Predictors of health-related quality of life in Serbian patients with head and neck cancer.

BACKGROUND: The aim of this study was to identify predictors of the Health-Related Quality of Life (HRQoL) in patients with head and neck cancers (HNCs). MATERIAL AND METHODS: In total, 345 patients with HNCs were interviewed. A self-report questionnaire was administered to collect data about demographic characteristics, health status, smoking, alcohol consumption habits, and HRQoL. It were used the EORTC Instruments - Quality of Life Questionnaire-Core 30-questions (QLQ-C30), Quality of Life Questionnaire - Head and Neck Module 35-questions (QLQ-H&N 35) and OHIP-14 instrument for HRQoL assessments. Clinical information and treatment data were collected from medical records. RESULTS: Five groups of HRQoL predictors were identified: demographic, socioeconomic, behavioral, psychophysical, and clinical/treatment. These HRQoL predictors had a strong (i.e., age, level of social support and social contact, level of education, depression, fatigue, presence of gastrostomy, comorbidities, and use of pain medications and supplements), a moderate (i.e., marital status, smoking, sexuality problems, time since diagnosis, presence of tracheostomy, and side effects outcomes of radio and chemotherapy) and a small impact (i.e., employment/financial difficulties, tumor site and stage, and surgical procedure). CONCLUSIONS: Study identified nineteen predictors that had significant, moderate and small impact on the HRQoL of patients with HNCs. Some of the predictors, like levels of social support and social contact, depression, and comorbidities could be targets for innervations to improve HRQoL.

[Diagnostic algorithm in patients with cervical metastasis of malignant tumours unknown primary location].

Carcinoma of unknown primary location are heterogeneous group of metastatic tumours where primary location could not be discovered with detail anamnesis, clinical examination and diagnostic procedures. Patients with metastasis carcinoma of unknown primary location in clinical oncology are represent with about 4% of total number of patients with solid tumours. The most frequent location carcinoma of unknown primary location, discovered with autopsy, are lungs, pancreas, colon, kidney, prostate and breast. Metastasis in cervical lymph nodes carcinoma of unknown primary location are represent between 3-9% of total number of patients with head and neck carcinoma. Patients with persistent cervical lymph node should be examined through diagnostical plan "step by step" for identification carcinoma of unknown primary location.

Nonvibrating segment predicting glottis carcinoma.

Endovideolaryngostroboscopy is the obliged evaluation tool in our everyday practice. Standardized protocol in management of broad spectrum of vocal pathology is useful in clinical, scientific and educational evaluation of patient from the first interview till the end of the treatment. Using of contemporary computerised multidimensional analysis of stroboscopic image we are approaching to optimum evaluation of any kind of interpersonal communication disorder. There were 66 patients in prospective clinical study of correlation between suspect endovideolaryngostroboscopic findings and histo-pathology verification of glottis carcinoma. Asymmetric and irregular vibrations with absent mucosal wave or absent vibrations of one part or of the whole vocal fold was improved as carcinoma in 85% of patients. The most frequent diagnosis was Ca planocellularae invasivum G2 NG 2, with subsequent open chordectomy. In every case of hoarseness longer more than 14 days, endovideolaryngostroboscopy is the golden standard for evaluating the need for microlaryngoscopy and biopsy.

[Phoniatricians aspect of international statistical classification of diseases and related health problems].

INTRODUCTION: In everyday phoniatrician practice there are problems in finding adequate coding in current version of International Classification of Diseases. There is grey area for additional explanation under the official diagnosis and its code in Computer program window, but that has bad consequences on efficacy in writing the final medical report. OBJECTIVE: Suggestions for solving this problem that can contribute in next Revision are presented. METHOD: The comparation between diagnoses in 7 years period of Phoniatric Department everyday practice and given diagnoses in current version of International Classification of Diseases. RESULTS: Certain percent of diagnoses that are overviewed during last 7 years in our Phoniatric Department has no adequate expression in given diagnoses in Tenth Revision. One can say that there is some kind of communication disorder. CONCLUSION: This is the moment for Communication Disorders Care Center experts to participate in constitution of widespread acceptable nomenclature. The role of phoniatrician is necessary and logical in this system. The phoniatrician aspect of contribution in next Revision, is presented.

[Correlation between results of PCR and specific serological tests in diagnosis of Epstein-Barr virus in patients with mononucleosis syndrome].

