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1.
J Prev Med Hyg ; 59(4 Suppl 2): E31-E37, 2018 Dec.
Article in English | MEDLINE | ID: mdl-31016265

ABSTRACT

INTRODUCTION: Elderly people are more likely to develop influenza-related complications. However, despite the recommendations, the optimal vaccination coverage is not reached. The use of deprivation indexes can help to identify subgroups with lower vaccination uptake. We analyzed vaccination coverage among elderly subjects living in the city of Rome on the basis of their socioeconomic characteristics by using a local deprivation index. METHODS: We focused on the population aged ≥ 65 years living in the city of Rome from 2009 to 2013. Information on vaccination coverage was collected from general practitioners. A combination of multivariate techniques, including multiple linear regression, factor and cluster analysis, was used to construct a composite area-based Index of Socio-Economic and Health Deprivation (SEHDI). The index was calculated for each census tract on the basis of data from the 2001 Italian census. RESULTS: The majority of elderly subjects living in Rome belonged to the medium (40.4%) and medium-high (24%) deprivation groups; only 4.5% of the population was in the low-deprivation group. An inverse relationship was found between influenza vaccination coverage and the deprivation index: elderly subjects in the low-deprivation group displayed lower coverage (55.45%) than those in the high-deprivation group (57.59%). Specifically, vaccination coverage decreased with the increase of replacement index, employment rate and the percentage of: single and divorced individuals; university and high-school graduates; employees, entrepreneurs and freelancers, family assistants, students; foreigners and stateless persons residing in Italy; families consisting of one person. CONCLUSIONS: Our results show an inverse relationship between deprivation and vaccination coverage and may help to identify subgroups that could benefit from targeted initiatives to increase vaccination coverage.


Subject(s)
Influenza, Human/prevention & control , Poverty , Social Class , Vaccination Coverage , Vaccination Refusal , Aged , Female , Humans , Influenza Vaccines , Male , Mortality/trends , Registries , Rome
2.
Thromb Res ; 140 Suppl 1: S171, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27161679

ABSTRACT

INTRODUCTION: There are few prediction tools for estimating the risk of thrombosis but they are based on studies performed on hospitalized medical patients without cancer or on hospitalized neutropenic cancer patients without special consideration to lymphoma patients. AIM: Aim of our study was to determine incidence of thromboembolic (TE) events in patients with non Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) who were hospitalized to the lymphoma department in the Clinic of hematology, Clinical Center Serbia, Belgrade and Clinic of hematology, Clinical Center Kragujevac. Also, we assessed 2 predictive models (Padua and Khorana score) and create new model for the identification of lymphoma patients at risk for thromboembolism. MATERIALS AND METHODS: We reviewed all medical records of patients with with NHL, HL and CLL/SLL diagnosed and treated at two previously mentioned institution between January 2006 and December 2014. RESULTS: The study population included 1820 eligible lymphoma patients. Of all the patients included in the study, 99 (5.4%) developed at least one TE during a follow-up period of 3 months from the end of therapy. In the final multivariate analysis, the following variables were independently associated with risk of TE: previous VTE and/or arterial events, reduced mobility (ECOG 2-4), obesity (BMI >30 kg/m(2)), extranodal localization, mediastinum involvement, development of neutropenia during therapy and hemoglobin level less than 100g/L. Subsequently, we assigned points for the risk model based on the regression coefficients obtained from the final model and developed Thrombosis Lymphoma (ThroLy) score consisting of all significant variables from the multivariate analysis. The Throly score was arrived at by assigning 2 points for all parameters with an OR >5 in multivariate regression analyses (e.g., previous VTE and arterial events, mediastinum involvement, and BMI) and 1 point for rest all other significant variables. Finally, population were divided into 3 risk categories for TE based on the score from the risk model: low (score 0-1), intermediate (score 2-3) and high (score >3). High risk score had a positive predictive value (probability of TE in those designated high risk) of 65.2%. CONCLUSIONS: Significance of our investigation is development of score that help phisicians to recruit lymphoma patients at risk for development of thromboembolic complications. Also, we can say that our score is dynamic allowing us to change approach during different phase of therapy and is not limited to outpatient settings or with some complicated laboratory analysis.

