Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma.

PURPOSE: Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown. Materials and METHODS: We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation. RESULTS: Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P =.007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P =.009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P =.03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV. CONCLUSION: Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.     

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.     

Immunoassays for proteins alkylated by nicotine-derived N-nitrosamines

Polyclonal antibodies recognizing the pyridyloxobutyl (POB) moiety of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were produced in rabbits immunized either with POB-bovine albumin or POB-Sepharose. The POB intermediates necessary to modify the protein were generated by alkaline (pH 9.0) treatment of the synthetic precursor 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone. In a competitive enzyme linked immunoabsorbent assay (ELISA), 70 pmole NNK inhibited 50% of the binding of the anti-POB antibodies to POB-protein absorbed on microtiterplates. This 50% inhibition varied from 70 pmole to 200 nmole using a series of NNK analogues, depending on the integrity of the POB moiety. Immunological techniques initiated in this study detect NNK-protein conjugates or measure the quantity of POB groups liberated upon alkaline or acid treatment of NNK modified protein.     

Interference of oral poliovirus vaccine on RIT 4237 oral rotavirus vaccine

A vaccination trial, performed on 86 3-month-old infants, has shown that the ability of the RIT 4237 live attenuated rotavirus strain to induce seroconversion is dramatically reduced when administered with live poliovirus vaccine. In a subsequent trial performed on 93 infants the attempt to overcome the poliovirus interference by administering two doses of associated vaccines was unsuccessful. No interference by the RIT 4237 strain on live attenuated polioviruses was observed.     

Surgical treatment of stapes fixation

The aim of surgical treatment of a fixed stapes is to restore an as effective as possible impedance transfer of the ossicular chain and acoustic impedance of the annular ligament of the footplate, when it has lost elasticity, and this in order to achieve the best possible physiological vibration of the inner ear fluids.     

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.