Liviu Tamas | University Of Medicine And Pharmacy Timisoara (original) (raw)

Papers by Liviu Tamas

Research paper thumbnail of Prevalence of a Iodothyronine Deiodinase 2 gene single nucleotide polymorphism in children with congenital hypothyroidism from Western Romania and impact on TSH levels

Revista Romana de Medicina de Laborator, 2019

The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92... more The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92Ala polymorphism in children from West of Romania with congenital hypothyroidism (CH) and association with TSH levels in response to levothyroxine monotherapy. Genotyping in 50 children with CH and 52 healthy controls was done using real time PCR. The results showed that there was no statistical difference between the frequencies of genotypes in patients vs. controls. Patients were treated with L-thyroxine and most had normal values for fT3 and fT4. However, high TSH values were found in 21 patients (42%) after treatment. Among patients with high TSH values, AA genotypes were significantly more prevalent (p = 0.044) than TT and AT genotypes. Our results suggest that for the D2 gene Ala92Thr polymorphism, the AA genotype may be detrimental for achieving euthyroidism in patients with CH and levothyroxine monotherapy, therefore polytherapy could be considered as a better approach in these p...

Research paper thumbnail of Estrogen Receptor Alpha Polymorphisms and the Risk of Malignancies

Pathol. Oncol. Res., 2010

Estrogens represent risk factors for endocrinerelated cancers and play also an important role in ... more Estrogens represent risk factors for endocrinerelated cancers and play also an important role in the development and progression of other malignancies. In order to analyze the associations between estrogen receptor gene alpha polymorphisms and cancers susceptibility, we genotyped six single nucleotide polymorphisms (SNPs) in 163 Caucasian cancer patients-103 breast cancers and 60 other malignancies (colorectal, bladder, hepatocellular carcinoma and acute myeloid leukemia)-and 114 healthy controls using hybridization probes. We performed Armitage`s association trend-test to evaluate the risk. Linkage disequilibrium (LD) was assessed for each pair of markers. The genotypes CC and CT of rs3798577 were significantly associated with the cancers risk (p-trend breast =4×10-5 ; p-trend cancers =1×10-5); in discrepancy with breast cancer where the C-allele represented the risk allele, for bladder, hepatocellular carcinomas and leukemia, the T allele seems to confer susceptibility. The minor G allele of rs1801132 was protective in our cases (p=1×10-4); for rs2228480, the heterozygous frequency was higher for cancer groups (p=0.03); the SNP pairs rs2228480&rs3798577 and rs2234693&rs9340799 were in low LD; the haplo types T-A of rs2234693&rs9340799 and G-C of

Research paper thumbnail of Prevalence of a Iodothyronine Deiodinase 2 gene single nucleotide polymorphism in children with congenital hypothyroidism from Western Romania and impact on TSH levels

Revista Română de Medicină de Laborator, 2019

The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92... more The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92Ala polymorphism in children from West of Romania with congenital hypothyroidism (CH) and association with TSH levels in response to levothyroxine monotherapy. Genotyping in 50 children with CH and 52 healthy controls was done using real time PCR. The results showed that there was no statistical difference between the frequencies of genotypes in patients vs. controls. Patients were treated with L-thyroxine and most had normal values for fT3 and fT4. However, high TSH values were found in 21 patients (42%) after treatment. Among patients with high TSH values, AA genotypes were significantly more prevalent (p = 0.044) than TT and AT genotypes. Our results suggest that for the D2 gene Ala92Thr polymorphism, the AA genotype may be detrimental for achieving euthyroidism in patients with CH and levothyroxine monotherapy, therefore polytherapy could be considered as a better approach in these patients.

Research paper thumbnail of Pro-inflammatory Cytokines (IL6, IL8 and TNF-a) in the Evaluation of Ovarian Endometriosis Cyst

Revista de Chimie, 2019

Endometriosis is the abnormal growth of cells (endometrial cells) similar to those that form the ... more Endometriosis is the abnormal growth of cells (endometrial cells) similar to those that form the inside of the uterus, but in a location outside of the uterus. Endometriosis is most commonly found on other organs of the pelvis. These lesions are most commonly found on the ovaries, the Fallopian tubes, the surface of the uterus, the bowel, and on the membrane lining of the pelvic cavity (i.e. the peritoneum). We corroborate TNF-a, IL-6 and IL-8 markers with intraoperative laparoscopic on 39 patients diagnosed with endometriosis in January 2016 - December 2017, aged 20-45 years. There has been a preoperative evaluation in the patients from this that included the anamnesis, clinical examination and laboratory tests. Anamnesis recorded demographic details, patient�s personal, physiological and pathological medical history. Evaluation of preoperative investigations consisted of general and local systems examination, a gynecological examination in order to identify the specific signs of e...

Research paper thumbnail of Proceedings of the 2017 WAO Symposium on Hot Topics in Allergy: Pediatric & Regulatory Aspects: Rome, Italy/Vatican City. 27-29 April 2017

The World Allergy Organization journal, 2017

BACKGROUND In pediatric ages, sublingual immunotherapy (SLIT) allows allergic children to approac... more BACKGROUND In pediatric ages, sublingual immunotherapy (SLIT) allows allergic children to approach the inhaling desensitizing therapy. However, SLIT causes quite a few compliance problems and sometimes it is difficult to carry it out for the required long term. The alternative is subcutaneous immunotherapy (SCIT), commonly performed with a syringe. This technique hasn't changed much in time and it is not without risks or discomfort. This has led to the search for alternative ways of vaccine administration, in order to reduce discomfort to children by improving compliance and diminishing the potential risks of adverse reactions. OBJECTIVE The study aimed to assess the patient's perceived pain and the safety of a new way of administration of SCIT, with a needleless device. METHODS Children with grass or mite-induced allergic rhinoconjunctivitis and/ or bronchial asthma were prescribed a glutaraldehyde-polymerized allergenic extract (Allergovac Polymeryzed®, Bial Aristegui, Italy). Each dose was divided in two parts: half injected with the traditional syringe (dose A), half in the other arm with a needleless device (Injex, Greytree, Ross on Wye, UK; dose B). Patients were blindfolded. The perceived pain and the difficulties of the procedure were registered on a dedicated VAS scale immediately (time 1) and 20 minutes after the first injection (time 20). Also, we evaluated the occurrence of occasional adverse events during such procedure and we assessed the perceived difficulty by the doctor administering with such method. RESULTS 39 patients, aged 5-18 years, were recruited and assessed. All patients completed the study, which involved 468 grass pollen AIT SCIT doses, of which 234 with needleless device. At time 1, the use of the needleless device led to an 88% reduction of the pain perception average rate (from 16,8 to 1,97). The difficulty for the technician to make the inoculum was also analyzed (expressed by an increasing rate, from 0 to 4). In all 6 doses, for each child, the difficulty rate 2 relates to an almost constant number of patients, while the highest difficulty rates (grade 3 and grade 4) gradually decrease (until they disappear). CONCLUSIONS The vaccine administration with needleless device has various advantages and it ensures a better acceptance in comparison with administration by traditional SCIT. This is important in order to start the immunotherapy at an early stage, as it is recommended by the most recent studies, so that the natural evolution of the allergic disease can be immediately modified. The new technique ensures a higher safety both for the vaccinator and for the patient, with a better acceptance of the procedure by the patient and therefore a better and wider compliance to the vaccination schedules.

