Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines

It is not understood why some head and neck squamous cell carcinomas, despite having identical morphology, demonstrate different tumor aggressiveness, including radioresistance. High levels of the free radical nitric oxide (NO) and increased expression of the NO-producing enzyme nitric oxide synthase (NOS) have been implicated in tumor progression. We previously adapted three human tongue cancer cell lines to high NO (HNO) levels by gradually exposing them to increasing concentrations of an NO donor; the HNO cells grew faster than their corresponding untreated (“parent”) cells, despite being morphologically identical. Herein we initially characterize the HNO cells and compare the biological properties of the HNO and parent cells. HNO/parent cell line pairs were analyzed for cell cycle distribution, DNA damage, X-ray and ultraviolet radiation response, and expression of key cellular enzymes, including NOS, p53, glutathione S-transferase-pi (GST-pi), apurinic/apyrimidinic endonuclease-1 (APE1), and checkpoint kinases (Chk1, Chk2). While some of these properties were cell line-specific, the HNO cells typically exhibited properties associated with a more aggressive behavior profile than the parent cells (greater S-phase percentage, radioresistance, and elevated expression of GST-pi/APE1/Chk1/Chk2). To correlate these findings with conditions in primary tumors, we examined the NOS, GST-pi, and APE1 expression in human tongue squamous cell carcinomas. A majority of the clinical samples exhibited elevated expression levels of these enzymes. Together, the results herein suggest cancer cells exposed to HNO levels can develop resistance to free radicals by upregulating protective mechanisms, such as GST-pi and APE1. These upregulated defense mechanisms may contribute to their aggressive expression profile.     

Prognostic factors in elderly patients with non-small cell lung cancer: a two-center experience

Non-small cell lung cancer (NSCLC) is usually at advanced stage when it is diagnosed. There is no consensus about the standard treatment in elderly patients with advanced NSCLC. Generally, data regarding elderly patients with NSCLC are withdrawn from general NSCLC studies based on subgroup analyses and suggestions. We evaluated prognostic factors in elderly patients with advanced NSCLC. We reviewed retrospectively 338 patients from August 2005 to July 2009 in two centers in Turkey. Medical records of the patients ≥65 years with advanced NSCLC were collected. Collected data included demographic informations, clinical assessments and information on treatment, toxicities and outcomes. Survival was estimated by using Kaplan–Meier method and prognostic factors were evaluated with log-rank and Cox regression tests. The median overall survival (OS) for the entire group was 15.4 months (95% CI: 12.7–18.0). In univariate analysis, weight loss, stage, combination therapy, second-line chemotherapy and tumor response (P < 0.01) and performance status significantly affected OS (P < 0.05). The median progression-free survival (PFS) was 10 months (95% CI: 8.4–11.6). In univariate analysis, there was only a significant association between tumor response and PFS (14.6 vs. 8.5 months; P < 0.001). Multivariate analysis showed that only response to therapy was an important prognostic factor for OS (P < 0.001). Survival of elderly patients with advanced NSCLC is significantly influenced by performance status, weight loss, stage, combination therapy, second-line chemotherapy and response to therapy. Not only age but also these factors may be kept in mind in the treatment planning of the elderly patients with NSCLC. These results may be of benefit in changing clinical practice in elderly patients with NSCLC who are often undertreated.     

Fetal therapy in twin reserve arterial perfusion sequence pregnancies with alcohol ablation or bipolar cord coagulation

