Mutation Status and Immunohistochemical Correlation of EGFR Mutations in Gastrointestinal Stromal Tumors.

Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

Relationship of hematologic markers with IL-17 and IL-1 beta in patients with rheumatoid arthritis.

OBJECTIVES: In this study, we aimed to investigate the relationship of NLR (Neutrophil lymphocyte ratio), MPV (mean platelet volume), PDW (distribution width) rates in rheumatoid arthritis (RA) patients with IL-17 and IL-1 beta which are within the cytokines playing an important role in etiopathogenesis and activity of the disease. PATIENTS AND METHODS: Fifty-seven RA patients diagnosed according to RA classification criteria of ACR/EULAR 2010 and 37 controls were included into the study. WBC (white blood cell), NEU (neutrophil), PLT (platelet), LYM (lymphocyte) values in complete blood count received from routine blood examination of patients were recorded, and NLR, PLR (platelet lymphocyte ratio) rates were recorded. IL-17 and IL-1 beta were studies in serum samples. Disease activity of RA patients was evaluated with Disease Activity Score (DAS28). Age, gender, disease age, BMI (body mass index), medications used, co-morbid diseases, smoking of the patients were recorded. RESULTS: Fifty-seven RA patients (46 (80.7%) females, 11 (19.3%) males), and 34 patients (24 (70.6% females and 10 (29.4) males) as a control group were involved. Demographic characteristics were similar between two groups, and statistically significant difference was not detected between patient and control groups in terms of gender, age, and BMI (p> 0.05). We found higher NLR, MPV, PDW, IL-17 values in RA patients compared to control group (p< 0.05). There was a positive correlation of NLR with DAS28, CRP. While erythrocyte sedimentation rate (ESR) had negative correlation with MPV and PDW, it had positive correlation with PLT. We found positive correlation of C-reactive protein (CRP) with NLR and PLT. We could not find correlation of IL-1 beta and IL-17 with hematologic markers. CONCLUSION: In this study, we investigated the relationship of IL-17 and IL-1 beta which play an important role in pathogenesis of RA patients with the parameters analyzed in routine complete blood count, providing information about disease activity such as DAS 28, CRP, and ESR. We illuminated on an issue which has not discussed before by looking from a different angle. More extensive, follow-up studies are needed to emphasize the importance of these parameters and to reveal the relationship between cytokines during the follow-up of the disease activity.

Evaluation of arterial stiffness and cardiac function in patients with vascular erectile dysfunction: acute effects of phosphodiesterase-5 inhibitor tadalafil.

This study aimed to detect endothelial dysfunction in erectile dysfunction (ED) patients free from cardiovascular diseases or atherosclerotic risk factors and to evaluate acute effects of phosphodiesterase-5 inhibitor tadalafil on endothelial dysfunction and cardiac function. Thirty ED patients and 20 healthy male subjects (mean ages: 48.7±11.7 and 48.3±8.7 years, respectively) were enrolled. Endothelium functions were assessed by applanation tonometry. Aortic stiffness and cardiac function were evaluated by transthoracic echocardiography. Pulse pressure was greater in the ED group (P<0.05), whereas aortic strain and aortic distensibility were significantly lower (P<0.001). Treatment with tadalafil reduced pulse pressure (P=0.0179), systolic blood pressure (P=0.001) and diastolic blood pressure (P=0.054) and increased aortic distensibility (P=0.001) and aortic strain (P=0.003) in the ED group. Tadalafil administration also increased large artery and small artery elasticity indices that were reduced in the ED group at baseline (P=0.02 and 0.003, respectively). Systemic vascular disease and compromised left ventricular diastolic function (LVDF) were present in ED patients with no known atherosclerotic risk factors and cardiac diseases. Tadalafil positively affected arterial stiffness and LVDF.

Associations between polymorphisms of IL-17F and IL-17A genes with disease activity and clinical outcome of Ankylosing Spondylitis.

Aims In this study, we aimed to investigate the associations between the 7383A/G and 7488A/G polymorphisms of the interleukin (IL)-17F gene and the G197A polymorphism of the IL-17A gene with disease activity and clinical outcomes in Turkish patients with ankylosing spondylitis (AS). METHODS: The study included 101 AS patients and 106 healthy controls. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, in addition to scores of the Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index and Bath Ankylosing Spondylitis Functional Index (BASFI) of the patients, were recorded. The frequencies of genotypes 7383A/G and 7488A/G of the IL-17F and G197A of IL-17A genes and alleles were compared between the patients and healthy controls. MAJOR RESULTS: There were significant differences in the allele frequencies and genotype distribution of IL-17F 7488A/G. There were also significant differences in the CRP levels and BASFI scores of patients due to the genotype distribution of the IL-17F 7488A/G polymorphism (p= 0.029, 0.045, respectively). CONCLUSIONS: This study suggests that the IL-17F 7488A/G polymorphism may be associated with susceptibility to AS, disease activity and functional status in Turkish patients. Further studies with larger numbers of AS patients, with a long-term follow-up, are needed to elucidate the observed relations.

