A simple qualitative scale for diagnosis of laryngopharyngeal reflux: high correlations with pH measurements and disease severity. The usefulness of the Warsaw Scale in LPR diagnostics compared to other diagnostic tools.

PURPOSE: Diagnosis and monitoring of laryngopharyngeal reflux (LPR) is a constant challenge in otolaryngological practice, chiefly because there are no specific symptoms characteristic of the disease. In this paper, we present the validation of a simple, 6-level qualitative scale to gauge the clinical findings of LPR. It has been previously published in Polish as the Warsaw Scale. METHODS: In the study, we enrolled 100 patients with voice problems who had registered in our clinic, and we performed an extended battery of diagnostic tests for LPR, together with 24-h pH monitoring. RESULTS: The Warsaw Scale significantly outperformed other instruments in both predicting LPR status and correlating with pH measurements. Moreover, the rating provided by the scale showed a strong association with patient-reported symptoms. CONCLUSION: The data indicate that the Warsaw Scale could be used as an affordable, consistent, and effective diagnostic and monitoring tool for LPR.

The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients. / Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. MATERIALS AND METHODS: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. RESULTS: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. CONCLUSIONS: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers.

Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder. / Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3.

INTRODUCTION AND OBJECTIVES: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. PATIENTS OR MATERIALS AND METHODS: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. RESULTS: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. CONCLUSIONS: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression.

Is the Genetic Background of Co-Stimulatory CD28/CTLA-4 Pathway the Risk Factor for Prostate Cancer?

The impairment of immunological surveillance caused by aberrant T cell activation can lead to an inadequate anti-tumor response. Therefore, deregulation in co-stimulatory pathway might be associated with cancer susceptibility. Here we undertook a prospective study to investigate whether genetic variations in gene encoding molecule CD28 and CTLA-4 playing pivotal role in regulating adoptive immune response can influence susceptibility to prostate cancer. Single nucleotide polymorphisms (SNPs) in CTLA-4 and CD28 genes were genotyped in 301 prostate cancer (PCa) patients and 301 controls. The distributions of the genotypes and haplotypes in the CTLA-4/CD28 SNPs were similar in both studied groups. However, the overrepresentation of carriers of CTLA-4c.49A>G[A] allele and carriers of CTLA-4g.319C>T[T] allele in PCa as compared to controls was observed (p = 0.082 and p = 0.13, respectively). The risk of disease was higher (OR 1.78) for carriers of both susceptibility alleles as compared to carriers of protective genotypes (p = 0.03). The CTLA-4c.49A>G and CTLA-4g.319C>T SNPs might be considered as low risk susceptibility locus for PCa.

Retrobulbar Hematoma After Heart Transplantation: Case Report and Literature Review.

Spontaneous retrobulbar hemorrhage is a rare phenomenon observed after surgery not directly involving the orbit. When it occurs, presentation is usually obvious, and it carries high morbidity unless emergent and timely surgical treatment is instituted. There are only a handful of cases associated with cardiac surgery, and to our knowledge no cases with heart transplantation. We present a case of a 35-year-old woman who underwent orthotopic heart transplantation for peripartum cardiomyopathy and developed spontaneous retrobulbar hemorrhage.

CTLA-4 and CD28 genes' polymorphisms and renal cell carcinoma susceptibility in the Polish population--a prospective study.

Polymorphisms in co-stimulatory genes are associated with susceptibility to several malignances such as breast cancer, cervical cancer and chronic lymphocytic leukemia, but have been scarcely investigated in renal cell cancer (RCC). A total of 310 RCC patients and 518 controls were genotyped for single-nucleotide polymorphisms (SNPs) in the CTLA-4 and CD28 genes: CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*6230G>A (CT60; rs3087243), CTLA-4g.*10223G>T (Jo31; rs11571302), CD28c.17+3T>C (rs3116496) and CD28c.-1042G>A (rs3181098). The distribution of the alleles, genotypes and haplotypes in the CTLA-4 and CD28 genes were similar in the RCC patients and in the controls. However, among the patients with a clear cell RCC (CCRCC), the G allele carriers of CT60 and Jo31 SNPs were overrepresented, and the overrepresentation became significant for the carriers of CT60[G] allele in CCRCC patients with necrosis in the primary tumor (P = 0.046). The CTLA-4c.49A>G[A]/CTLA-4g.319C>T[C]/CT60[A]/Jo31[T]/CD28c.17+3T>C[T]/ CD28c.1042G>A[G] haplotype was associated with an approximately threefold increased risk of primary tumor necrosis in CCRCC patients (P corrected = 0.0000007) and with the advanced stage of disease (IV) (P corrected = 0.001). When stratified by gender, CD28c.-1042G>A[GG] genotype was more frequent in the female CCRCC patients compared with healthy women (P = 0.042). Polymorphisms in the CTLA-4 and CD28 genes, in particular considered together as haplotypes, were associated with increased risk of CCRCC, especially with necrosis and with the advanced stage of disease. The CD28c.-1042G>A SNP modulates the risk of CCRCC in women. These findings indicate that the associations of the CTLA-4 and CD28 polymorphisms with the risk of renal cancer are worth further study in a larger group of patients.