3.
Neoplasma ; 62(6): 988-95, 2015.
Article in English | MEDLINE | ID: mdl-26458307

ABSTRACT

Diffuse large B cell lymphoma (DLBCL) affects more commonly patients over 60 years. These patients have vast number of comorbidities which can modify survival as well as other clinical parameters. The aim of this study was to evaluate prognostic significance of the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), absolute lymphocyte count (ALC), absolute monocyte count (AMC), lymphocyte-to-monocyte ratio (LMR) and comorbidities expressed with Charlson Comorbidity Index (CCI). A total of 182 DLBCL patients 60 years old and older were included, focusing on whole group and patients older than 70. All patients were treated with immunochemotherapy.Overall treatment response was achieved in 84.6% of patients. The NCCN-IPI was of highly prognostic value in the analyzed group (p<0.0001). Survival analysis showed that ALC>1.1x109/L, AMC≤0.59x109/L, and LMR>2.8 were associated with more favorable outcome (p=0.029, p=0.019, p=0.028, respectively). The patients with CCI≥2 had poorer outcome (p=0.008) compared to the patients with CCI 0-1. Multivariate analysis showed that among ALC, AMC, LMR, NCCN-IPI and CCI, the NCCN-IPI was the critical parameter that significantly affected survival (p<0.0001). Furthermore, comorbidities were also valuable independent factors which influenced survival (p=0.031) as well as the ALC (p=0.024). In elderly DLBCL patients, NCCN-IPI and ALC proved their prognostic validity, while poorer outcome could be expected in older patients with high CCI (≥2). Furthermore, mentioned prognostic parameters retained their prognostic value in the group of patients older than 70.

4.
Ann Oncol ; 26(8): 1741-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25997818

ABSTRACT

BACKGROUND: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. PATIENTS AND METHODS: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). RESULTS: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease >6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). CONCLUSION: Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients >6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Aged , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Docetaxel , Female , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Humans , L-Lactate Dehydrogenase/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Proportional Hazards Models , Proto-Oncogene Proteins p21(ras)/genetics , Taxoids/administration & dosage , Treatment Outcome , Triazoles/administration & dosage
5.
Nurse Educ Today ; 35(4): 590-6, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25623630

ABSTRACT

BACKGROUND: In a country with a poor economy and limited job opportunities, the outmigration of students is not commonly perceived as a problem but rather is perceived as a solution to the high unemployment facing young health professionals. OBJECTIVES: Study objectives were to identify the prevalence of intention to work abroad of nursing graduates to point to the predictors of intention to work abroad and predictors of having a firm plan to work in a foreign country. DESIGN: Descriptive study, a survey. SETTINGS: College and specialist nursing schools, Serbia. PARTICIPANTS: 719 nursing graduates from the 2012/2013 school year. METHODS: Voluntarily completed a questionnaire that was designed with regard to similar surveys administered in EU-candidate countries during the pre-accession period. Data were analysed with descriptive and multivariate regression analyses. RESULTS: Almost 70% (501) of respondents indicated an intention to work abroad. Of the nurses, 13% already had established a firm plan to work abroad. Single graduates and those with a friend or relative living abroad were more likely to consider working abroad than were their counterparts (odds ratios were 2.3 and 1.7, respectively). The likelihood of considering working abroad decreased by 29% when the individuals' financial situation was improved. Factors associated with having a firm plan were previous professional experience in a foreign country, having someone abroad and financial improvement (5.4 times, 4.8 times and 2 times greater likelihood, respectively). CONCLUSIONS: The high prevalence of intention to work abroad suggests the need to place the issue of the out-migration of nursing graduates on the policy agenda. College and specialty nursing graduates and health technicians are prepared to work abroad in search of a better quality of life, better working conditions and higher salaries.


