Original Article Expression of fibroblast growth factor receptor 1, fibroblast growth factor 2, phosphatidyl inositol 3 phosphate kinase and their clinical and prognostic significance in early and advanced stage of squamous cell carcinoma of the lung

Abstract: Aim: Non-small cell lung carcinoma is the leading cause of cancer related to death in the world. Squamous cell lung carcinoma (SqCLC) is the second most frequent histological subtype of lung carcinomas. Recently, growth factors, growth factor receptors, and signal transduction system-related gene amplifications and mutations are extensively under investigation to estimate the prognosis and to develop individualized therapies in SqCLC. In this study, besides the signal transduction molecule phosphatidyl inositol-3-phosphate kinase (IP3K) p110α, we explored the expressions of fibroblast growth factor 2 (FGF2) and receptor-1 (FGFR1) in tumor tissue and also their clinical and prognostic significance in patients with early/advanced SqCLC. Materials and methods: From 2005 to 2013, 129 patients (23 early, 106 advanced disease) with a histopathological SqCLC diagnosis were selected from the hospital files of Cukurova University Medical Faculty for this study. Two independent pathologists evaluated FGFR1, FGF2, and PI3K (p110α) expressions in both tumor and stromal tissues from 99 of the patients with sufficient tissue samples, using immunohistochemistry. Considering survival analysis separately for patients with both early and advanced stage diseases, the relationship between the clinical features of the patients and expressions were evaluated by univariate and multivariate analyses. Results: FGFR1 expression was found to be low in 59 (60%) patients and high in 40 (40%) patients. For FGF2; 12 (12%) patients had high, 87 (88%) patients had low expression and for IP3K; 31 (32%) patients had high and 66 (68%) patients had low expressions. In univariate analysis, overall survival (OS) was significantly associated with stage of the disease and the performance status of the patient (P<0.0001 and P<0.001). There was no significant difference in OS of the patients with either low or high expressions of FGFR1, FGF2, and IP3K. When the patients with early or advanced stage disease were separately taken into consideration, the relationship did not differ, either. Any of FGFR1, FGF2 or IP3K expressions was not found predictive for the treatment of early or advanced staged patients. On the other hand, the expressions of both FGFR1 and FGF2 were significantly different with respect to smoking, scar of tuberculosis and scar of radiotherapy (P=0.002; P=0.06 and P=0.05, respectively). Discussion: There has not been identified an effective individualized treatment for SqCLC yet. Therefore, in order to be able to develop such a treatment in the future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviors and carcinogenesis of SqCLC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SqCLC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. In conclusion, we want to put some emphasis on the fact that, pulmonary fibrosis which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions

Verification bias on sensitivity and specificity measurements in diagnostic medicine: a comparison of some approaches used for correction

Verification bias may occur when the test results of not all subjects are verified by using a gold standard. The correction for this bias can be made using different approaches depending on whether missing gold standard test results are random or not. Some of these approaches with binary test and gold standard results include the correction method by Begg and Greenes, lower and upper limits for diagnostic measurements by Zhou, logistic regression method, multiple imputation method, and neural networks. In this study, all these approaches are compared by employing a real and simulated data under different conditions

The effect of seizure type, age at onset and drug protocols on prognosis of juvenile myoclonic epilepsy

