Audiological comparison between two different clips prostheses in stapes surgery.

OBJECTIVES: To compare audiometric results and complications of stapes surgery with two different types of piston prosthesis, the Portmann Clip Piston (Medtronic) (PCP) and the Soft Clip Piston (Kurz) (SCP). MATERIAL AND METHODS: Study conducted on 64 patients who underwent primary stapedotomy from 2008 to 2011. We matched for each case of stapedotomy with the PCP (Medtronic Xomed Inc. Portmann Clip Piston Stainless Steel/Fluoroplastic) a case with the SCP (Heinz Kurz GmbH Medizintechnik Soft Piston Clip Titanium). Each group consisted of 32 patients, and patients in both groups were matched with respect to gender, age, bilateral or unilateral otosclerosis, otological symptoms (tinnitus, vertigo or dizziness), family history, operated side and the Portmann grading for otosclerosis. The length of the prosthesis used was reported. Post-operative complications such as tinnitus, vertigo, hearing loss and altered taste were documented. Each patient was subjected to a preoperative and postoperative audiogram (follow-up at the second month after the surgery). We used the Student test for statistical analysis. Statistical significance was set at < 0.01. RESULTS: None of the patients experienced a post-operative hearing loss and none required a later revision surgery. No statistically significant difference was found between the two populations regarding demographic data (age, sex, side, bilaterality, family history, stage and lenght of piston) and hearing level (> 0.01) in the air, bone conduction and air-bone gap (ABG). Postoperative complications did not result to be significantly different between the two groups. Also, both groups showed a significant improvement (< 0.01) in the post-operative air, bone conduction and air-bone gap. There was no statistically significant difference (> 0.01) between the post-operative hearing results (bone conduction, air conduction, air-bone gap) using the two pistons. The mean ABG improvement was respectively 16.63 dB in the SCP group and 20.59 dB in the PCP group. CONCLUSION: The titanium Soft clip piston (SCP) is a good alternative to the Portmann clip piston (PCP). Nevertheless there are some differences in the surgical fixing of these two pistons in the correct position.

Compensatory role of saccule in deaf children and adults: novel hypotheses.

The aim of the present study is to measure sound sensitivity of the saccule for low frequencies in a population of both young and adult prelingual deaf patients using cervical Vestibular Evoked Myogenic Potentials (cVEMPs) and to correlate the findings obtained with the phonological features. The sensitivity of the saccule to sound stimuli is well known in previous studies. The functional role of the human saccule in responding to sound stimuli is still unclear. The study was conducted on a control population of young and adults with normal hearing. The outcomes showed that the amplitude of myogenic vestibular evoked potentials resulted the most significant parameter, indicating the degree of saccular response. We found in the group of deaf adults that the saccule retained an unaltered responsiveness to sound stimuli, without suffering the age-related functional decrease as demonstrated in normal hearing patients. We assumed that the high saccular response in deaf patients is determined by a constant somatosensory stimulation (rehabilitation) of the saccule, represented by the phonetic training. We correlated the phonetic features typical of the deaf with the sensitivity of the saccule to low frequencies. Such sensitivity makes this organ the ending point of the phonetic information (perception) but also the starting point of its regulation (production). Our experience demonstrates the phonetic role of saccule in the regulation of the human voice and provides the basis for further development of this topic. Thus we strongly believe that in the deaf the saccule plays a compensatory role. The high response of the saccule allows phonemic self-regulation, compensating the low/absent tone-verbal feedback. The saccule would come rightfully to be the accessory inner ear in deaf patients. We recommend the cVEMPs in the audio-phonological assessment before starting the speech therapy or during treatment to assess the degree of responsiveness of the saccule. The resulting data would give an extremely useful information that could be ignored by the pure tone audiometry. The presence of the cVEMPs in the deaf patient may improve the expectation of the performance of speech therapy.

Distortion-product otoacoustic emissions: a useful test for monitoring ototoxicity induced by pegylated interferon and ribavirin treatment in patients with chronic hepatitis C.