Routine laboratory diagnosis of infectious mononucleosis is based on EBV serological testing, but due to problems in interpretation of results, molecular methods, especially PCR, are often necessary. The aim of the present study was to investigate correlation between results of PCR and specific serological tests in diagnosis of Epstein-Barr virus in patients with mononucleosis syndrome. The study comprised 68 patients with mononucleosis syndrome. Their blood samples were tested using ELISA for detection of 4 EBV specific antibodies (anti-VCA IgM and IgG, anti-EA-D IgG and anti-EBNA-1 IgG) and PCR for detection of EBV DNA. According to results of serology 42 patients had acute primary infection, 2 reactivation, 1 chronic active infection, 19 past infection, and 4 have been EBV seronegative. EBV DNA was detected in 17 patients (25%) and all of them were serologically defined as acutely infected. PCR was useful for resolving unclear serology results. Specific serology is the first step in diagnosis of IM, but PCR may serve as a useful additional diagnostic tool for clarifying serological dilemmas, reaching final diagnosis and defining status of the infection.

[Forensic importance of face, mouth, teeth, ear, throat, nose and labyrinth injuries].

Evaluation of bodily injuries and diminished general vital activity from face and facial bones injuries accompanied by scars and disfiguration ranges from 5 to 50 percent depending on the disfiguration, loss of function and degree of aesthetic marring. They are graded accordingly and they may be: mild (5 to 20%), medium (20 to 35%) and serious when the degree of bodily injury and diminished general vital activity is 35 to 50%. Percentage of bodily injuries and diminished general vital activity from jaw defects ranges from 30 to 80 percent depending on the disfiguration, loss of function and degree of aesthetic marring. Percentage of bodily injuries and diminished general vital activity from nose structure nasal pyramid defects ranges from 10 to 20 percent depending on the disfiguration, loss of function and degree of aesthetic marring. Partial loss of nose structure is estimated at 15%, whereas the complete one may go up to 30%. Diminished general vital activity and percentage of bodily injury with partial laryngectomy ranges from 20 to 40%. In case of subtotal laryngectomy, this is up to 60% and with total one, it reaches 80%.

[Postoperative morbidity and quality of live in patients after radical and modified radical neck dissection].

Useful of radical neck dissection would not be questioned if the effects would be perfect. When postoperative morbidity is associated with oncological shortage of radical neck dissection in functional and cosmetics disfunction, looking for a new therapeutics procedures are justify. In our study were 319 patients. They were treated in period from 01 January 2000 to 31 December 2002. The follow-up was 5 year. We tried to consolidate distribition of n. accesorius operative injuries in modified radical neck dissection and relationship beetwen shoulder pain and shoulder droop after modified and radical neck dissection. Injured n.accesorius in modified radical neck dissection was significantly decreased in patients with modified radical neck dissection. The frequence of patients is significantly different (chi m2=26.662; df = 1; p<0.01) in categories of complications of n.accesorius (shoulder pain, shoulder droop). Shoulder pain and shoulder droop were significantly decreased in modified radical neck dissection (p<0.01).

Anthracycline-based combined chemotherapy in the mouse model.

Our research was aimed at establishing if and how selenium (Se) ion, N-acetylcysteine (NAC), sodium salt of monoketocholic acid (MKH) and superoxide-dismutase (SOD), administered in the experimental animal model, could affect the possible cytotoxicity associated with anthracycline-based combined chemotherapy with doxorubicin, vincristine and prednisolone (DVP). The following biochemical parameters were investigated: the extent of lipid peroxidation (LPx), and the activity of peroxidase (Px), catalase (CAT), glutathione-peroxidase (GSHPx), and xanthine-oxidase (XOD). A statistical increase in LPx activity was obtained by SOD, MKH, DVPSe and DVPMKH. All chemotherapeutic agents reduced Px activity in a statistically significant manner. There was no statistical significance for the results regarding the effects of the administered substances on GSHPx activity. The results for DVP, SOD, MKH, DVPSOD, DVPSe and DVPMKH showed reduced XOD activity which was statistically significant, which was lowest in the case of MKH, while NAC and Se reduced the activity of this enzyme but statistically non significant. NAC, Se, DVP, MKH and DVPMKH caused a reduction in CAT activity, while DVPSOD and DVPSe caused an increase of the latter.