Subject(s)
Emigration and Immigration , Intention , Nurses, International , Salaries and Fringe Benefits/economics , Adult , Attitude of Health Personnel , Career Choice , Female , Humans , Male , Serbia , Surveys and Questionnaires , Young Adult
6.
Ultraschall Med ; 32(1): 62-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20414856

ABSTRACT

PURPOSE: Transcranial Doppler (TCD) can be used as a confirmatory test in brain death. The aim was to present the usefulness of TCD in brain death confirmation. MATERIALS AND METHODS: Forty-four patients with severe brain lesions leading to brain death were treated over a 4-year period. After the clinical diagnosis of brain death was made, the appropriate confirmatory test was chosen according to patient condition, taking into consideration the restrictions of the test protocol. Due to the inconclusive test results, some patients underwent repeat testing. RESULTS: Among 44 patients, 19 had neurotrauma, 11 massive aneurysmal subarachnoidal hemorrhages, 1 arteriovenous subarachnoidal and parenchymal hemorrhage, 12 hypertensive parenchymal hemorrhages, and 1 ischemic stroke. As a primary test, TCD was used in 30, brain scintigraphy in 2, multislice CT angiography (CTA) in 10, and cerebral angiography in 2 patients, and the diagnosis was confirmed in 26, 3, 9 and 2 patients, respectively. Due to inconclusive results CTA was repeated in five patients. In patients in whom TCD was applied, the time to confirm the diagnosis was the shortest, and in most (61 %) cerebral circulatory arrest was confirmed within 2 hours of clinical diagnosis. CONCLUSION: TCD is a favorable confirmatory test for cerebral circulatory arrest in brain death diagnosis.


Subject(s)
Brain Death/diagnostic imaging , Ultrasonography, Doppler, Transcranial/methods , Adolescent , Adult , Aged , Brain Injuries/diagnostic imaging , Cerebral Angiography , Cerebral Infarction/diagnostic imaging , Female , Fourier Analysis , Humans , Intracranial Hemorrhage, Hypertensive/diagnostic imaging , Male , Middle Aged , Sensitivity and Specificity , Subarachnoid Hemorrhage/diagnostic imaging , Tissue and Organ Procurement , Tomography, Spiral Computed , Young Adult
7.
Eur J Neurol ; 16(9): 1060-5, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19469836

ABSTRACT

BACKGROUND AND PURPOSE: The aim of this hospital-based survey was to determine baseline stroke knowledge in Croatian population attending the outpatient services at the Department of Neurology. METHODS: A multiple choice questionnaire was designed, divided into three sections: (i) demographic data, (ii) knowledge of stroke risk factors and stroke signs and (iii) actions the patients would undertake if confronted with risk of stroke and information resources regarding health. RESULTS: The analysis included 720 respondents (54.9% women). The respondents most frequently indicated stroke symptoms as following: speech disorder 82%, paresthesiae on one side of the body 71%, weakness of arm or leg 55%, unsteady gait 55%, malaise 53%, monocular loss of vision 44%. The risk factors most frequently identified were hypertension 64%, stress 61%, smoking 59%, elevated lipids 53%, obesity 52%, coagulation disorder 47%, alcoholism 45%, low-physical activity 42%, elderly age 39%, cardiac diseases 38%, weather changes 34%, drugs 33% and diabetes 32%. If confronted with stroke signs 37% of respondents would consult the general practitioner and 31% would call 911 or go to a neurologist. Amongst patients with a risk factor, only diabetics were aware that their risk factor might cause stroke (P < 0.001). Respondents with lowest education had the least knowledge regarding stroke signs (P < 0.01). DISCUSSION: The results of this study indicate that respondents showed a fair knowledge about stroke signs and risk factors for stroke. The results of our study will help to create and plan programmes for improvement of public health in Croatia.


Subject(s)
Health Knowledge, Attitudes, Practice , Outpatients , Stroke/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Croatia , Educational Status , Female , Health Surveys , Humans , Male , Middle Aged , Risk Factors , Socioeconomic Factors , Stroke/physiopathology , Surveys and Questionnaires
8.
Acta Neurol Scand ; 119(1): 17-21, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18549415

