Archive issue


Current Health Sciences Journal

vol. 41 no. 4, 2015

1. Genetic Factors Involved in the Development and Progression of Nonalcoholic Fatty Liver Disease

ANCA-MARIA AMZOLINI, MARIA FORTOFOIU, SIMONA ELENA TUDORICA-MICU, M.C. FORTOFOIU, DANIELA NEAGOE, MIHAELA POPESCU, F. BURADA, C.C. VERE, T. CIUREA

Purpose. The aim of our study was to identify the possible involvement of adiponutrine polymorphysm and of human leukocyte antigens (HLA) in the development of non-alcoholic fatty liver disease (NAFLD). Material and Methods. We included in this study a total of 138 subjects with non-invasive diagnosis of non-alcoholic hepatic steatosis. The patatin-like phospholipase domain containing protein 3 (PNPLA3) rs738409 (adiponutrine) polymorphism was genotyped by allelic discrimination TaqMan PCR assay (5` nuclease assay), using predesigned TaqMan SNP Genotyping Assays. Class I and II HLA antigens were determined by the polymerase chain reaction sequence specific oligonucleotide method (ADN-PCR-SSO). The results were compared with the same data from the control group subjects. Results. For PNPLA 3 polymorphism we found [CC] genotype in 82 subjects (59,42%), [GC] genotype in 45 (32,61%) and [GG] genotype in 11 subjects (7,97%). The frequency of minor [G] risk allele was 0.25. We found class I and II HLA antigens HLA A24, HLA B15, HLA DR15, HLA DR16, HLA DQ3 and HLA DQ5 more frequent in subjects with hepatic steatosis without any other risk factor and HLA-A2, HLA-32, HLA B18, HLA B49 and HLA B53 in patients with obesity or metabolic syndrome. Conclusions. Our results are consistent with the literature and show an association of PNPLA3 rs738409 polymorphism with hepatic steatosis. Regarding histocompatibility antigens, we studied for the first time in our country the relationship between HLA and non-alcoholic fatty liver disease.

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2. Blood Clearance of Citric Acid-Coated Superparamagnetic Iron Oxide Nanoparticles in Rats-a Pilot Study

N.F. TRINCU, T.A. BALSEANU, B.S. UNGUREANU, A. FIFERE, IONICA PIRICI, A. SAFTOIU, J. NEAMTU

Superparamagnetic iron oxide nanoparticles are primarily utilized for different biomedical applications such as magnetic resonance imaging (MRI), hyperthermia, cancer treatment, targeted delivery of drugs or genes and biosensors. Nanoparticles are interesting due to their unique proprieties together with minor side effects. It is essential to determine the blood clearance of superparamagnetic nanoparticles (SPIONs) for in vivo biomedical applications, to ensure their optimum clinical use. The purpose of this study was to evaluate the elimination kinetic of citric-acid iron oxide nanoparticles in blood via intravenous injection in rats. Animals were blood sampled at different time intervals, ranging from 30 minutes to 24 hours after injection. The decay of SPIONs in blood was analyzed using electron paramagnetic resonance (EPR) technique. The results suggest that the injected iron oxide nanoparticles are rapidly cleared from circulation, with half-life of elimination process from the bloodstream about 14.06 minutes.

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3. NOD2 Arg702Trp Polymorphism in Romanian Patients with Gastric Cancer

D.N. FLORESCU, DIANA TUDORASCU, F. BURADA, M.G. CUCU, M.E. CIUREA

Purpose. Our study aimed to assess a possible correlation between NOD2 Arg702Trp (rs2066844) polymorphism and gastric cancer risk in a Romanian population. Material/Methods. A total of 322 subjects (72 patients with gastric adenocarcinoma and 250 healthy controls) were included. Genomic DNA was extracted from blood leukocytes and NOD2 Arg702Trp polymorphism was genotyped by Real-Time PCR using specific TaqMan probes. Results. No statistically significant difference was observed between gastric cancer patients and controls when we compared one genotype with other genotype (the CC genotype serves as reference) (OR 0.45, 95% CI: 0.10 - 2.05) or when we compared allele frequencies (the C allele serves as reference) (OR 0.46, 95% CI: 0.11 - 2.04). We examined separately the association of this polymorphism with tumor site and histologic type and no correlation was found. Conclusion. NOD2 Arg702Trp polymorphism is not associated with gastric cancer risk and further investigations are needed to elucidate the contribution of NOD2 gene in gastric carcinogenesis.