Glucose oxidase from Aspergillus niger: the mechanism of action with molecular oxygen, quinones, and one-electron acceptors.

Glucose oxidase from the mold Aspergillus niger (EC 1.1.3.4) oxidizes beta-D-glucose with a wide variety of oxidizing substrates. The substrates were divided into three main groups: molecular oxygen, quinones, and one-electron acceptors. The kinetic and chemical mechanism of action for each group of substrates was examined in turn with a wide variety of kinetic methods and by means of molecular modeling of enzyme-substrate complexes. There are two proposed mechanisms for the reductive half-reaction: hydride abstraction and nucleophilic attack followed by deprotonation. The former mechanism appears plausible; here, beta-D-glucose is oxidized to glucono-delta-lactone by a concerted transfer of a proton from its C1-hydroxyl to a basic group on the enzyme (His516) and a direct hydride transfer from its C1 position to the N5 position in FAD. The oxidative half-reaction proceeds via one- or two-electron transfer mechanisms, depending on the type of the oxidizing substrate. The active site of the enzyme contains, in addition to FAD, three amino acid side chains that are intimately involved in catalysis: His516 with a pK(a)=6.9, and Glu412 with pK(a)=3.4 which is hydrogen bonded to His559, with pK(a)>8. The protonation of each of these residues has a strong influence on all rate constants in the catalytic mechanism.

[Distribution of cervical metastases from carcinoma of the cervicofacial region]. / Distribucija cervikalnih metastaza karcinoma cervikofacijalne regije.

The primary goal in the therapy of patients with cervico-facial cancers has been always the control of loco-regional disease. It is more difficult to control metastasis than primary tumor. According to numerous authors, metastases to cervical lymphonodus reduce the survival of patients with planocellular cancer of the upper aero-digestive pathways for about 50%. Precise classification of primary tumor and regional lymphonodus is highly significant for adequate and timely treatment of patients with cancers of cervico-facial region. The objective of our study was to make clinical classification of cervico-facial tumors and to establish the distribution of nodes according to node groups and cervical levels. In our series of 319 subjects, T2 category of primary tumors was most prevalent accounting for 40.44%. Clinically palpable lymphonodes were found in 87.15%, with most prevalent N1 category accounting for 42.95%. The incidence of clinically negative cervical nodus (N0) was reported in 12.85%. The nodes of the upper, medium and lower jugular group were most frequent in cancers of the larynx and pharynx. In cancer of the oral cavity, submental and submandibular nodes were the most commonly involved. In distribution of nodes based on oncological cervical levels, 45.86% of nodes at level II of the neck were found in laryngeal cancer, while 40% the neck level I was involved in the cancer of the oral cavity. In epipharyngeal cancer, 3.15% of cervical metastases were detected in the posterior triangle of the neck. The incidence of cervical metastases in specific primary localizations has a significant role for indications of one of the dissections of the neck.

[Surgery of cholesteatoma: surgical technique and cholesteatoma recurrences]. / Hirurgija holesteatoma: hirurska tehnika i recidivi holesteatoma.

Past experience with open and closed techniques of tympanoplasty in surgery of cholesteatoma has shown that recurring illness is one of the major causes of surgical failure. The literature has reported varying trend of surgical treatment of cholesteatoma. The objective of the study was to analyze the significance of surgical technique in relation to the incidence and most frequent localization of recurrent cholesteatoma. Our study analyzed 120 patients operated on for cholesteatoma. The patients were divided into two groups, group I (45) with recurring disease and group II (75) without any recurring condition, which were followed up three years. Statistical analysis was carried out by modified t-test. The largest number of patients was re-operated in the first two years from the initial surgery (50%), In the majority of patients (50%), recurrent cholesteatoma was most commonly localized (stage I) in attic (20%) and much rarely in mesotympanum (11.9%). Stage III recurrent cholesteatoma was verified in 35% of patients, most frequently diffuse form (13.4%). The involvement of attic by all three stages of disease accounted for over 60%. The analysis of the used techniques of surgical treatment in both groups revealed significant difference. Open techniques of tympanoplasty were used in 60% of patients with no recurrence. Closed techniques were used more frequently in patients with recurring disease, i.e. in over 90% of cases. Recurerrent cholesteatoma develops, in the majority of cases, during the first two years after the surgical intervention. Attic is the most common localization of cholesteatoma. More frequent utilization of open technique of tympanoplasty for surgery of cholesteatoma significantly reduces the incidence of recurring condition. The indications for CWD technique are the initial spread of cholesteatoma, possibility of complete removal of cholesteatoma and postoperative follow-up of patients.

