Altas dosis de dexametasona en niños y adolescentes con epilepsia de difícil control / High doses of dexamethasone in children and adolescents with epilepsy of difficult control

Objetivo: Describir las principales características clínicas y evolutivas de una serie de pacientes con epilepsia de difícil control, tratados con altas dosis de dexametasona intravenosa.Métodos: Se realizó un estudio descriptivo con una serie de 12 casos tratados por epilepsia de difícil control en el Servicio de Neuropediatría del Hospital Pediátrico Docente “Juan Manuel Márquez” de enero de 2010 a septiembre de 2018. Se les administró dexametasona intravenosa a altas dosis en tres días consecutivos cada mes(ciclo) y durante cinco meses, además de los fármacos antiepilépticos que tenían indicados. Se analizó la edad de inicio de la epilepsia y al diagnóstico, la edad al inicio del tratamiento, el tipo de crisis y de epilepsia, el tiempo entre el inicio de la epilepsia y el tratamiento y, además, la causa. Se utilizó el test exacto de Fisher para la determinación de la asociación entre estas dos últimas variables y la evolución clínica.Resultados: Predominaron los pacientes del sexo masculino, los que iniciaron lasmanifestaciones clínicas en el primer año de vida, aquellos que presentaron varios tipos de crisis, los que usaban politerapia y tenían una causa conocida de la epilepsia (sintomática). Luego de los cinco ciclos de tratamiento, se detectó una evolución satisfactoria (disminuyó en al menos 50 Por ciento la frecuencia de las crisis) en 8 de 12 enfermos. Solo en dos casos se presentaron reacciones adversas al tratamiento (hipertensión arterial), que no requirieron la retirada de la terapéutica.Conclusiones: Hubo predominio en los pacientes con varios tipos de crisis epilépticas y en los que la causa de la epilepsia fue reconocida (estructural). En ellos, el uso de la dexametasona intravenosa a altas dosis, añadido a otros fármacos antiepilépticos, fueuna alternativa eficaz para disminuir la frecuencia de las crisis epilépticas(AU)

Objective: To describe the main clinical and evolutionary characteristics of a series of patients with difficult control epilepsy treated with high doses of intravenous dexamethasone.Methods: A descriptive study was conducted with a series of 12 cases treated for difficult control epilepsy in the Neuropediatric Service at Juan Manuel Márquez Pediatric Teaching Hospital from January 2010 to September 2018. They receivedintravenous dexamethasone at high doses on 3 consecutive days each month (cycle) and for five months, in addition to the antiepileptic drugs they had indicated. This study analyzed the ages at epilepsy onset and at diagnosis, at the beginning of treatment, the type of seizures and epilepsy, the time between the epilepsy onset and treatment and, inaddition, the cause. The fisher exact test was used to determine the association between these last two variables and the clinical evolution.Results: Male patients predominated, those who started clinical manifestations in the first year of life, those who presented several types of seizures, those who used polytherapy and had a known cause of epilepsy (symptomatic). After five treatment cycles, a satisfactory evolution was detected. The frequency of seizures decreased by at least 50 Per cent in 8 of 12 patients. Only in two cases showed adverse reactions to the treatment (arterial hypertension), which did notrequire the withdrawal of the therapy.Conclusions: There was a predominance of patients with several types of epilepticseizures and of those that the cause of epilepsy was recognized as structural. In them, the use of intravenous dexamethasone at high doses, added to other antiepileptic drugs, was an effective alternative to reduce the frequency of epileptic seizures(AU)

Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. ß-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle.

Effects of anabolic and therapeutic doses of dexamethasone on thymus morphology and apoptosis in veal calves.

Three groups of 10 veal calves were treated, respectively, with 5 mg of dexamethasone-21-isonicotinate administered intramuscularly on days 0 and 7 (group A); 0.4 mg/day of dexamethasone-21-phosphate administered orally for 20 days (group B); or left untreated as controls (group C). Two animals from each group were slaughtered on day 3, 7, 14, 32 and 52. The size and weight of the thymus decreased progressively in both treated groups until day 32. On day 14, in comparison with the controls, there was a mean reduction of 76 per cent in the thymus weight of group A and 35 per cent in group B. On day 32, the reductions were 13 per cent in group A and 50 per cent in group B, but the thymus weight of both groups had recovered completely by day 52. Dexamethasone-induced changes in thymus weight associated with lymphoid depletion and fat replacement, and there were clear correlations between these changes and apoptosis of thymocytes.

The effects of a single injection of dexamethasone-21-isonicotinate on the lymphocyte functions of dairy cows at two weeks post partum.