Research paper thumbnail of Neurofibromatosis Type 1–MOLECULAR Testing and Clinical Presentation of Two Cases

Analele Ştiinţifice ale Universităţii „Alexandru Ioan Cuza”, Secţiunea Genetică şi Biologie Moleculară, 2010

Neurofibromatosis type 1 is caused by mutations in the NF1 gene located on chromosome 17q. Case 1... more Neurofibromatosis type 1 is caused by mutations in the NF1 gene located on chromosome 17q. Case 1: A 1 year 7-month-old boy had progressive right ptosis which began when he was 19 months of age and numerous café-au-lait spots. Case 2: A 28 years old woman presents: café-au-lait spots, one subcutaneous tumor on the left leg, a first degree family member, who has NF1-malignant form. Molecular Genetic analysis consisted of: 1. Amplification of the entire coding region of the NF1 gene. 2. Screening for deletions and duplications in the NF1 gene by MLPA analysis. Results: Case 1: A heterozygous c.1719delT mutation was identified in exon 11 of the NF1 gene. Case 2: A heterozygous c.6709C>T mutation was identified in exon 45 of the NF1 gene. Conclusions: The mutations founded in both cases determined a truncated NF1 protein, which is disease-causing.

Research paper thumbnail of Functional Analysis of Human Gene Promoters

REVISTA DE CHIMIE- …, 2007

The complexity of gene control processes and the perspectives opened by understanding how to cont... more The complexity of gene control processes and the perspectives opened by understanding how to control a target gene are several important reasons for researchers to try to find out more information about gene control mechanisms and the molecular networks responsible for that. The ...

Research paper thumbnail of Genetic analysis of CFTR mutations in cystic fibrosis patients from Romania

Timisoara Medicala, 2006

Cystic fibrosis is the most common autosomal recessive disease in Caucasian populations. The aim ... more Cystic fibrosis is the most common autosomal recessive disease in Caucasian populations. The aim of this study was to improve the number of cystic fibrosis mutations detected in patients from the National Center of Cystic Fibrosis from Timisoara and to establish a solid method of genetic analysis for cystic fibrosis mutations in Timisoara. The study included a retrospective part, which consisted of analyzing the genetic tests results for 79 patients from the National Center of Cystic Fibrosis from Timisoara, already investigated in collaboration with Royal Manchester Children's Hospital - Genetic Unit (UK), and an original, prospective part, in which we selected 17 patients in evidence at the Center for genetic analysis, based on clinical findings and sweat test. 29 mutations were investigated and the detection was performed using a ElucigeneTM CF29 kit, which detects point mutations or small deletions in deoxyribonucleic acid (DNA) using a method based on ARMS allele specific amplification technology. DNA was extracted from lymphocytes from peripheral blood samples, genomic DNA was amplified by PCR and the PCR products were visualized on a UV transiluminator after electrophoresis on agarose gel and staining with ethidium bromide. Results: We identified 18 mutated alleles from a total number of 34 alleles and three mutations: ΔF508, G542X and I148T. We combined the new, original data with data from the retrospective part and we obtained new estimates of the frequency for CF mutations in Romania. Conclusion: The most frequent mutation in Western and Central Europe, ΔF508 (70%) has a lower frequency in Romania (47,92%). There are still many mutations that remain unidentified (34 %) by investigating only the usual mutations. The great number of mutations and polymorphisms identified up to date reflects the genetic heterogeneity of Romanian population.

Research paper thumbnail of Antibiotherapy in Children with Cystic Fibrosis—An Extensive Review

Children

In cystic fibrosis (CF), the respiratory disease is the main factor that influences the outcome a... more In cystic fibrosis (CF), the respiratory disease is the main factor that influences the outcome and the prognosis of patients, bacterial infections being responsible for severe exacerbations. The etiology is often multi-microbial and with resistant strains. The aim of this paper is to present current existing antibiotherapy solutions for CF-associated infections in order to offer a reliable support for individual, targeted, and specific treatment. The inclusion criteria were studies about antibiotherapy in CF pediatric patients. Studies involving adult patients or those with only in vitro results were excluded. The information sources were all articles published until December 2021, in PubMed and ScienceDirect. A total of 74 studies were included, with a total number of 26,979 patients aged between 0–18 years. We approached each pathogen individual, with their specific treatment, comparing treatment solutions proposed by different studies. Preservation of lung function is the main g...

Research paper thumbnail of Microbiology Characteristics Among Cystic Fibrosis Patients in Western Romania

Central European Journal of Clinical Research, 2018

Background: Pulmonary infectious inflammation is a major cause of decline in lung function in pat... more Background: Pulmonary infectious inflammation is a major cause of decline in lung function in patients with cystic fibrosis (CF) marked by exacerbations, consequently, slowing evolution of lung disease is a primary aim in CF management. The objective of the study was to analyze the microbiological spectrum from epidemiological point of view in our patients. Methods: An observational, cross-sectional transversal study including fifty-seven patients evaluated the prevalence of CF-related microbes in the study group and their pulmonary status. Results: The most frequent microorganism found in our group, regardless age, was Staphyloccocus aureus, closely followed by Pseudomonas aeruginosa. Bacillus tuberculosis was a rare germ, despite the important frequency in our country. The microbes frequency was different with age groups, thus 3.5% of 1-3 years old children had the methicillin sen sitive Staphylococcus aureus (MSSA) strain, while for the 6-12 years group, Pseudomonas aeruginosa wa...

