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Biomedical subjects

Gaetano Paludetti

Publications and source records attributed to Gaetano Paludetti.

At least 19 recordsLinked to original sources

Vestibular evoked myogenic potentials in children.

OBJECTIVE: The aim of this work is to establish if the vestibular evoked myogenic potentials (VEMPs) could be used as a clinical test of vestibular function in children. MATERIALS AND METHODS: Forty normal hearing children, aged between 3 and 15 years, and classified in preschool and scholar group, have been investigated in order to study normal development of vestibular potentials and to define fundamental parameters of VEMPs, establishing normal data of latencies and amplitude ratio. Electromyographic activity of sternocleidomastoid muscle was recorded while children were laid supine on a bed and asked to raise their head off of the bed in order to activate their neck flexors bilaterally. The saccular receptors were acoustically stimulated with a logon of 500Hz at an intensity of 130dB peSPL presented monaurally through earphones. In each recording, we analysed latencies and amplitudes of the p13 and n23 waves and the amplitude ratio between the two ears. RESULTS: VEMPs were normally detected in all subjects. In preschool group mean p13 and mean n23 latencies were, respectively, 16.13 (+/-2.12)ms and 21.17 (+/-2.77)ms; mean amplitude ratio was 28.49 (+/-18.10). In scholar group mean p13 and n23 were respectively 16.14 (+/-3.48)ms and 21.78 (+/-3.39)ms, while mean amplitude ratio 20.44 (+/-13.24). Comparison of latencies and amplitude ratio between the children groups and control adult group did not showed any significant differences. CONCLUSION: In conclusion, VEMPs could represent a valid and non-invasive technique able to investigate vestibular function in children and, in particular, vestibulo collic reflex.

Acoustic Stimulation↗

GSTT1 and GSTM1 allelic polymorphisms in head and neck cancer patients from Italian Lazio Region.

BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC) and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is currently controversial. The present study investigates the prevalences of GSTT1 and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100 healthy donors and 200 controls with non-neoplastic head and neck diseases from Italian Lazio Region. METHODS: The patients with benign head and neck pathologies, as well as the healthy donors were matched for age, sex, cigarette smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1 and GSTM1 genotype has been performed by means of allele-specific PCR technique. RESULTS: A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I. 1.69-6.67) while no significant association was found with GSTT1 null genotype (p>or=0.14). No interactive association was observed when combining the different genotypes of the two polymorphisms. These results were confirmed after correction for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme as a risk factor for the development of HNSCC in patients from the Italian Lazio Region, independently of age, sex and other confounding variables.

Alleles↗

Pilot phase IIA study for evaluation of the efficacy of folic acid in the treatment of laryngeal leucoplakia.

BACKGROUND: It has been previously observed that patients with head and neck squamous cell carcinoma or with laryngeal leucoplakia present a significant reduction in plasma folate levels. The current Phase IIA pilot study assessed the effectiveness of folic acid as a chemopreventive agent in patients affected by glottic laryngeal leucoplakia. METHODS: Forty-three untreated patients affected by glottic laryngeal leucoplakia were enrolled in the Ear, Nose, and Throat Department (Universita Cattolica del Saco Cuore, Rome, Italy). Glottic leucoplakia was initially diagnosed by indirect laryngoscopy and successively confirmed by diagnostic direct microlaryngoscopy with a biopsy for histologic assessment. Folic acid (Folina, Schwarz Pharma, Germany) was administered orally (5 mg every 8 hours) for 6 months. Patients were monitored every 30 days by videolaryngoscopy. RESULTS: Twelve (28%) patients had no response, 19 (44%) had a partial response, and 12 (28%) had a complete response. The mean increase in serum folate levels (10.06 +/- 0.53) and the mean decrease in homocysteine serum (3.65349 +/- 0.85526) at the end of the study were highly significant (P = .0001). CONCLUSIONS: The larynx is 1 of the sites of major interest and a good model for the development of chemopreventive agents, but so far the proposed agents have shown no clear efficacy on precancerous lesions or on the development of second malignancies.

Adult↗

Protective properties of idebenone in noise-induced hearing loss in the guinea pig.

Idebenone is a synthetic analogue of coenzyme Q10 with antioxidant properties. The present study investigated the antioxidant activity of idebenone in the rescue of acoustic trauma. Noise-induced hearing loss was induced by exposing guinea pigs to a continuous pure tone and idebenone was injected intraperitoneally 1 h before noise exposure and once daily for 3 days. Guinea pigs treated with idebenone showed significantly smaller auditory threshold shifts than unprotected control animals. Missing and apoptotic cells were identified with scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Protected animals presented a lesser extent of both apoptotic activation and hair cell loss in the organ of Corti. Our results suggest an antioxidant function of idebenone in protection from noise-induced hearing loss and provide a rationale for exploring therapeutic strategies in humans.

