Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss.

BACKGROUND: In recent years there has been a significant increase in the diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with an incidence of 20 of 100,000 people affected every year. No clear causes for this disease have been found thus far, but cochlear ischemia has been hypothesized in patients in whom an infectious episode or acoustic neurinoma have been excluded. OBJECTIVES: The aim of this case-control study was to investigate a number of acquired and inherited thrombophilic risk factors [antithrombin, protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy); lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to cardiovascular risk factors in patients with idiopathic SSHL (ISSHL). PATIENTS AND METHODS: We investigated 155 patients (67 male/88 female; age: 55 (range 19-79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms, and 155 controls (67 male/88 female; age 54 (range 19-78 years). Fasting Hcy levels were significantly higher in patients than in controls [11.6 (6.7-60) micromol/L vs. 8.7 (5.0-24) micromol/L] as well as PAI-1 levels [19 (2-95) mg/dL vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%) patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no patient was a deficiency of physiological clotting inhibitors antithrombin, protein C and protein S found. No significant differences between patients and controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11-695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant G20210A (3.8% vs. 3.2%). RESULTS AND CONCLUSIONS: Independent risk factors for ISSHL at the multivariate analysis (adjusted for age, sex and the traditional cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0-15.3); cholesterol levels within the second and third tertiles (with respect to the first tertile): T2 = OR 4.8 (95% CI 1.9-12.6)/T3 = OR 19 (95% CI 7-50.1); PAI-1 and Hcy levels within the third tertile (with respect to the first tertile): OR 20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1 levels and anticardiolipin antibodies are associated with ISSHL, so indirectly supporting the hypothesis of a vascular occlusion in the pathogenesis of the disease.

Betahistine dihydrochloride in the treatment of peripheral vestibular vertigo.

The present study compares the efficacy and safety of betahistine dihydrochloride to that of a placebo in recurrent vertigo resulting from Meniere's disease (MD) or in paroxysmal positional vertigo (PPV) of probable vascular origin. The design was double-blind, multicentre and parallel-group randomised. Eleven Italian centres enrolled 144 patients: 75 of the patients were treated with betahistine (41 MD/34 PPV) and 69 with placebos (40 MD/29 PPV). The betahistine dosage was 16 mg twice per day for 3 months. Compared to the placebo, betahistine had a significant effect on the frequency, intensity and duration of vertigo attacks. Associated symptoms and the quality of life also were significantly improved by betahistine. Both the physician's judgement and the patient's opinion on the efficacy and acceptability of the treatment were in agreement as to the superiority of betahistine. The effective and safe profile of betahistine in the treatment of vertigo due to peripheral vestibular disorders was confirmed.

Effects of the major Pasteurella multocida porin on bovine neutrophils.

OBJECTIVE: To evaluate in vitro effect of the major fraction of outer membrane proteins of Pasteurella multocida with porin-like activities on some biological functions of bovine neutrophils. ANIMALS: Neutrophils from 5 adult cattle. PROCEDURE: Variations in such biological processes as actin polymerization and chemotaxis and evaluation of hydrogen peroxide attributable to variable concentrations of P multocida were recorded and compared. Data were obtained, using the porin and lipopolysaccharide (LPS) isolated from a strain of P multocida cultivated in brain-heart infusion (BHI) broth. Various concentrations of porin and LPS were analyzed to evaluate changes in functional activation and microbicidal activity of bovine neutrophils. RESULTS: The 37.5-kd major polypeptide of the outer membrane of P multocida was isolated. Presence of this porin was significantly correlated with variations of some biological functions of bovine neutrophils. These immunocompetent cells had a concentration-dependent increase in actin polymerization and chemotactic activity. A concentration-dependent variation in the oxidative burst also was observed. CONCLUSIONS: The porins of gram-negative bacteria affect several biological functions of cells involved in the immune response as well as in inflammation. Significant correlation of results of in vitro experiments also was identified between porin and LPS effect. Pretreatment of bovine neutrophils with various concentrations of porin always caused a concentration-dependent increase in examined biological activities.

Role of Pasteurella multocida porin on cytokine expression and release by murine splenocytes.

