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Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse.

Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were assayed. The results show that the synovial fluid level of triamcinolone was 7.5 micrograms/ml 1 day following treatment and decreased to 10 ng/ml by the 4th day. These low levels were maintained for approximately 14 days. By the 15th day, the triamcinolone was below a detectable level. Serum levels of triamcinolone increased to 3 ng/ml within 1 h and further increased to a peak of 4.3 ng/ml at 4th h. The level then decreased to 2 ng/ml at 24 h and to nearly an undetectable level in 48 h. The mean level of serum cortisol, on the other hand, gradually decreased as the serum level of triamcinolone increased. As the serum level of triamcinolone reached an undetectable level on the 2nd day, the serum cortisol level gradually increased and returned to the pre-administration level by the 5th day. These results showed that the intra-articular administration of triamcinolone maintained triamcinolone in the synovial fluid for 4-14 days and that the triamcinolone reached the blood within 1 h. The serum level of triamcinolone was maintained for 2 days and resulted in the inhibition of adrenal function for 4 days.

Animals

High-dose intramuscular triamcinolone in severe, chronic, life-threatening asthma.

BACKGROUND: Despite oral corticosteroid therapy, some patients with asthma have frequent exacerbations requiring emergency room visits, hospitalization, and occasionally, mechanical ventilation. We compared the effects of high-dose intramuscular triamcinolone with oral prednisone in patients with severe chronic asthma. METHODS: In a double-blind, placebo-controlled, cross-over study that spanned all seasons, we treated 12 patients with high-dose intramuscular triamcinolone (360 mg over the first three days of the treatment period) or low-dose oral prednisone (median dose, 12.5 mg per day throughout the period; range 0 to 30). The two three-month treatment periods were separated by a three-month washout period. During all periods the patients were allowed to take additional doses of prednisone for acute exacerbations of asthma. RESULTS: After receiving triamcinolone, the patients had significantly better peak expiratory flow rates than while receiving prednisone (the average [+/- SEM] weekly percent of the predicted value during the triamcinolone period was 91.5 +/- 6.9, as compared with 75.0 +/- 5.9 for the prednisone period; P less than 0.05). During the prednisone period there were 21 emergency room visits and 10 hospitalizations, but there were none during the triamcinolone period (P less than 0.05). There were two episodes of ventilatory failure during the prednisone period. Total steroid doses were significantly smaller during the triamcinolone period than during the prednisone period (P less than 0.04). Steroidal side effects were more pronounced after treatment with triamcinolone than after treatment with prednisone (P less than 0.1). CONCLUSIONS: We conclude that high-dose intramuscular triamcinolone is more effective than low-dose prednisone in patients with severe, chronic, life-threatening asthma, but steroidal side effects are somewhat worse.

Administration, Oral

Efficacy of once-a-day intranasal administration of triamcinolone acetonide in patients with seasonal allergic rhinitis.

A 4-week, double-blind, parallel group study compared the safety and efficacy of once-a-day intranasal administration of triamcinolone acetonide (Nasacort) versus placebo in 304 patients (155 adult and 149 adolescent) with seasonal allergic rhinitis. Patients were randomized to receive triamcinolone acetonide (110, 220, or 440 microgram) or placebo once daily each morning. Daily rhinitis symptoms scores, weekly patient and physician global assessments, and weekly nasal eosinophil smears were obtained. In each triamcinolone acetonide group, significant (P less than .05) improvement over placebo was noted in the nasal index (sum of ratings for stuffiness, discharge, and sneezing) by week 1, the first point of analysis, and maintained throughout the study. Triamcinolone acetonide groups also demonstrated significant (P less than .05) improvement over placebo in all individual rhinitis symptoms evaluated. The greatest improvement in symptoms was observed at the 440 microgram dose. A significant decrease in eosinophil counts paralleled clinical improvement in all triamcinolone acetonide groups. Physicians and patients rated triamcinolone acetonide significantly (P less than .05) more effective than placebo. Responses of adult and adolescent patients were comparable. Adverse experiences, clinical laboratory values, and results of physical examinations were unremarkable and comparable between the triamcinolone acetonide and placebo groups. We conclude that triamcinolone acetonide is safe, well tolerated, and superior to placebo as a once-a-day treatment for seasonal allergic rhinitis.

Administration, Intranasal

Diabetogenic effect of triamcinolone in man with impaired thyroid function: serum free fatty acids, inorganic phosphorus, calcium and total protein pattern after an oral glucose load.