Acoustic Stimulation↗

A case-control study investigating the role of sulfotransferase 1A1 polymorphism in head and neck cancer.

PURPOSE: Sulfotransferases (SULT) 1A1 detoxify and bio-activate a broad spectrum of substrates including xenobiotics. The SULT1A1 gene possesses a G-->A polymorphism that results in an Arg to His substitution at codon 213, with the His allele having a low activity. The purpose of this study was to evaluate whether SULT1A1 Arg213His polymorphisms are risk factors for head and neck squamous cell carcinoma (SCCHN). METHODS: A total of 124 consecutive primary SCCHN patients and 249 age- and sex-matched hospital controls were enrolled in this study. Genomic DNA was isolated from peripheral blood lymphocytes and genotyping was performed by PCR-RFLP. A comprehensive epidemiological interview was conducted on all participants to collect their lifestyle data. RESULTS: The His/His frequencies in cases and controls were 6.5% (8/123) and 3.6% (9/247), respectively (P=0.049). Multivariate logistic regression analysis showed a significant association of SCCHN and His/His genotype (OR=3.60; 95% CI=1.01-12.88). This association was stronger amongst older people, alcohol and low fruit consumers. The resulted SULT1A1 His/His genotype also associated with a higher risk of neck node positive status (OR=5.82; 95% CI=1.10-30.68). CONCLUSIONS: These preliminary findings show for the first time that the SULT1A1 His (213) allele is a possible risk factor for head and neck cancer development.

Adenine↗

Aural acquired cholesteatoma in children: surgical findings, recurrence and functional results.

OBJECTIVE: This study was designed to compare clinical features, surgical findings and treatment results from children and adults affected by aural acquired cholesteatoma. METHODS: a retrospective review of 60 children (Group I: mean age 8.8 years, range 3-16 years) and 308 adults (Group II: mean age 45.4 years, range 18-81 years) with aural acquired cholesteatoma who underwent surgery from January 1992 to December 2002, was performed with a follow-up of 5 years. All patients were submitted to single-staged canal wall down tympanoplasty. Variables analysed were otoscopic features, extent of cholesteatoma, surgical findings and the rate of recidivism. RESULTS: The pathologic changes in the tympanic membrane were no different in the two groups. According to Stangerup et al. 40 cases (66.6%) of children were classified as stage III or more, with a significant higher incidence compared to adults (152 cases; 49.3%). Analysis of the ossicular chain state showed, in group I, a significant higher incidence of eroded or absent incus (76.6% versus 61.68%) and malleus (76.6% versus 56.48%), if compared to adults. Children, therefore, had a significantly higher risk of recurrence with a rate of 26.6% in Group I and 6.81% in group II. After surgery the mean gain measured in children group, was 11 dB and 13 dB in adults. CONCLUSION: In our study we found that the behaviour of cholesteatoma in children appears more aggressive than in adults. In fact, we found a greater extension of the cholesteatoma, a worse state of the ossicular chain and a higher incidence of recurrence. Therefore, we obtained acceptable hearing results both in children and in adults.

Adolescent↗

Detection in human saliva of different statherin and P-B fragments and derivatives.

Statherin is a multifunctional polypeptide specific of human saliva involved in oral calcium homeostasis, phosphate buffering and formation of protein networks. Salivary P-B peptide is usually included into the basic proline-rich protein family but it shows some similarities with statherin and its specific biological role is still undefined. In this study, various fragments and derivatives of statherin and P-B peptide were consistently detected by RP-HPLC ESI-IT MS in 23 samples of human saliva. They were: statherin mono- and non-phosphorylated, statherin Des-Phe(43) (statherin SV1), statherin Des-Thr(42),Phe(43), statherin Des-Asp(1), statherin Des(6-15) (statherin SV2), statherin Des(1-9), statherin Des(1-10), statherin Des(1-13) and P-B Des(1-5). Statherin SV3 (statherin Des(6-15), Phe(43)) was detected only in one sample. Identity of the fragments was confirmed either by MS/MS experiments or by enzymatic digestion or by Edman sequencing. Detection of the fragments suggests that statherin and P-B peptide are submitted to post-translational proteolytic cleavages that are common to other classes of salivary proteins.

Adult↗

Voice and swallowing changes after thyroidectomy in patients without inferior laryngeal nerve injuries.