Research paper thumbnail of Microarray Technology for the Detection of Antimicrobial Resistance Genes Present in Hospital and Community Acquired Methicillin Resistant S.aureus Strains

Revista de Chimie, 2017

Antimicrobial resistance (AMR) represents a real burden for the modern medicine. One of the most ... more Antimicrobial resistance (AMR) represents a real burden for the modern medicine. One of the most frecvently isolated hospital acquired (HA) pathogens wordlwide, is Methicillin resistant Staphylococcus aureus (MRSA). Recently not only HA, but also community-acquired MRSA (CA-MRSA) infections have been reported. A prospective study was performed between February 2009 and October 2010, with the aim to investigate bacterial resistance of CA-MRSA and HA-MRSA. DNA microarray technology has been used for the detection of 4 AMR genes for the studied MRSA strains. A number of 218 HA- S.aureus strains have been isolated, from which 89 (40. 82%) were MRSA. In the community, 1.553 S.aureus strains were isolated, out of which, 356 (22. 92%) were MRSA. From these, a number of 17 HA and 12 CA �MRSA strains have been analyzed by DNA microarray technology. From 100% phenotypically described HA- MRSA, we identified mecA gene in 10 strains (58. 83%). Other 6 strains (35. 29%) have been erm(A) positive...

Research paper thumbnail of The genetic investigation of old tissue samples paraffin-embedded as source for molecular autopsies in sudden cardiac death cases

Studia Universitatis Vasile Goldis Arad, Seria Stiintele Vietii, 2014

Sudden cardiac death (SCD) is a major cause of death in young adults and children. Standard foren... more Sudden cardiac death (SCD) is a major cause of death in young adults and children. Standard forensic autopsy procedures are often unsuccessful in explicating the causes of SCD. “Gene” or “molecular autopsy” has a great potential for identifying unknown causes of death. The aim of our study was to design a methodology of molecular analysis for investigating old tissue samples paraffin-embedded, collected from subjects with SCD. For molecular analysis we selected a Real Time PCR method with Taqman probes, the SCN5A gene which can be mutated in several channelopathies – Brugada syndrome, LQT, FAF and a frequent mutation of SCN5A gene - E1784K. 51 samples were investigated and the genotype was determined for 47 subjects. By this study we showed that the molecular analyze of genomic DNA extracted from formalin-fixed and paraffin-embedded tissues by Real Time with TaqMan probes method is an efficient and suitable approach for samples with old and fragmented DNA molecules, which can be used for the successful identification of normal alleles or specific pathogenic mutations. By molecular dissection, old cases with no identified cause of death can be deciphered and the positive molecular diagnosis will provide the basis for genetic counseling and treating surviving family members.

Research paper thumbnail of J07.20 Management and molecular diagnosis in romanian patients with Duchenne/Becker muscular dystrophy

European journal of human genetics: EJHG

Duchenne and Becker muscular dystrophy (DMD/BMD) are the most common muscular dystrophies with X-... more Duchenne and Becker muscular dystrophy (DMD/BMD) are the most common muscular dystrophies with X-linked inheritance caused by mutations in the DMD gene. DMD is the most severe form with a complete absence of dystrophin synthesis. The most frequent DMD gene mutations are large deletions and duplications of one or more exons. Method. For molecular diagnosis of patients diagnosed with DMD/BMD only on the base of clinical symptoms, family history and creatine kinase levels we used MLPA (Multiplex Ligation-dependent Probe Amplification) technique. Genomic DNA was extracted from blood samples and 35 unrelated patients and 20 relatives were analyzed. The MLPA products were quantified by capillary electrophoresis and interpreted using Coffalyser software. Results. Large deletions were identified in 24 patients (68,57%) and large duplications in four patients (11,42%). 14 female patients with heterozy gous genotypes confirmed previously identified mutations in male patients and in 6 subjects...

Research paper thumbnail of Cystic fibrosis liver disease - from diagnosis to risk factors

Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2014

Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmit... more Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency,
meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases.
Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

Research paper thumbnail of 187 Evaluation of cystic fibrosis liver disease and the relation with risk factors in a Romanian centre

Journal of Cystic Fibrosis, 2014

SERPINA1 gene is present in about 2% of patients with cystic fibrosis, but more frequently, in ap... more SERPINA1 gene is present in about 2% of patients with cystic fibrosis, but more frequently, in approximately 5% of patients with cystic fibrosis (CF) and concomitant changes in the liver. Aim: The aim of this study was to assess the impact of SERPINA gene mutation on the occurrence of liver damage and cholestasis in patients diagnosed with cystic fibrosis. Patients and Methods: The analysis included 30 children, 13 girls (43.3%) and 17 boys (56.6%), aged from 6 months to 18 years, with diagnosed CF. All patients underwent genetic testing for SERPINA gene mutation. The analysis included age, sex, clinical symptoms, type of mutation of the CFTR protein, laboratory abnormalities (levels of transaminases, GGTP, FA, protein, acid steatocrit) and ultrasound examination of the abdomen. Results: Elevated transaminases were found in 9/30 (30%), whereas elevated levels of gamma-glutamyl transferase in 6/30 (20%) children. In 5/30 patients the ultrasound examination demonstrated liver enlargement with increased echogenicity. The mutation in SERPINA gene was found in 1/30 (3.3%) patient with cystic fibrosis. Currently, this patient has normal values of transaminases, GGTP and FA, whereas, a significant worsening of respiratory symptoms is observed. There was no correlation between the occurrence of SERPINA gene mutation and clinical symptoms, type of CFTR protein mutation, results of laboratory tests of liver function and hepatocyte damage, and ultrasound examination of the abdomen. Conclusions: There was no correlation between the occurrence of SERPINA gene mutation and the presence of features of liver damage and cholestasis in children diagnosed with cystic fibrosis.

Research paper thumbnail of 123 How frequent is Clostridium in our CF patients?