Fluvastatin Decreases Oxidative Stress in Kidney Transplant Patients.

OBJECTIVE: Oxidative stress has been suggested to have a pivotal role in the development of cardiovascular disease in kidney transplant patients (KTPs). The effects of fluvastatin on oxidative status in KTPs have not been well evaluated. The aim of the present study was to evaluate the effects of fluvastatin on oxidative status by investigating erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx), serum paraoxonase (PON1), and serum arylesterase (ARE), along with lipid peroxidation products, serum malonldialdehyde, and apolipoprotein B malondialdehyde (ApoB MDA). METHODS: Eighteen KTPs were included in the present study. Blood samples were obtained after 1 night's fast. Erythrocyte SOD, erythrocyte GPx, serum PON1, serum ARE, serum MDA, and ApoB MDA were measured using methods described previously. Paired-sample t test was used for comparing the changes from week 0 to week 4 of parameters that might be associated with fluvastatin treatment. RESULTS: The present study has shown that erythrocyte SOD and GPx, and serum PON1 and ARE activities increased at the fourth week of the statin treatment. Furthermore an increase in the antioxidant enzymes following fluvastatin may be a clue for the antioxidant effects of this drug. Four weeks of fluvastatin long-acting tablets 80 mg/day led to a decrease in plasma Apo-MDA and MDA levels. CONCLUSION: The findings of the present study demonstrate that fluvastatin 80 mg long-acting tablets may be used safely for 4 weeks and decrease atherogenic lipoproteins in KTPs. Furthermore, after 4 weeks of fluvastatin treatment, the levels of antioxidant parameters increased and oxidative parameters decreased. Further placebo-controlled treatment studies would be helpful to evaluate the effects of fluvastatin on oxidant and antioxidant parameters including PON1 in patients with KT.

MICROARRAY DELINEATION OF DE NOVO DUPLICATION 1q32q42 IN A CHILD SHOWING MULTIPLE ANOMALIES AND DYSMORPHISM.

We present a 9 month-old baby girl with de novo pure interstitial duplication 1q. The girl has dysmorphic craniofacial features as well as neuromotor retardation, multiple subcutaneous solid tissue lesions, urogenital anomalies, cardiac defect, liver parenchyma heterogeneity and intracranial anomaly. The case of de novo duplication of 1q32q42 defined by G-banding and Microarray Comparative Genomic Hybridization (Microarray CGH) was presented with its clinical findings.

A NOVEL MUTATION IN NPR2 GENE IN A PATIENT WITH ACROMESOMELIC DYSPLASIA, MAROTEAUX TYPE.

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive disease characterized by disproportionate shortening of skeletal elements, predominantly affecting the middle segments (forearms and forelegs) and distal segments (hands and feet) of appendicular skeleton. Furthermore it is related to axial skeleton and leads to wedging of vertebral bodies, with shorter dorsal margins than the ventral margins. Bartels et al. defined mutations in NPR2 gene, encoding natriuretic peptide receptor B (NPR-B), underlying Acromesomelic dysplasia, type Maroteaux. We present here molecular and clinical findings of a case with AMDM. In a patient, a novel homozygous mutation c.1435C>T p.R479X in exon 7 of NPR2 gene was found. Further testing confirmed the heterozygous carrier status of the parents. Our findings expand the spectrum of causative mutations in AMDM.

A novel mutation in the FRAS1 gene in a patient with Fraser syndrome.

Fraser Syndrome (FS) is a rare disease with autosomal recessive inheritance characterized by cryptophthalmus, cutaneous syndactyly, laryngeal and urogenital anomalies. Mutations in the genes FRAS1 and FREM2 encoding components of a protein complex of the extracellular matrix, and recently also mutations in GRIP1 have been found to be causative for FS. We present here molecular and clinical findings of a patient with FS who was found to have a novel homozygous frameshift mutation c.9739delA, p.(T3247Pfs*44) in exon 63 of FRAS1 gene. Further testing confirmed the heterozygous carrier status of parents.

A fertile patient with 45X/47XXX mosaicism.