ABSTRACT

OBJECTIVES: Until today there is no reliable test that can clearly distinguish Parkinson's disease (PD) from the essential tremor (ET). Our aim was to determine the usefulness of the transcranial sonography (TCS) in the differential diagnosis of the PD and ET as well as the interobserver reliability for this method. METHODS: Transcranial sonography of substantia nigra and clinical examination were performed on 80 PD patients, 30 ET patients, and 80 matched controls by two independent physicians. RESULTS: Bilateral SN hyperechogenicity over the margin of 0.20 cm(2) was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET. Interobserver agreement for this method was significant (Student's t-test, P = 1.000). CONCLUSIONS: Substantia nigra hyperechogenicity on TCS is a highly specific finding of PD, where in healthy individuals or in ET patients, it might correspond to an increased risk of developing PD later in life or might also be because of the impairment of nearby area of nucleus ruber in ET patients, as suggested by positron emission tomography studies. TCS may serve as a practical and sufficiently sensitive neuroimaging tool in PD diagnoses and in distinguishing it from ET; its repeatability and accuracy might add to its practical value.


Subject(s)
Essential Tremor/diagnostic imaging , Parkinson Disease/diagnostic imaging , Ultrasonography, Doppler, Transcranial/methods , Age of Onset , Aged , Diagnosis, Differential , Functional Laterality , Humans , Middle Aged , Reference Values
9.
Acta Chir Iugosl ; 56(4): 77-81, 2009.
Article in Serbian | MEDLINE | ID: mdl-20420001

ABSTRACT

Breast cancer is the leading cause of mortality among women aged 25 to 44 years in Serbia. The purpose of this study was to determine basic clinical and radiological features of breast cancer in young women. 93 women aged 31.0 +/- 3.5 years with breast cancer were identified. The analysis included clinical characteristics (TNM classification) and radiological features (mammography and breast ultrasound). 53.8% of the patients had locoregional disease. The mean diameter of breast cancer was 2.6 +/- 6 cm. Carcinoma in situ was found in 2.2%. Mammography was performed in 25.8% of the patients and breast ultrasound in 68.8%. The results of our study indicate that the diagnosis of breast cancer in young women is late, in the stage with palpable breast tumor and lymph node metastases. Mammography or breast ultrasound are not routinely used. The implementation of algorithms for breast cancer detection and diagnosis in young women helps in earlier detection of breast cancer and consequently improves outcomes.


Subject(s)
Breast Neoplasms/diagnosis , Mammography , Ultrasonography, Mammary , Adult , Breast Neoplasms/pathology , Female , Humans
10.
J Dairy Sci ; 90(10): 4863-71, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17881710

ABSTRACT

Test-day data for daily milk yield and fat, protein, and lactose content were sampled from the years 1988 to 2003 in 17 flocks belonging to 2 genetically well-tied buck circles. In total, records from 2,111 to 2,215 goats for content traits and 2,371 goats for daily milk yield were included in the analysis, averaging 2.6 and 4.8 observations per goat for the 2 groups of traits, respectively. The data were analyzed by using 4 test-day models with different modeling of fixed effects. Model [0] (the reference model) contained a fixed effect of year-season of kidding with regression on Ali-Schaeffer polynomials nested within the year-season classes, and a random effect of flock test-day. In model [1], the lactation curve effect from model [0] was replaced by a fixed effect of days in milk (in 3-d periods), the same for all year-seasons of kidding. Models [2] and [3] were obtained from model [1] by removing the fixed year-season of kidding effect and considering the flock test-day effect as either fixed or random, respectively. The models were compared by using 2 criteria: mean-squared error of prediction and a test of bias affecting the genetic trend. The first criterion indicated a preference for model [3], whereas the second criterion preferred model [1]. Mean-squared error of prediction is based on model fit, whereas the second criterion tests the ability of the model to produce unbiased genetic evaluation (i.e., its capability of separating environmental and genetic time trends). Thus, a fixed structure with year (year, year-season, or possibly flock-year) was indicated to appropriately separate time trends. Heritability estimates for daily milk yield and milk content were 0.26 and 0.24 to 0.27, respectively.


