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Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.

Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.

Allopurinol↗

Effects of betamethasone on the stimulation of corticosterone secretion in rats.

The effects of betamethasone on the elevation of rat plasma corticosterone levels by nicotine (400 microgram/kg s.c.), urethane anaesthesia and psychological stress have been studied. Betamethasone pretreatment (5 mg/kg given in the drinking water over 24 hr) initially suppressed the response to all three stimuli but, after 24 hr, only the response to urethane remained totally suppressed. Nicotine administered at this time to the urethane anaesthetised rats caused an increase in plasma corticosterone, apparently by stimulation of the autonomic nervous system. The results suggest that, following betamethasone, there is a prolonged delay in the recovery of the specific mechanism through which urethane stimulates pituitary-adrenal function rather than a total blockade of the effects of all stressful or chemical stimuli on ACTH secretion.

Adrenocorticotropic Hormone↗

[Intra-articular treatment of osteoarthrosis of the knee with betamethasone dipropionate and disodium phosphate. Non-controlled, open 5 years' experience].

We reviewed the result of treatment of knee osteoarthritis with intraarticular injection of betamethasone derivatives in 100 patients over a 5 year period. Knee involvement was bilateral in 34 of these patients. 1 ml of a mixture of betamethasone dipropionate and betamethasone phosphate was injected intraarticularly in each patient and repeated if needed at 3 week intervals. A total of 496 injections (mean 3.7 per knee, minimum 1 and maximum 18) were performed. Clinical and radiological evaluation before and midway through therapy revealed no side effects. The clinical response in terms of pain, mobility and functional capacity was good. We conclude that the therapy described results in good clinical and functional results over long periods of time in patients with knee osteoarthritis.

Adult↗

Betamethasone and the human fetal ductus arteriosus.

We used a sensitive Doppler echocardiographic technique to evaluate in utero the effects of betamethasone on the human ductus arteriosus. Transient, mild constriction of the ductus arteriosus 4-5 hours after the first injection of betamethasone occurred in two of 11 trials. The relatively mild and brief effects on the human ductus of betamethasone in usual doses are probably not clinically significant in most instances. Hence, they do not appear to contraindicate the use of glucocorticoids to promote fetal lung maturation.

Betamethasone↗

[Influence of betamethasone on glucose consumption in the human placenta perfused in vitro].

The study was carried out on 48 human placentas perfused in vitro. Betamethasone was administered into the arterial systems in the following single doses: 0.4 mg, 2 mg and 10 mg. The authors found a highly significant or statistically insignificant decreased glucose consumption after administering each dose of betamethasone and at all times of the experiment. The phenomenon of a decrease in glucose consumption was attributed to an increased gluconeogenesis and releasing glucose from placental glycogen. The action of betamethasone consisting in supplying an increased amount of glucose is of great importance in the process of maturing fetal lungs in the uterus and in states threatening the fetus.

Betamethasone↗

The influence of dimetindene maleate on the endogenous hydrocortisone synthesis suppressing potency of betamethasone.

Plasma hydrocortisone (cortisol) levels in 7 healthy volunteers were measured following administration of 0.25 mg betamethasone or 0.25 mg betamethasone and 1 mg dimetindene maleate. The H1-receptor antagonist dimetindene maleate did not influence the hydrocortisone suppressing activity of betamethasone, which was proved by comparison with the published plasma hydrocortisone levels of 162 young healthy untreated volunteers.

Adult↗

[Effect of betamethasone on the lipid composition of pulmonary surfactant, ependymal cells and lung tissue after surgical procedures on the thorax of dogs].