[Mastoiditis in adults: diagnostic and therapeutic aspects]. / Mastoiditis u odraslih--dijagnosticki i terapijski aspekti.

The purpose of the present study is to report our experience in the diagnosis and treatment of mastoiditis in adults. Five patients with an active chronic otitis and mastoiditis were presented. All of them had a history of chronic ear discharge for long period of time and have been diagnozed and treated sufficiently. All relevant data were analyzed from the medical records. The most common symptoms of the disease were otalgia, otorrhea and hearing loss, but the physical signs of mastoiditis (swelling, erithema and tenderness of the retroauricular region) were presented in all cases. Localization and enlargement of the pathological process within the middle ear spaces was determined by CT. All patients were treated surgically and with intravenous antibiotics. In one patient the other treatment was applied due to a specific (TBC) process in the ear. Early diagnosis and adequate treatment (surgery combined with an effective antibiotics therapy) is most important to prevent a serious complications of mastoiditis (extracranial and/or intracranial).

Structure-function studies of human 5-alpha reductase type 2 using site directed mutagenesis.

Site directed mutagenesis of human steroid 5alpha-reductase types 1 (5AR1) and 2 (5AR2) has been used to identify residues involved in inhibitor/substrate binding by 5AR2. Replacing residues 21-24 (GALA) in 5AR2 with the analogous residues 26-29 (AVFA) from 5AR1 did not significantly alter either the Km for testosterone or the Ki for the competitive inhibitor Finasteride. Replacement of AVFA in 5AR1 with GALA from 5AR2 however, significantly decreased the Km and increased the resistance to Finasteride. These findings confirm that 5AR1 residues 26-29 are involved in inhibitor/substrate binding but suggest residues 21-24 of 5AR2 are not. Replacing residues 20-29 (QCAVGCAVFA) of 5AR1 with the analogous residues 15-24 (ATLVALGALA) from 5AR2, changed the Km and Ki to values approaching those for wild type 5AR2. Replacing residues VAL in wild type 5AR2 with VGC from 5AR1 did not change Km or Ki but replacing ATL in 5AR2 with QCA from 5AR1 significantly decreased the Km and increased the resistance to Finasteride. Conversely, replacing QCA with ATL in 5AR1 containing GALA in place of AVFA, increased the Km and decreased resistance to Finasteride. These findings indicate residues 15-17 of human 5AR2 participate in inhibitor/substrate binding whereas residues 18-20 do not.

Comparison of the chemical mechanisms of action of yeast and equine liver alcohol dehydrogenase.

The pH-dependence of the steady-state kinetic parameters and the ligand-binding parameters for competitive dead-end inhibitors for the yeast alcohol dehydrogenase (EC 1.1.1.1, constitutive, cytoplasmic) reaction was studied in the pH range 6-10. These studies were designed in order to assign the appropriate pKa values to all dissociation forms of enzyme in the chemical mechanism of action for the yeast enzyme, previously proposed by Cook and Cleland [P. F. Cook & W. W. Cleland (1981) Biochemistry 20, 1796-1816]. In addition, the chemical mechanism of action for the yeast enzyme, proposed in this work, was compared with a similar mechanism of action for the horse liver enzyme, proposed by Cook and Cleland. Substantial differences were found, especially in the binding of coenzymes and in the structure of enzyme-coenzyme complexes.

Novel substrates of yeast alcohol dehydrogenase--4. Allyl alcohol and ethylene glycol.

In the present work, we have determined the steady-state kinetic constants for yeast alcohol dehydrogenase-catalyzed oxidation of allyl alcohol (H2C = CH.CH2OH) and ethylene glycol (HOCH2.CH2OH) with NAD+, at pH 8.0; also, a kinetic mechanism for the former reaction was determined at the same pH. In addition, it was found that acrolein is a potent inhibitor of yeast alcohol dehydrogenase.

Use of competitive dead-end inhibitors to determine the chemical mechanism of action of yeast alcohol dehydrogenase.