Dexamethasone is a potent therapeutic for treatment of the fatty liver syndrome or primary ketosis in post partum dairy cows. Reservations exist, however, among practitioners with respect to the risk of immunosuppression induced by corticosteroids. The aim of this study was to investigate the effect of a single injection of dexamethasone-21-isonicotinate on distinct immune functions of postpartum dairy cows because only scarce information is available on the effects of corticosteroid preparations when administered at a dosage and frequency for treatment of the fatty liver syndrome or primary ketosis. Sixteen Swedish red-pied dairy cows, between days 9 and 15 post partum, were allotted to either a control group (n = 8) or a treatment group (n = 8). The cows in the treatment group received a single intramuscular injection of a dexamethasone-21-isonicotinate suspension at a dosage of 0.02 mg/kg i.m. at the start of the experiment. White blood cell counts and selected lymphocyte functions (lymphocyte proliferation, expression of lymphocyte markers and the b2 and a4 chain of adhesion molecules belonging to the integrin family) and some parameters of the energy metabolism (glucose, insulin) were determined before the administration of corticosteroids (day 0) and subsequently at days 2, 4, 7 and 9 of the experiment. Changes in glucose and insulin were within the target range for treatment of the fatty liver syndrome or primary ketosis. Significant (P < 0.05) increases in the number of circulating white blood cells were observed in treated cows on the second day following treatment which was exclusively caused by an increase in the number of circulating neutrophils. Lymphocyte blastogenesis in response to ConA and the percentages of lymphocytes positive for CD2, CD4, CD8, CD49d and CD18 as well as the intensity of CD49d expression did not differ between the treatment and control groups. There was, however, a significant reduction (P < 0.01) in the intensity of CD18 expression on lymphocytes in the treated animals on the fourth day after treatment. In conclusion, a single administration of dexamethasone-21-isonicotinate in a dosage of 0.02 mg/kg i.m. at two weeks post partum in healthy cows had a significant but highly transient effect on CD18 expression on lymphocytes and the number of peripheral blood neutrophils, but did not affect lymphocyte blastogenesis or lymphocyte subpopulation patterns in peripheral blood.

Pemphigus foliaceus in a goat.

A 7-year-old-female goat was referred with a 3-month history of chronic dermatitis, which partially responded to combined corticosteroid and antibiotic therapy. At dermatological examination diffuse alopecia, pustules and crusts were observed on the head, neck, dorsum and perianal area. Dermatophyte culture and skin scrapings were negative. Trichoscopic examination revealed a concurrent infestation with Damalinia caprae, which was successfully treated with ivermectin. Cytological examination of pus from intact pustules revealed nondegenerate neutrophils, absence of bacteria and numerous nucleated, irregularly shaped keratinocytes. Histopathological examination of lesional skin revealed intracorneal pustules containing neutrophils and acantholytic cells, and a mixed cell superficial perivascular dermatitis. Immunohistochemical stains of lesional skin showed intercellular IgG deposits in the spinous layer. Remission of the dermatitis was obtained with injectable dexamethasone-21-isonicotinate, every two months for one year. This is the first report to describe the cytological appearance of impression smears from intact pustules of pemphigus foliaceus in a goat and to document the presence of IgG deposits in lesional skin by means of immunohistochemistry.

Efficacy of three corticosteroids for the treatment of heaves.

This study used a cross-over design to compare the efficacy of 3 corticosteroids for the relief of airway obstruction and inflammation in 9 heaves-affected horses. The severity of airway obstruction and inflammation was quantified by measurement of lung function and by bronchoalveolar lavage fluid (BALF) cytology, respectively. Airway obstruction was induced by stabling the horses and they remained stabled during the 10 day treatment period. Lung function was measured before treatment (baseline), at Days 3, 7, and 10 of treatment, and after 30 days at pasture. BALF cytology was investigated at baseline, Day 10, and at pasture. All 9 horses received the following 4 treatments in random order: no treatment, daily oral prednisone tablets (1 mg/kg), daily i.v. dexamethasone solution (0.1 mg/kg), and i.m. dexamethasone-21-isonicotinate (0.04 mg/kg) every 3 days. When horses received no treatment, lung function did not change significantly during stabling but improved at pasture. In all horses, daily i.v. administration of dexamethasone solution improved lung function within 3 days to levels as good as or better than those measured at pasture. Dexamethasone-21-isonicotinate was rapidly effective in 8 of 9 horses. The other horse did not respond to this drug. Prednisone tablets were without effect on Days 3 and 7 of treatment, but by Day 10, 5 of 9 horses showed some improvement in lung function. Dexamethasone i.v. solution decreased the percent neutrophils in BALF at Day 10. Other treatments had no effect on BALF cytology. These results demonstrate that dexamethasone rapidly relieved airway obstruction in heaves-affected horses. Oral prednisone had inconsistent effects but may be beneficial in some horses after more than a week of treatment.

Dexamethasone concentrations in bovine blood plasma and milk after intravenous injection.