Pegylated-interferon (peg-IFN) and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) infection is well known to be associated with significant adverse effects. Several studies have investigated a possible auditory pathway involvement during IFN therapy, but a method to monitor the potential auditory involvement during treatment has not yet been described. The aim of this study is to evaluate possible modifications of the outer hair cell (OHC) function in HCV patients receiving peg-IFN and ribavirin combination therapy. Thirteen adult HCV patients (8 F/5 M, mean age 52∓12 years) treated with peg-IFN and ribavirin combination therapy underwent Pure Tone Audiogram and Distortion Product Otoacoustic Emission (DPOAE) tests. We compared mean auditory thresholds (PTA) and mean DPOAE amplitude before, at month 3 during, and at the end of treatment (T0, T3, and Tend, respectively), and 3 months after treatment discontinuation (Tfu). No significant differences were found in hearing levels at the different time points analyzed. During treatment, three patients developed tinnitus, which in 2 cases resolved spontaneously after the end of therapy. Compared to T0 (19.5±0.83), a statistically significant DPOAE increase at T3 (30±1,26) and Tend (28.6±2.16) was found (p<0.05 at both time points), while DPOAEs returned to pre-treatment levels at Tfu (19.3±1.3). In our group, none of the patients reported a permanent auditory impairment, excluding one patient with persistent tinnitus. Peg-IFN could produce an increase of motility of the OHCs by means of intracellular pathways. DPOAE test could be considered a new method for monitoring ototoxicity induced by IFN. On the basis of recent literature and our audiological results, physicians should be aware of the possible ototoxic effects of peg-IFN, requiring appropriate surveillance, and the patient should be informed of the potential side effects of IFN therapy on the auditory pathway.

[Silent sinus syndrome--two cases report]. / Syndrome des sinus silencieux--a propos de deux cas.

INTRODUCTION: Silent Sinus Syndrome (SSS) is a rare pathology, characterized by retraction of the maxillary sinus walls, leading to enophthalmos, sometimes diplopia and midfacial depression. It is usually not associated with sinonasal symptoms. Sinus ventilation and drainage stops its progression, but usually cannot reverse the process. This empiric treatment supports the Hypoventilation Theory that would explain the pathogenesis of this disorder. MATERIALS & METHODS: We describe two cases of SSS. A 65 year-old-man complaining of enophthalmos with an insidious onset whose CT-Scan confirmed SSS. After he was submitted to drainage surgery, the ocular asymmetry showed slight improvement. The second case describes a 34 year-old-woman with a sudden onset enophthalmos associated with diplopia, in only 5 days. She didn't have nasal or sinus related symptoms. CT-scan revealed SSS due to maxillary and ethmoidal sinus. Early endoscopic surgery enabled reversal of enophthalmos and correction of diplopia.

Evaluation of ear function after cardiopulmonary bypass with otoacoustic emissions: a pilot study.

OBJECTIVES: During extracorporeal circulation (ECC) there is a great hemodynamic stress with possible impact on the microcirculation, including cochlear one. Previous studies have evaluated the effect of ECC on inner ear with contrasting results. The aim of this study is to evaluate possible modifications of the outer hair cells (OHC) function after open heart surgery (OHS) under ECC with transient evoked (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). METHODS: Ten patients (5 F and 5 M), undergoing OHS with ECC, were subjected to an audiological assessment pre- and postoperatively. We compared the pre-operative and post-operative mean auditory thresholds, mean TEOAEs reproducibility and amplitude, and mean DPOAEs amplitude. Student's t-test was used to compare different values. RESULTS: No significant differences were found between pre- and post-operative audiological assessment both in hearing level and in otoacoustic emissions. CONCLUSION: OHC function seems to be not affected by hemodynamic stress induced by ECC. Further studies on a larger scale will be necessary to confirm our preliminary data.

Mucosal expression of carcinoembryonic antigen and carbohydrate antigen 19-9 in patients with gastritis and gastric cancer.

Sixty-eight patients (45 males, 23 females) were studied in order to assess the usefulness of mucosal tissue concentrations of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in detecting patients at high risk for gastric cancer. CEA and CA19-9 were assayed on cytosol obtained from multiple endoscopic biopsies of 41 patients with chronic superficial gastritis, 18 with chronic atrophic gastritis, and 9 with gastric cancer. Mucosal tissue concentrations of both CEA and CA19-9 increased from chronic superficial gastritis to chronic atrophic gastritis and to gastric cancer (p = 0.005 and p = 0.002, respectively). Mucosal CEA levels in patients with intestinal metaplasia (IM) were significantly higher than in nonmetaplastic mucosa (p = 0.04). Epithelial dysplasia was associated with higher, though not significant, tissue concentrations of both CEA and CA19-9 when compared with IM. Finally, a correlation between serum levels and tissue concentrations was observed only for CA19-9 (Pearson's correlation coefficient = 0.7). In conclusion, these data indicate that gastric mucosa of patients with chronic atrophic gastritis and intestinal metaplasia express high levels of both CA19-9 and CEA.

Tumor clearance of technetium 99m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer.