The lipid composition of pulmonary surfactant, ependymal cells and pulmonary tissue after surgery on the thorax in dogs was determined. 24 hrs after removal of one lung, in the other one there occurred changes in the quantity of respective classes of phospholipids of the pulmonary surfactant, manifesting themselves by a considerable drop in the amount of phosphatidylcholine (by 25%), phosphatidylethylamine (by 47%), phosphatidylglycerol (by 98%) and phosphatidylcholine: sphingomyelin ratio (by 63%), as well as by a rise in the amount of lysophosphatidylcholine (by 83%), phosphatidylserine (by 54%) and sphingomyelin (by 25%). In dogs receiving betamethasone in the post-operative period the changes were less intense: the amount of phosphatidylcholine decreased by 15%, phosphatidylethanolamine by 29%, phosphatidylglycerol by 94% and phosphatidylcholine: sphingomyelin ratio by 63%. The amount of lysophosphatidylcholine increased by 26.7%, phosphatidylserine by 29.1% and sphingomyelin by 22.2%. Similar changes were observed in the phospholipids of lining cells, while changes in the composition of phospholipids of pulmonary tissue in most cases appeared insignificant. Insignificant, too, were changes in the composition of neutral lipids of the tissular fractions examined. The described changes in dogs not receiving betamethasone correspond to those found in man in the course of acute respiratory insufficiency syndrome. Betamethasone was found to exert a protective effect on the phospholipids of pulmonary surfactant, soothing the biochemical changes brought about by surgical removal of one lung.

Animals↗

[Antenatal administration of betamethasone. Effects upon neonatal blood glucose in premature infants (author's transl)].

This effect was studied in 23 preterm neonates at the age of 2--8 hours. Betamethasone was administered at a dose of 12 mg intramuscular once or several times before delivery. This glycemia was compared with the glycemia of 52 control preterm infants studied at the same period. In the control preterm neonates, the mean (+/- 1 S.D.) blood glucose level was 0.51 +/- 0.26 g/l versus 0.53 +/- 0.24 g/l in the preterm infants pretreated with betamethasone. The incidence of glycemia less than 0.30 or 0.20 g/l was not significantly different in the two groups. These data show that prenatal betamethasone therapy has no harmful or diserable effect on the neonatal glycemia of preterm infants.

Betamethasone↗

SCH 370 (clotrimazole-betamethasone dipropionate) cream in patients with tinea cruris or tinea corporis.

The safety and efficacy of SCH 370 (1 percent clotrimazole/0.05 percent betamethasone dipropionate) cream was compared with each of its individual components in 331 patients with tinea cruris or tinea corporis. The study was a multicentered, randomized, double-blind, parallel-groups design. The patients received one of three treatments applied twice a day for two weeks and returned for a follow-up visit two weeks after the last application. Total signs and symptoms scores of infections were evaluated at baseline, once between days three to five, and after weeks one, two, and four. Culture and potassium hydroxide preparations were done at baseline and weeks two and four. SCH 370 cream demonstrated more rapid therapeutic activity than the antifungal agent alone, resulting in significantly better clinical results in early treatment and in midtreatment. As expected with a steroid, betamethasone dipropionate achieved relief of inflammatory signs and symptoms early in the course of treatment, but SCH 370 was superior from one week on in the patients with tinea cruris and at post-treatment in the patients with tinea corporis. Mycologically, SCH 370 cream and clotrimazole were comparable at the end of the study and results were significantly better than those for betamethasone dipropionate. All three treatments were safe with no reports of unexpected or serious adverse experiences.

Adult↗

Betamethasone administration to the mother and problems in foeto-placental monitoring.

The administration of betamethasone to the mother in order to accelerate maturation of foetal lungs induces significant modifications in the foeto-placental hormonal secretion. Both the total estriol and unconjugated estriol present a sharp fall in the days immediately following the administration and a rise 10-12 days later, depending on a rebound effect. The HPL levels do not variate except for a progressive and constant rising due probably to better cardiocirculatory maternal condition with, consequently, a higher utero-placental blood-flow. All these phenomena increase when the administration of betamethasone to the mother is repeated more then once. The AA. believe that the sharp fall of the estriol doesn't represent a danger for the foetus being only an effect of maternal and fetal adrenal depression. Consequently the AA. suggest to drive the management during and after the administration of betamethasone to the mother on the basis of other foeto-placental functional tests, as cardiotocography. The results were analysed.