Journal of Cystic Fibrosis, 2014

Research paper thumbnail of Safety of Vascular Endothelial and Hepatocyte Growth Factor Gene Therapy in Patients with Critical Limb Ischemia

Current Neurovascular Research, 2011

The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expres... more The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expressing vascular endothelial and hepatocyte growth factors in patients with critical limb ischemia. The study included 43 patients: 29 in the treatment group and 14 allocated to the placebo group. The primary end points were the rate of major amputations and the clinical safety of the method. Secondary end points were improvement of pain at rest, walking ability and the ankle/brachial pressure index. The overall major amputation rate was 31.04% in the treatment group and 71.42% in the
placebo group (p=0.029). Pain at rest was improved in 65% of patients in the gene therapy group and in 7% in the placebo group (p=0.0006). There were no significant adverse effects in the treatment group. Conclusion: Gene therapy with vascular endothelial and hepatocyte growth factors is therapeutically safe and reduces the rate of major amputations and relieves pain at rest in patients with critical limb ischemia.

Research paper thumbnail of 12 Associated conditions in cystic fibrosis: findings at diagnosis and changes in time, impact on clinical outcomes and quality of life

Journal of Cystic Fibrosis, 2014

Objectives: To determine the burden of associated conditions in Cystic Fibrosis and their impact ... more Objectives: To determine the burden of associated conditions in Cystic Fibrosis and their impact on clinical outcomes in a pediatric cohort. Methods: Retrospective clinical file analysis of pediatric CF patients followed up during 1999-2013, correlated with diagnosis of CF and non CF related associated conditions. Results: 56 patients followed up, mean age at diagnosis 11 months, 22/56 died (11 before the age of 1 year). Causes of early deaths: severe lung disease and malnutrition correlated with poor socioeconomic status. 13/56 had meconium ileus (2/56 meconium peritonitis, 2/56 parcelar intestinal athresia), all underwent surgery with difficult recovery and high rate of complications. Related CF conditions: 4/56 nasal polyposis, 4/56 CFrelated diabetes, 5/56 early CFRLD, 4/56 ABPA; all negatively impacted clinical outcomes. Diagnosis of other chronic diseases in 13/56 patients (some genetic traits): juvenile myoclonic epilepsia (1/56), horseshoe kidney (1/56), spastic paraparesis (1/56), congenital cardiac malformations (4/56), ADHD (3/56), asthma and allergic rinitis (4/56). Higher rate of hospitalization, lower clinical and radiological scores were observed in patients with CF related conditions (p < 0.05). Quality of life was negatively impacted by both presence of CF related and nonCF related conditions, regardless age. Conclusion: Associated CF related conditions are frequent observed as survival increases in CF. Diagnosis of other chronic conditions in CF may negatively impact clinical outcomes, more so with increasing of age. Early diagnosis of other chronic traits in CF, specialized and multidisciplinary care is needed to improve QoL and life span.

Research paper thumbnail of 5 Regular genetic kit for CF mutations detection

Journal of Cystic Fibrosis, 2012

Background: A characteristic aspect for Romania is the CF mutations heterogeneity which leads to ... more Background: A characteristic aspect for Romania is the CF mutations heterogeneity which leads to a reduced percentage of genotype identification. Objectives: Assessment of the efficacy of a mixed panel for CF mutation detection in Romanian patients. Methods: We evaluated retrospectively 40 patients(pts) with typical CF, registered in the National CF Center Timisoara. The genetic tests were performed using a mixed panel − (29 mutations − panel 1) − ARM and another kit for 38 mutations (panel 2) − PCR. 18 mutations were common to the two kits; the total number of identifiable alleles was 49. Results: The first panel identified the following mutation, in order of frequency: DF508, G542X, N1303K, 621 + 1 G>T, I148T, representing 17.2% from panel 1 mutation. We found the following patients genotypes: 21 pts with F508del/F508del, 10 pts with F508del/ x, 5 pts F508del/G542X, 1 patient F508del/ N1303K. In 3 pts with compound genotype non-F508del (I148T, N1303K or G542X), the other alella could not be identified, complementary genetic testing done in parents have ruled out the possibility of homozygous genotype for non-F508del. In 13 patients (32.5%) we could not fully identify the genotypet, thus they were further tested with panel 2. Conclusions: Correspondence of kits with identified mutations in CF Romanian patients is low, although kits contain the most frequent mutations used in Europe. Genetic heterogeneity in Romania limits significantly the possibility of detection of both alleles, the diagnosis rate of heterozygote being reduced. The question of using additional kits or methods like CF gene sequencing raise the issue of a very high cost.

Research paper thumbnail of 233 Allergies in children with cystic fibrosis

Journal of Cystic Fibrosis, 2011

Introduction: Accurate serial assessment of FEV1 is essential to help the clinician combat deteri... more Introduction: Accurate serial assessment of FEV1 is essential to help the clinician combat deterioration in CF patients, and spirometry equipment must be capable of reliable and reproducible measurements. Traditional equipment (e.g. Vitalograph 2120) uses reusable flow sensors (i.e. pneumotachograph) which require disposable filters, thereby increasing equipment dead-space and resistance. Newer technology (SpirostikTM) uses disposable flow sensors which do not require filters, reducing dead-space and airflow resistance. We have recently switched over to this new technique and have compared its effect on the FEV1 measurement in our adult CF patients. Method: 85 consecutive adult CF patients (mean age 28 [range 17−53], mean FEV1 59% [12–120], 46 male) performed FVC manoeuvres (measuring FEV1) according to ATS/ERS guidelines, on SpirostikTM and Vitalograph 2120. Student’s paired t test was used for statistical analysis. Results: Patients found the new device easier to use, since it gave them more feedback during the manoeuvre. SpirostikTM recorded on average 9.7% higher FEV1 than Vitalograph 2120 (mean FEV1 2.41 litres [SD 1.00, range 0.8–5.14] versus 2.18 [0.89, 0.6–4.32], P< 0.001). Overall, 76 patients (91%) had higher values on SpirostikTM compared to 2120. Conclusions: This potentially more accurate measure of spirometry has increased the average value of FEV1 in our patients significantly. This not only has implications for clinical practice in that we are now having to “recalibrate” our views of individual patient’s clinical progress, but it will also alter the value of data sent to national registries.