Subject(s)
Goats/genetics , Models, Genetic , Animals , Dairying , Environment , Fats/analysis , Female , Genetic Variation , Heredity , Lactation/genetics , Lactose/analysis , Male , Milk/chemistry , Milk/metabolism , Milk Proteins/analysis , Norway , Phenotype , Seasons
11.
Ultraschall Med ; 27(3): 280-3, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16596508

ABSTRACT

The diagnosis of aortic dissection is frequently missed at the time of hospital admittance. Neurological presentations are rare, and neuro-sonography is rarely used. We describe a patient with atypical clinical presentation of aortic arch dissection in whom neuro-sonological investigations showed a "cathedral like" haemodynamic spectrum of aortic regurgitation, directing the investigation towards the diagnosis.


Subject(s)
Aortic Aneurysm/diagnostic imaging , Aortic Dissection/diagnostic imaging , Ultrasonography, Doppler, Transcranial , Aortic Arch Syndromes/diagnostic imaging , Aortic Valve Insufficiency/diagnostic imaging , Brain/diagnostic imaging , Diagnosis, Differential , Glasgow Coma Scale , Humans , Male , Middle Aged , Tomography, X-Ray Computed
12.
Cancer Res ; 61(20): 7394-8, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11606368

ABSTRACT

The hypoxia-inducible factor 1 (HIF-1) is known to induce the expression of several proteins linked to the maintenance of oxygen homeostasis, cellular energy metabolism, and tumor progression. Its alpha subunit (HIF-1alpha) is stabilized under hypoxic conditions and, therefore, might represent an intrinsic marker for tissue hypoxia. Here we report on the spatial relationship between HIF-1alpha and the nitroimidazole hypoxia marker EF5 in cervical carcinoma xenografts, and on their spatial relationship to tumor blood vessels. EF5 was administered to mice bearing ME180 and SiHa cervical cancer xenografts. Frozen tumor tissue sections, triple-stained for HIF-1alpha, the endothelial cell marker CD31, and EF5, were imaged using wide-field multiparameter immunofluorescence microscopy. Expression levels of EF5 and HIF-1alpha were similar in ME180 xenografts, but the percentage of tumor area stained with EF5 was significantly smaller than the percentage of HIF-1alpha-positive area in SiHa tumors. In both tumor types the EF5-HIF-1alpha overlap was statistically significant, thus confirming their spatial and temporal colocalization. Spatial distribution analysis of EF5 and HIF-1alpha is consistent with different pO2 value "thresholds" for EF5 binding and HIF-1alpha expression. Summarized, our results indicate that HIF-1alpha is a useful intrinsic marker for hypoxia in cervical carcinoma xenografts.


Subject(s)
Biomarkers, Tumor/biosynthesis , Carcinoma, Squamous Cell/metabolism , Etanidazole/analogs & derivatives , Uterine Cervical Neoplasms/metabolism , Animals , Carcinoma, Squamous Cell/blood supply , Cell Hypoxia/physiology , Etanidazole/metabolism , Female , Humans , Hydrocarbons, Fluorinated/metabolism , Mice , Mice, SCID , Microscopy, Fluorescence , Neoplasm Transplantation , Transplantation, Heterologous , Uterine Cervical Neoplasms/blood supply
13.
J Biomed Opt ; 6(3): 326-31, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11516323

ABSTRACT

Hypoxia caused by inadequate structure and function of the tumor vasculature has been found to negatively determine the prognosis of cancer patients. Hence, understanding the biological basis of tumor hypoxia is of significant clinical interest. To study solid tumor microenvironments in sufficient detail, large areas (several mm in diameter) need to be imaged at microm resolutions. We have used a novel confocal scanning laser MACROscope (CSLM) capable of acquiring images over fields of view up to 2cm x 2cm. To demonstrate its performance, frozen sections from a cervical carcinoma xenograft were triple labeled for tissue hypoxia, blood vessels and hypoxia-inducible transcription factor 1 alpha (HIF-1alpha), imaged using the CSLM and compared to images obtained using a standard epifluorescence microscope imaging system. The results indicate that the CSLM is a useful instrument for imaging tissue-based fluorescence at resolutions comparable to standard low-power microscope objectives.