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4. Preliminary Analysis of Capsicum Annuum L. Extracts

FELICIA CIULU-COSTINESCU, J. NEAMTU, MARIANA POPESCU, L. CHIRIGIU, ANDREEA SIMIONESCU, MARIA-VIORICA BUBULICA, IONELA BELU

The aim of this study was to investigate Capsicum Annuum L. ultrasonicated extracts and dry powder. The percentage of water, dry matter and ash were determined. FT-IR analysis confirmed the presence of important classes of secondary metabolites in the extracts and by GC-MS a large number of important pharmaceutical compounds were identified, including capsaicin.

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5. Real Time Elastography Assessment of Fibrosis In Chronic Viral Hepatitis

C.F. JIEANU, B.S. UNGUREANU, LARISA SANDULESCU, D.O. ALEXANDRU, G.S. FIRU, D.I. GHEONEA, I. ROGOVEANU, S. CAZACU, T. CIUREA, A. SAFTOIU

Fibrosis assessment is a necessary component of liver disease evaluation not only for prognosis but also for future therapeutic management. Our study objective was to evaluate the accuracy of quantitative assessment of liver fibrosis in patients with chronic viral hepatitis B or C, relying on RTSE results, a method approved and acknowledged in Europe. Material and Methods. Sixty-three consecutive patients diagnosed with chronic viral hepatitis B or C between January 2014 and December 2014 at the Emergency County Hospital of Craiova were enrolled in the study. Patients underwent both TE and RTSE. Results. The reference method used for staging liver fibrosis was TE, based on its recognition and validation by the European guidelines. Fibrosis was classified as follows: 17.47% of patients were staged as F0, 11.11% of patients staged as F1, 14.28% as F2, 17.47% as F3, and 39.68% as F4. Correlation coefficients between measurements for each parameter was done with ANOVA test, in order to identify any differences, according to the fibrosis stage. Valuable information was obtained suggesting that MEAN, SD, %AREA, COMP, Skewness, IDM and Contrast had highly significant differences when related to the Fibrosis Stage (FS) (p<0,001) and ASM had significant differences (p<0,05). As for Kurtosis, ENT and Correlation parameters no significant differences with the FS was found. Conclusions. Imaging methods of assessing liver fibrosis are of special interest in chronic liver fibrosis assessment. RTSE comes as a potential new technology based on elastogram evaluation which may prove to be more efficient along with larger prospective studies.

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6. Effect of VEGFR, PDGFR and PI3K/mTOR Targeting in Glioblastoma

STEFANA OANA PURCARU, DANIELA ELISE TACHE, FLORENTINA SERBAN, ROXANA MIHAELA FOLCUTI, ADA MARIA GEORGESCU, P.O. STOVICEK, MARIA-MIHAELA DANCIULESCU, LIGIA GABRIELA TATARANU, ANICA DRICU

Resistance to targeted therapy is a well known obstacle in cancer therapy. The cross-talk between several growth factor receptors generates redundancy in their intracellular pathways that usually mediates resistance to receptor targeted therapy. Simultaneous inactivation of two or more growth factor receptors has been suggested to prevent the cross-talk between their signaling pathways and to better eliminate malignant cells. Here we found that targeted therapy against these receptors induced moderate cell death in glioblastoma cells. More important, dual PDGFR and VEGFR inactivation induced more pronounceable cell death compared to inactivation of each receptor alone but failed to induce synergistic cell death in glioblastoma. PI3K/mTOR dual targeting has been identified as an efficient therapeutic approach in several malignant diseases, including glioblastoma. Therefore, we also investigated the PI3K/mTOR pathways inhibition effect in glioblastoma cells. Our results showed that inactivation of PI3K/mTOR pathways were more efficient than PDGFR or VEGFR single targeting or their dual inhibition.