BACKGROUND: We performed a prospective analysis on voice and swallowing alterations following total thyroidectomy (TT), in the absence of recurrent nerve injury. METHODS: Patients aged 21 to 65 years undergoing TT, in the absence of laryngeal/pulmonary disease, previous neck surgery, or malignant diseases, were subjected to videostrobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation time (MPT) tests preoperatively and 3 months postoperatively. Voice impairment scores (VIS) and swallowing impairment scores (SIS) were obtained preoperatively, and at 1 week, 1 month, and 3 months postoperatively. RESULTS: Among the 127 selected patients, 39 completed the postoperative evaluation. No recurrent nerve injury was observed during the postoperative VSL in any of the patients. Preoperative and postoperative AVA and MPT scores did not differ significantly. The mean postoperative VIS was significantly higher than the preoperative VIS at 1 week and 1 month after TT (13.7 and 9.6 vs 4.4, respectively; P < .05) but not 3 months after TT (6.7). The mean SIS was higher than the preoperative SIS at 1 week, 1 month, and 3 months after TT (10.3, 6.0, and 2.8 vs 0.5, respectively; P < .05). CONCLUSIONS: Physicians should inform patients that transient voice and swallowing symptoms may occur following total thyroidectomy, and our data suggest mild symptoms may occur in the majority of operated patients.

Adult↗

Biliary laryngopharyngeal reflux: a new pathological entity.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent understanding of the harmful effects of gastric and duodenal agents on mucosa of the upper aerodigestive tract in patients with duodeno-gastro-esophageal reflux. RECENT FINDINGS: The damaging action of duodeno-gastro-esophageal reflux on the gastro-esophageal mucosa and its potential etiological role in the development of many inflammatory and neoplastic patterns have been well documented in the literature. Recently, there has been increasing evidence that duodeno-gastro-esophageal reflux may also be related to several laryngeal disorders and clinical studies confirm that reflux after gastric resection may enhance the development of laryngeal malignancies. Finally, there have been experimental attempts to confirm that duodenal contents may contribute to inflammation and carcinogenesis in the pharynx or larynx, as it is known to do in the esophagus. SUMMARY: The association between duodeno-gastro-esophageal reflux and laryngeal lesions is of great interest to otolaryngologists because it focuses attention on a new pathological entity that could be classified as biliary laryngopharyngeal reflux. This condition, as an acid one, seems to represent an important dangerous, endogenous risk factor involved in the pathogenesis of inflammatory, precancerous and neoplastic laryngeal lesions. For these reasons, particular attention is required in the future regarding the understanding of the local environment, individual susceptibility and clinical treatment. Finally, new antireflux therapy should be considered to control not only the acid gastric component of the refluxate but also the duodenal component.

Bile↗

Lack of association between inherited thrombophilic risk factors and idiopathic sudden sensorineural hearing loss in Italian patients.

OBJECTIVES: We investigated the presence of congenital thrombophilic risk factors in a population of consecutive Italian patients affected by idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: We investigated 48 patients with idiopathic SSNHL for the presence of congenital thrombophilic risk factors. The factor V Leiden G1691A, the prothrombin G20210A allele, and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes were investigated. Allele frequencies and genotype distribution of all factors found in patients were compared to those of 48 healthy subjects of the same ethnic background by Chi2 and odds-ratio analysis. Odds ratios and 95% confidence intervals were calculated for allele and genotype frequencies of all thrombophilia variants. Statistical significance was accepted with a p value of less than .05. We also performed the following blood tests: hemacytometric analysis including platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, erythrocyte sedimentation rate, C-reactive protein, protein S, protein C, antithrombin III, and activated protein C resistance. RESULTS: In our series, we did not find an association between SSNHL and abnormal levels of antithrombin III, protein C, protein S, D-dimer, or fibrinogen; activated protein C resistance; or factor V G1691A, prothrombin G20210A, or MTHFR C677T mutations. CONCLUSIONS: At present, the few studies regarding genetic polymorphisms of congenital thrombophilic factors in SSNHL are not conclusive. According to our data, factor V G1691A, prothrombin G20210A, and MTHFR C677T variants should be not considered risk factors for SSNHL. Further large prospective studies are needed to provide currently lacking information and to improve our knowledge in the field before we recommend the determination of genetic polymorphism in SSNHL as routine practice.

Adolescent↗

Molecular markers in laryngeal squamous cell carcinoma: towards an integrated clinicobiological approach.