Subject(s)
Carcinoma/pathology , Microscopy, Confocal , Microscopy, Fluorescence , Transcription Factors , Uterine Cervical Neoplasms/pathology , Animals , Blood Vessels/pathology , Carcinoma/blood supply , Carcinoma/metabolism , DNA-Binding Proteins/metabolism , Female , Hypoxia/pathology , Hypoxia-Inducible Factor 1 , Hypoxia-Inducible Factor 1, alpha Subunit , Mice , Mice, SCID , Microscopy, Confocal/instrumentation , Microscopy, Fluorescence/instrumentation , Neoplasm Transplantation , Nuclear Proteins/metabolism , Uterine Cervical Neoplasms/blood supply , Uterine Cervical Neoplasms/metabolism
14.
Radiother Oncol ; 60(1): 69-73, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11410306

ABSTRACT

BACKGROUND AND PURPOSE: Recently we reported increased glutathione (GSH) levels in hypoxic regions of ME 180 and SiHa cervical cancer xenografts. Since this association might act synergistically to protect from radiotherapy, we examined the differential effects of the GSH depleting agent buthionine suiphoximine (BSO) in relation to tumor oxygenation. MATERIALS AND METHODS: The nitroimidazole EF5 was used to label tumor hypoxia. GSH levels were determined in cryostat sections using a sensitive HPLC assay and in parallel sections using fluorescence image analysis. Using a dual-labeling method, GSH levels were determined selectively in hypoxic and non-hypoxic tumor regions. RESULTS: GSH levels were higher in hypoxic than in non-hypoxic regions of cervical carcinoma xenografts. Treatment with BSO produced a more pronounced GSH depletion in regions of hypoxia, resulting in similar post-treatment levels in hypoxic and non-hypoxic areas. CONCLUSIONS: BSO effectively depletes GSH in hypoxic microregions of tumors. These findings suggest a potential role for BSO as an adjunct to radiotherapy in cervical cancer patients.


Subject(s)
Antineoplastic Agents/pharmacology , Buthionine Sulfoximine/pharmacology , Glutathione/metabolism , Uterine Cervical Neoplasms/drug therapy , Animals , Cell Hypoxia , Chromatography, High Pressure Liquid , Etanidazole/analogs & derivatives , Female , Humans , Hydrocarbons, Fluorinated , Image Enhancement , Mice , Mice, SCID , Radiation Tolerance/drug effects , Tumor Cells, Cultured , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/radiotherapy , Xenograft Model Antitumor Assays
15.
Clin Chem Lab Med ; 39(4): 346-50, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11388660

ABSTRACT

Although controversial, data on the genetic polymorphism of apoprotein E (APOE), methylenetetrahydrofolate (MTHFR) and paraoxonase (PON1) genes implicate their role in the development of cerebrovascular disease. The aim of this study was to assess the association of polymorphism of APOE, MTHFR and PON1 genes in 56 stroke and 36 carotid stenosis patients, and in 124 control subjects by PCR-restriction fragment length polymorphism analysis. In the stroke group a significantly different MTHFR genotype distribution (p=0.004, odds ratio for T/T of 17.571), but no significant difference in APOE and PON1 allele and genotype distribution compared to the control was found. The carotid stenosis group exhibited a significantly different APOE allele and genotype distribution (p=0.023, odds ratio APOEepsilon3epsilon4 of 4.24), but no significant difference in the MTHFR and PON1 allele and genotype distribution from the control group. The preliminary results obtained in this study revealed an association of the MTHFR and APOE gene polymorphism with cerebrovascular disease, suggesting a significant risk for stroke in subjects who are homozygous for the T allele and for carotid stenosis in subjects having APOEepsilon3epsilon4 genotype. Additional studies in larger patient groups are needed to confirm these observations.


Subject(s)
Apolipoproteins E/genetics , Cerebrovascular Disorders/genetics , Esterases/genetics , Oxidoreductases Acting on CH-NH Group Donors/genetics , Polymorphism, Genetic , Adult , Aged , Alleles , Aryldialkylphosphatase , Female , Genotype , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Middle Aged , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Factors , Stroke/genetics
16.
Coll Antropol ; 25(2): 501-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11811280