In a group of 35 subjects (12 hypothyroid, 11 euthyroid and 12 hyperthyroid) the changes of FFA, inorganic phosphorus, calcium and total proteins were investigated during glucose tolerance test with (TGTT) or without (OGTT) triamcinolone pretreatment. In hypothyroidism the decrease of FFA during TGTT was blunted, whereas the pattern of phosphatemia was unaltered and total proteins were increased. In euthyroidism triamcinolone exerts the opposite effect on the behaviour of FFA (decline was smaller and shorter) and phosphatemia (decline was pronounced and persists for longer period). In hyperthyroidism the fasting level of FFA decreased in TGTT but during the test no significant differences in FFA and phosphatemia patterns were observed. The calcemia was not influenced by triamcinolone in any subgroup. Our results suggest the importance of thyroid function as modifying factor in some metabolic effects of triamcinolone in man. Changes in hypothyroidism are in good agreement with changes of blood glucose and insulinemia, as described previously. Opposite effect of triamcinolone on FFA and phosphatemia pattern in euthyroidism may suggest the changes of sensitivity of some peripheral tissues to insulin action. The decline of fasting level of FFA after triamcinolone in hyperthyroidism is surprising and might be of importance in maintaining unaltered glucose tolerance after triamcinolone in this subgroup.

Blood Proteins

Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and lignocaine compared.

Corticosteroid injections are the mainstay of treating tennis elbow even though their effectiveness has not been well established by controlled studies. A survey of consultant rheumatologists confirmed a widespread preference for this treatment but they varied in their choice of steroid dose and preparation. We examined the value of some practices by comparing local injections of 2 ml 1% lignocaine with either 10 mg triamcinolone or 25 mg hydrocortisone made up to 2 ml with 1% lignocaine (Study 1). The investigation was conducted double blind. Within the first 8 weeks, pain relief was greater for triamcinolone than hydrocortisone although the differences were not statistically significant. The response to both steroid preparations was significantly better than for lignocaine up to this point but at 24 weeks, the degrees of improvement were similar for all three groups and many patients still had pain. Relapse was common. In a separate but similarly designed study, triamcinolone 10 mg was compared with 20 mg of the same agent. Improvements of pain were similar and followed the same time scale. Post-injection worsening of pain occurred in approximately half of all steroid treated patients in both studies and this was sometimes severe and persistent. It was less frequent amongst those given lignocaine alone. Skin atrophy was reported in all groups but was more frequent amongst those given triamcinolone in Study 1. In conclusion, more rapid relief of symptoms was achieved with 10 mg triamcinolone than with 25 mg hydrocortisone or lignocaine alone and there was less needed to repeat injections. Results obtained with 20 mg triamcinolone were similar to those of the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Subacromial triamcinolone mexacetonide and methylprednisolone injections in treatment of supra spinam tendinitis. A comparative trial.

This statistical report describes a clinical trial on 60 patients with supraspinal tendinitis for the comparison of triamcinolone hexacetonide (in a 20 mg/cc suspension in 1 cc ampoules) with methylprednisolone acetate (in a 40 mg/cc suspension in 1 cc ampoules). The objective of the study was to determine the therapeutic activity, including onset and duration of relief, of triamcinolone hexacetonide as a subacromial injection, and to compare these results with those obtained with similar injections of methylprednisolone acetate. The following results were obtained. Triamcinolone hexacetonide reduced pain, local tenderness and functional impairment to a greater degree than did methylprednisolone acetate. A significantly smaller proportion of patients needed a second injection of triamcinolone hexacetonide (33%) than needed a second injection of methylprednisolone acetate (63%). Triamcinolone hexacetonide appears to have longer duration of activity than does methyl-prednisolone acetate, judging by the percentage of patients still getting relief from their first injection at the end of the study period. The drugs were similar as regards side effect incidence rates and time to onset of action.

Adolescent

The effect of budesonide and triamcinolone acetonide on hepatic microsomal testosterone metabolism in the rat.

The hepatic microsomal metabolism of testosterone was studied in male rats after treatment with either budesonide or triamcinolone acetonide for 13 weeks. The in vitro metabolism was determined using a testosterone concentration of 35 nM which is comparable to the levels found in plasma. It was shown that the total microsomal testosterone metabolism was decreased in budesonide-treated rats and increased in rats treated with triamcinolone acetonide. The testosterone metabolites produced were measured and thus it was revealed that budesonide treatment brought about its effect through a 50% decrease in the activity of steroid 5 alpha-reductase, but did not affect other reductive enzymes, or the oxidation of testosterone. Triamcinolone acetonide treatment decreased steroid 5 alpha-reductase activity by 95% and also decreased the activities of steroid 3 alpha- and 3 beta-reductases by more than 90%. In addition, treatment with triamcinolone acetonide caused a 50% increase in the oxidative metabolism of testosterone, which resulted in the observed increase in total testosterone metabolism. The presence of 0.1 microM budesonide in the microsomal incubations was without effect on testosterone metabolism. However, 0.1 microM triamcinolone acetonide inhibited testosterone oxidation by 65%, without affecting the reductive pathway of testosterone metabolism.