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7. Iron Oxide Nanoparticles Biodistribution in an Experimental Pig Model – A New Approach for Delivery and Imaging

B.S. UNGUREANU, C. MARGARITESCU, D. PIRICI, IOANA ANDREEA GHEONEA, N.F. TRINCU, A. FIFERE, DIANA TUDORASCU, A. SAFTOIU

Iron oxide nanoparticles (IONs) are of great interest in medicine, with great potential for imaging diagnostics, as well as therapeutic. Biomedical applications of IONs have been suggested for magnetic resonance imaging (MRI), with two available contrast agents on the market. However, new developments in biocompatibility and biodistribution are necessary as many new physiochemical features of coatings have been proposed for a good safety profile. Materials and Methods. Our study objective was to assess a different setting in terms of biodistribution of IONs coated with citric acid on an experimental pig model, based on EUS-guided portal vein (PV) injection. Four pigs were subjected to EUS procedures and portal vein injection of an IONs solution. All animals were kept under surveillance for the next 24 hours and euthanized. Necropsy was performed and their organs were harvested, visualized with a 3T MRI scanner and sent to pathological examination. Results. All pigs had no change in their behavior and no signs of complications were encountered. There were no problems in identifying the pigs PV under EUS-guidance. The IONs solution was clearly visualized on ultrasound live imaging, during EUS-injection. MRI and histopathological data confirmed all the deposits using Prussian Blue staining. Conclusions. This paper comes forward as a first phase of assessing new future therapeutic options and their distribution within the main organs depending on their characteristics. In our opinion this new distribution option has a strong incentive to the research of therapeutic and imaging areas and is worthy of further appraisal.

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8. The Effect of Human Mesenchymal Stem Cells-Conditioned Media on Glioblastoma Cells Viability In Vitro

ROXANA MIHAELA FOLCUTI, ISABELA SILOSI, STEFANA OANA PURCARU, DANIELA ELISE TACHE, ADA MARIA GEORGESCU, GHAZALEH HOOSHYAR EMAMI, ANICA DRICU

A novel target for cancer treatment is based on the effects of non-tumor cells, including hMSCs on tumor growth. However, the results are controversial: some studies showed that hMSCs inhibit tumor progression, while others found they promote tumor cell proliferation. In this study, we analyse the effect of human mesenchymal cells derived from umbilical cord tissue (hUC-MSCs) and bone-marrow- mesenchymal stem cells (hBM-MSCs) on glioblastoma cells viability in vitro. GB cell cultures were established from fresh sample tissues provided by “Bagdasar-Arseni” Hospital, Bucharest, from consented GB patients. hUC-MSCs, HUC-1 and HUC-2 cell lines, were established from human umbilical cord tissue collected after delivery from natural term births at the Emergency Hospital of Craiova, Romania. hBM-MSCs cell line was purchased from Life Technologies. Conditioned media (CM) from MSCs was used to treat GB cells for 24, 48, 72 and 96 hours. To determine GB cell viability was used MTT cell proliferation assay. Statistical analyses were performed using Students t-test. hUC-MSCs CM displayed the potential to be cytotoxic to GB cells, while the treatment with hBM-MSCs CM significantly stimulated GB cell growth 24 hours after the treatment and showed minor growth cell inhibition 48, 72 and 96 hours after the treatment. This report proved that hUC-MSCsCM inhibited GB cell proliferation, while little inhibitory effect was exerted by hBM-MSCs CM.

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9. Correlations Between Intratumoral Interstitial Fibrillary Network and Vascular Network in Gleason Patterns of Prostate Adenocarcinoma

R.M. PLESEA, M.S. SERBANESCU, D.O. ALEXANDRU, V. CIOVICA, A. STOICULESCU, O.T. POP, CRISTIANA SIMIONESCU, I.E. PLESEA

Purpose: The study aims to assess the correlation between stromal fibrillary component (SFC) and vascular density (VD) in Gleason architectural patterns of prostate carcinoma. Materials and Methods: 680 digital images of prostate adenocarcinoma labeled following both Gleason and Srigley systems were acquired with X20 objective from serial sections, one stained using Gömöri technique for SFC and one immunomarked with anti-CD34 antibody for vessels. The SFC amount and VD were determined and compared. Gleason patterns were divided in: "Solid" group (Gleason 3a, 3b, 4b, 5b) and "Necrotizing" group (Gleason 3c 4a and 5a). For each parameter were assessed: the lowest value (VMIN), the highest value (VMAX), the half range value (HRV), mean value (AV), standard deviation (STDEV), mean value + standard deviation (AV+ STDEV ) and mean value + standard deviation (AV+ STDEV). The Pearson product-moment correlation coefficient and the χ2 test were used. Results: The relationship between SFC and VD values had an inverse, descending correlation in Gleason 2 pattern and a direct, ascending correlation in Gleason 4 and 5 patterns. In Gleason 3 pattern, although the trend line had a direct ascending trend, it was not validated by the Pearson`s and χ2 tests. However, SFC and VD values had a direct, ascending correlation for all determinations (p<0.05), but also for "Solid" (p<0.05) and "Necrotizing" (p<0.05) groups. Conclusions: The assessment of the relationship between the two main components of the intratumoral stroma in prostate carcinoma showed that they are evolving in a parallel manner. There is still need for studies on larger groups in order to decipher and more clearly define the way the stromal microenvironment is remodeling according to the malignant cell population degree of differentiation.