ABSTRACT

The major interest in vertebral artery (VA) hypoplasia comes from its possible connection to migraines with aura as well as from the fact that it is one of the risk factors for a stroke. Therefore, the aim of this preliminary study was to investigate the mode of inheritance of VA hypoplasia. Initially, color Doppler of VA was performed in 64 first- and second-degree relatives of 33 probands, and the presence of VA hypoplasia was confirmed according to the already established criteria. Since a higher prevalence of VA hypoplasia (15.6%) in probands'relatives in comparison with 2.34% in the general population of Croatia was indicative of a strong familial predisposition for this condition, an analysis of family data by means of Pearson's chi-square statistics has been performed. In this analysis, the observed sex-specific frequencies of 36 parent-offspring pairs composed only of affected parent and his/her (affected or non-affected) offspring are compared to the frequencies as expected under eight proposed models. For both--autosomal and X-linked monogenetic inheritance--four hypotheses have been chosen, assuming that the individuals having the affected allele (in combination with a healthy one) have 100%, 50%, 40% and 0% chances of developing VA hypoplasia. Out of eight tested models only two--completely dominant and completely recessive X-linked models--were rejected. But, from the six non-rejected models, goodness-of-fit statistics showed that the hypothesis of X-linked inheritance of VA hypoplasia with the "healthy" allele being stronger (60% effect on phenotype)--almost perfectly fit the data (chi2 = 2.0023; df = 7; p = 0.9597). Further research encompassing a more enlarged family sample is needed to confirm the present findings.


Subject(s)
Intracranial Arterial Diseases/genetics , Vertebral Artery/pathology , X Chromosome/genetics , Female , Functional Laterality , Humans , Intracranial Arterial Diseases/pathology , Male , Migraine with Aura/etiology , Migraine with Aura/genetics , Models, Genetic , Pedigree , Prevalence , Sex Factors
17.
Int J Radiat Biol ; 76(6): 757-62, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10902729

ABSTRACT

PURPOSE: To examine the extent to which nuclear metallothionein protects from radiation-induced DNA damage under aerobic and hypoxic conditions. MATERIALS AND METHODS: A semiquantitative fluorescence image analysis method measured the nuclear content of metallothionein (MT) in ME180 and SiHa human squamous cervical carcinoma cell lines under normal growth conditions, and following MT induction by zinc. The extent of initial DNA damage following 60Co irradiation under aerobic and hypoxic conditions was assessed using the alkaline comet assay. RESULTS: Provided that cells were maintained at 37 degrees C, most of the cellular content of MT was in the nucleus. Incubation at 4 degrees C caused the rapid translocation of MT from the nucleus into the cytoplasm in both cell lines, with no net loss of cellular MT. Baseline nuclear MT levels were about four times greater in ME180 cells, and were much more readily induced by treatment with 100 microM zinc acetate, compared with SiHa cells. Under aerobic conditions, MT induction by zinc resulted in no protection in either of the cell lines. Under hypoxic conditions, however, the number of DNA single-strand breaks in zinc-treated cells was reduced by approximately 40% in ME180, but not in SiHa cells, when compared with non-induced controls. CONCLUSIONS: Nuclear MT can exert a significant level of protection from radiation by a mechanism that involves competition with oxygen for DNA radical sites and/or scavenging of free radicals. Because increased MT levels have been reported in hypoxic micro-regions of some solid tumours, this protective mechanism might have clinical relevance.


Subject(s)
DNA Damage , DNA, Neoplasm/radiation effects , Metallothionein/biosynthesis , Aerobiosis , Cell Hypoxia , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Nucleus/radiation effects , Cysteine/metabolism , Female , Glutathione/metabolism , Humans , Radiation-Protective Agents/metabolism , Temperature , Tumor Cells, Cultured , Zinc/pharmacology
18.
Clin Cancer Res ; 6(5): 1826-32, 2000 May.
Article in English | MEDLINE | ID: mdl-10815904

