hours (odds ratio = 2.25, 95% confidence interval = 1.66, 3.06) and 24 hours (odds ratio = 3.19, 95% confidence interval = 1.70, 5.99) posttreatment and a significantly reduced incidence of endotracheal intubation (odds ratio = 0.21, 95% confidence interval = 0.05, 0.84). Higher initial doses of steroid (greater than or equal to 125 mg of cortisone or greater than or equal to 100 mg of hydrocortisone) were associated with a larger proportion of patients improved 12 hours posttreatment than was seen with lower doses. These results support the use of steroids in the treatment of hospitalized children with croup and, in the absence of a randomized clinical trial of sufficient size, provide the most reliable estimate of the impact of steroid therapy on the morbidity associated with croup. In addition, the results of this meta-analysis may be used to estimate the number of subjects who would be required to conduct a randomized clinical trial of steroids for the treatment of croup.

Coccidioidal Meningitis Narcotic—Amphotericin B Intracisternal Therapy-Reply

In Reply. —It is gratifying to know that high-dose intrathecal amphotericin B has been used on three patients by a neurological group in Phoenix, thus at least corroborating our published report that high single doses can be administered safely and high total dosage can be reached rapidly. Yudell and colleagues offer a personal innovation in the combined use of amphotericin and the opiate, fentanyl, to alleviate instillation discomfort. On receiving their letter to the editor, we tried that combination on a patient with active coccidioidal meningitis who was undergoing therapy. We used 1 mg of amphotericin, and 10 μg of fentanyl as they suggested, as well as 25 mg of hydrocortisone, but avoided the premedication regimen outlined in our article. A total of four direct intracisternal injections were performed. It was noticed that the patient was significantly more apprehensive and restless prior to the first two injections, and we had

Effects of hydrocortisone on the ultrastructure of the thymic cysts of chicks

Thymi from 10-day old male chicks injected subcutaneously with 5 mg of hydrocortisone for 2 consecutive days and sacrificed on the 4th day were examined by electron microscopy. With depletion of the lymphoid cells, cystic structures, consisting of inter- and intracellular cysts are more apparent in the hydrocortisone-treated chicks. The intercellular cysts vary in size and shape and are lined by cystic, endocrine-like and lymphoid cells. Luminal surfaces of the cystic cells contain microvilli. The lateral plasma membranes show complex interdigitations. The prominent terminal web contains vesicles and numerous core rootlets. Frequent membrane invaginations are apparent at the bases of the microvilli. The endoplasmic reticulum and the Golgi complex are moderately developed. Mitochondria are variable in number but are numerous in some cells. The cytoplasm also contains dense bodies, vacuoles and myelin figures. Endocrine-like cells, containing numerous secretory granules and bordering directly on the follicular lumen suggest that their secretion may be discharged into the lumen. Cystic cells containing intracellular cysts are observed. Presence of cleft-like spaces, microvilli closely opposed to adjacent cytoplasmic processes or lateral microvilli may reflect responses to increase in absorptive or transport function. The present data suggest that hydrocortisone may modulate the structure and function of the cystic structures in the chick thymus.

Metastatic enhancement and growth inhibition by glucocorticoid and its receptors in mouse teratocarcinoma OTT6050 in vivo.

To elucidate the mechanism of glucocorticoid-induced metastases and growth inhibition of mouse teratocarcinoma OTT6050, syngeneic 129/Sv-CP+SlJ mice were subcutaneously (s.c.) injected with the tumor and treated with daily intraperitoneal (i.p.) injections of hydrocortisone in doses of 1.5 to 12.5 mg per mouse. The number of lymph-node and visceral metastases was greatly increased by the treatment with hydrocortisone unrelated to the doses and sexes. Tumor growth (the products of three principal diameters) of lymph-node metastases was dose-dependently inhibited by the treatment. Histologically, lymph-node metastatic tumors contained large masses of well-differentiated tissues compared with the s.c. transplanted tumor of the same size. The glucocorticoid receptors were measured using dextran-coated charcoal adsorption techniques with [3H] hydrocortisone. Glucocorticoid receptor contents were higher in lymph-node metastatic tumor (100 fmole/mg cytoplasmic protein, mean) than in s.c. transplanted tumors (74.5 fmole/mg, mean) respectively treated with 12.5 mg of hydrocortisone. The metastatic growth inhibition by hydrocortisone might be closely related to the receptor-mediated mechanisms and histological differentiation.