Turner syndrome (TS) is a sex chromosome abnormality with a frequency of 1/2,000-3,000 among female live births. Characteristic findings are short stature and gonadal dysgenesis. Short and webbed neck, low posterior hairline, broad chest, widespread nipples, cubitus valgus, short 4th and 5th metacarpals, multiple pigmented nevi, primary amenorrhea, lack of secondary sexual characteristics, cardiovascular and renal anomalies are the most common presentations. Most of the cases are infertile. Spontaneous pregnancy is unusual and the risk for congenital anomaly, spontaneous abortion, stillbirth and aneuploidy is increased. Fifty percent of the patients have classical monosomy X (45,X). However mosaicism of 45,X/47,XXX is rare and accounts for 1.7% of the TS cases. Some cases may not reflect the characteristic phenotype. Some cases with normal height, normal menstrual cyclus and fertility have been defined before. The case we present herein is a 26 years old woman who was admitted to our clinic due to recurrent pregnancy loss. In her medical history she had type 1 diabetes mellitus and endometrium cancer, in her family history her mother had recurrent pregnancy loss. The patient's first, third, fourth, fifth and sixth pregnancies had resulted in spontaneous abortions in the first trimester. She had a healthy daughter with 46,XX karyotype from her second pregnancy. A 45,X[8]/47,XXX[12] karyotype was detected by conventional cytogenetic analysis of the patient who did not have dysmorphic findings. The mosaicism was confirmed by FISH analysis with CEP X probe. Of the 100 cells evaluated, 65 of them had 3 signals of X chromosome while 35 had 1 signal. We present the case because of its scarcity in the literature.

Association between the catechol-o-methyltransferase val158met polymorphism with susceptibility and severity of carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. In this study, we aimed to clarify the relationships between the catechol-O-methyltransferase (COMT) gene Val158Met (rs4680) polymorphism and development, functional and clinical status of CTS. Ninety-five women with electro diagnostically confirmed CTS and 95 healthy controls were enrolled in the study. The functional and clinical status of the patients was measured by the Turkish version of the Boston Questionnaire and intensity of pain related to the past 2 weeks was evaluated on a visual analog scale (VAS). The Val158Met polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), method. We divided patients according to the genotypes of the Val158Met polymorphism as Val/Val, Val/Met and Met/Met. There were not any significant differences in terms of Val158Met polymorphisms between patients and healthy controls (p >0.05). We also did not find any relationships between the Val158Met polymorphism and CTS (p >0.05). In conclusion, although we did not find any relationships between CTS and the Val158Met polymorphism, we could not generalize this result to the general population. Future studies are warranted to conclude precise associations.

De novo partial trisomy distal 4q: a case report.

We present a case of de novo distal partial trisomy 4q with firstly described chronic cholecystitis, rarely seen hypothyroidism, and bilateral membranous choanal atresia. The patient, a 10-month-old baby girl had dysmorphic facial features as well as neuromotor retardation, congenital hypothyroidism, atrial septal defect (ASD), white matter atrophy in cranial MRI, grade 2 dilatation in pelvicalyceal system of the left kidney, and bilateral ureteral reflux. In peripheral blood chromosome analysis 46, XX, dup(4) (q21q35) karyotype was detected. In FISH analysis using 4p/4q subtelomeric probe; 3 signals for 4 q region and 2 signals for 4p region were observed. In chromosome analyses of her healthy parents, no anomaly was detected. Herein we present a case of de novo partial distal trisomy 4q syndrome to contribute to the literature since it is rarely seen and this is the first patient with partial trisomy distal 4q syndrome presented with chronic cholecystitis and the second patient with hypothyroidism.

Effects of Origanum onites on endothelial function and serum biochemical markers in hyperlipidaemic patients.

The effects of Origanum onites on endothelial function and antioxidative status were investigated in 48 patients with mild hyperlipidaemia who required no drug therapy. All participants were given lifestyle and low-fat dietary advice, however 32 of the patients (study group) were also prescribed 25 ml of aqueous distillate of Origanum onites to be taken after each meal for 3 months. The remaining 16 patients were the control group. Various biochemical markers and endothelial function parameters were measured at baseline and after 3 months. A significantly greater increase in high density lipoprotein-cholesterol and significantly greater decreases in low density lipoprotein-cholesterol, apolipoprotein B, lipoprotein(a) and high sensitivity C-reactive protein occurred in the study group compared with the control group over the 3-month study period. Paraoxonase and arylesterase activities, and flow- and nitroglycerine-mediated dilatation of the brachial artery showed significantly greater increases in the study group compared with the changes in the control group. In conclusion, consumption of Origanum onites distillate had beneficial effects on lipid profiles, antioxidant status and endothelial function in patients with mild hyperlipidaemia.