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10. Acceptability of Intrapartum Ultrasound Monitoring- Experience from a Romanian Longitudinal Study

D.G. ILIESCU, STEFANIA TUDORACHE, MONICA-LAURA CARA, ROXANA DRAGUSIN, O. CARBUNARU, MARIA FLOREA, C. PATRU, L. ZORILA, NICOLETA ALICE DRAGOESCU, LILIANA NOVAC, N. CERNEA

Objectives: To assess the acceptability of intrapartum ultrasound (IPUS) labor monitoring in unselected Romanian women attending a tertiary maternity unit and the patients’ experience of the examination (i.e. the perceived difficulty regarding the evaluation protocol). Methods: The research was a prospective longitudinal observational study on unselected low-risk women that delivered in our unit. IPUS monitoring of active labor was proposed for observational purposes in low-risk population. Transabdominal and transperineal scans were performed hourly in the first stage of labor and at every 15 minutes in the second stage. The second day after birth, consenting women were invited to take part in a questionnaire survey with features regarding the patient’s impression about the ultrasound monitoring scans during labor, and the acceptability of having an IPUS protocol for labor monitoring in the future. Results: From 200 parturient women questioned, 98% of them agreed to IPUS investigation protocol. The demographic characteristics did not influence the acceptance. However, due to the small number of women declining IPUS we were not able to compare the characteristics and perceptions of women who declined the scan with those who accepted it. Most of the women (93% of accepters and 75% of decliners) had little difficulty deciding whether or not to have the scan protocol. All laboring women who had the IPUS scan found it an acceptable experience; 21% of women without epidural anesthesia rated the perceived difficulty as “mild” or “discomforting”. Women rated having the IPUS scan as being significantly less difficult than having a cervical smear, transvaginal scan or having a digital clinical evaluation. 67% of the studied patients expressed increased confidence while being able to follow along the medical personnel the progression of the labor on the ultrasound screen. 97% of the consenting women who had the IPUS scans and all the 4 decliners said they would de

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11. Mental Disorders in Chronic Liver Diseases with Viral Etiology

V.V. GHEORMAN, ANCA LIVIA CHIRITA, MADALINA DUMITRESCU, R. STANESCU, I. ROGOVEANU

The study of chronic viral hepatitis represents a real challenge for modern medicine. If we also analyze this illness from the point of the mental changes involved, the complexity of the study increases. To the etiological, symptomatological polymorphism, alongside the paraclinical and conduct diagnosis, there may be easily added the multitude of mental disorders. The authors have tried, through this paper, to draw the attention upon the importance of studying certain mental disorders connected to a somatic disease, each and every representing a distinct entity, but which together may reach a remarkable complexity.

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12. The Evaluation of Concentration - In-Vitro Release Relationship for Topical Semisolid Formulations of Sodium Cromoglycate

ANA ANDREEA STANESCU

Purpose. The aim of the study was to evaluate the concentration - in-vitro release relationship for topical semisolid formulations of sodium cromoglycate. Materials / Methods. According to usual pharmaceutical compounding practice, commercially available cosmetic emulsions were used as vehicles for topical semisolid dosage forms containing 0.5, 2, 4 and 10% disodium cromoglycate (CS). The in-vitro release profiles and structural parameters of the resulting formulations was evaluated in a correlated manner, in order to reveal potential differences in the in-vivo performance. Results. Depending on the hydro-lipophilic characteristics of the vehicle and on the quantity of drug dissolved or dispersed, the structure and the release kinetics are distinct. Conclusions. The results suggested that current lack of an unitary approach for the compounding of semisolid dosage forms of CS, resulting from the lack of widely available, standardized dosage form could be a reasonable explanation for the apparent discrepancy in the reports of clinical outcome after topical administration.