Survival Improvement in Coccidioidal Meningitis by High-Dose Intrathecal Amphotericin B

Eleven patients with coccidioidal meningitis were treated with high individual doses (1.0 to 1.5 mg) of intrathecal amphotericin B mixed with 25 to 50 mg of hydrocortisone in an attempt to reach a dose of 12 mg per month for at least two consecutive months. Patients received a mean intrathecal dose of amphotericin B of 82 mg (range, 40 to 157 mg) and 2.4 g intravenously (range, 1.0 to 3.5 g). No deaths related to disease or treatment occurred, and overall survival was 91% during an average follow-up period of 75 months (range, 30 to 137 months). Comparative analysis with eight well-known series in the literature reveals that our survival rate and follow-up time are significantly greater than the more recent series (1977-1981). Rank correlation and linear regression showed that the mean intrathecal dose of amphotericin B used in all series corresponds well with mean survival time. Our clinical results and analysis of the literature suggest that intrathecal amphotericin B administered at a high dose rate of 0.75 mg (or greater) three times per week promptly reaching 20 mg and a total surpassing 40 mg is associated with significantly enhanced survival rates.

Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae : I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity

Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18–72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7–14 days previously. Negative selection studies of nylonwool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy-1+, Lyt 1+, Lyt 2−, surface Ig- lymphocytes.

Dose-dependent effects of hydrocortisone on memory in human males

Eighty male undergraduates were administered either glucose or 5, 10, 20, or 40 mg of hydrocortisone in a double-blind procedure. After 60 min they were asked to listen to eight 12 word lists and then asked to recall the words. In addition to the expected effects of rate of presentation, serial position, and practice there was a significant interaction between dose of hydrocortisone and practice. Early recall was facilitated by all doses used whereas later recall was facilitated by treatment with 40 mg and impaired by treatment with 5 mg. These findings are discussed in the context of the effects of pituitary adrenocortical hormones and memory function.

Hydrocortisone and airflow impairment in aspirin-induced asthma

We studied the effects of intravenous injection of hydrocortisone, as compared to its solvent, in 31 patients with aspirin-induced asthma. Mean FEV 1 fell significantly 5 minutes after an intravenous bolus of 300 mg of hydrocortisone, but not after the solvent, and returned to the initial values 1 hour later. Only three of 31 patients displayed at this time clinical signs of increased impairment of airflow that resolved spontaneously. Neither in these three patients nor in another patient known already to respond with bronchoconstriction to 30 to 50 mg of hydrocortisone did intravenous injections of 20 mg of methylprednisolone, 4 mg of dexamethasone, or 4 mg of betamethasone produce any signs of bronchial obstruction. In the whole group of patients, mean FEV 1 increased significantly 3 to 5 hours after hydrocortisone injection. It is hypothesized that hydrocortisone might induce early bronchoconstriction in patients with aspirin-induced asthma through its inhibitory effects on prostanoid biosynthesis. Use of intravenous steroids other than hydrocortisone is advisable in patients with aspirin-induced asthma.

A CASE OF HYDROCORTISONE SODIUM SUCCINATE-INDUCED ASTHMA

This is a report of a 62-year-old man with a history of asthmatic attack following therapy for bronchial asthma with intravenous injection of hydrocortisone sodium succinate (Saxizon®, Solu-Cortef®).He had had episodes of dyspnea since 1979 and was treated with oral bronchodilators and intermittent cortimosteroids (prednisolone), and at the exacerbation of asthmatic symptoms he was treated with intravenous drip infusion containing aminophylline and Saxizon®. On June 15, 1983, he complained of dyspnea. As a result, he was given 200mg of Saxizon® intravenously. After then, his asthmatic attack worsened. To confirm the suspected relationship between the drugs and asthmatic attack, intravenous provocative challenge tests were performed, and 100mg of Saxizon® and Solu-Cortef® revealed positive results, but intravenous challenge tests with 100mg of hydrocortisone disodium phosphate (Hydrocortone®) and 20mg of prednisolone sodium succinate (Predonine®, Shionogi) and oral challenge with 100mg of hydrocortisone (Hydrocortone®, Japan Merck-Banyu) were negative. Skin and P-K tests with hydrocortisone sodium succinate were positive. Although this type of adverse reaction to steroidal products is rare, it is very important in allergy practice.