Passage of dexamethasone from plasma to milk in five lactating dairy cows after an intravenous injection was evaluated by a high performance liquid chromatographic technique for measurement of concentrations in blood plasma and milk. The dexamethasone ester was 21-isonicotinate as a solution and was administered at .1 mg/kg bodyweight. The drug was detected in milk postinjection from 15 min to 8 h with a peak concentration of 20.6 ng/ml at the second sample time (30 min). Half-times of dexamethasone in plasma and milk were 4.5 and 3.0 h. The ratio of mean concentration for milk/plasma was .39. It is anticipated that no residues of dexamethasone would be detected in milk if normal dairy practices are followed.

Dexamethasone in cattle: pharmacokinetics and action on the adrenal gland.

The pharmacokinetics of Dexamethasone (DXM) was studied in four cows all of which received DXM alcohol and DXM 21 isonicotinate (as a solution) by the intravenous and intramuscular routes. Concentrations of DXM and cortisol were determined using high performance liquid chromatography. An additional study was made in a second group of four cows which received intramuscular DXM 21 isonicotinate suspension for the assessment of DXM suppression of adrenal gland function. This was determined by measurements of base-line and ACTH-stimulated cortisol concentrations, before and following DXM administration. Following intravenous administration, the disposition kinetics of both formulations were described by a two-compartment open model. The half-times of elimination were similar; 335 and 291 min, respectively, for DXM alcohol and DXM 21 isonicotinate. All other pharmacokinetic parameters were not statistically different indicating that DXM was almost totally available (from DXM 21 isonicotinate). Following intramuscular administration, no significant difference in parameters was observed between the two formulations. Peak plasma concentrations were reached at 3 to 4 h post injection and bioavailability was approximately 70%. DXM was not detected in the plasma after the intramuscular administration of the suspension. The mean control plasma cortisol concentration was 8.8 +/- 3.03 ng/ml. Following intravenous and intramuscular administrations of DXM alcohol and DXM 21 isonicotinate (solution), cortisol concentrations initially increased. However, at 120 min (intravenous) and 2-4 h (intramuscular), concentrations were negligible; 24-72 h and 48-96 h, respectively elapsed before concentrations returned control values. Following DXM 21 isonicotinate (suspension) there was no initial increase and concentrations had not returned to normal in all four cows until 52 days post administration. Similarly, ACTH-stimulated plasma cortisol concentrations decreased progressively and significantly post administration. At 52 days, response to ACTH was normal in all animals.

[Corticotherapy of bronchial asthma, using dosed aerosols]. / Corticoterapia astmului bronsic cu aerosoli dozalti

Corticoid therapy with dosed aerosols is one of the achievements that have been made lately in the treatment of bronchial asthma. In view of establishing the efficiency of this type of treatment two preparations have been used: Auxiloson (isonicotinate of dexamethasone), and Becotide (dipropionate of belcomethasone), in two groups of patients. The favourable results obtained involved over 80% of the patients treated with each of these drugs. The use of corticoid therapy with dosed aerosols in the treatment of bronchial asthma reduces many of the risks of the general therapy with corticoids, and is indicated in the maintenance therapy of patients, between asthma attacks, in the intervals when the risk of such attacks is increased, and especially in the long term treatment of corticoid-dependent bronchial asthma.

[Penetration of the tympanum by active substances (author's transl)]. / Penetration von Wirkstoffen durch das Trommelfell

In a specially designed animal model the penetration of glucocorticoid and oxytetracycline through the intact tympanic membrane was studied. Dogs were anesthetised for up to 8 h, and the substances were administered to the external auditory meatus. The measured concentration of the applied glucocorticoid in the tympanum showed a level which can be expected to be therapeutically active. When treating the inflamed middle ear, an adjuvant therapy with the combination dexamethasone-21-isonicotinate/oxytetracycline/natamycine/;etracain (Incut) should be taken into consideration. Although oxytetracycline was administered as well, this substance could not be measured in the small samples due to technical reasons. To find out about penetration of o%ytetracycline will have to be the object of another series of experiments.

Treatment of pregnancy toxaemia in ewes by induction of parturition.

Treatment of pregnancy toxaemia in ewes by induction of parturition is reported. The efficacy of 3 formulations of dexamethasone, at different dosages, is recorded and discussed.

Therapeutic index of steroid aerosols in asthma. A single-blind comparative trial of beclomethasone dipropionate vs dexamethasone isonicotinate.

1) A 4-week single-blind study is reported which compares the responses of 10 matched pairs of adult asthmatic patients to Beclomethasone Dipropionate and Dexamethasone Isonicotinate aerosols, each at 12 metered-doses per day. 2) Therapeutic efficacy was evaluated by measurement of pulmonary function (PEFR) and by a physician's "overall evaluation" scale. 3) Side-effects related to systemic absorption were evaluated by A.M. blood cortisol levels and total eosinophil counts. 4) At the doses studied, Beclomethasone Dipropionate produced both no side-effects and a significant favourable clinical response, while Dexamethasone Isonicotinate produced significant side-effects and a lesser clinical response.