Syndromic hereditary deafness. Usher's syndrome. Oto-neurologic and genetic factors

Usher syndrome (USH) is an autosomal recessive hereditary disorder characterized by congenital bilateral sensorineural hearing loss and progressive loss of vision due to retinitis pigmentosa (RP). The prevalence of Usher syndrome is estimated to be 3-4.4 cases per 100.000 people. Several clinical types have been distinguished by age at onset, rate of progression, and severity of symptoms. Type I (USH1) is characterized by a congenital, severe-to-profound deafness and absent vestibular function. Type II (USH2) shows a congenital and moderate-to-severe hearing loss and normal vestibular response. It is also suggested a third type (USH3), clinically similar to USH2, but with progressive hearing loss. Genetic heterogeneity of USH is quite extensive. Up to now, seven different loci responsible for the defect are known: 14q, 11q, 11p, 10q and 21q for USH1; 1q for USH2 and 3q for USH3. Moreover, there are USH1 and USH2 families that fail to show linkage to these candidate regions demonstrating that should exist other loci causing USH, although their ubications are unknown. To date, only two genes involved in the USH pathology are known, although together they are responsibles of about the 80% of total USH cases: myosin VIIA, an unconventional myosin, involved in the USH1b phenotype and a protein similar to the laminina, responsible for the USH2a phenotype.     

An evaluation of tissue polypeptide antigen (TPA) in the two bronchoalveolar lavage fractions of lung cancer patients

BACKGROUND: It has been proven that cytokeratins (CKs) are useful tumor markers for the follow-up, treatment monitoring and prognosis evaluation of lung cancer and among these, tissue polypeptide antigen (TPA) plays an important role. Nevertheless, only a small number of studies have been reported about their diagnostic capacity. Bronchoalveolar lavage (BAL) can be divided into two fractions: bronchiolar (BF) and alveolar (AF). For the above reasons, our aims were (1) to analyze the diagnostic usefulness of TPA in the BAL of lung cancer patients and (2) to observe if, in lung cancer patients, TPA levels in the two BAL fractions are different. This should mean that the study of tumor markers in the BAL should be carried out in both fractions to increase their diagnostic capacity. METHODS: We studied 289 BALs divided into two phases. In phase I, TPA was analyzed in the BAL of six groups of subjects (healthy persons, chronic bronchitis, asthma, respiratory infections, diffuse interstitial pulmonary diseases and lung cancer). In phase II, TPA was studied in both BAL fractions of a group of patients with lung cancer. RESULTS: We observed that TPA levels were significantly higher in the BAL of patients with bronchogenic neoplasias. In these patients, TPA was increased in the BF of the lavage in relation to the AF. In smoker patients with pulmonary carcinomas, TPA was higher in the AF of the BAL than in the lavage of non-smokers. This did not occur in the BF. We found no relation between the TPA concentrations and cancer histology. CONCLUSIONS: We believe that TPA is a useful tumor marker with diagnostic capacity and this capacity is increased when it is studied in the two BAL fractions. Smoking habit may play a role in the secretion of tumor markers by the tumor cells.     

Behavior of squamous cell carcinoma of the floor of the mouth. Is supraomohyoid neck dissection sufficiently safe to manage clinically N0 patients?

Aim

The main aim of the present report is to study the behavior of SCC of the floor of the mouth.

Nasopharyngeal/nasal type T/NK lymphomas: analysis of 14 cases and review of the literature

AIMS AND BACKGROUND: Lymphoid malignancies expressing CD56 are rare and most occur in the nasal or nasopharyngeal region. They derive from natural killer cells or from a small subset of T cells that have granular cytoplasm containing molecules that mediate cytotoxic activity: TIA-1, granzyme B and perforin. Both types are closely associated with Epstein-Barr virus. METHODS: We report the pathologic, immunophenotypic and molecular findings in 14 cases of nasopharyngeal/nasal type T/NK lymphomas. RESULTS: Clinically, all patients had localized disease and also had symptoms limited to the nose. The neoplastic cells were frequently pleomorphic, and angiocentric growth was common. Combined immunophenotypic and gene rearrangement analyses demonstrated that most of the cases were true NK cell tumors and were either CD56+ and CD3- or CD56+ and CD3+. Immunohistochemical study showed TIA-1 and granzyme B expression in all cases. By in situ hybridization, most of the cases were associated to Epstein-Barr virus, harboring type 1 virus, and polymerase chain reaction amplification across the 30 bp deletion showed high frequency of latent membrane protein-1-deleted variants. CONCLUSIONS: The nasal type T/NK cell lymphoma shows distinctive clinicopathologic, immunophenotypic and molecular features. These results confirm the important role of Epstein-Barr virus as a local factor in their pathogenesis.     

Familial isolated unilateral large vestibular aqueduct syndrome

Large vestibular aqueduct syndrome (LVAS) is one of the most frequent inner ear malformations. It is associated with varying degrees of hearing loss, that may be progressive, sudden or fluctuant; nevertheless normal hearing in cases with LVAS has been described. Although unilateral LVAS has been described, all patients show clinical and radiological findings in both ears, in contrast to the family presented here, where 2 siblings are affected by unilateral sensorineural hearing loss associated with ipsilateral LVAS, with an autosomal recessive pattern. In order to search for the origin of this inner ear malformation, mutations in genes GJB2 (connexin-26 gene), PDS (Pendred's syndrome gene) and mitochondrial 12sRNA were studied, without positive results. In this paper we hypothesize the probable embryological origin for this malformation.     

Chronic benzylamine administration in the drinking water improves glucose tolerance,reduces body weight gain and circulating cholesterol in high-fat diet-fed mice

Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600 μmol/(kg day)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.     

A new family with hereditary choreo-acanthocytosis

We describe a new family with hereditary choreo-acanthocytosis. Two members of this family were affected; neither of them suffered from anaemia or signs of haemolysis. The acanthocytes showed an impaired deformability with an increase in whole blood viscosity. The composition of the plasma and erythrocyte membrane lipids was normal, as was the fatty acid composition of the erythrocyte ghost membranes. The only alteration found was a decrease in the fluidity of the erythrocytic membrane.