Research paper thumbnail of Prevalence of a Iodothyronine Deiodinase 2 gene single nucleotide polymorphism in children with congenital hypothyroidism from Western Romania and impact on TSH levels

Revista Romana de Medicina de Laborator, 2019

The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92... more The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92Ala polymorphism in children from West of Romania with congenital hypothyroidism (CH) and association with TSH levels in response to levothyroxine monotherapy. Genotyping in 50 children with CH and 52 healthy controls was done using real time PCR. The results showed that there was no statistical difference between the frequencies of genotypes in patients vs. controls. Patients were treated with L-thyroxine and most had normal values for fT3 and fT4. However, high TSH values were found in 21 patients (42%) after treatment. Among patients with high TSH values, AA genotypes were significantly more prevalent (p = 0.044) than TT and AT genotypes. Our results suggest that for the D2 gene Ala92Thr polymorphism, the AA genotype may be detrimental for achieving euthyroidism in patients with CH and levothyroxine monotherapy, therefore polytherapy could be considered as a better approach in these p...

Research paper thumbnail of Estrogen Receptor Alpha Polymorphisms and the Risk of Malignancies

Pathol. Oncol. Res., 2010

Estrogens represent risk factors for endocrinerelated cancers and play also an important role in ... more Estrogens represent risk factors for endocrinerelated cancers and play also an important role in the development and progression of other malignancies. In order to analyze the associations between estrogen receptor gene alpha polymorphisms and cancers susceptibility, we genotyped six single nucleotide polymorphisms (SNPs) in 163 Caucasian cancer patients-103 breast cancers and 60 other malignancies (colorectal, bladder, hepatocellular carcinoma and acute myeloid leukemia)-and 114 healthy controls using hybridization probes. We performed Armitage`s association trend-test to evaluate the risk. Linkage disequilibrium (LD) was assessed for each pair of markers. The genotypes CC and CT of rs3798577 were significantly associated with the cancers risk (p-trend breast =4×10-5 ; p-trend cancers =1×10-5); in discrepancy with breast cancer where the C-allele represented the risk allele, for bladder, hepatocellular carcinomas and leukemia, the T allele seems to confer susceptibility. The minor G allele of rs1801132 was protective in our cases (p=1×10-4); for rs2228480, the heterozygous frequency was higher for cancer groups (p=0.03); the SNP pairs rs2228480&rs3798577 and rs2234693&rs9340799 were in low LD; the haplo types T-A of rs2234693&rs9340799 and G-C of

Research paper thumbnail of Prevalence of a Iodothyronine Deiodinase 2 gene single nucleotide polymorphism in children with congenital hypothyroidism from Western Romania and impact on TSH levels

Revista Română de Medicină de Laborator, 2019

The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92... more The aim of this study was to evaluate the prevalence of the Iodothyronine Deiodinase 2 gene Thr92Ala polymorphism in children from West of Romania with congenital hypothyroidism (CH) and association with TSH levels in response to levothyroxine monotherapy. Genotyping in 50 children with CH and 52 healthy controls was done using real time PCR. The results showed that there was no statistical difference between the frequencies of genotypes in patients vs. controls. Patients were treated with L-thyroxine and most had normal values for fT3 and fT4. However, high TSH values were found in 21 patients (42%) after treatment. Among patients with high TSH values, AA genotypes were significantly more prevalent (p = 0.044) than TT and AT genotypes. Our results suggest that for the D2 gene Ala92Thr polymorphism, the AA genotype may be detrimental for achieving euthyroidism in patients with CH and levothyroxine monotherapy, therefore polytherapy could be considered as a better approach in these patients.

Research paper thumbnail of Pro-inflammatory Cytokines (IL6, IL8 and TNF-a) in the Evaluation of Ovarian Endometriosis Cyst

Revista de Chimie, 2019

Endometriosis is the abnormal growth of cells (endometrial cells) similar to those that form the ... more Endometriosis is the abnormal growth of cells (endometrial cells) similar to those that form the inside of the uterus, but in a location outside of the uterus. Endometriosis is most commonly found on other organs of the pelvis. These lesions are most commonly found on the ovaries, the Fallopian tubes, the surface of the uterus, the bowel, and on the membrane lining of the pelvic cavity (i.e. the peritoneum). We corroborate TNF-a, IL-6 and IL-8 markers with intraoperative laparoscopic on 39 patients diagnosed with endometriosis in January 2016 - December 2017, aged 20-45 years. There has been a preoperative evaluation in the patients from this that included the anamnesis, clinical examination and laboratory tests. Anamnesis recorded demographic details, patient�s personal, physiological and pathological medical history. Evaluation of preoperative investigations consisted of general and local systems examination, a gynecological examination in order to identify the specific signs of e...

Research paper thumbnail of Proceedings of the 2017 WAO Symposium on Hot Topics in Allergy: Pediatric & Regulatory Aspects: Rome, Italy/Vatican City. 27-29 April 2017

The World Allergy Organization journal, 2017

BACKGROUND In pediatric ages, sublingual immunotherapy (SLIT) allows allergic children to approac... more BACKGROUND In pediatric ages, sublingual immunotherapy (SLIT) allows allergic children to approach the inhaling desensitizing therapy. However, SLIT causes quite a few compliance problems and sometimes it is difficult to carry it out for the required long term. The alternative is subcutaneous immunotherapy (SCIT), commonly performed with a syringe. This technique hasn't changed much in time and it is not without risks or discomfort. This has led to the search for alternative ways of vaccine administration, in order to reduce discomfort to children by improving compliance and diminishing the potential risks of adverse reactions. OBJECTIVE The study aimed to assess the patient's perceived pain and the safety of a new way of administration of SCIT, with a needleless device. METHODS Children with grass or mite-induced allergic rhinoconjunctivitis and/ or bronchial asthma were prescribed a glutaraldehyde-polymerized allergenic extract (Allergovac Polymeryzed®, Bial Aristegui, Italy). Each dose was divided in two parts: half injected with the traditional syringe (dose A), half in the other arm with a needleless device (Injex, Greytree, Ross on Wye, UK; dose B). Patients were blindfolded. The perceived pain and the difficulties of the procedure were registered on a dedicated VAS scale immediately (time 1) and 20 minutes after the first injection (time 20). Also, we evaluated the occurrence of occasional adverse events during such procedure and we assessed the perceived difficulty by the doctor administering with such method. RESULTS 39 patients, aged 5-18 years, were recruited and assessed. All patients completed the study, which involved 468 grass pollen AIT SCIT doses, of which 234 with needleless device. At time 1, the use of the needleless device led to an 88% reduction of the pain perception average rate (from 16,8 to 1,97). The difficulty for the technician to make the inoculum was also analyzed (expressed by an increasing rate, from 0 to 4). In all 6 doses, for each child, the difficulty rate 2 relates to an almost constant number of patients, while the highest difficulty rates (grade 3 and grade 4) gradually decrease (until they disappear). CONCLUSIONS The vaccine administration with needleless device has various advantages and it ensures a better acceptance in comparison with administration by traditional SCIT. This is important in order to start the immunotherapy at an early stage, as it is recommended by the most recent studies, so that the natural evolution of the allergic disease can be immediately modified. The new technique ensures a higher safety both for the vaccinator and for the patient, with a better acceptance of the procedure by the patient and therefore a better and wider compliance to the vaccination schedules.