Animals

Cheilitis granulomatosa. Successful treatment with combined local triamcinolone injections and surgery.

Cheilitis granulomatosa is a rare condition that has traditionally proved difficult to treat satisfactorily. Excellent results were obtained in our case with local triamcinolone acetonide injections and surgery. Histopathologic features of the classic, untreated condition were reviewed and compared to the histopathologic features of labial tissues after a seris of triamcinolone injections. It was found that the injected medication was effective in achieving some reduction of labial volume, apparently through a necrotizing effect of granulomas with subsequent replacement by fibrous scars. Discontinuation of local injections after initial surgery apparently contributed to an exacerbation, as shown by the histopathology of a second cheiloplastic procedure. We therefore recommended that patients with chelitis granulomatosa who are receiving combinaed triamcinolone-surgical therapy continue to receive local triamcinolone injections after surgery in order to minimize the tendency for recurrence.

Cheilitis

Triamcinolone-induced mammary activation in virgin mice.

Intact ICR mice receiving Triamcinolone showed extensive proliferation within the mammary gland. Galactophores and ducts were enlarged. In contrast with the non-treated animals, those treated with Triamcinolone had an evident lobuloalveolar system. Triamcinolone failed to activate the glands of oophorectomized animals. It is thus evident that systemic administration of Triamcinolone to young virgin mice causes mammary stimulation and that this effect only occurs in the presence of the ovary.

Animals

Oropharyngeal candidiasis in patients treated with triamcinolone acetonide aerosol.

Thirty asthmatic patients participating in a trial of triamcinolone acetonide aerosol were evaluated to determine the relationships among symptons of sore throat or hoarseness, the appearance of the throat on physical examination, and the presence of yeasts on pharyngeal culture. Observations were recorded prior to aerosol therapy and repeated after 2 wk, 4 wk, 6 wk, 4 mo, and 6 mo of therapy. A total of 15 patients (50%) experienced sore throat or hoarseness, 15 (50%) had yeasts cultured from the pharynx on at least one occasion, and 11 (37%) at some point had an abnormal throat examination; however, there was no predictable relationship between symptoms or abnormal physical examinations and the presence of a positive culture. The frequency of positive cultures did not change significantly during the observation period. Twelve patients had positive yeast cultures on 50% or more of their samples. The incidence of symptoms was not sigficantly increased in these chronically colonized patients. Symptoms were usually transient, and discontinuation of the aerosol or antifungal therapy was unnecessary. Triamcinolone aerosol was not associated with significantly increased pharyngeal colonization with yeasts in this 6-mo study. Existing chronic colonization is not necessarily a contraindication to triamcinolone therapy. Sore throat and hoarseness are usually unrelated to yeast infection in patients using triamcinolone acetonide aerosol.

Adult

The influence of thyroid function on the diabetogenic action of triamcinolone in man. Glucose, insulin and growth hormone patterns after on oral glucose load.

In subjects with varying thyroid function (12 hypothyroid, 11 euthyroid and 12 hyperthyroid) an oral glucose tolerance test was performed without sensitization (OGTT) and after sensitizing with triamcinolone (TGTT). The blood glucose, serum immunoreactive insulin (IRI) and growth hormone (HGH) levels were assessed. In hypothyroid subjects a marked deterioration of the glucose tolerance was found during the TGTT as compared with OGTT, a reduction of the glucose disappearance index (GDI) and almost unchanged IRI values. The decrease of insulinogenic index (II) was not significant. In euthyroid subjects the decrease of glucose tolerance after triamcinolone was only mild, GDI values remained unaltered, IRI values and II increased. In hyperthyroid persons the decrease of glucose tolerance during TGTT was even less pronounced than in the euthyroid group, although the IRI value increased only on fasting. No significant differences of HGH pattern were observed in any group. In our patients the diabetogenic effect of triamcinolone was inversely related to the saturation with thyroid hormones and an increased response of insulin to glucose load was observed only in euthyroidism. In hyperthyroidism the participation of non-insular factors in the mechanism of maintaining the glucose tolerance after triamcinolone should be assumed.

Adult

Influence of local triamcinolone acetonide on patch test reactions to nickel sulfate.