Causes of Chronic Cough in Non-smoking Patients.

Chronic cough is a common medical problem. The aim of the study was to analyze chronic cough causes in non-smoking patients and to search for demographic factors associated with different cough reasons. The etiology of cough was determined by medical history, diagnostic tests and response to specific treatment. Patients with significant abnormalities in the chest radiograph or spirometry were not included. The study included 131 non-smoking patients; median age 54 years, 77 % female. The most frequent causes of cough were gastroesophageal reflux disease (GERD) (62 %) and upper airway cough syndrome (UACS) (46 %). Cough variant asthma and non-asthmatic eosinophilic bronchitis (NAEB) were diagnosed in 32 (25 %) and 19 (15 %) patients, respectively. Other cough causes were found in 27 patients (21 %). Asthma was a significantly more common cause of chronic cough in women than in men (31 % vs. 3 %, p = 0.005). A reverse relationship was demonstrated for UACS (39 % vs. 67 %, p = 0.01). Patients with chronic cough aged >50 yrs were more likely to be diagnosed with less common cough causes. In conclusion, the most common chronic cough reasons are GERD and UACS. Asthma-related cough is diagnosed more frequently in females, while UACS-related cough is more frequent in males.

Spectroscopic characterization of Co3O4 catalyst doped with CeO2 and PdO for methane catalytic combustion.

The study deals with the XPS, Raman and EDX characterization of a series of structured catalysts composed of cobalt oxides promoted by palladium and cerium oxides. The aim of the work was to relate the information gathered from spectroscopic analyses with the ones from kinetic tests of methane combustion to establish the basic structure-activity relationships for the catalysts studied. The most active catalyst was the cobalt oxide doped with little amount of palladium and wins a confrontation with pure palladium oxide catalyst which is commercially used in converters for methane. The analyses Raman and XPS analyses showed that this catalyst is composed of a cobalt spinel and palladium oxide. The quantitative approach to the composition of the catalysts by XPS and EDX methods revealed that the surface of palladium doped cobalt catalyst is enriched with palladium oxide which provides a great number of active centres for methane combustion indicated by kinetic parameters.

Does the established cause of chronic cough depend on diagnostic approach?

The objective of the present study was to evaluate the prevalence of chronic cough causes and to compare the efficacy of two diagnostic approaches used in ambulatory vs. hospitalized setting. Eighty patients with chronic cough, 40 in each group, were enrolled into the study. The etiology of cough was determined on medical history and on either basic (in out-patients) or detailed (in in-patients) investigations on most common causes of chronic cough. We diagnosed etiology of cough in all subjects. The most frequent causes of cough were gastroesophageal reflux disease (GERD) and upper airway cough syndrome (UACS). Nonasthmatic eosinophilic bronchitis (NAEB) and multiple cough causes were recognized more often in hospitalized patients (P<0.05). We conclude that the main causes of chronic cough were GERD and UACS. An extensive diagnostic approach allows recognizing NEAB more frequently and reveals the complex nature of chronic cough.

Treatment of high-risk superficial bladder cancer with maintenance bacille Calmette-Guérin therapy: preliminary results.

OBJECTIVE: To evaluate, in a prospective study, the effects and results of maintenance therapy with bacille Calmette-Guérin (BCG) in treating patients with high-risk superficial bladder cancer. PATIENTS AND METHODS: In all, 155 patients were enrolled in a randomized study of transurethral resection alone (53) or combined with intravesical BCG (102) as a treatment for superficial bladder cancer. BCG was administered for six consecutive weeks followed by three weekly instillations in months 3, 6, 12, 18, 24, 30 and 36 after resection. Recurrence, progression, prognostic factors and side-effects were assessed and analysed. RESULTS: After a median (range) follow-up of 23 (6-42) months, 83 of the 102 patients treated with BCG (81%) were disease-free, compared with 24 of the 53 treated with resection alone (45%). There was also a significant difference in tumour progression and time to progression between the trial arms. The disease progressed in eight patients (8%) treated with BCG and in 12 (23%) of those treated by resection alone. Independent risk factors for progression were DNA ploidy status and stage. Only the completion of treatment was predictive of outcome (risk of recurrence) for patients treated with BCG. CONCLUSION: Maintenance BCG therapy was better than resection alone in reducing the incidence of recurrence and progression in patients with high-risk superficial bladder cancer.

