Comparison of the Nasality of the Unoperated Soft Cleft Palate Patient, with and without Obturator

Prosthetic rehabilitation of the patient with a cleft soft palate has three main objectives. Foremost is the need to improve the function of speech and comfortable swallowing, that are impaired by the potency of the soft palate, which allows the escape of air or fluid into the nasopharynx and nasal cavity. Unrepaired clefts of the soft palate produce a deficient velar-pharyngeal seal and require the construction of an obturator toward the speech bulb. Measurement of the nasality of a patient wearing a speech bulb for 18 years is described in this paper. This was done by means of Nasal View System, Tiger Electronics Inc. (Seattle, WA), which developed this system based on the work of Awan (1996, 1997). The Nasal View system is a PC/Windows based system, which enables the recording of high-resolution speech signals using Windows compatible sound cards (sampling at up to 44100 Hz at 8 or 16 bits of resolution). The hardware components included in the Nasal View system include headgear and a portable custom dual-channel pre-amplification unit.The key component of the headgear is a rigid plate, constructed of 5 mm thick styrene, which is used to separate an oral from a nasal microphone. The special sentence was used for our assessment. In this sentence 5 sounds out of 28 are nasal sounds (17.86%). The results are as follows: With the obturator in place the values of nasality were: Ave 19.32% SD 14.31%, Max 66.53% Min 1.28% Median 15.04% Mode 12.70%. The measurements of nasality without the obturator were: Ave 41.31% SD 24.39% Max 97.03% Min 7.61% Median 30.02% Mode 23.26%. Nasality measurement is displayed in the histogram of the nasality distribution, in the real-time analysis, power spectrum, LPC spectrum power and LPC spectrum, and in spectrograms

A randomized trial to assess the biological activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 500 mg alone or anastrozole alone on primary breast cancer

Introduction: Fulvestrant shows dose-dependent biological activity. Greater estrogen-receptor (ER) blockade may feasibly be achieved by combining fulvestrant with anastrozole. This pre-surgical study compared fulvestrant plus anastrozole versus either agent alone in patients with ER-positive breast cancer. Methods: In this double-blind, multicenter trial, 121 patients received: fulvestrant 500 mg on day 1 plus anastrozole 1 mg/day for 14-21 days (F+A); fulvestrant plus anastrozole placebo (F); or fulvestrant placebo plus anastrozole (A), 2-3 weeks before surgery. ER, progesterone-receptor (PgR), and Ki67 expression were determined from tumor biopsies before treatment and at surgery. Results: 103 paired samples were available (F, n = 35; F+A, n = 31; A, n = 37). All treatments significantly reduced mean ER expression from baseline (F: 41%, P = 0.0001; F+A: 39%, P = 0.0001; A: 13%, P = 0.0034). F and F+A led to greater reductions in ER versus A (both P = 0.0001); F+A did not lead to additional reductions versus F. PgR and Ki67 expression were significantly reduced with all treatments (means were 34% to 45%, and 75% to 85%, respectively; all P = 0.0001), with no differences between groups. Conclusions: In this short-term study, all treatments reduced ER expression, although F and F+A showed greater reductions than A. No significant differences were detected between the treatment groups in terms of PgR and Ki67 expression. No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F+A is unlikely to have further clinical benefit over F alone. Trial registration: Clinicaltrials.gov NCT00259090

Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen

Transferrin receptor (CD71) is involved in the cellular uptake of iron and is expressed on cells with high proliferation. It may be implicated in promoting the growth of endocrine resistant phenotypes within ER+/luminal-like breast cancer. We used a panel of in vitro cell models of acquired resistance to tamoxifen (TAMR), Faslodex (FASR) or severe oestrogen deprivation (MCF-7X) and the ER+ luminal MCF-7 parental line to determine CD71 mRNA expression and to study transferrin (Tf) effects on in vitro tumour growth and its inhibition. Furthermore, CD71 protein expression was assessed in a well-characterized series of patients with invasive breast carcinoma using tissue microarrays. Our results demonstrated a striking elevation of CD71 in all cell models of acquired resistance. Exogenous Tf significantly promoted growth in MCF-7-X and MCF-7 cells but more so in MCF-7-X; this growth was significantly reduced by Faslodex (FAS) or a phosphoinositide-3 kinase inhibitor (LY294002). Increased CD71 expression was associated with poor NPI score, tumour proliferation, basal CKs, p53, EGFR, HER2, steroid receptor negativity and shortened breast cancer specific survival (P < 0.001). On multivariate analysis, CD71 was found to be an independent prognostic factor in the ER+ cohort of patients. In conclusion, therapies of current interest in breast cancer (e.g. FAS, PI3K-inhibitors) appear able to partially impact on transferrin/CD71-promoted growth, but further investigation of this important mitogenic mechanism may assist in designing new therapeutic strategies to target highly proliferative, endocrine resistant breast cancers. CD71 appears to be a candidate marker of a subgroup of ER+/luminal-like breast cancer characterised by poor outcome and resistance to tamoxifen