Amaç: Bu çalışmada Juvenil Myoklonik Epilepsili (JME) olgularda, nöbetlerin başlama yaşı, nöbet tipi, tedaviye başlamada gecikme ve tedavi protokolünün prognoz üzerindeki etkilerinin araştırılması amaçlanmıştır. Gereç ve yöntemler: Uluslararası epilepsi ile savaş derneği (ILAE)sınıflandırmasına (1989) göre J M E tanılı, düzenli antiepileptik ilaç sağaltımı alan, yaş ortalaması 22.16 ± 4.77 (16 - 37) olan 23 kadın, 9 erkek, toplam 32 olgu çalışmaya alındı. Olguların, cinsiyet, nöbet başlangıç yaşı ve klinik özellikleri, tedavide gecikme süresi, kullanılan tedavi protokolleri, antiepileptik ilaçların kullanım süresi, tedaviye yanıt özellikleri, interiktal elektroensefalografi (EEG) ve magnetik resonans incelemesi (MRI) değerlendirmeye alınmıştır. Bulgular: Olgularımızın %75 (n: 24)'inde nöbetler 12 yaş ve sonrasında başlamıştır. Hastaların, %68,8 (n: 22)'inde üç, % 31.2 (n:10)'sinde iki tip nöbet kombine olarak görülmüştür. Olguların % 31.3 (n:8)'ünde nöbetlerin başladığı ilk yıl tanı aldıkları ve tedaviye başlandığı, %68.7 (n:22)'sinde ise ortalama 4,5 (1-14) yıl gecikme olduğu belirlendi. Hastalar ortalama 5.4 (1-13) yıl süre ile takip edildiler. Olguların %37.5 (n: 12)'inde tam, % 62.5 (n: 20)'inde ise kısmi düzelme gözlendi. Sonuç: Nöbetlerin 12 yaş ve sonrasında başladığı olgularda prognozun kısmen daha iyi olduğu görüldü. Bununla birlikte ikili nöbet kombinasyonu olan (p:0.001) ve monoterapi alan hasta grubunda (p: 0.034) prognozun daha iyi olduğu, tedaviye ilk bir yıl içinde başlananların (n:10) % 50'sinde, tedaviye geç başlananların ise %.21.8 'inde nöbetlerin tam olarak kontrol altına alındığı belirlendi.The Effect Of Seizure Type, Age at Onset and Drug Protocols on Prognosis of Juvenile Myoclonic Epilepsy Objectives: The aim of this study is to evaulate the effect of age at seizure onset, seizure types, drugs protocols and the duration of treatment delay on prognosis in juvenile myclonic epilepsy (ME). Material and methods: The study included 32 patients (23 women, 9 men; mean age 22.2 ±4.8 years; range 16 to 37 years) with JME according to ILAE clasification (1989). Clinical characteristics of patients including gender, age at seizure onset, seizure types, duration of delay in the initiation of therapy, treatment protocols, response to therapy, interictal electroencephalography (EEG) and magnetic resonans imaging (MRI) were reviewed. Results: The seizures started at or after 12 years of age in 75 % (n: 24) of the patients. All of our patients had multiple seizures types; 68.7 % (n: 22) of our cases had three types and 31.2 % (n:8) had two types. Thirty one percent were diagnosed as JME and placed on therapy within one year of disease onset, howewer 68.7 % (n:22) of the cases had a delay in the diagnosis and treatment by a mean of 4.5 (1-14) years. The patients were followed up for a mean of 5.4 (1-13) years. In this study we found that 37 % of patients were seizure free and 62.5 % had partially controlled seizures at the end of our follow -up. Conclusion: The prognosis was very good in patiens on monotherapy (p: 0.034), and it was better in patients'with disease onset after 12 years of age. On the other hand, prognosis was very good in patiens who had two types of seizures compared to the ones with three types (p:0.001). Seizures were under control in 50 % of patients who did not have any delay in diagnosis and therapy and only in 21.8% of patients with a delay in the initiation of therapy

Prognosis of patients with seizures occurring in the first 2 years

PubMedID: 17621501The aim of this study is to determine the prognosis of patients with seizure onset from 1 to 24 months of age in respect to epilepsy, developmental outcome, and neurological status. It also aims to determine predictive factors regarding an unfavorable prognosis. Seventy-five patients were retrospectively analyzed. Univariate analysis revealed the following findings: (1) mental retardation at initial admission, abnormal neurological finding, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on electroencephalography (EEG) of neonatal seizure, and perinatal anoxia were significant risk factors with regard to developmental outcome; (2) mental retardation at initial admission, abnormal neurological finding, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on EEG, symptomatic etiology, history of neonatal seizure, and perinatal anoxia were significant risk factors regarding neurological status; and (3) mental retardation at initial admission, neurological abnormality, infantile spasm, use of more than 1 antiepileptic drug, epileptic activity on EEG, status epilepticus, symptomatic etiology, seizure frequency of more than once per week, history of perinatal anoxia, and neonatal seizure were significant risk factors regarding epilepsy prognosis. In addition, multivariate analysis revealed that neurological abnormality and use of more than 1 antiepileptic drug were significant for developmental outcome, that epileptic activity on EEG and use of more than 1 antiepileptic drug were significant for neurological status, and that perinatal anoxia, infantile spasm, and status epilepticus were significant for epilepsy prognosis. These findings suggest that neurological abnormality, use of more than 1 antiepileptic drug, infantile spasm, status epilepticus, and perinatal anoxia are unfavorable predictive risk factors regarding the prognosis of patients with seizures that have an onset from 1 to 24 months of age

General characteristics of supratentorial astrocytoma cases treated with high dose external radiotherapy