PURPOSE: Since we have previously shown that the efflux rate of technetium 99m (99mTc) sestamibi, a transport substrate of P-glycoprotein (Pgp), is directly correlated with Pgp levels in untreated breast carcinoma, we tested whether tumor clearance of 9mTc-sestamibi may be predictive of therapeutic response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS: Thirty-nine patients with stage III disease, median tumor diameter 5.8 cm (range, 3 to 10) were enrolled onto this prospective clinical trial and underwent 99mTc-sestamibi scan before neoadjuvant chemotherapy. Patients were injected intravenously (i.v.) with 740 MBq of 99mTc-sestamibi; a 15-minute dynamic study was performed, and static planar images were obtained at 0.5, 1, 2, and 4 hours. The time to half clearance of 99mTc-sestamibi was calculated in each patient from decay corrected time-activity curves using a monoexponential fitting. Patients were treated with epirubicin 150 mg/m2 i.v. every 2 weeks for three courses and then underwent surgery within 3 weeks from the completion of chemotherapy. Residual tumor was assessed by pathologic examination of mastectomy specimens. RESULTS: Seventeen of 39 patients showed a rapid tumor clearance of 9mTc-sestamibi (time to half clearance [t1/2] < or = 204 minutes) and 15 of these 17 (88%) showed a highly cellular macroscopic residual tumor at histology that indicated lack of tumor response to neoadjuvant chemotherapy. In contrast, only eight of 22 (36%) with prolonged retention of 99mTc-sestamibi (t1/2 > 204 minutes) showed residual macroscopic tumor at histology (Fisher's exact test, P < .01). CONCLUSION: A rapid tumor clearance of 99mTc-sestamibi may predict lack of tumor response to neoadjuvant chemotherapy with drugs affected by the multidrug-resistant phenotype in patients with locally advanced breast carcinoma.

Fractional retention of technetium-99m-sestamibi as an index of P-glycoprotein expression in untreated breast cancer patients.

UNLABELLED: The multidrug-resistant phenotype is characterized by the reduced intracellular retention of several structurally and functionally unrelated cytotoxic compounds due to the energy-dependent pump activity of P-glycoprotein (Pgp). Because 99mTc-sestamibi is a suitable transport substrate of Pgp, we tested whether the time-dependent fractional retention of this tracer could be used as an index of Pgp expression in untreated breast carcinomas. METHODS: Twenty-seven patients with histologically confirmed breast carcinoma were intravenously injected with 740 MBq (20 mCi) of 99mTc-sestamibi, and static planar images of the breast were obtained at 10, 60 and 240 min. The fractional retention of 99mTc-sestamibi was then calculated as the ratios between 60 and 10 min (R60/10) and between 240 and 10 min (R240/10) of decay-corrected counts/pixel registered in the region of interest drawn around the tumor. Surgically excised tumors were then obtained from each patient, and Pgp levels were determined using 125I-labeled MRK16 monoclonal antibody and in vitro quantitative autoradiography. RESULTS: The fractional retention of 99mTc-sestamibi at 60 and 240 min was significantly higher in tumors with low Pgp levels (Group I, n = 18) as compared to that measured in tumors with high Pgp expression (Group II, n = 9) (p < 0.001). In particular, R60/10 values were 0.86 and 0.59 in breast carcinomas of Groups I and II, respectively, whereas the values of R240/10 were 0.56 and 0.25 in low- and high-Pgp-expressing tumors, respectively. CONCLUSION: The determination of fractional retention of 99mTc-sestamibi may be used as a simple functional test for Pgp expression in untreated breast cancer. A preliminary estimate of the sensitivity and the specificity of the test indicates its potential use in clinical practice to identify patients with a high probability of developing multidrug resistance.

Vitronectin binding to urokinase receptor in human breast cancer.

