Effects of impulse noise on transiently evoked otoacoustic emission in soldiers

The aim of the study was to assess the effects of exposure to impulse noise on TEOAE, as compared to PTA. The study comprised 92 soldiers, subjected to impulse noise during military service. The control group consisted of secondary school students, not exposed to noise. Extended high frequency PTA, and TEOAE were recorded before and after one year of military service. The total level of noise and spectrum analysis were performed for all kinds of weapons, separately. The highest levels of noise for weapons were related to frequencies from 1.6-16 kHz. After military service significant deterioration of hearing was observed on average by 6 dB exclusively at the frequencies of 10 and 12 kHz. TEOAE reduction was registered predominantly at frequencies of 2, 3 and 4 kHz, with the greatest decrease at 2 kHz (p <0.02). The control group did not show any significant audiometric changes as well as TEOAE during the time of experiment.     

Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption-induced apoptosis

The cytoskeleton is critical to neuronal functioning and survival. Cytoskeletal alterations are involved in several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We studied the possible pathways involved in colchicine-induced apoptosis in cerebellar granule neurons (CGNs). Although colchicine evoked an increase in caspase-3, caspase-6 and caspase-9 activation, selective caspase inhibitors did not attenuate apoptosis. Inhibitors of other cysteine proteases such as PD150606 (a calpain-specific inhibitor), Z-Phe-Ala fluoromethyl ketone (a cathepsins-inhibitors) and N(alpha)-p-tosyl-l-lysine chloromethyl ketone (serine-proteases inhibitor) also had no effect on cell death/apoptosis induced by colchicine. However, BAPTA-AM 10 microM (intracellular calcium chelator) prevented apoptosis mediated by cytoskeletal alteration. These data indicate that calcium modulates colchicine-induced apoptosis in CGNs. PARP-1 inhibitors did not prevent apoptosis mediated by colchicine. Finally, colchicine-induced apoptosis in CGNs was attenuated by kenpaullone, a cdk5 inhibitor. Kenpaullone and indirubin also prevented cdk5/p25 activation mediated by colchicine. These findings indicate that cytoskeletal alteration can compromise cdk5 activation, regulating p25 formation and suggest that cdk5 inhibitors attenuate apoptosis mediated by cytoskeletal alteration. The present data indicate the potential therapeutic value of drugs that prevent the formation of p25 for the treatment of neurodegenerative disorders.     

Viral community-acquired pneumonia in nonimmunocompromised adults

INTRODUCTION: Viral community-acquired pneumonia (CAP) has been poorly studied and clinically characterized. Using strict criteria for inclusion, we studied this type of infection in a large series of hospitalized adults with CAP. MATERIALS AND METHODS: All nonimmunocompromised adult patients with a diagnosis of CAP having paired serology for respiratory viruses (RVs) [338 patients] were prospectively included in the study from 1996 to 2001 at our 1,000-bed university teaching hospital, and subsequently were followed up. We compared patients with pure viral (PV), mixed viral (RV + bacteria), and pneumococcal CAP. RVs (ie, influenza, parainfluenza, respiratory syncytial virus, and adenovirus) were diagnosed by means of paired serology. RESULTS: Sixty-one of 338 patients (18%) with paired serology had an RV detected, and in 31 cases (9%) it was the only pathogen identified. Influenza was the most frequent virus detected (39 patients; 64%). Patients with chronic heart failure (CHF) had an increased risk of acquiring PV CAP (8 of 26 patients; 31%) when compared to a mixed viral/bacterial etiology (2 of 26 patients; 8%; p = 0.035) or CAP caused by Streptococcus pneumoniae (1 of 44 patients; 2%; p = 0.001). Multivariate analysis revealed that CHF (odds ratio [OR], 15.3; 95% confidence interval [CI], 1.4 to 163; p = 0.024) and the absence of expectoration (OR, 0.14; 95% CI, 0.04 to 0.6; p = 0.006) were associated with PV pneumonia compared to pneumococcal CAP. CONCLUSION: RVs are frequent etiologies of CAP (single or in combination with bacteria). Patients with CHF have an increased risk of acquiring a viral CAP.     

Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome

OBJECTIVES: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance, compensatory hyperinsulinemia, and increased levels of free insulin-like growth factor-I (IGF-I), presumably due to a decline in IGF binding protein 1 (IGFBP-1). This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I. STUDY DESIGN: Twenty-seven obese, hyperandrogenic PCOS women with elevated fasting insulin were treated for 12 weeks with metformin (500 mg p.o., t.i.d.). Serum levels of insulin, testosterone, sex hormone binding globulin (SHBG), IGF-I, and IGFBP-1 were measured before and after treatment. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy. RESULTS: Metformin therapy significantly increased IGFBP-1 concentration by 38% (P = 0.05) but had no demonstrable effect on the total IGF-I levels. Fasting insulin levels declined by 38% (P = 0.0001) while the glucose/insulin ratio increased by 72% (P = 0.0001) and quantitative insulin sensitivity check index (QUICKI) increased by 8% (P = 0.0001). Metformin treatment also significantly decreased testosterone (by 37%, P = 0.0001) and increased SHBG concentration (by 16%, P = 0.04). Multiple linear regression analysis revealed that baseline IGFBP-1 levels correlated inversely and independently with two baseline parameters: WHR (P = 0.003) and free testosterone index (P = 0.04). CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1. We provide further arguments in favor of metformin therapy in hyperinsulinemic women with PCOS.     

Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation

Preliminary reports suggested that hepatitis C virus (HCV) infection has a more aggressive course following living donor liver transplantation (LDLT) compared to cadaveric liver transplantation (CLT). The aim of this prospective study was to establish if HCV disease recurrence differs between LDLT and CLT. A cohort of 116 consecutive HCV-infected patients undergoing 117 LTs in a single center from March 2000 to August 2003 were followed-up, including systematic liver biopsies. Severe recurrence (SR) was defined as biopsy-proven cirrhosis and/or the occurrence of clinical decompensation. After a median follow-up of 22 months (2.6-44 months), 26 (22%) patients developed SR (decompensation in 12), involving 17 (18%) of 95 patients undergoing CLT and 9 (41%) of 22 undergoing LDLT. The 2-year probability of presenting SR was significantly higher in LDLT compared to CLT (45% vs. 22%, P = .019). By univariate analysis LDLT (P = .019) and an ALT higher than 80 IU/L 3 months after LT (P = .022) were predictors of SR. In 93 patients from whom a liver biopsy was available 3 months after LT, a lobular necroinflammatory score >1 (P < .01), LDLT (P < .01), and biliary complications (P = .046) were associated with SR. However, the only variables independently associated with SR were LDLT (odds ratio [OR], = 2.8; 95% CI,1.19-6.6; P = .024) and a lobular necroinflammatory score > 1 (OR, 3.1; 95% CI, 1.2-8; P = .013). In conclusion, HCV recurrence is more severe in LDLT compared to CLT. Although our results were based on a single-center experience, they should be considered in the decision-making process of transplant programs, since severe HCV recurrence may ultimately compromise graft and patient survival.     

Glucocorticoid receptor isoforms alpha and beta in in vitro cytokine-induced glucocorticoid insensitivity

We stimulated peripheral blood mononuclear cells from 14 healthy subjects, 14 patients with stable asthma, and 13 patients with unstable asthma with interleukin (IL)-2 and IL-4 to induce glucocorticoid insensitivity and we examined the relationship between insensitivity and the expression of glucocorticoid receptor (GR) isoforms. Results are expressed as IC(50) (nanomolar) values (means +/- SD) in proliferation assays and as 10(3) cDNA molecules per microgram of total RNA (means +/- SD) in real-time polymerase chain reaction analysis. Cells from patients with unstable asthma were less sensitive (316 +/- 7 nM) to dexamethasone antiproliferative effects than those from healthy control subjects (102 +/- 4 nM, p < 0.05) and patients with stable asthma (107 +/- 2 nM, p < 0.05). Coincubation with IL-2 and IL-4 repressed the inhibitory effect of dexamethasone on proliferation in all groups (unstable: 851 +/- 47 nM, p < 0.01; stable: 912 +/- 52 nM, p = 0.001; control subjects: 537 +/- 45 nM, p = 0.001). GR-alpha mRNA baseline expression was higher in patients with unstable asthma [(1.95 +/- 0.40) x 10(3) cDNA molecules/microg total RNA, p < 0.05] than in patients with stable asthma [(1.46 +/- 0.35) x 10(3) cDNA molecules/microg total RNA] and healthy subjects [(1.35 +/- 0.25) x 10(3) cDNA molecules/microg total RNA]. GR-beta mRNA was 600 times lower than GR-alpha in the three groups. Coincubation with IL-2 and IL-4 significantly increased GR-alpha mRNA expression in the three groups (p < 0.01), but caused no significant change in GR-beta mRNA. GR-alpha, but not GR-beta, protein was detected at baseline and after cytokine exposure. Our data do not support the hypothesis that increased GR-beta expression can contribute to cytokine-induced glucocorticoid insensitivity.     

Complex voice assessment--Polish version of the Voice Handicap Index (VHI)

The aim of this work was to present own modification of Jacobson's The Voice Handicap Index, the self-estimation scale of the voice as a one part of the complex voice evaluation. The VHI contains three groups of questions of physical, emotional and functional subscales, which specify complaints during phonation scored in 4 points (0-4). The presented our own modification of the VHI may be useful in everyday clinical practice.     

Evaluation of the inner ear fluorescence

Searching for the methods, which may improve the visualisation of the membranous labyrinth, authors decided to evaluate autofluorescence of the membranous structures of the inner ear. The analysis of the inner ear autofluorescence parameters was performed. We assessed, whether the detected differences in autofluorescence between the bony elements and the membranous structures, allows the practical apply, owning to increased contrast in the operating microscope. The optimal wave length inducing autofluorescence of membranous labyrinth amounts to 465 nm. Obtained in these circumstances contrast of the membranous structures don't cause a significant improvement in their visualisation, comparing with the picture received in the traditional optical microscope.