Valeria Cuccarini

Genetic and acquired prothrombotic risk factors and sudden hearing loss.

Objectives: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a frequently encountered condition, and various pathogenetic mechanisms have been hypothesized, such as viral infections, autoimmune processes, and ischemic events; however, whatever the cause, impaired cochlear perfusion appears to be the most important event. A number of inherited prothrombotic risk factors and their related genetic alterations have recently been correlated with vascular disorders.

Prothrombotic Gene Mutations in Patients with Sudden Sensorineural Hearing Loss and Cardiovascular Thrombotic Disease

Objectives: Impaired cochlear perfusion seems to be an important event in sudden sensorineural hearing loss. Prothrombotic gene mutations have been related to vascular disorders and sudden hearing loss. We assessed the prothrombotic risk in 10 patients with sudden sensorineural hearing loss who had previously experienced cardiovascular events to support its vascular pathogenesis. Methods: Ten patients underwent hematologic tests (MTHFR C677T/A1298C, prothrombin G20210A, platelet GlyIIIaA1/A2, and V Leiden G1691A genotyping; fibrinogenemia; cholesterolemia; homocysteinemia; folatemia). The results were compared with those of 100 previously investigated patients with sudden hearing loss alone and those of 200 healthy controls. DNA was isolated from peripheral blood leukocytes, and the gene mutations were investigated by polymerase chain reaction and a LightCycler DNA analyzer. Results: Two patients had 2 mutant alleles, 6 had 3, and 2 had 4. The mean homocysteine, cholesterol, and fibrinogen levels were above the upper limit of normal; the mean folate levels were slightly above the lower limit of normal. Multiple mutations were more frequent in the patient group than in the previously analyzed patients and healthy controls. Conclusions: The association between inherited and acquired prothrombotic factors in patients with sudden sensorineural hearing loss and thrombotic diseases in other sites suggests that a multifactorial mechanism may underlie microvascular cochlear impairment. Hematologic investigation, including MTHFR, prothrombin, platelet, and V Leiden genotyping, may help to detect patients at potential risk of recurrent hearing loss and multiple microvascular diseases, and could be usefully performed in otherwise idiopathic sudden sensorineural hearing loss.

Association between methylenetetrahydrofolate reductase polymorphisms, alcohol intake and oropharyngolaryngeal carcinoma in northern Italy

Folate metabolism dysregulation may lead to abnormal cell proliferation and predispose to carcinogenesis by inducing DNA hypomethylation. Folate pathways may be modified by polymorphisms in relevant genes, such as that for methylenetetrahydrofolate reductase (MTHFR), or by alcohol consumption. We investigated the relationship between MTHFR mutations at nucleotides C677T and A1298C, which cause reduced MTHFR enzyme activity, and susceptibility to oropharyngolaryngeal carcinoma in 65 patients and 100 controls. We isolated DNA from peripheral blood leukocytes. In oropharyngolaryngeal carcinoma cases the C677T heterozygous genotype was more frequent (p = 0.018), the allele frequency of MTHFR 677T was greater (p = 0.019) and the genotype 677TT/1298AA was more frequent (p = 0.001). A higher risk of carcinoma was found in the case of moderate drinkers with mutant MTHFR homozygosis or double heterozygosis (OR = 21.2 and OR = 9.1, respectively; p trend = 0.002), and the association was maintained for the different cancer sites (glottic, supraglottic, oropharyngeal). Our findings support the hypothesis that the interaction of alcohol intake and MTHFR polymorphisms might contribute to susceptibility to carcinogenesis of the oropharyngolaryngeal tract.

Comparative ultrasonographic, magnetic resonance sialographic, and videoendoscopic assessment of salivary duct disorders.

Objectives: Salivary duct disorders are the second most common cause of obstruction after calculi. Magnetic resonance sialography has been recently proposed as a means of diagnosing a heterogeneous group of salivary disorders, and so we compared it with sialoendoscopy in evaluating stenoses and sialectasia in 24 patients with obstructive symptoms and ultrasonographic results negative for calculi or masses. Methods: All of the patients (19 of whom had recurrent unilateral or bilateral swollen parotid glands and 5 of whom also had recurrent swollen submandibular glands) underwent dynamic color Doppler ultrasonography and dynamic magnetic resonance sialography with lemon juice stimulation of saliva; 18 patients also underwent diagnostic sialoendoscopy. Results: Ultrasonography and color Doppler ultrasonography showed duct dilatation in all patients (bilateral in 5 with parotid stenosis). Magnetic resonance sialography confirmed duct dilatation and stenosis in all of the patients, and revealed the simultaneous presence of calculi in 4 cases. A parotid sialocele was found in 4 cases. The magnetic resonance sialographic findings were confirmed in the patients who underwent sialoendoscopy. No side effects were observed. Conclusions: Magnetic resonance sialography following prediagnostic ultrasonography allows an adequate diagnosis of salivary duct disorders such as stenosis and sialectasia, as confirmed by objective sialoendoscopic assessment. Magnetic resonance sialography also makes it possible to visualize the salivary duct system up to its tertiary branches and, in this regard, may be considered a valid, noninvasive method for the evaluation of salivary duct disorders.

Sudden hearing loss and MTHFR 677C>T/1298A>C gene polymorphisms.

Purpose: Sudden hearing loss (SHL) can be caused by vascular disorders favoring impaired cochlear perfusion. A number of inherited prothrombotic risk factors have been considered in the pathogenesis of vascular impairment and the possible role of genetic alterations has recently been suggested. We aimed to investigate the relationship between SHL and MTHFR 677 and 1298 gene polymorphisms.Methods: DNA genotyping was performed on peripheral blood leukocytes in 45 SHL patients and 135 controls.Results: Wild-type MTHFR (677CC/1298AA) was significantly more frequent in the controls (P = 0.01), and gene polymorphisms (677CT, 677TT, 1298AC, 1298CC, compound 677CT/1298AC) were significantly more frequent in the patients (P = 0.005; Ptrend = 0.001).Conclusion: These data suggest that MTHFR gene polymorphisms may be considered as risk factors for SHL and participate on vascular impairment related to this disorder. Further studies, based on large series of patients, are needed to definitely assess the role of this prothrombotic factor in the etiopathogenesis of SHL.

Surgery and topic cidofovir for nasal squamous papillomatosis in HIV+ patient

Intranasal schneiderian exophytic squamous papillomatosis is rare and often secondary to human papilloma virus infection. Treatment usually consists of repeated surgical or endoscopic excisions due to recurrences. The use of intravenous or intralesional or topically applied cidofovir, a cytidine nucleotide analogue suppressing viral replication, alone or as adjuvant therapy has been proposed and described in the literature for the treatment of other human papillomavirus (HPV)-related lesions. We firstly describe a successful combined approach of surgery and topical cidofovir for recurrent nasal HPV-related exophytic squamous papillomatosis in a HIV-infected patient. As no untoward effects were encountered this therapeutical option should be considered in the management of recurrent nasal papillomatosis in HIV-infected patients.