Research paper thumbnail of Neurofibromatosis Type 1–MOLECULAR Testing and Clinical Presentation of Two Cases

Analele Ştiinţifice ale Universităţii „Alexandru Ioan Cuza”, Secţiunea Genetică şi Biologie Moleculară, 2010

Neurofibromatosis type 1 is caused by mutations in the NF1 gene located on chromosome 17q. Case 1... more Neurofibromatosis type 1 is caused by mutations in the NF1 gene located on chromosome 17q. Case 1: A 1 year 7-month-old boy had progressive right ptosis which began when he was 19 months of age and numerous café-au-lait spots. Case 2: A 28 years old woman presents: café-au-lait spots, one subcutaneous tumor on the left leg, a first degree family member, who has NF1-malignant form. Molecular Genetic analysis consisted of: 1. Amplification of the entire coding region of the NF1 gene. 2. Screening for deletions and duplications in the NF1 gene by MLPA analysis. Results: Case 1: A heterozygous c.1719delT mutation was identified in exon 11 of the NF1 gene. Case 2: A heterozygous c.6709C>T mutation was identified in exon 45 of the NF1 gene. Conclusions: The mutations founded in both cases determined a truncated NF1 protein, which is disease-causing.

Research paper thumbnail of Functional Analysis of Human Gene Promoters

REVISTA DE CHIMIE- …, 2007

The complexity of gene control processes and the perspectives opened by understanding how to cont... more The complexity of gene control processes and the perspectives opened by understanding how to control a target gene are several important reasons for researchers to try to find out more information about gene control mechanisms and the molecular networks responsible for that. The ...

Research paper thumbnail of Genetic analysis of CFTR mutations in cystic fibrosis patients from Romania

Timisoara Medicala, 2006

Cystic fibrosis is the most common autosomal recessive disease in Caucasian populations. The aim ... more Cystic fibrosis is the most common autosomal recessive disease in Caucasian populations. The aim of this study was to improve the number of cystic fibrosis mutations detected in patients from the National Center of Cystic Fibrosis from Timisoara and to establish a solid method of genetic analysis for cystic fibrosis mutations in Timisoara. The study included a retrospective part, which consisted of analyzing the genetic tests results for 79 patients from the National Center of Cystic Fibrosis from Timisoara, already investigated in collaboration with Royal Manchester Children's Hospital - Genetic Unit (UK), and an original, prospective part, in which we selected 17 patients in evidence at the Center for genetic analysis, based on clinical findings and sweat test. 29 mutations were investigated and the detection was performed using a ElucigeneTM CF29 kit, which detects point mutations or small deletions in deoxyribonucleic acid (DNA) using a method based on ARMS allele specific amplification technology. DNA was extracted from lymphocytes from peripheral blood samples, genomic DNA was amplified by PCR and the PCR products were visualized on a UV transiluminator after electrophoresis on agarose gel and staining with ethidium bromide. Results: We identified 18 mutated alleles from a total number of 34 alleles and three mutations: ΔF508, G542X and I148T. We combined the new, original data with data from the retrospective part and we obtained new estimates of the frequency for CF mutations in Romania. Conclusion: The most frequent mutation in Western and Central Europe, ΔF508 (70%) has a lower frequency in Romania (47,92%). There are still many mutations that remain unidentified (34 %) by investigating only the usual mutations. The great number of mutations and polymorphisms identified up to date reflects the genetic heterogeneity of Romanian population.

Research paper thumbnail of Antibiotherapy in Children with Cystic Fibrosis—An Extensive Review

Children

In cystic fibrosis (CF), the respiratory disease is the main factor that influences the outcome a... more In cystic fibrosis (CF), the respiratory disease is the main factor that influences the outcome and the prognosis of patients, bacterial infections being responsible for severe exacerbations. The etiology is often multi-microbial and with resistant strains. The aim of this paper is to present current existing antibiotherapy solutions for CF-associated infections in order to offer a reliable support for individual, targeted, and specific treatment. The inclusion criteria were studies about antibiotherapy in CF pediatric patients. Studies involving adult patients or those with only in vitro results were excluded. The information sources were all articles published until December 2021, in PubMed and ScienceDirect. A total of 74 studies were included, with a total number of 26,979 patients aged between 0–18 years. We approached each pathogen individual, with their specific treatment, comparing treatment solutions proposed by different studies. Preservation of lung function is the main g...

Research paper thumbnail of Microbiology Characteristics Among Cystic Fibrosis Patients in Western Romania

Central European Journal of Clinical Research, 2018

Background: Pulmonary infectious inflammation is a major cause of decline in lung function in pat... more Background: Pulmonary infectious inflammation is a major cause of decline in lung function in patients with cystic fibrosis (CF) marked by exacerbations, consequently, slowing evolution of lung disease is a primary aim in CF management. The objective of the study was to analyze the microbiological spectrum from epidemiological point of view in our patients. Methods: An observational, cross-sectional transversal study including fifty-seven patients evaluated the prevalence of CF-related microbes in the study group and their pulmonary status. Results: The most frequent microorganism found in our group, regardless age, was Staphyloccocus aureus, closely followed by Pseudomonas aeruginosa. Bacillus tuberculosis was a rare germ, despite the important frequency in our country. The microbes frequency was different with age groups, thus 3.5% of 1-3 years old children had the methicillin sen sitive Staphylococcus aureus (MSSA) strain, while for the 6-12 years group, Pseudomonas aeruginosa wa...