Betamethasone↗

Alternate-day betamethasone treatment does not affect intestinal absorption of calcium and phosphate and growth rate of chicks.

The effect of oral administration of betamethasone in single daily doses (25 microgram kg-1 d-1) and in single alternate-day doses (50 microgram kg-1 every other day) on the duodenal absorption of calcium, on the jejunal absorption of phosphate and on weight gain has been studied in chicks using the in vivo ligated loop technique. The daily administration of betamethasone for three weeks markedly reduced the absorption of calcium and phosphate as well as the growth rate. Alternate-day treatment lacked all these adverse effects of betamethasone and the results did not differ significantly from those in the control chicks.

Animals↗

School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone.

The cognitive development of children whose mothers had been included in the first Auckland trials of betamethasone therapy in premature labor were studied. An earlier study of these children used psychometric tests during the fifth year of life. In the present study tests were given during the seventh year of life (the second year of school) to 250 (82.2%) of 304 surviving children. Of the 250 children, 139 were in the group whose mothers had received betamethasone and 111 were in the control group. Further tests of cognitive development were made, together with assessment of the children's progress in school. Again, on the majority of measures there were no significant differences between children whose mothers had received betamethasone and the children in the control group. Calculations of statistical power showed that important differences were unlikely to have been missed.

Anthropometry↗

Premature rupture of the membranes: maternal and neonatal infectious morbidity related to betamethasone and antibiotic therapy.

A retrospective study of patients delivering in 1976-77 at Duke University Medical Center was performed to assess the impact of betamethasone and prophylactic antibiotics on infectious morbidity in mothers with premature rupture of the membranes (PROM) at 26 to 34 weeks' gestation and in their neonates. Ninety-five records were reviewed for evidence of maternal and neonatal infection and perinatal mortality. Betamethasone had no impact on maternal or neonatal infection. Antibiotics given concurrently with betamethasone significantly reduced the incidence of maternal and/or neonatal infection (18.0% vs. 0). Perinatal mortality increased when the duration of the latent period was 72 hours and greater because of factors other than infection.

Anti-Bacterial Agents↗

Effect of betamethasone administration on estrone, estradiol-17 beta, and progesterone in maternal plasma and amniotic fluid.

As part of a series of studies on the endocrine consequences of corticosteroid treatment during late pregnancy, the levels of unconjugated estrone (E1), estradiol-14 beta (E2), and progesterone were followed in maternal plasma and amniotic fluid before and after treatment. Ten gravidas in the 30th-35th gestational week received 12 mg betamethasone daily for 3 days for prevention of idiopathic respiratory distress syndrome (IRDS) and were compared to 5 controls. The steroid concentrations were determined by radioimmunoassay. The plasma levels of E1 and E2 were depressed to 38% and 29%, respectively, while that of progesterone was not affected. No significant change of the steroid concentrations in amniotic fluid was observed. The decreased E2: progesterone ratio in maternal blood after betamethasone treatment in the human is in contrast to the increased ratio observed in ruminants after corticosteroid administration and preceding the spontaneous onset of labor. The fall in the E2: progesterone ratio accords with the earlier observed inability of intramuscular corticosteroid treatment of elicit labor in women at this stage of gestation. The earlier demonstrated marked depression of cortisol in fetal plasma after betamethasone seems paradoxical in view of the seemingly high availability of progesterone, considered as a precursor for the cortisol biosynthesis in the human fetal adrenal cortex.

Amniotic Fluid↗

Contact allergy to hydrocortisone and systemic contact dermatitis from prednisolone with tolerance of betamethasone.