In this work, we have postulated a comprehensive and unified chemical mechanism of action for yeast alcohol dehydrogenase (EC 1.1.1.1, constitutive, cytoplasmic), isolated from Saccharomyces cerevisiae. The chemical mechanism of yeast enzyme is based on the integrity of the proton relay system: His-51....NAD+....Thr-48....R.CH2OH(H2O)....Zn++, stretching from His-51 on the surface of enzyme to the active site zinc atom in the substrate-binding site of enzyme. Further, it is based on extensive studies of steady-state kinetic properties of enzyme which were published recently. In this study, we have reported the pH-dependence of dissociation constants for several competitive dead-end inhibitors of yeast enzyme froin their binary complexes with enzyme, or their ternary complexes with enzyme and NAD+ or NADH; inhibitors include: pyrazole, acetamide, sodium azide, 2-fluoroethanol, and 2,2,2-trifluorethanol. The unified mechanism describes the structures of four dissociation forms of apoenzyme, two forms of the binary complex E.NAD+, three forms of the ternary complex E.NAD+.alcohol, two forms of the ternary complex E.NADH.aldehyde and three binary complexes E.NADH. Appropriate pKa values have been ascribed to protonation forms of most of the above mentioned complexes of yeast enzyme with coenzymes and substrates.

Influence of Tris(hydroxymethyl)aminomethane on kinetic mechanism of yeast alcohol dehydrogenase.

Acetaldehyde, propionaldehyde, glyceraldehyde-3-P and 4-dimethylaminocinnamaldehyde form Schiff bases in Tris. HCl buffers; the rates of formation and dissociation of Schiff bases, and equilibrium constants for their formation are very similar for the first three aldehydes. The steady-state kinetic constants for the yeast alcohol dehydrogenase-catalyzed reaction, propan-1-ol + NAD+ reversible propionaldehyde + NADH + H+, have been determined in several Tris. HCl buffers of increasing concentration at pH 8.1. In the forward direction, oxidation of alcohol, most kinetic constants are increased by increasing concentrations of Tris. In the reverse direction, reduction of aldehyde, substrate, NADH, Tris and Schiff base were equilibrated before enzyme reaction was started. It was found that Schiff base, rather than Tris, binds to free enzyme competitively with respect to NADH. Tris and Schiff base do not influence the binding of aldehyde to enzyme in any way.

Novel substrates of yeast alcohol dehydrogenase-3. 4-dimethylamino-cinnamaldehyde and chloroacetaldehyde.

4-Dimethylamino-trans-cinnamaldehyde and chloroacetaldehyde are novel substrates of yeast alcohol dehydrogenase (EC 1.1.1.1). In the present work, we have reported the steady-state kinetic constants for both substrates, and their chemical reactions with the enzyme protein itself. Both substrates are potentially useful for biotechnology, chemoenzyme syntheses and analytical biochemistry.

Use of pH studies to determine the kinetic and chemical mechanism of yeast alcohol dehydrogenase with primary aliphatic alcohols and aldehydes.

A complete list of all steady-state kinetic constants for the yeast alcohol dehydrogenase (EC 1.1.1.1) catalyzed oxidation of ethanol, propan-1-ol and butan-1-ol, and for the reduction of acetaldehyde and propionaldehyde was collected in the pH range 6-10, and an appropriate pH profile for each constant was constructed. A common minimal mechanism with all these substrates has been postulated and pKa values and the pH independent limiting values have been assigned for the rate constants.

Yeast alcohol dehydrogenase catalyzed reduction of p-nitroso-N, N-dimethylaniline by NADH.

The steady-state kinetics, product identification, stoichiometries, and solvent isotope effects of yeast alcohol dehydrogenase catalyzed reduction of p-nitroso-N,N-dimethylaniline (NDMA) by NADH, are reported. NDMA is enzymatically reduced to p-hydroxylamine-N,N-dimethylaniline, which is further enzymatically dehydrated to corresponding quinonediimine cation (QDI+). QDI+ undergoes nonenzymatic transformations. QDI+ is rapidly reduced by NADH to p-amino-N,N-dimethylaniline (ADMA). Also, QDI+ is readily dismutated with ADMA to form N,N-dimethyl-p-phenylenediamine radicals; radicals are stable under steady-state conditions, below pH 7.5. A complete kinetic mechanism for above reactions has been proposed.