The aim of this study was to verify whether Pasteurella multocida porin can affect the expression and release of IL-1alpha, IL-6, TNF-alpha, IL-4, IFN-gamma, IL-10 and IL-12 by murine splenocytes in vitro. P. multocida porin and lipopolysaccharide (LPS) were able to induce the release of IL-1alpha, IL-6, TNF-alpha, IFN-gamma and IL-12 in a dose-dependent fashion. The greatest release of these cytokines was obtained using P. multocida porin at a concentration of 5 microg ml(-1) and LPS at a concentration of 1 microg ml(-1). The time-courses of release showed that P. multocida LPS was able to stimulate the production of IL-1alpha, IL-6, TNF-alpha, IFN-gamma and IL-12 earlier than porin and at a greater rate. No effect was observed on IL-4 and IL-10 release under the same experimental conditions. P. multocida porin and LPS were also able to up-regulate the mRNA expression of IL-1alpha, IL-6, TNF-alpha, IFN-gamma and IL-12 p40. Our findings suggest that P. multocida porin is able to modulate inflammatory and immunological responses by affecting the release of several cytokines and the expression of their genes.

In vitro cytotoxicity of recombinant ricin A chain-antitransferrin receptor immunotoxin against human adenocarcinomas of the colon and pancreas.

The sensitivity of three human colon adenocarcinoma cell lines (LoVo, LS174T, and SW1116) and a human pancreatic adenocarcinoma cell line (Hs766T) to a recombinant ricin A chain-antitransferrin receptor immunotoxin was studied. In addition, the carboxylic ionophore monensin was used in conjunction with the immunotoxin to determine the possibility of increased cytotoxicity without loss of specificity. The immunotoxin, 454A12-rRTA, is composed of the monoclonal antibody 454A12 directed against transferrin receptor and of ricin A chain, which was produced by recombinant DNA techniques. In 18 h dose-response cytotoxicity assays, the median inhibitory dose (ID50) against LoVo, LS174T, and SW1116 was found to be 3 X 10(-10), 3.6 X 10(-11), and 3.6 X 10(-10) M, respectively; in the same assay, the ID50 for Hs766T was found to be 4 X 10(-10) M. In the presence of monensin, the ID50 for the adenocarcinoma cell lines was reduced 9-fold, 28-fold, and 5-fold, respectively. In cytotoxic kinetic assays, 50% of control protein inhibition was reached in immunotoxin-treated LS174T cells 12-fold faster in the presence of monensin than in its absence. Immunotoxin-treated LoVo cells reached 50% inhibition of control protein synthesis fivefold faster in the presence of monensin than in its absence. Furthermore, no toxicity of immunotoxin or potentiation by monensin was observed in either a control cell line (Swiss albino mouse 3T6) treated with specific immunotoxin or with a control immunotoxin assay. These results show the in vitro specificity and selectivity of 454A12-rRTA immunotoxin for human gastrointestinal and pancreatic cancer cell lines.

Enhancement of the specific cytotoxicity of a breast cancer-associated antigen immunotoxin by the carboxylic ionophore monensin.

Monensin is a carboxylic ionophore which dissipates proton gradients across cell membranes. Monensin is known to potentiate the cytotoxic activity of immunotoxins (antibody-toxin conjugates) directed against several human tumor-associated antigens. We have investigated the effect of monensin on an immunotoxin cytotoxic to the human breast cancer cell line MCF-7. This immunotoxin is composed of an antibody directed against a human breast cancer membrane antigen, and ricin A chain, which has been produced by recombinant DNA techniques. In a 16-hour cytotoxicity assay, monensin reduced 34-fold the median inhibitory dose, from 1.4 X 10(-8)M (without monensin) to 4.1 X 10(-10)M (with monensin). In timed cytotoxicity assays, 50% of control protein synthesis was reached in immunotoxin treated cells 8-fold faster in the presence of monensin (0.5 hours) than in its absence (4 hours). Monensin produced no enhancement of immunotoxin effect on a control cell line, nor on a control immunotoxin on MCF-7 cells, demonstrating specificity of monensin effect. In addition, specific immunotoxin alone or with monensin produced no toxicity on MCF-7 cells maintained at 23 degrees C. These results suggest that both binding and internalization of immunotoxin are necessary for the monensin effect. Monensin was a potent enhancer of immunotoxin effect on human breast cancer cells. This effect occurs without the presence of ricin B chain in the conjugate.

Visual suppression test and ocular dysmetria: some electronystagmographic findings relevant to the assessment of size of cerebellopontine angle tumors.

Patients with cerebellopontine angle tumors underwent vestibular examination, testing of voluntary fast and slow conjugate eye movements and of visual-vestibular interaction (visual suppression test--VST) by electronystagmography (ENG). Both spontaneous and evoked nystagmus (Ny) and dysmetric alterations of the voluntary conjugate eye movements are relevant to cerebellopontine pathology. This study shows that ENG may reveal damage to the vestibular brain-stem and archicerebellar structures, the ENG signs of which very often precede the clinical signs of compression. In cranial nerve VIII neuromas vestibular and oculomotor instrumental investigations yield valuable clues for early diagnosis of tumor transition from the otological to the neurosurgical stage.