[Selected issues of health certification among teachers]. / Wybrane problemy badan orzeczniczych u nauczycieli.

The authors propose a standardized model of phoniatric consultations aimed at certifying occupational diseases of the organ of voice. The study included the administration of an expanded questionnaire, laryngological and phoniatric examinations, stroboscopy and determination of the voice acoustic parameters essential in assessing the phonatory function of the larynx. A four-scale hoarness by Yanagihara was employed in the consulting examination and the measurement was taken for three vowels. The model presented should facilitate the diagnosis of occupational diseases of the voice organ.

Direct measurement of small ligand-induced conformational changes in the aspartate chemoreceptor using EPR.

Ligand-binding-induced conformational changes in the Salmonella typhimurium aspartate receptor were studied using spin-labeling electron paramagnetic resonance. Cysteine residues, introduced by site-directed mutagenesis at several positions in the aspartate receptor periplasmic domain, were used to attach covalently a thiol-specific spin label. The electron paramagnetic resonance spectra of these labeled proteins were obtained in the presence and absence of the ligand aspartate, and used to calculate the distance change between spin labels. The results support a model in which transmembrane signaling is executed by a combined movement of alpha helix 4 (which leads into transmembrane domain 2) relative to alpha helix 1 (connected to transmembrane domain 1), as well as a coming together of the two subunits. Ligand binding causes spin labels at position 39 and 179 (within one subunit) to move further from each other and spin labels at position 39 and 39' (between two subunits) to move closer to each other. Both of these changes are very small-less than 2.5 A. No similar changes were detected in any aspartate receptor samples solubilized in detergent, suggesting that the membrane is required for these conformational changes. This is the first case of physically measured ligand-induced changes in a full-length 1-2 transmembrane domain receptor, and the results suggest that very small ligand-induced movements can result in large effects on the activity of downstream proteins.

Producing positive, negative, and no cooperativity by mutations at a single residue located at the subunit interface in the aspartate receptor of Salmonella typhimurium.

Site-directed mutagenesis of the aspartate receptor of Salmonella typhimurium (Tars) at serine 68, a residue located within the aspartate binding pocket and at the subunit interface, identified this residue as an allosteric switch in this receptor. Substitutions at this position can affect both the type and degree of binding cooperativity observed. Negative cooperativity is observed in the wild-type receptor (nH = 0.7 +/- 0.1) and is maintained by the mutations S68C (nH = 0.8 +/- 0.02), S68V (nH = 0.9 +/- 0.05), and S68D (half-of-the-sites). Binding at only half of the sites was detectable in the S68D mutant, an extreme form of negative cooperativity. No cooperativity (nH = 1.0 +/- 0.03) was observed in the mutant S68A. Positive cooperativity was generated by the substitutions S68T (nH = 1.2 +/- 0.09), S68L (nH = 1.2 +/- 0.1), S68N (nH = 1.3 +/- 0.2), and S68I (nH = 1.4 +/- 0.2). Binding measurements indicated that the substitutions S68Q, S68E, and S68F decrease affinity of the first ligand binding 500-fold, 7000-fold, and 1600-fold, respectively.

Intra-atrial course of the right coronary artery and its branches.

OBJECTIVE: To illustrate and describe an anomaly of right coronary artery (RCA) course. SETTING: Postmortem examination of cardiac tissue. DESIGN AND PATIENTS: Three cases where the RCA had an intracavitary position in the right atrium are described. Additionally, light microscopic analysis of random sections of posterior right atrium from 100 consecutive autopsy cases was undertaken. MAIN RESULTS: Each of the index cases was an incidental finding at autopsy. In two cases, the RCA, after passing the acute angle of the heart (epicardially), entered the right atrium posteriorly and ran subendocardially for distances of 1.5 and 3.0 cm, respectively. In the third case, the RCA entered the right atrial cavity 2.5 cm from its origin and ran subendocardially for 2.0 cm. In all three cases, the RCA exited the atrial cavity and once again attained an epicardial course. In the first two cases, the RCA ran 1.0 cm above the atrioventricular groove, rather than in its normal location at the annulus. The random sections of right atrial wall showed that medium calibre arterial branches of the RCA also commonly run in subendocardial positions (29 of 100 cases) and sometimes project into the atrial cavity (five of 29 cases). CONCLUSIONS: The genesis of this epicardial coronary anomaly is unclear, but may relate to the 'higher' than normal course of the artery in these cases, in concert with the normal thinness of the right atrial wall, and the tendency for even medium calibre arteries to assume this subendocardial location. Despite the benign outcome of the index cases described here, the authors believe that this intracavitary course of the RCA could pose special technical problems during coronary artery catheterization and bypass grafting.

