Acquired symptomatic inhibitors of plasma clotting factors in nonhemophilic children.

Three children presenting with severe symptomatic bleeding episodes (one child developing a life-threatening subdural hematoma) due to acquired coagulation inhibitors are reported. In two patients, there was a history of an antecedent viral syndrome. None had evidence of drug exposure or an underlying immune disorder. All responded to the administration of corticosteroids, although one patient was steroid-dependent and required immunosuppressive therapy to achieve a complete response. Laboratory characteristics did not clearly distinguish the type of circulating inhibitor present in these children. Since bleeding was a prominent feature, we suggest that the inhibitors noted represent multiple specific coagulation factor inhibitors, rather than a "lupus-like" inhibitor which represents a common antibody to phospholipid-dependent coagulation tests. Such inhibitors may not be as benign as the common lupus anticoagulant seen in adult patients and should be considered in the child with symptomatic bleeding and a prolonged partial thromboplastin time. The true incidence and exact mechanism of action of acquired inhibitors in children has not been established.

Pulmonary fibrosis: a complication of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy.

A pediatric patient is reported who experienced fatal progressive pulmonary fibrosis as a complication of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy. The patient received a cumulative dosage of 1.29 g (1.72 g/m2) over a two-year period as adjuvant therapy for a medulloblastoma. Two and one-half years after cessation of therapy, cough, tachypnea and fatigue were noted. Progressive pulmonary insufficiency developed. Pulmonary pathologic findings included interstitial fibrosis and alveolar dysplasia. Other cases of BCNU pulmonary toxicity are cited from the medical literature.

Slipped capital femoral epiphysis following radiotherapy and chemotherapy.

There may be an increased frequency of slipped femoral epiphysis in pediatric patients who have received radiation to the pelvic area and combination chemotherapy. Previous reports include bilateral slipping of the epiphysis, eight years after radiation, in a patient with a pelvic neuroblastoma and the occurrence in a patient who had received radiation for Hodgkin disease, with a primary site in the pelvic region. No direct correlation was established in either case. This is a report of two patients who received pelvic radiation and combination chemotherapy who subsequently developed slipped femoral epiphysis. Our purpose is to heighten the suspicion in patients who have received radiation and chemotherapy for pelvic tumors. It is recommended that the femoral heads and acetabula be shielded when their inclusion in the treatment fields is not crucial to the treatment of the underlying disease.

Aerosol administration of fenoterol hydrobromide (Th 1165a) in subjects with reversible obstructive airway disease.

Bronchodilatory and side effects of fenoterol hydrobromide (Th1165a; hydroxyphenylorciprenaline; Berotec) and isoproterenol given by inhalation were compared in a double-blind crossover study involving 20 volunteer subjects with reversible obstructive disease of the airways. Subjects inhaled medications from aerosol canisters containing fenoterol hydrobromide (0.1 mg, 0.2 mg, or 0.4 mg) or isoproterenol (0.15 mg) or an inert placebo propellant in a random sequence of five testing days. All active drugs substantially increased the forced expiratory volume in one second, the mean forced expiratory flow during the middle half of the forced vital capacity, and the specific conductance. The onset of bronchodilation after both fenoterol and isoproterenol was rapid, but the effect from fenoterol lasted much longer, up to eight hours. None of the medications cuased significant tachycardia or hypertension. After inhalation of 0.1 mg of fenoterol hydrobromide, none of the subjects reported nervousness, headache, tremor, or nausea, incontrast with results reported for isoproterenol, higher aerosol doses fo fenoterol, or oral administration of fenoterol. No additional therapeutic benefit was found in the administration of higher doses of fenoterol.