Of the most frequent malignancies in the United States, cancers of the larynx and of the uterine corpus are the only ones not to show an increase in 5-year survival rates over the last 30 years. The increasing use of chemo- and radiotherapy and conservative surgery to preserve organs and their functions has probably led to a better quality of life in patients with laryngeal cancer, but has definitely failed to improve survival, which remains the primary aim. In our opinion, to reduce laryngeal cancer-related mortality, a change in clinical approach is required. We have reviewed the literature on the potential role of molecular markers in the clinical management of laryngeal cancer. We believe that some of the most significant biological markers might be integrated with the evaluation of behavioural risk factors, clinical TNM staging and histopathological grading for a novel clinicomolecular approach to laryngeal cancer. We foresee the use of the most promising biological markers in the phases of prevention, diagnosis, prognostic assessment and drug design.

Biomarkers, Tumor↗

Erbium: yttrium-aluminum-garnet laser application in stapedotomy.

OBJECTIVE: To assess clinical safety and efficacy of the erbium: yttrium-aluminum-garnet (Er:YAG) laser in the stapes surgery; to define and optimize parameters that render the procedure safe for the inner ear. STUDY DESIGN: Retrospective study. MATERIAL AND METHODS: A microscope-integrated Er:YAG laser stapedotomy was performed on 29 patients and a conventional stapedotomy on 41 patients. An early (within 1 to 3 days after stapes surgery) and late (at least 6 weeks) pure-tone bone-conduction threshold audiogram was obtained. RESULTS: No statistically significant differences were found by Student's t test over all measured frequencies between pre- and postoperative bone-conduction thresholds in each group. There was no statistically significant difference for all frequencies between early (3 days) and late postoperative mean bone-conduction thresholds. CONCLUSIONS: The results of our preliminary clinical study showed that erbium laser poses no risk to inner ear function. However, the lack of standardization obliges further investigation to establish safe clinical parameters of the Er:YAG laser.

Adult↗

Postlaryngectomy pharyngocutaneous fistula: incidence, predisposing factors, and therapy.

OBJECTIVE: The pharyngocutaneous fistula (PCF) is a serious complication after total laryngectomy, and its etiology is not well understood yet. The aim of our study was to evaluate predisposing factors, incidence, and management of this complication. STUDY DESIGN AND SETTING: This was a retrospective study of 268 patients who underwent total laryngectomy in our clinic (January 1990-December 2001). A number of factors potentially predisposing to PCF formation were evaluated. RESULTS: A PCF was observed in 16% of patients. Systemic diseases, previous radiotherapy, supraglottic origin of tumor, and concurrent radical neck dissection were significantly associated with PCF. Spontaneous closure was noted in 28 patients, whereas a surgical closure was necessary in 15 patients. CONCLUSIONS: In presence of a specific risk factor, PCF can be expected; nevertheless, its prevention remains very difficult. Moreover, given the high percentage of spontaneous closure, we suggest the "wait and see" approach for 28 days before proceeding with a surgical approach. EBM RATING: C.

Adult↗

Wegener's granulomatosis: a challenging disease for otorhinolaryngologists.

Diagnosis of Wegener's granulomatosis (WG) can be delayed because of its aspecific presenting symptoms. Detection of serum circulating antineutrophil cytoplasm antibodies (c-ANCAs), in combination with histology, permits one to identify WG at an early stage and to implement stage-adapted therapy. c-ANCA levels may also help to evaluate the response to medical therapy. Recently, the quality of life of WG patients has been improved by administering cotrimoxazole in order to prevent infections and recurrent diseases during the remission period.WG is of special significance to the otorhinolaryngologist because it is often initially limited to the upper respiratory tract before becoming systemic. The aim of this paper was to describe a series of WG patients and underline the difficulties involved in diagnosing and treating this challenging disease. This was a prospective study in 23 consecutive patients with head and neck manifestations of WG (17 systemic, 6 limited). Diagnosis was performed by means of both c-ANCAs detection using indirect immunofluorescence and histology in biopsy specimens. Treatment consisted of daily cyclophosphamide (CYC; 2 mg/kg/day) and glucocorticoids (prednisone; 1 mg/kg/day). If an improvement or toxic events occurred, CYC was discontinued and methotrexate was started. If, during remission of the disease, low serum c-ANCAs levels were detected, CYC was suspended and cotrimoxazole (1 g/day) was introduced. Serum c-ANCAs detection was positive for all patients. Biopsy was diagnostic from the beginning in 19/23 cases. The six patients with limited WG did not show a progression to systemic disease. Only 3 patients with a diagnosis of delayed systemic WG died, whereas 19/23 patients were alive with good control of relapses.