1990-1994 yılları arasında Çukurova Üniversitesi Tıp Fakültesi Radyasyon Onkolojisi Anabilim Dalında 73 supratentoriyal astrositoma olgusu, normal beyin dokusunun toleransını aşmayan yüksek radyoterapi dozları ile tedavi edildi. Grade 1,11 astrositomalara median 66 Gy, Grade III,IV astrositomalara 68 Gy eksternal radyoterapi verildi. 13 Grade III,IV astrositoma olgusunda ise total tümör dozu 70 Gy 156 fraksiyon 138 gün hiperfraksiyone radyoterapi (2x1.25 Gy/gün) programı kullanıldı. Olguların %15'ine total rezeksiyon, % 45'ine subtotal rezeksiyon, %40'ına biyopsi yapılmıştı. E/K oranı tüm olgularda 1.4, Grade 1,11 astrositomalarda 1, Grade III,IV astrositomalarda ise 1.8 idi. Olguların %13'ü Grade I, %25'i Grade II, %20'si Grade III, %42'si Grade IV'tür. Olgular 3-76 yaş {ortalama 34, median 32+2.06 (standart sapma 17.67)} arasındaydı. Olgularımızın %28'i takipli, %60'ı ex., %12'si kayıptır. Ortalama takip süresi 76 ay (3-48), median 14±1.27 (standart sapma 10.92) aydır. Grade 1,11 astrositomalı 28 olgunun 1, 2, 3 yıllık sağkalım oranları sırasıyla %76, %52, %48 (ortalama 31, median 25±4 ay) dir. 45 Grade III,IV astrositomada ise bu oranlar sırasıyla %60, %24, %12 (ortalama 18, median 15±2 ay) dir. Grade 1,11 astrositomalar ile Grade III,IV astrositomalar arasında sağkalım açısından anlamlı bir ilişki tespit edildi (p< 0.05). Grade III ve Grade IV olgularda 1, 2, 3 yıllık sağkalım oranları sırasıyla Grade lll'te %80, %44, %16 (ortalama 23, median 21±l.62 ay), Grade IV'te %48, %16, %8 (ortalama 14, median 11 ay) dir (p=0.05 ). Yüksek doz eksternal radyoterapi, morbidite riskine rağmen sağkalım oranları açısından sonuçları olumlu etkilemektedir

Renal tubular dysfunction in epileptic children on valproic acid therapy

PubMedID: 11322374To investigate the effects of valproic acid (VPA) on renal tubular function, we examined 15 ambulatory children with epilepsy who received VPA for at least 6 months. None of the patients had mental retardation. Fourteen age- and sex-matched children were used as a control group. No statistically significant differences were found between patients and control subjects with respect to blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance (Ccr), tubular reabsorption of phosphorus (TRP), urinary Ca:creatinine ratio, urinary pH and mean urinary ß2-microglobulin concentrations (P&gt;0.05). Protein and glucose in patient urine samples were negative. Urine microscopic examinations and amino acid chromatographies of patients were also normal. However, significant differences were found between patient and control groups with respect to mean urinary N-acetyl-beta-D-glucosamine: creatinine ratio (NAG:Cr) and mean urinary malondialdehyde: creatinine (MDA:Cr) ratio (P&lt;0.05). In conclusion, ambulatory children with epilepsy taking VPA therapy may develop proximal renal tubular dysfunction. Although this finding is clini-cally insignificant, it should be kept in mind during VPA therapy

The Effect of Intravenous Magnesium Sulphate Treatment on the Spinal Anaesthesia Produced by Bupivacaine in Pre-eclamptic Patients

OBJECTIVE: In our study, the effect of intravenous magnesium sulphate in normal and pre-eclamptic patients on spinal anaesthesia produced by bupivacaine was investigated. METHODS: Sixty-four pregnant (32 normal and 32 pre-eclamptic) were accepted in this study. Pregnants were divided into four groups as patients given intravenous magnesium sulphate and as control. Spinal anaesthesia was induced with 12.5 mg 0.5% hyperbaric bupivacaine. Intraoperative and postoperative haemodynamic variables, sensorial block periods, onset times of sensorial and motor block, maximum sensorial block levels, the time to reach maximum block level, Bromage scores, consumptions of intraoperative analgesic and ephedrine, the quality of anaesthesia, the duration of spinal anaesthesia and magnesium levels in blood and cerebrospinal fluid were measured and recorded. RESULTS: The level of magnesium in blood and cerebrospinal fluid was significantly higher in the group given magnesium in pre-eclamptic patients (p<0.01). Onset of sensory block times were significantly longer in intravenous magnesium group than in groups 1, 2 and 3 (p<0.05). Onset of motor block times were significantly longer and the duration of anaesthesia was shorter in groups given magnesium (p<0.05). Although the quality of anaesthesia was similar, supplemental analgesic consumption was significantly higher in pre-eclamptic pregnants given magnesium sulphate than in pre-eclamptic pregnants who were not given magnesium sulphate (p<0.05). CONCLUSION: Intravenous magnesium sulphate treatment during the spinal anaesthesia produced by bupivacaine extended the onset of sensory and motor block times, shortened the duration of spinal anaesthesia and therefore led to early analgesic requirement