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13. Spontaneous Cure of Acute Hepatitis C

ALEXANDRA FLORIANA ROSU, CARLOS FREITAS, RUI TATO MARINHO, JOSE VELOSA

The statistics proved that approximately 25% of the patients with acute HCV present with jaundice, and only 10-20% develop gastrointestinal symptoms. We present the case of a 58 year-old woman, with prior antecedents of arterial hypertension and diabetes mellitus since 25 years old, hypercholesterolemia and hypertriglyceridemia, psoriasis, epilepsy and depressive syndrome. She clinically presents asthenia, anorexia, itching, jaundice and choluria. The objective examination showed an orientated patient, without flapping, hemorrhagic dyscrasia or signs of chronic hepatic disease, with icteric mucosa and skin, abdominal pain, with hepatomegaly and splenomegaly. The laboratory tests have been compatible with acute hepatitis with colestatic pattern: AST/ALT 969/798 UI/ml, FA 796 UI/ml, GGT 2476 UI/ml, BT/BD 7.39/6.10, INR 0.9. The abdominal echography showed: hepatomegaly, regular borders, hepatic steatosis, splenomegaly without ascitic fluid. The viral serological tests revealed protection for hepatitis A ( IgM neg/IgG pos), negative for HVB infection (AgHBs neg, anti-HBc neg), negative for HVE and other viruses (CMV Herpes virus, Epstein Barr, HIV), positive antibodies for HCV and positive RNA VHC (164200 UI/ml), HCV genotype 3a, IL-28B CT, negative autoimmunity. The previous HCV tests were negative, sustaining the recent infection. We assumed an acute hepatitis C. The patient was symptomatically treated with hydroxyzine for the skin itch, with vitamin K for INR correction and she was closely monitored. She had good clinical and laboratorial evolution and she was discharged after one week, maintaining hepatology consultation. She spontaneously cleared HCV infection after 3 months, maintaining negative RNA VHC 6 months after infection. The patient has cured the HCV infection with no need for antiviral treatment.

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14. Pegylated Interferon-Induced Sarcoidosis Presenting With Anterior Uveitis in a Patient with Chronic Hepatitis C - Case Report

ADINA KAMAL, P. MITRUT, C.K. KAMAL, D.O. ALEXANDRU, A. TICA

Sarcoidosis is a chronic inflammatory systemic disorder of unknown etiology. It is known to be triggered by an autoimmune process, and is currently recognized as a rare adverse event to interferon therapy for Hepatitis C Virus Infection. Clinical presentation of interferon-triggered sarcoidosis is varied, but ocular manifestation as a first symptom was only once, previously reported. We report the case of a 32 year old woman, infected with hepatitis C, for whom antiviral therapy was initiated. Prior to treatment, the patient had outstanding medical history. Three months from the initiation, patient accused pain and redness of the left eye and mild visual loss. The diagnosis of Interferon induced sarcoidosis was established. We are presenting this case because it illustrates the possibility of sudden and severe complications and we want to emphasize the importance of performing ophthalmological examination in patients treated with pegylated interferon α

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15. Differential Diagnosis between Duchenne Muscular Dystrophy and Limb Girdle Muscular Dystrophy 2a

MIHAELA AMELIA DOBRESCU , GRATIELA CHELU , DANIELA ELISE TACHE, STEFANA OANA PURCARU, ILEANA OCTAVIA PETRESCU

Limb Girdle Muscular Dystrophy 2A (LGMD 2A) is the most common form of limb girdle muscular dystrophies caused by mutations in the calpain-3 gene (CAPN-3). The pattern of LGMD 2A can be clinically indistinguishable from that of Duchenne Muscular Dystrophy (DMD). We report a case of a 14-year-old boy which has the initial diagnosed as DMD at 6 years old, based on clinical features and very elevated serum creatine kinase levels. A muscle biopsy at the age of 10 showed atypical features which suggested a histiocytosis or neural damage. An MRI conducted 2 years later revealed fatty degeneration predominantly in the posterior region of the thigh and led the diagnosis to LGMD 2A, as well as the necessity to repeat the biopsy. Immunohistochemical analysis was normal for dystrophin, but the Western Blott showed a normal/borderline amount of calpain-3 in the muscle. We also performed a molecular analysis that identified a compound heterozygous mutation of the calpain 3 gene (CAPN 3). LGMD 2A was often misdiagnosed as DMD due to the similarities in clinical manifestations and technique limitations; the immunohistochemical examination, the magnetic resonance imaging examination and the molecular analysis are an essential tool for establishing a right diagnosis.