Inhibition of the ACTH Adrenal Response to Stress by Treatment with Hydrocortisone, Prednisolone and Dexamethasone in the Rat

16- and 4-week-old intact and adrenalectomized rats have been treated with different doses of the three glucocorticoids hydrocortisone, prednisolone and dexamethasone by gavage. The delayed feedback effect on plasma ACTH and corticosterone response to an ether stress have been assessed. Almost complete suppression of corticosterone response 20 min after an ether stress and an ACTH suppression to 20% of control values 5 min after an ether stress were observed with 25 micrograms of dexamethasone, 10 mg of prednisolone and 20 mg of hydrocortisone. Although the percent inhibition of corticosterone and ACTH response to stress was comparable, a striking dissociation of the ACTH and corticosterone release was observed in terms of absolute concentrations. A mean ACTH concentration of 462 ng/l after 25 micrograms of dexamethasone was measured together with a barely measurable corticosterone concentration of 3 micrograms%. Similarly, after 10 mg of prednisolone, the mean ACTH concentration was 404 ng/l, whilst the mean corticosterone concentration was 3 micrograms%. This dissociation demonstrates that the corticosterone concentration on its own does not necessarily reflect the ACTH release. At 4 weeks of age, the ACTH response to stress is more difficult to suppress than in adult animals. This is more obvious after adrenalectomy, where the excessive ACTH secretion was less inhibited by all glucocorticoids used. The time between the last steroid gavage and stress must be considered. In 4-week-old animals the ACTH response 16 h after 12.5 micrograms of dexamethasone was inhibited by 22%, whereas 4 h after the same dexamethasone dose the inhibition was 85%.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical effect of aminoglutethimide, medical adrenalectomy, in treatment of 43 patients with advanced prostatic carcinoma.

The initial treatment of patients with Stage D prostatic carcinoma with orchiectomy or estrogens is successful in giving objective and subjective improvement for variable periods of time. However, after initial endocrine treatment patients generally relapse, and go on to further progression of their disease. However, a subgroup of approximately 22% of these Stage D prostatic cancer patients respond to either surgical adrenalectomy or hypophysectomy, indicating some degree of continued hormonal responsiveness. Forty-three previously castrated patients with Stage D prostatic carcinoma were treated with 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily and have been evaluated using the criteria of the National Prostatic Cancer Project. Progression of disease after initial hormonal therapy has varied from 3 to 25 months. One patient has had a complete response, and continues in remission after 290 weeks of therapy. Partial objective responses have been observed in 6 patients, and 10 patients have remained objectively stable for an average of 35 weeks in this latter group.

Effects of aminoglutethimide on adrenal steroid secretion.

Effects of various doses of aminoglutethimide (AG) alone upon adrenal steroidogenesis were studied in normal postmenopausal women, whereas the effects of combined treatment with aminoglutethimide in variable doses together with 40 mg of hydrocortisone were studied in postmenopausal women with advanced mammary cancer and compared to effects of treatment with cortisol alone. Despite the well known inhibitory effect of AG on cortisol biosynthesis, plasma cortisol levels were unaffected by AG in doses of 150-1000 mg/d, probably due to a compensatory increase in ACTH in subjects with an intact pituitary-adrenal axis. The aromatase system appeared to be very sensitive to inhibition by AG, a clearcut inhibition being shown at doses as low as 150 mg/d. Evaluated from the ratio of plasma oestrone (E1) to plasma androstenedione (AN), treatment with AG at a dose of 150 mg/d appeared to reduce the aromatase activity to 33% of the basal value; 250 mg/d resulted in a reduction to 20% and 1 g/d to 5% of basal values. Whereas AG at 150 mg/d did not appear to affect 11 beta-hydroxylase, the latter was clearly inhibited by 250 mg/d and even more so by 1000 mg/d, as indicated by the increase in plasma 11-desoxycortisol and 17-OH progesterone (17-OHP) levels. Due to the increase of the latter, their biosynthetic precursor, AN and to a lesser degree testosterone (TS) levels increased significantly during AG treatment at a dose of 250 or 1000 mg/d. delta 5 steroid levels remained practically unchanged, probably because 11-(as well as the 21-) hydroxylation concerns essentially the delta 4 pathway. During combined treatment with 500-1000 mg/d of AG and cortisol 40 mg/d, AN and TS were significantly higher than during treatment with cortisol alone, suggesting that cortisol had not completely blocked ACTH secretion. E1 and E2 levels were however lower than during treatment with cortisol alone, a consequence of the inhibition of the aromatase activity. Although at a dose of 500-1000 mg/d AG is a highly effective aromatase inhibitor, oestrogen levels during treatment with AG with or without concomitant administration of cortisol are still significantly different from zero. Therefore if one aims at complete elimination of any oestrogen effect, addition of an antioestrogen to AG treatment may be required.