BACKGROUND: Contact allergy to corticosteroids is not uncommon. As the clinical pattern that the patients exhibit may be misleading, the discovery at patch testing may be unexpected and solely a result of the fact that marker molecules for corticosteroid contact allergy are incorporated into standard series and that tests are read twice, on D3/4 and D7. OBJECTIVE: We describe a patient allergic to hydrocortisone who was given a cross-reacting corticosteroid, prednisolone, that led to a systemic contact dermatitis. The patient cleared when betamethasone, a non¿Ncross-reacting corticosteroid, was administered. METHODS: The patient was patch tested to a standard series including tixocortol pivalate, and an extended corticosteroid series including betamethasone. RESULTS: Patch testing with tixocortol pivalate provoked an allergic patch test reaction (+? D3, +D7), whereas betamethasone did not. CONCLUSION: Our patient's allergy was undiagnosed for 5 years, and it was not until she was given a cross-reacting corticosteroid, which led to exacerbation of her dermatitis, that her physician suspected corticosteroid allergy. The incorporation of marker molecules for the detection of corticosteroid contact allergy into standard series with two reading occasions, 3 to 4 days apart, is advocated.

Anti-Inflammatory Agents↗

Systemic allergic reaction and diffuse bone pain after exposure to a preparation of betamethasone.

Allergic reactions to corticosteroids are unexpected as they seem to contradict their pharmacodynamic action. Nevertheless, they are not infrequent, with an estimated incidence of up to 4% for cutaneous reactions. Systemic reactions are rarely reported, but their incidence might be underestimated. We report here an unusual allergic reaction to betamethasone presenting with diffuse bone pain, erythema, and bronchoconstriction, which was confirmed by a positive rechallenge in a double-blind procedure. This is the first case report of a systemic reaction to betamethasone confirmed by a positive rechallenge. An impurity in betamethasone diproprionate cannot be excluded. As this substance is frequently used in rheumatologic soft-tissue injections, it is important to recognize this potentially life-threatening side effect.

Journal Article↗

Comparison of epidural Depo-Medrol vs. aqueous betamethasone in patients with low back pain.

Despite the popularity of epidural steroid injections for low back pain, there still remains a lack of consensus on which type of steroid to inject. Most comparison studies regarding epidural steroids are based on an assumption that different types of steroids are equal as long as equipotent doses are utilized. In the spring of 2002, a national shortage of all depo steroids allowed the authors to compare epidural methylprednisolone (Depo-Medrol) to a non depo form of betamethasone in patients with low back pain. Patients who received epidural methylprednisolone (Depo-Medrol) reported significant reduction in pain ratings as well as disability scores after 4 weeks, while patients receiving betamethasone showed no significant difference in pain or disability scores. This study shows that the aqueous steroid betamethasone is not an effective alternative to the commonly used depo-steroid methylprednisolone (Depo-Medrol) when injected epidurally in patients with lumbar pain. The study also shows that the anti-inflammatory effect of a depo-steroid can be greater than a non-depo steroid, even at equipotent doses. This should be an important factor to consider when reviewing epidural steroid outcome studies, where the type of steroid might affect results as much as other variables such as route of administration, volume of injectate, or use of fluoroscopy.

Journal Article↗

Combination therapy for psoriasis. Psoralens plus long-wave ultraviolet radiation with betamethasone valerate.

In the treatment of psoriatic patients with psoralens plus long-wave ultraviolet radiation (PUVA), clearing of psoriatic lesions was obtained more quickly and with smaller doses of ultraviolet light when topically applied corticosteroid therapy was added. Twelve patients with symmetrical plaque-type psoriasis were given PUVA on one side of the body and PUVA plus betamethasone valerate on the other side in a paired comparison study. Ten of the patients had faster clearing of lesions on the side that was treated with PUVA and betamethasone than on the side treated with PUVA alone. The other two patients had equal clearing on both sides. All patients remained clear of lesions during maintenance with PUVA alone for at least five months after steroid therapy was discontinued. Combination therapy may save the patient time, expense, and unnecessary exposure to radiant energy.

Adult↗