Anti-Inflammatory Agents↗

Expression of vascular endothelial growth factor and its receptors in the cochlea of various experimental animals.

CONCLUSION: The results of this study indicate that vascular endothelial growth factor (VEGF) may be an important regulator of the vascular network of the inner ear and suggest that the VEGF signalling pathway may play a role in pathophysiologic conditions. OBJECTIVE: In order to clarify the role of vascular growth factor in the modulation of the vascular network of the cochlea, we studied the expression of VEGF and its receptors-fms-like tyrosine kinase (Flt-1) and foetal liver kinase (Flk-1)-in the inner ear of 3-month-old rodents of different species: C57BL/6J mice, Wistar albino rats and Hartley albino guinea pigs. MATERIAL AND METHODS: Qualitative immunohistochemical studies were performed by using specific antibodies to VEGF and its receptors on paraffin sections of the cochlea. The expression levels of VEGF and its receptors were quantified by means of Western blot analysis of cochlea protein extracts. RESULTS: We demonstrated that VEGF and its receptors are expressed in the cochlea and described their distribution in the inner ear. In particular, VEGF and Flt-1 are present at the level of the modiolus, spiral ganglion, spiral ligament, basilar membrane, supporting cells, outer and inner hair cells and stria vascularis. Flk-1 was less strongly expressed in the cochlea and was not detected in the organ of Corti.

Animals↗

Percutaneous translaryngeal versus surgical tracheostomy: A randomized trial with 1-yr double-blind follow-up.

OBJECTIVE: To compare the outcomes and the short- and long-term complications of percutaneous translaryngeal tracheostomy (TLT) and surgical tracheostomy (ST). DESIGN: Prospective, randomized clinical trial with 1-yr double-blind follow-up. SETTING: A general intensive care unit of a university hospital. PATIENTS: A total of 139 consecutive critically ill patients who required a tracheostomy between February 2001 and June 2002 were randomly assigned to receive either ST or TLT. RESULTS: TLTs were performed more rapidly than STs (17 +/- 10 mins vs. 22 +/- 6 mins, p = .003). Early complications were rare in both groups. Major postoperative bleeding was less frequent with TLT (0 [0%] vs. 6 [8%], p = .03). Only one case of bleeding (in the ST group) required blood transfusion. Immediately after tracheostomy, six TLT patients (9%) and six patients (8%) in the ST group (p = .56) developed culture-confirmed bacteremia with microbes previously isolated from the pharynx or trachea. Group rates for stomal infections and pneumonia after tracheostomy were similar. At 1-yr follow-up, the overall survival rate was 27%, and 14 patients (45% of survivors) still had open tracheostomies. Both groups rated their quality of life as moderately to severely compromised, and the deterioration was strictly related to the presence of tracheostomy. One TLT and two ST survivors (p = .53) had clinical signs of tracheal stenosis, and bronchoscopy revealed narrowing of >50%. CONCLUSIONS: Compared with ST, the main advantages of TLT are that it is more rapid and associated with less postoperative bleeding. Infectious complications, particularly postoperative bacteremia, and long-term effects (physical and emotional) are similar with the two procedures.

Comorbidity↗

Hypofolatemia as a risk factor for head and neck cancer.

Head and neck cancer (HNSCC) includes squamous cell carcinomas of the oral cavity, pharynx and larynx. Approximately 38,500 cases of HNSCC are estimated to occur in the USA in 2004, with 11,000 deaths. HNSCCs represent about 3% of all malignant tumors in the USA. However, in other parts of the world, as India, Southeast Asia or Brazil, the disease is much more prevalent. The standard therapeutic approach, focused on surgery, irradiation and chemotherapy, alone or in combination, has been in part modified in the last 30 years, but the overall survival of HNSCC patients has not substantially improved. To characterize and thus identify high-risk mucosal areas and preclinical tumors, molecular abnormalities in head and neck carcinogenesis have been extensively studied. Metabolic aspects in head and neck carcinogenesis have been less extensively studied. Nevertheless, we know that metabolic alterations, often aspecific, are frequently associated with cancer. These may be secondary or may precede tumor development and favorite progression. In particular, based upon our results, a role for folate deficiency as a risk factor in head and neck carcinogenesis seems plausible. A chemoprevention protocol with folate is at present feasible and ethically correct and is already in progress at our institution. Homocysteine levels in cancer patients are probably largely affected by the HNSCC phenotype. An accumulation of homocysteine might reveal a genetic defect which is theoretically a target for pharmacological therapy, for example by antifolic drugs.

Adult↗