The influence of local application of triamcinolone acetonide on patch test reactions was investigated in patients with a contact allergy to nickel sulfate. In 15 patients the reaction to patch tests with a mixture of 5% nickel sulfate and 0.1% triamcinolone acetonide in petrolatum was compared with the reaction to 5% nickel sulfate in petrolatum. In eight patients the test area on the skin was infiltrated with triamcinolone acetonide or saline solution after which test were performed with nickel sulfate. In eight patients the test area was pretreated with 0.1% triamcinolone acetonide cream or the cream base alone before the patch tests with nickel sulfate were done. In general, all three methods gave partial suppression of the size of the reaction.

Adult

Comparison of intra-articular methotrexate with intra-articular triamcinolone hexacetonide by thermography.

A comparison of intra-articular methotrexate and intra-articular triamcinolone hexacetonide was made in 42 arthritic patients with persistent bilateral knee effusions. One knee was injected with either 5 mg methotrexate (two injections of 2.5 mg a week apart) or a single injection of 20 mg triamcinolone. An objective assessment of both knees was made by quantitative thermography at 0,3,7,14 and 21 days. Joints injected with triamcinolone showed a greater fall in thermographic index (T.I) than the joints injected with methotrexate, which showed similar change to the non-injected knee joints in both groups. Four patients received larger doses of methotrexate, up to 20 mg, though the fall in T.I. was still less than the mean fall for triamcinolone injected joints. Peak venous blood levels of methotrexate were reached 1 hour after intra-articular injection, and a sphygmomanometer cuff inflated around the leg above the injected knee for periods of up to 1 hour did not appreciably delay this. Methotrexate had no immediate anti-inflammatory effect, even in psoriatic arthropathy, and did not give the relief of intra-articular steroid.

Adult

[Suppression of pituitary-adrenal axis by triamcinolone acetonide in asthmatics].

To assess the inhibitory effect of triamcinolone acetonide on pituitary-adrenal axis, we measured plasma cortisol, plasma ACTH and performed short ACTH stimulation test before and after injection of 40 mg of triamcinolone acetonide intramuscularly in 34 asthmatic patients. At the same time salivary cortisol levels had been followed up for four weeks in ten of the 34 patients. Maximum adrenal suppression was found in two to three days after the administration. The suppression rates of salivary cortisol, plasma cortisol, plasma ACTH and ACTH stimulation test were 81.5%, 53.2%, 70% and 45.6% respectively. Such suppression lasted for two weeks. Afterwards the secretion of pituitary and adrenal glands recovered gradually. The secretion of plasma ACTH and salivary cortisol returned to normal in four weeks and that of plasma cortisol in five weeks. Triamcinolone acetonide, 40 mg monthly, is comparable with prednisone 10 mg daily, or oral dexamethasone 0.75 mg daily. The inhibitory effect of the steroids on pituitary-adrenal axis was in the order of dexamethasone, triamcinolone acetonide and prednisone.

Adolescent

Clinical effect of aerosol triamcinolone acetonide in bronchial asthma.

In a double-blind, 12-week study of corticosteroid-dependent reversible bronchial asthma, 20 of 31 (64.5%) patients receiving triamcinolone acetonide aerosol, 800 microgram daily, were able to discontinue oral steroid therapy. This compares with three of 29 (10.3%) treated with aerosol placebo. At the end of the 12-week period, the mean 8 AM plasma cortisol level had increased from 5.3 +/- 4.1 to 8.6 +/- 5.2 microgram/dl in those receiving triamcinolone acetonide. The mean percent predicted values in the triamcinolone group for forced expiratory volume in the first second rose from 44.8 to 62.4 at two weeks (P less than .005), for forced vital capacity from 64.1 to 79.9 (P less than .005), and for maximum midexpiratory flow rate from 26.7 to 46.7 (P less than .005). The improved pulmonary function values persisted while the oral prednisone equivalent daily dose decreased from a mean of 13.3 to 2.9 mg at 12 weeks. Significant oral candidiasis was detected in two patients. Aerosol triamcinolone acetonide appears to be an effective alternative to beclomethasone dipropionate for use in patients with bronchial asthma.

Adolescent

Triamcinolone aerosol. Treatment of aspirin-hypersensitive asthmatic patients.

The efficacy of triamcinolone acetonide aerosol in the management of asthma in six patients with aspirin hypersensitivity was evaluated during a one-year trial. Five patients were previously chronically dependent on systemic corticosteroids and had undergone unsuccessful trials with cromolyn sodium therapy. Substantial reduction in corticosteroid requirements was observed; in two patients, oral prednisone therapy was completely eliminated. Forced expiratory volume and flow were maintained at levels better than those recorded before triamcinolone therapy throughout the year of follow-up. No substantial side effects due to triamcinolone were observed.

Aerosols

Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats.

The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placenta. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action.

Acetyl-CoA Carboxylase