Research paper thumbnail of Microarray Technology for the Detection of Antimicrobial Resistance Genes Present in Hospital and Community Acquired Methicillin Resistant S.aureus Strains

Revista de Chimie, 2017

Antimicrobial resistance (AMR) represents a real burden for the modern medicine. One of the most ... more Antimicrobial resistance (AMR) represents a real burden for the modern medicine. One of the most frecvently isolated hospital acquired (HA) pathogens wordlwide, is Methicillin resistant Staphylococcus aureus (MRSA). Recently not only HA, but also community-acquired MRSA (CA-MRSA) infections have been reported. A prospective study was performed between February 2009 and October 2010, with the aim to investigate bacterial resistance of CA-MRSA and HA-MRSA. DNA microarray technology has been used for the detection of 4 AMR genes for the studied MRSA strains. A number of 218 HA- S.aureus strains have been isolated, from which 89 (40. 82%) were MRSA. In the community, 1.553 S.aureus strains were isolated, out of which, 356 (22. 92%) were MRSA. From these, a number of 17 HA and 12 CA �MRSA strains have been analyzed by DNA microarray technology. From 100% phenotypically described HA- MRSA, we identified mecA gene in 10 strains (58. 83%). Other 6 strains (35. 29%) have been erm(A) positive...

Research paper thumbnail of The genetic investigation of old tissue samples paraffin-embedded as source for molecular autopsies in sudden cardiac death cases

Studia Universitatis Vasile Goldis Arad, Seria Stiintele Vietii, 2014

Sudden cardiac death (SCD) is a major cause of death in young adults and children. Standard foren... more Sudden cardiac death (SCD) is a major cause of death in young adults and children. Standard forensic autopsy procedures are often unsuccessful in explicating the causes of SCD. “Gene” or “molecular autopsy” has a great potential for identifying unknown causes of death. The aim of our study was to design a methodology of molecular analysis for investigating old tissue samples paraffin-embedded, collected from subjects with SCD. For molecular analysis we selected a Real Time PCR method with Taqman probes, the SCN5A gene which can be mutated in several channelopathies – Brugada syndrome, LQT, FAF and a frequent mutation of SCN5A gene - E1784K. 51 samples were investigated and the genotype was determined for 47 subjects. By this study we showed that the molecular analyze of genomic DNA extracted from formalin-fixed and paraffin-embedded tissues by Real Time with TaqMan probes method is an efficient and suitable approach for samples with old and fragmented DNA molecules, which can be used for the successful identification of normal alleles or specific pathogenic mutations. By molecular dissection, old cases with no identified cause of death can be deciphered and the positive molecular diagnosis will provide the basis for genetic counseling and treating surviving family members.

Research paper thumbnail of J07.20 Management and molecular diagnosis in romanian patients with Duchenne/Becker muscular dystrophy

European journal of human genetics: EJHG

Duchenne and Becker muscular dystrophy (DMD/BMD) are the most common muscular dystrophies with X-... more Duchenne and Becker muscular dystrophy (DMD/BMD) are the most common muscular dystrophies with X-linked inheritance caused by mutations in the DMD gene. DMD is the most severe form with a complete absence of dystrophin synthesis. The most frequent DMD gene mutations are large deletions and duplications of one or more exons. Method. For molecular diagnosis of patients diagnosed with DMD/BMD only on the base of clinical symptoms, family history and creatine kinase levels we used MLPA (Multiplex Ligation-dependent Probe Amplification) technique. Genomic DNA was extracted from blood samples and 35 unrelated patients and 20 relatives were analyzed. The MLPA products were quantified by capillary electrophoresis and interpreted using Coffalyser software. Results. Large deletions were identified in 24 patients (68,57%) and large duplications in four patients (11,42%). 14 female patients with heterozy gous genotypes confirmed previously identified mutations in male patients and in 6 subjects...

Research paper thumbnail of Cystic fibrosis liver disease - from diagnosis to risk factors

Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2014

Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmit... more Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency,
meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases.
Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

Research paper thumbnail of 187 Evaluation of cystic fibrosis liver disease and the relation with risk factors in a Romanian centre

Journal of Cystic Fibrosis, 2014

SERPINA1 gene is present in about 2% of patients with cystic fibrosis, but more frequently, in ap... more SERPINA1 gene is present in about 2% of patients with cystic fibrosis, but more frequently, in approximately 5% of patients with cystic fibrosis (CF) and concomitant changes in the liver. Aim: The aim of this study was to assess the impact of SERPINA gene mutation on the occurrence of liver damage and cholestasis in patients diagnosed with cystic fibrosis. Patients and Methods: The analysis included 30 children, 13 girls (43.3%) and 17 boys (56.6%), aged from 6 months to 18 years, with diagnosed CF. All patients underwent genetic testing for SERPINA gene mutation. The analysis included age, sex, clinical symptoms, type of mutation of the CFTR protein, laboratory abnormalities (levels of transaminases, GGTP, FA, protein, acid steatocrit) and ultrasound examination of the abdomen. Results: Elevated transaminases were found in 9/30 (30%), whereas elevated levels of gamma-glutamyl transferase in 6/30 (20%) children. In 5/30 patients the ultrasound examination demonstrated liver enlargement with increased echogenicity. The mutation in SERPINA gene was found in 1/30 (3.3%) patient with cystic fibrosis. Currently, this patient has normal values of transaminases, GGTP and FA, whereas, a significant worsening of respiratory symptoms is observed. There was no correlation between the occurrence of SERPINA gene mutation and clinical symptoms, type of CFTR protein mutation, results of laboratory tests of liver function and hepatocyte damage, and ultrasound examination of the abdomen. Conclusions: There was no correlation between the occurrence of SERPINA gene mutation and the presence of features of liver damage and cholestasis in children diagnosed with cystic fibrosis.

Research paper thumbnail of 123 How frequent is Clostridium in our CF patients?