ABSTRACT

Under low oxygen conditions, non-protein thiols (NPSHs, non-protein sulfhydryls) can effectively compete for DNA radicals sites and hence represent a potentially important cause of radiation resistance in the clinic. Intra- and intertumoral heterogeneity of glutathione (GSH) and cysteine were assessed in cryostat sections of multiple biopsies obtained from 10 cervical carcinomas by the combined use of a sensitive high-performance liquid chromatography (HPLC) method and a fluorescence image analysis technique to examine the spatial distribution of NPSHs in tumor tissue. Glutathione concentrations ranged from 1.98 to 4.42 mM; significant (> or =1 mM) concentrations of cysteine, a more effective radioprotector than GSH, were found in some tumors. By HPLC, the intratumoral heterogeneity of NPSHs was relatively small compared with the intertumoral heterogeneity. The histochemical stain 1-(4-chloromercuryphenoylazo)-2-napthol (mercury orange), which binds to GSH and cysteine, was used to determine the spatial distribution of NPSHs in tumor tissue. A comparison of NPSH levels in serial cryostat sections showed a close correlation between NPSH values determined by HPLC and mercury orange fluorescence quantification. Using fluorescence image analysis, an approximately 2-fold increase of NPSHs in tumor versus nonmalignant tissue was observed in the same section. Because some cervical carcinomas contain radiobiologically important levels of cysteine, agents that target the biochemical pathways maintaining tumor cysteine have therapeutic potential as adjuncts to radiotherapy in cervix cancer patients.


Subject(s)
Adenocarcinoma/metabolism , Carcinoma, Squamous Cell/metabolism , Cysteine/analysis , Glutathione/analysis , Uterine Cervical Neoplasms/metabolism , Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Cervix Uteri/chemistry , Cervix Uteri/pathology , Chromatography, High Pressure Liquid , Female , Humans , Image Processing, Computer-Assisted , Microscopy, Fluorescence , Uterine Cervical Neoplasms/pathology
19.
Coll Antropol ; 23(1): 175-81, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10402720

ABSTRACT

In order to assess mean diameters and blood flow velocities (BFV), Color Doppler Flow Imaging (CDFI) of vertebral arteries (VA) was performed. Five hundred and ninety six persons without carotid disease or symptoms related to vertebrobasilar system were analyzed by CDFI of VA. Mean right VA diameter was 3.37 +/- 0.6 mm and left 3.55 +/- 0.61 mm. Women had thinner VA (p < 0.05). Left VA was wider (p < 0.05). Mean right BFV was 48.31 +/- 14.09 cm/s and left 48.93 +/- 13.94 cm/s. Females had higher BFV (p < 0.05). BFV didn't very with age (p > 0.05). The VA hypoplasia was present in 2.34%, asymmetry in 15% (left VA dominant in 64%). Visualisation of V1 and V2 segment was possible in 100% and of the origin in 81.7% on the right, and 80.7% on the left side. CDFI is a reliable method for evaluation of VA. Left VA was wider. Women had thinner VA. Hypoplasia was present in 2.34% and asymmetry in 15%.


Subject(s)
Blood Flow Velocity , Ultrasonography, Doppler, Color , Vertebral Artery/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reference Values , Vertebral Artery/physiology
20.
Cephalalgia ; 18(10): 684-6, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9950625

ABSTRACT

The role of cerebral hypoperfusion in the posterior circulation has not been clearly established in migraine. The purpose of this study was to determine the role of vertebral artery (VA) hypoplasia in the pathogenesis of migraine. We studied the extracranial part of VA in 59 migraine patients (17 with and 42 without aura) using color Doppler. In migraine with aura, 29% of patients had hypoplastic VA, and in migraine without aura 7%. In migraine with aura, mean diameter of the right VA was 2.7+/-0.7 mm, and of the left 3.3+/-0.7 mm; in migraine without aura mean diameter was 3.1+/-0.5 mm on the right, and 3.3+/-0.6 on the left. In migraine with aura, mean systolic blood flow velocity was 55+/-16 cm/s on the right, 60+/-17 cm/s on the left, in migraine without aura 57+/-18 cm/s on the right, 57+/-18 cm/s on the left. We observed higher frequency of hypoplastic VA in migraine with aura, suggesting that hypoplasia of VA may be an additional factor which can lead to hypoperfusion in the posterior circulation during the aura phase.


Subject(s)
Migraine Disorders/pathology , Ultrasonography, Doppler, Color , Vertebral Artery/pathology , Adult , Case-Control Studies , Female , Humans , Male , Middle Aged , Migraine Disorders/etiology
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