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.

A comparison of botulinum toxin a and intralesional steroids for the treatment of plantar fasciitis: a randomized, double-blinded study.

BACKGROUND: The objective of this study was to compare intramuscularly applied botulinum toxin A (BTX-A) in the gastroc-soleus complex with intralesional steroids for the treatment of plantar fasciitis. METHODS: The patients were randomly divided into 2 groups according to the treatment received. The patients were evaluated over 6 months. The evaluation scores included the Visual Analog Scale (VAS), Maryland Foot and Ankle, Foot and Ankle Disability Index (FADI), and American Orthopaedic Foot and Ankle Society (AOFAS) score. Moreover, patients were instructed to perform plantar fascia stretching exercises over the course of the study. The final number of patients was 36, of whom 19 received BTX-A (10 men and 9 women) and 17 (6 men and 11 women) received steroids. RESULTS: When compared to patients who received steroids, the patients who received BTX-A exhibited more rapid and sustained improvement over the duration of the study. CONCLUSION: A combination of BTX-A and plantar fascia stretching exercises yielded better results for the treatment of plantar fasciitis than intralesional steroids. LEVEL OF EVIDENCE: Level I, therapeutic studies.

Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung function, bronchoalveolar lavage fluid cytology, and transcription factor expression in airways of horses with recurrent airway obstruction.

Glucocorticoid (GC) therapy is recognized to be effective for the treatment of recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC are thought to be mediated by suppression of inflammatory gene expression via inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). The purpose of this study was to evaluate the effect of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21-isonicotinate on clinical signs, pulmonary function, airway cytology, and activity of NF-kappaB and AP-1 in bronchial cells of RAO-affected horses. Seven horses with RAO were exposed to moldy hay until they developed airway obstruction on 3 separate occasions. In a crossover design, they were then treated with a placebo (injection on day 1), inhaled beclomethasone (500 microg q12h for 10 days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days. Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kappaB and AP-1 activity in bronchial brushing cells were measured before (day 1) and after treatment (day 10). Treatment with beclomethasone resulted in significantly improved pulmonary function of RAO-affected horses compared with placebo and dexamethasone treatments. However, none of the treatments had an effect on bronchoalveolar lavage fluid cytology or NF-kappaB and AP-1 activity. These findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled beclomethasone on pulmonary function are not accompanied by a decrease in airway inflammatory cells or a suppression of transcription factors NF-kappaB and AP-1 DNA-binding activity.

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.

Adrenocorticotropin-corticosterone relationship during dexamethasone therapy in 17 alpha-hydroxylase deficiency.

A previous study in an untreated girl with 17 alpha-hydroxylase deficiency syndrome (17-OHDS) indicated that in the absence of cortisol production, ACTH and corticosterone (B) may interact to modulate the brain-pituitary-adrenocortical system. The ACTH-B interplay was further examined in this patient under dexamethasone therapy and after withdrawal of treatment. Plasma ACTH and B were highly correlated (r = 0.89) during two different schedules of dexamethasone treatment and two weeks off treatment at all blood sampling times (morning, afternoon or 24-h period). A logarithmic-sigmoidal relationship seems to exist between ACTH and B secretion. The time course of ACTH-B relationship early after withdrawal of therapy showed good parallelism between these two variables. Plasma B may be a useful guide for monitoring therapy in 17-OHDS. The present study also indicates the ACTH-B interplay feedback set-points.

Action of dexamethasone in an equine model of acute non-immune inflammation.

In a crossover study in seven New Forest ponies the actions of dexamethasone, at a dose rate of 0.06 mg kg-1 administered intravenously, were compared with those of a placebo treatment. Dexamethasone exerted expected effects on plasma and inflammatory exudate concentrations of cortisol and on blood glucose concentration and circulating leucocyte numbers, but it failed to affect exudate concentrations of the eicosanoids, prostaglandin E2, thromboxane B2, 6-keto-PGF1 alpha and leukotriene B4. These findings do not support the hypothesis that the anti-inflammatory actions of dexamethasone in the horse are mediated by inhibition of phospholipase A2.