Electron paramagnetic resonance observations on the cytochrome c-containing nitrous oxide reductase from Wolinella succinogenes.

Nitrous oxide reductase from Wolinella succinogenes, an enzyme containing one heme c and four Cu atoms/subunit of Mr = 88,000, was studied by electron paramagnetic resonance (EPR) at 9.2 GHz from 6 to 80 K. In the oxidized state, low spin ferric cytochrome c was observed with gz = 3.10 and an axial Cu resonance was observed with g parallel = 2.17 and g perpendicular = 2.035. No signals were detected at g values greater than 3.10. For the Cu resonance, six hyperfine lines each were observed in the g parallel and g perpendicular regions with average separations of 45.2 and 26.2 gauss, respectively. The hyperfine components are attributed to Cu(I)-Cu(II) S = 1/2 (half-met) centers. Reduction of the enzyme with dithionite caused signals attributable to heme c and Cu to disappear; exposure of that sample to N2O for a few min caused the reappearance of the g = 3.10 component and a new Cu signal with g parallel = 2.17 and g perpendicular = 2.055 that lacked the simple hyperfine components attributed to a single species of half-met center. The enzyme lost no activity as the result of this cycle of reduction and reoxidation. EPR provided no evidence for a Cu-heme interaction. The EPR detectable Cu in the oxidized and reoxidized forms of the enzyme comprised about 23 and 20% of the total Cu, respectively, or about one spin/subunit. The enzyme offers the first example of a nitrous oxide reductase which can have two states of high activity that present very different EPR spectra of Cu. These two states may represent enzyme in two different stages of the catalytic cycle.

Extended x-ray absorption fine structure and electron paramagnetic resonance of nitrous oxide reductase from Pseudomonas aeruginosa strain P2.

The copper centers of nitrous oxide reductase from Pseudomonas aeruginosa strain P2 were studied by x-ray and electron paramagnetic resonance (EPR) spectroscopy. The enzyme is dimeric and contains four Cu atoms and about seven cysteine residues/subunit of Mr = 73,000. The extended x-ray absorption fine structure (EX-AFS) spectrum was analyzed for enzyme as isolated (oxidized or slightly reduced), enzyme exposed briefly to air, reduced enzyme, and enzyme at pH 7 after having been activated by standing at pH 10. The average Cu ligand environment in the first shell was best modeled for all forms of the enzyme by a combination of N/O and S atoms at a total coordination number between 3 and 4 and bond distances ranging from 1.96-2.03 A for Cu-N/O and 2.20-2.25 A for Cu-S. The data could be fit without using Cu-Cu interactions. Overall the results are similar to those reported for the enzyme for Pseudomonas stutzeri (Scott, R. A., Zumft, W.G., Coyle, C.L., and Dooley, D.M. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4082-4086). The first derivative EPR spectra of the Cu(II) centers at 15 and 45 K were qualitatively similar among enzyme as isolated and enzyme exposed to N2O or air. These three nominally oxidized samples showed an axial signal with g perpendicular = 2.03 and g parallel = 2.15-2.16. Hyperfine structure was observed in both the g parallel and g perpendicular regions with splittings of 43 and 25 gauss, respectively. These hyperfine components are attributed to exchange coupled Cu(I)-Cu(II) S = 1/2 (half-met) centers. In the enzyme as isolated and after exposure to N2O, about 3/4 of the Cu was EPR silent, whereas after exposure to air the signal integrated to about half the Cu concentration. The EPR spectrum of enzyme activated at pH 10 but frozen at pH 7 was a composite of spectra from activated and inactive species. The activated species presented a complex set of narrow hyperfine components which may arise from contributions from more than one species of half-met center.

A hydrogenase-linked gene in Methanobacterium thermoautotrophicum strain delta H encodes a polyferredoxin.

The genes mvhDGA, which encode the subunit polypeptides of the methyl viologen-reducing hydrogenase in Methanobacterium thermoautotrophicum strain delta H, have been cloned and sequenced. These genes, together with a fourth open reading frame designated mvhB, are tightly linked and appear to form an operon that is transcribed starting 42 base pairs upstream of mvhD. The organization and sequences of the mvhG and mvhA genes indicate a common evolutionary ancestry with genes encoding the small and large subunits of hydrogenases in eubacterial species. The product of the mvhB gene is predicted to contain six tandomly repeated bacterial-ferredoxin-like domains and, therefore, is predicted to be a polyferredoxin that could contain as many as 48 iron atoms in 12 Fe4S4 clusters.