Functional assembly of the plasminogen-dependent proteolytic system on the cell surface requires multiple interactions involving urokinase (uPA), urokinase receptor (uPAR), plasminogen activator inhibitors, and other molecules that mediate cell migration and adhesion. We analyzed the in vitro interaction of uPAR-containing particulate cell fractions with the amino-terminal fragment (ATF) of human urokinase and the matrix-like form of vitronectin. Binding and cross-linking of 125I-labeled ATF to crude membrane extracts from LB6-19 mouse cells overexpressing human uPARs in the presence of 25 nM urea-denatured vitronectin led to the formation of Mr 137,000, 92, 000, and 82,000 covalent complexes. Immunoprecipitation of the preformed cross-linked 125I-labeled complexes with anti-vitronectin, anti-uPA, or anti-uPAR antibodies revealed that the Mr 82,000 and 92, 000 species do contain ATF and vitronectin and identified the Mr 137, 000 species as a ternary complex formed by ATF, uPAR, and vitronectin. A similar electrophoretic pattern was displayed by acid-pretreated membranes extracted from MCF-7 breast carcinoma or HT1080 fibrosarcoma cell lines, as well as a ductal breast carcinoma specimen; the latter exhibited complex formation at concentrations of vitronectin lower than 10 nM. Finally, uPAR-vitronectin interaction was further documented by the decreased reactivity of an anti-uPAR polyclonal antibody to acid-pretreated sections of 10 breast carcinomas that had been preincubated with vitronectin. Our findings highlight the ability of uPAR to interact simultaneously with vitronectin and uPA in breast cancer, supporting a dynamic coupling of the molecular mechanisms underlying plasminogen-dependent matrix degradation and cell adhesion.

In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients.

Technetium-99m sestamibi is a transport substrate recognised by the multidrug-resistant P-glycoprotein (Pgp). To test whether 99mTc-sestamibi efflux is enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates of 99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intravenously injected with 740 MBq of 99mTc-sestamibi and underwent a 15-min dynamic study followed by the acquisition of static planar images at 0.5, 1, 2 and 4 h. Tumour specimens were obtained from each patient 24 h after 99mTc-sestamibi scan and Pgp levels were determined using 125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All breast carcinomas showed high uptake of 99mTc-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of 99mTc-sestamibi, calculated from decay-corrected time-activity curves, ranged between 0.00121 and 0.01690 min-1 and were directly correlated with Pgp levels measured in the same tumours (r=0.62; P<0.001). Ten out of 30 breast carcinomas (33%) contained 5 times more Pgp than benign breast lesions and showed a mean concentration of 5.73+/- 1.63 pmol/g of tumour (group A). The remaining 20 breast carcinomas had a mean Pgp concentration of 1.29+/-0.64 pmol/g (group B), equivalent to that found in benign breast lesions. 99mTc-sestamibi efflux from tumours of group A was 2.7 times higher than that observed in tumours of group B (0.00686+/-0.00390 min-1 vs 0.00250+/-0.00090 min-1, P<0.001). The in vivo functional test with 99mTc-sestamibi showed a sensitivity and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of 99mTc-sestamibi may be used for the in vivo identification of the multidrug resistant (MDR1) phenotype in untreated breast cancer patients.

Local concentration of folate binding protein GP38 in sections of human ovarian carcinoma by in vitro quantitative autoradiography.

UNLABELLED: Folate binding protein (FBP) GP38 is a membrane-associated glycoprotein that mediates the intracellular transport of folates. The enhanced expression of FBP in ovarian carcinomas provided a rational basis for clinical studies with specific monoclonal antibodies and some newly synthesized antifolate drugs. Because the outcome of these clinical studies ultimately depends on the degree of FBP expression, we measured the local concentration of FBP using 125I-MOv18 monoclonal antibody and quantitative autoradiography. METHODS: Tissue sections from 37 specimens of ovarian carcinoma and 13 nonmalignant ovaries were incubated with increasing concentrations of 125I-MOv18 with and without an excess of unlabeled antibody. Tissue-bound radioactivity was measured by quantitative autoradiography. RESULTS: Folate binding protein was found to be overexpressed in 91% of nonmucinous ovarian carcinomas, with local concentrations ranging between 1.14 and 82.84 pmole/g. Adjacent tumor sections simultaneously studied with 125I-MOv18 and a 125I-labeled folic acid derivative showed matching and superimposable regional distributions of bound radioactivity of the two radioligands, indicating that the antigen, specifically recognized by 125I-MOv18 in nonmucinous ovarian carcinomas, is capable of binding folates. Nonmalignant ovaries did not contain measurable amounts of antigen when assayed with 125MOv18 but showed a limited and specific binding of the 125I-folic acid derivative to tissue sections. The autoradiographic findings were confirmed by testing sections from mixtures of antigen-positive and antigen-negative cells, by immunoperoxidase staining with MOv18 on tumor sections and by biochemical identification of FBP in membrane fractions from tissue samples. CONCLUSION: Folate binding protein is overexpressed up to 80-90-fold in nonmucinous ovarian carcinomas compared with nonmalignant ovaries. Quantitation of FBP may provide a useful tool in the design of clinical studies with specific monoclonal antibodies and certain antifolate drugs that enter the cell through FBP.