Journal of Cystic Fibrosis, 2014

Research paper thumbnail of Safety of Vascular Endothelial and Hepatocyte Growth Factor Gene Therapy in Patients with Critical Limb Ischemia

Current Neurovascular Research, 2011

The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expres... more The present clinical trial analyzed the safety of gene therapy using plasmidial constructs expressing vascular endothelial and hepatocyte growth factors in patients with critical limb ischemia. The study included 43 patients: 29 in the treatment group and 14 allocated to the placebo group. The primary end points were the rate of major amputations and the clinical safety of the method. Secondary end points were improvement of pain at rest, walking ability and the ankle/brachial pressure index. The overall major amputation rate was 31.04% in the treatment group and 71.42% in the
placebo group (p=0.029). Pain at rest was improved in 65% of patients in the gene therapy group and in 7% in the placebo group (p=0.0006). There were no significant adverse effects in the treatment group. Conclusion: Gene therapy with vascular endothelial and hepatocyte growth factors is therapeutically safe and reduces the rate of major amputations and relieves pain at rest in patients with critical limb ischemia.

Research paper thumbnail of 12 Associated conditions in cystic fibrosis: findings at diagnosis and changes in time, impact on clinical outcomes and quality of life

Journal of Cystic Fibrosis, 2014

Objectives: To determine the burden of associated conditions in Cystic Fibrosis and their impact ... more Objectives: To determine the burden of associated conditions in Cystic Fibrosis and their impact on clinical outcomes in a pediatric cohort. Methods: Retrospective clinical file analysis of pediatric CF patients followed up during 1999-2013, correlated with diagnosis of CF and non CF related associated conditions. Results: 56 patients followed up, mean age at diagnosis 11 months, 22/56 died (11 before the age of 1 year). Causes of early deaths: severe lung disease and malnutrition correlated with poor socioeconomic status. 13/56 had meconium ileus (2/56 meconium peritonitis, 2/56 parcelar intestinal athresia), all underwent surgery with difficult recovery and high rate of complications. Related CF conditions: 4/56 nasal polyposis, 4/56 CFrelated diabetes, 5/56 early CFRLD, 4/56 ABPA; all negatively impacted clinical outcomes. Diagnosis of other chronic diseases in 13/56 patients (some genetic traits): juvenile myoclonic epilepsia (1/56), horseshoe kidney (1/56), spastic paraparesis (1/56), congenital cardiac malformations (4/56), ADHD (3/56), asthma and allergic rinitis (4/56). Higher rate of hospitalization, lower clinical and radiological scores were observed in patients with CF related conditions (p < 0.05). Quality of life was negatively impacted by both presence of CF related and nonCF related conditions, regardless age. Conclusion: Associated CF related conditions are frequent observed as survival increases in CF. Diagnosis of other chronic conditions in CF may negatively impact clinical outcomes, more so with increasing of age. Early diagnosis of other chronic traits in CF, specialized and multidisciplinary care is needed to improve QoL and life span.

Research paper thumbnail of 5 Regular genetic kit for CF mutations detection

Journal of Cystic Fibrosis, 2012

Background: A characteristic aspect for Romania is the CF mutations heterogeneity which leads to ... more Background: A characteristic aspect for Romania is the CF mutations heterogeneity which leads to a reduced percentage of genotype identification. Objectives: Assessment of the efficacy of a mixed panel for CF mutation detection in Romanian patients. Methods: We evaluated retrospectively 40 patients(pts) with typical CF, registered in the National CF Center Timisoara. The genetic tests were performed using a mixed panel − (29 mutations − panel 1) − ARM and another kit for 38 mutations (panel 2) − PCR. 18 mutations were common to the two kits; the total number of identifiable alleles was 49. Results: The first panel identified the following mutation, in order of frequency: DF508, G542X, N1303K, 621 + 1 G>T, I148T, representing 17.2% from panel 1 mutation. We found the following patients genotypes: 21 pts with F508del/F508del, 10 pts with F508del/ x, 5 pts F508del/G542X, 1 patient F508del/ N1303K. In 3 pts with compound genotype non-F508del (I148T, N1303K or G542X), the other alella could not be identified, complementary genetic testing done in parents have ruled out the possibility of homozygous genotype for non-F508del. In 13 patients (32.5%) we could not fully identify the genotypet, thus they were further tested with panel 2. Conclusions: Correspondence of kits with identified mutations in CF Romanian patients is low, although kits contain the most frequent mutations used in Europe. Genetic heterogeneity in Romania limits significantly the possibility of detection of both alleles, the diagnosis rate of heterozygote being reduced. The question of using additional kits or methods like CF gene sequencing raise the issue of a very high cost.

Research paper thumbnail of 233 Allergies in children with cystic fibrosis

Journal of Cystic Fibrosis, 2011

Introduction: Accurate serial assessment of FEV1 is essential to help the clinician combat deteri... more Introduction: Accurate serial assessment of FEV1 is essential to help the clinician combat deterioration in CF patients, and spirometry equipment must be capable of reliable and reproducible measurements. Traditional equipment (e.g. Vitalograph 2120) uses reusable flow sensors (i.e. pneumotachograph) which require disposable filters, thereby increasing equipment dead-space and resistance. Newer technology (SpirostikTM) uses disposable flow sensors which do not require filters, reducing dead-space and airflow resistance. We have recently switched over to this new technique and have compared its effect on the FEV1 measurement in our adult CF patients. Method: 85 consecutive adult CF patients (mean age 28 [range 17−53], mean FEV1 59% [12–120], 46 male) performed FVC manoeuvres (measuring FEV1) according to ATS/ERS guidelines, on SpirostikTM and Vitalograph 2120. Student’s paired t test was used for statistical analysis. Results: Patients found the new device easier to use, since it gave them more feedback during the manoeuvre. SpirostikTM recorded on average 9.7% higher FEV1 than Vitalograph 2120 (mean FEV1 2.41 litres [SD 1.00, range 0.8–5.14] versus 2.18 [0.89, 0.6–4.32], P< 0.001). Overall, 76 patients (91%) had higher values on SpirostikTM compared to 2120. Conclusions: This potentially more accurate measure of spirometry has increased the average value of FEV1 in our patients significantly. This not only has implications for clinical practice in that we are now having to “recalibrate” our views of individual patient’s clinical progress, but it will also alter the value of data sent to national registries.