Dexamethasone isonicotinate inhibits dual and late asthmatic reactions but not the increase of airway responsiveness induced by toluene diisocyanate in sensitized subjects.

To determine whether treatment with aerosolized dexamethasone isonicotinate inhibits asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied six sensitized subjects with previously demonstrated dual or late asthmatic reaction after inhalation challenge with TDI. Dexamethasone isonicotinate (four puffs bid for seven days, ie, 0.5 mg bid for seven days; last four puffs 30 minutes before TDI) was administered for seven days before the inhalation challenge with TDI (0.010 to 0.015 ppm for 10 to 30 minutes) to each subject, according to a single-blind study design. When the subjects received no treatment, FEV1 markedly decreased and airway responsiveness increased after exposure to TDI. By contrast, when the subjects were treated with dexamethasone-isonicotinate, FEV1 decreased significantly less, but airway responsiveness still significantly increased after exposure to TDI. These results suggest that aerosolized dexamethasone isonicotinate may be used in the prophylaxis of TDI-induced late asthmatic reactions.

Dexamethasone-isonicotinate aerosol in the long-term treatment of steroid-dependent asthmatic children.

Dexamethasone-isonicotinate aerosol (DIA) was administered to twenty-nine steroid-dependent children with chronic perennial asthma, in an open trial during one year. An attempt was made to withdraw systemic corticosteroid therapy. As judged by clinical results, inhaled dexamethasone-isonicotinate controlled the asthma quite as well as did previous therapy. Oral corticosteroids were withdrawn in 27 patients, and the dosage considerably reduced in another two. Cushingoid features subsided. There was a statistically significant improvement in most pulmonary function parameters (airway obstruction and lung hyperinflation were reduced towards normal). Reduction of systemic steroid dosage resulted in the appearance of previously suppressed manifestations such as hay fever, eczema, and nasal polyps. There was no increased tendency to the occurrence of respiratory tract infection; routine examination showed Candida albicans in about 37% cultures.

Dexamethasone isonicotinate aerosol therapy in patients with chronic bronchial asthma.

Dexamethasone isonicotinate aerosols were used for the management of 106 patients (33 men, 73 women) with bronchial asthma (mean age 32.7 years); 62 of the patients were steroid-dependent (maintenance dose 1 to 25 mg prednisone/day for 0.5 to 11 years) at the start of the study. A diary of symptoms (including consumption of antiasthmatic drugs) was kept; physical examination and measurement of pulmonary function (peak flow rate, forced expiratory volume in one second) were performed during a one-to-four week control period, as well as at various intervals (up to 14 months) after the start of corticosteroid aerosol therapy. Clinical subjective and objective improvement was accompanied by a significant increase in ventilatory function indices (e.g. the FEV1.0 rose from a control average of 55.5% of predicted to 72% after 4 weeks and 85% after 12 months). The antiasthmatic drug consumption decreased markedly. Administration of systemic steroids could be withdrawn in 49 of the 62 steroid-dependent patients (79%); in the remaining 13 the dose was only lowered. The side-effects were minor (hoarseness of the voice, oropharyngeal candidosis), and limited to a few cases. It is concluded that bronchial asthma can be successfully controlled in four fifths of the patients by very low doses of dexamethasone isonicotinate aerosols, with practically no systemic effects.

Severe radiation injuries of the lung.

The lung is a radiosensitive organ whose limited tolerance must be treated with great respect in the radiation management of malignant tumors in the thorax. Severe radiation pneumonopathy can cripple and kill as the outcome of faulty judgment, error, accident, or calculated risk in an effort to control a locally advanced cancer. The clinical and radiologic profile of this unique and challenging syndrome is described and the histopathology and pathogenesis are reviewed. The clinical and technical factors of high risk are discussed, and guidelines for therapeutic management and safer clinical practice are offered.