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16. Molecular Imaging of Cancer Stem Cells for Assessment of Rectal Cancer

IRINA CHERCIU, TATIANA CARTANA, IOANA STREATA, M. IOANA, A. SAFTOIU

Rectal cancer is one of the most common diagnosed malignancies in the world. We present the case of a 54 years old patient, diagnosed with adenocarcinoma of the rectum and unsuccessful treatment. The possible involvement of cancer stem cells in tumor relapse and treatment failure represents the motivation behind an extensive imaging evaluation. The aim of our case report was to assess the outcome of rectal cancer assessment using standard and state-of-the-art techniques, including evaluation of colorectal cancer stem cells. Our results suggest concordant outcomes of modern versus gold standard techniques but further studies are necessary to evaluate the utility during routine clinical work-up.

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17. Chemotherapy Related Severe Cardiac Dysfunction – Case Report

DIANA-ALEXANDRA CHERATA, DOINA CARSTEA, MIRELA ZAHARIE, C. BATAIOSU, D. LUNGULESCU

Cardiotoxicity is the most important side effect of cancer therapy resulting in increased patient morbidity and mortality, therefore understanding its occurrence mechanism and a correct and early diagnosis are essential for patients at risk of irreversible heart failure. We present the case of a patient who developed cancer therapeutics-related cardiac dysfunction, emphasizing the importance of regular echocardiographic evaluation for early detection of subclinical cardiac dysfunction and further cardiac monitoring. More sensitive parameters should be used to predict cardiotoxicity because the probability of cardiac function recovery diminishes in time, despite optimal heart failure treatment.

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18. Variability of Normal Values of Electroretinogram Parameters Due to Aging in Healthy Individuals

A. OSMAN, M.S. CIOLOFAN, ELENA IONITA, I. IONITA, F. ANGHELINA, CARMEN-AURELIA MOGOANTA, ANCA-STEFANIA ENESCU, AURELIA ENESCU, MIORITA TOADER

The basaloid carcinoma is a rare and distinct type of squamous carcinoma. Of all the squamous carcinomas, the basaloid tumor is noted for its high aggressivity and fast replication rate. It is usually discovered within the upper levels of the larynx (supraglottis), the tongue base or the piriform sinuses in male patients ranging from sixty to eighty years old. The aggressivity of the tumor also means its discovery is usually a late event thus associating a relatively low survival rate within the first 5 years. The current paper presents the case of a patient diagnosed with a malign tumor of the larynx which is then identified as being a squamous basaloid carcinoma. The medical review of the patient reveals a long history of smoking and also pulmonary tuberculosis, for which the patient underwent left pneumonectomy.

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19. The Recovery Physical Therapy Effects upon the Ventilation Dysfunction in Patients with Ankylosing Spondylitis

OTILIA ROGOVEANU, DIANA KAMAL, C.T. STREBA, RODICA TRAISTARU

Purpose - The evaluation of the ventilation function improval in patients with ankylosing spondylitis following the medical recovery procedures. Methods - The study included 24 patients that were diagnosed with AS stages I and IV that were monitored for 24 months. We recorded ventilation functional tests, respiratory gas levels, thorax involvement in inspiration and expiration, the medical, physical and balneotherapy that they had followed. The activity of the disease was evaluated using the BASDAI score. The evaluation of the functional disability was based on the BASFI score and the life quality needed the QLQ questionnaire. The age of the disease has started was also considered. Results - The study included 24 patients, 22 men and two women (11/1 men/female ratio), ages between 35 and 55 years. The disease has begun 18 plus or minus 2 years before. After 24 months a significant improval was noticed concerning the restrictive ventilation dysfunction specific parameters and also an increase of oxygen pressure by 7 plus or minus 2 mmHg. Conclusions - The constant and correct application of respiration recovery and the spine mobility procedures lead to better life quality regarding the patients with AS and the main parameters that evaluate ventilation dysfunction.

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