Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.     

Gonadotrophin releasing hormone agonist suppressive treatment of ovarian function decreases serum LH-β and bloactive LH but maintains elevated levels of LH-α

Ten patients with endometriosis were treated by a continuous subcutaneous infusion of the GnRH agonist buserelin for 6 months. Although serum oestradiol decreased into the menopausal range within 2 weeks after starting treatment, serum LH levels as measured by immunoassay remained elevated at least fivefold over baseline during the entire treatment. However, the bioactivity of LH as determined by mouse Leydig cell assay was rapidly lost, changing the mean +/- SEM bioactivity/immunoassay ratio from 2.4 +/- 0.5 before treatment to 0.4 +/- 0.01 after only 1 week of medication. When LH-alpha and LH-beta immunoreactivities were assessed by specific antibodies, the serum LH-alpha profile was parallel to immunoreactive LH whereas the LH-beta profile corresponded to the pattern of bioactive LH. LH-alpha was elevated at least tenfold over baseline whereas LH-beta decreased to less than 35% of pretreatment level. The alpha/beta ratio shifted from 1.3 +/- 0.2 before treatment to 0.04 +/- 0.06 after 2 weeks of buserelin infusion. Thus in response to continuous buserelin exposure, the gonadotrophin releases excessive amounts of LH having predominant LH-alpha immunoreactivity. The effective loss of LH bioactivity would be related to decreased LH-beta subunits. The significance of high levels of LH-alpha subunits. The significance of high levels of LH-alpha or possibly modified LH molecules remains to be evaluated during GnRH agonist treatment using well characterized assays.     

Radiographic assessment of the condylar position after Le Fort I osteotomy in patients with asymptomatic temporomandibular joints: a prospective study.

PURPOSE: A prospective radiographic study analyzed condylar position in patients who had undergone orthodontic treatment and isolated maxillary advancement after Le Fort I osteotomy. PATIENTS AND METHODS: Eleven patients were selected and radiographic images were taken in the immediate preoperative, immediate postoperative (1-2 weeks), and late postoperative periods (minimum of 6 months). Tracings were done on acetate paper for the submento-vertex radiograph, to measure the axial angulation of the condyles, and for the tomographic images of both sides, in the maximal intercuspation, rest position, and maximal opening, for the 3 periods. Linear measurements were taken for the tomograms over the posterior, superior, and anterior articular spaces. These images with the tracings were digitized and measured by means of computer software (UTHSCSA Image Tool 3.0; University of Texas Health Science Center at San Antonio, San Antonio, TX), after it had been adequately calibrated. RESULTS: The analysis of variance (ANOVA; 5% of significance) demonstrated 1) that there was no statistically significant difference for the linear measurements of the articular spaces in any of the periods, and 2) also not for the angular measure of the condyles (P > .05). In the maximal opening, there was a significant difference for the immediate postoperative period for both sides (P = .003). CONCLUSION: Le Fort I osteotomy for maxillary advancement did not cause any significant changes in this specific group of patients evaluated.     

Anti-liver microsomes autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug.

Anti-liver microsomes (anti-LM) autoantibodies in patients with dihydralazine-induced hepatitis were found to react specifically with cytochrome P4501A2 (P4501A2) but not with P4501A1 expressed in yeast and bacteria. These results were confirmed by immunoinhibition of methoxyresorufin-O-demethylase activity (supported by the P4501A subfamily); anti-LM antibodies more strongly inhibited this activity in yeast expressing P4501A2 than in yeast expressing P4501A1. Anti-LM were shown to be specific to the disease; in three cases, these autoantibodies were present at high titers during disease, whereas the titers decreased upon recovery and became undetectable a few months after recovery. Thus, there exists a time-dependent relationship between the disease and the autoantibodies, which does not prove that the autoantibodies are causative of the hepatitis; they might only be a marker. The inductive capacity of dihydralazine toward P450 was also studied. In rats treated in vivo and in human hepatocytes treated in vitro with dihydralazine, a 2-fold increase in P4501A2- and P4501A-supported monooxygenase activities was found. The levels of the other P450 isoforms tested were unchanged during treatment, both in vivo in rats and in vitro in cultures of human hepatocytes. In human hepatocytes, dihydralazine produced a dose-dependent increase in the level of P4501A up to 0.1 mM; induction of P4501A was less strong at 0.2 mM and disappeared at 0.5 mM. The same treatment did not change the level of P4503A4, taken as control. The strong heterogeneity in the expression of P4501A enzymes in human liver and the capacity of these enzymes for induction by dihydralazine and by other compounds might be predisposing factors in this autoimmune disease.     

Computerized axial tomo-epidurographic and radiographic documentation of unilateral epidural analgesia

A 23-year-old primigravid patient who received epidural analgesia for pain of labour presented with persistent, apparently irremediable, unilateral analgesia. Computerized axial tomo-epidurography demonstrated absence of circumferential spread due to lateral placement of the catheter. Transforaminal escape of contrast medium into the paravertebral area had occurred and anterior and posterior midline partitioning of the epidural space was obvious. All the usual measures to promote contralateral analgesia, except re-insertion of the catheter, had been tried without success.