Objective  We aimed to evaluate perinatal outcome of seven pregnancies with twin reserve arterial perfusion sequence. Materials and methods  Study group included seven cases of acardiac twins. Out of seven acardiac twins, two cases were followed without interventions. We performed four alcohol ablation and one bipolar caogulation. For alcohol ablation, a 20-gauge needle guided with color Doppler USG was directed to abdominal insertion site of the single umbilical artery of the acardiac twin, and 1.0–2.0 mL of absolute alcohol was injected. For bipolar coagulation of the umbilical cord, we used 3.5 mm laparoscopic trocar and 3.0 mm bipolar forceps. The procedures were performed under the guidance of transabdominal ultrasonography. Results  Gestational age of the cases at diagnosis and at delivery was 15–32 and 17–38 weeks, respectively. Two cases without intervention were lost at 17 and 32 weeks. The mean time of procedure for bipolar coagulation and alcohol ablation were 30 and 10 min, respectively. One of the four cases of alcohol ablation group was aborted although alcohol ablation was succesful. Another one case was aborted after alcohol ablation due to lost of fetal cardiac activity of the pump fetus. In two other cases, umbilical cord ablation with alcohol was successful, and they delivered live birth at 36 and 38 weeks. In one case, we performed bipolar cord coagulation successfully, and the case delivered live birth at 39 weeks. The overall survival rate for intrauterine surgery was 60% (N 3/5). Conclusion  In twin reserve arterial perfusion sequence pregnancies with findings of poor prognosis, alcohol ablation or bipolar cord coagulation as fetal therapy under the guidance of ultrasonography can be done successfully, and should be offered as a choice to families upon discussion of intervention or follow-up with own complications.     

Efeitos da Heroína nos Parâmetros Eletrocardiográficos

BackgroundHeroin addiction is currently a significant health problem, and information on the electrocardiographic effects of heroin is limited.ObjetivoThe aim of the present study is to investigate effects of heroin addiction on electrocardiographic parameters.MethodsA total of 136 individuals, including 66 individuals who smoke heroin as the study group and 70 healthy individuals with no drug addiction as the control group, were included in the study. Individuals who inject heroin were excluded. Electrocardiographic (ECG) evaluation of those using heroin was performed and compared with those of the control group. In addition, pre-treatment and post-treatment ECG of the heroin group were compared. A p-value of <0.05 was accepted as statistically significant.ResultsHeart rate (77.2±12.8 versus 71.4±11.2; p=0.02) were found to be higher in the heroin group compared to the control group. QT (341.50±25.80 versus 379.11±45.23; p=0.01), QTc intervals (385.12±29.11 versus 411.3±51.70; p<0.01), and T peak to end time (Tpe) (65.41±10.82 versus 73.3±10.13; p<0.01) were significantly shorter in the heroin group. No difference was observed between the groups with regard to Tpe/QT and Tpe/QTc ratios. In the subgroup analysis of the heroin group, QT (356.81±37.49 versus 381.18±40.03; p<0.01) and QTc (382.06±26.41 versus 396.06±29.80; p<0.01) intervals were significantly shorter in the pre-treatment period.ConclusionHeroin addiction significantly affects the QT, QTc, and Tpe time intervals. The arrhythmia effects of these parameters are well known. More attention to the electrocardiographic parameters of these individuals should be given. (Arq Bras Cardiol. 2020; 115(6):1135-1141)     

Impact of Prematurity on the Tissue Properties of the Neonatal Brain Stem: A Quantitative MR Approach

BACKGROUND AND PURPOSE:Preterm birth interferes with regular brain development. The aim of this study was to investigate the impact of prematurity on the physical tissue properties of the neonatal brain stem using a quantitative MR imaging approach.MATERIALS AND METHODS:A total of 55 neonates (extremely preterm [n = 30]: <28 + 0 weeks gestational age; preterm [n = 10]: 28 + 0–36 + 6 weeks gestational age; term [n = 15]: ≥37 + 0 weeks gestational age) were included in this retrospective study. In most cases, imaging was performed at approximately term-equivalent age using a standard MR protocol. MR data postprocessing software SyMRI was used to perform multidynamic multiecho sequence (acquisition time: 5 minutes, 24 seconds)–based MR postprocessing to determine T1 relaxation time, T2 relaxation time, and proton density. Mixed-model ANCOVA (covariate: gestational age at MR imaging) and the post hoc Bonferroni test were used to compare the groups.RESULTS:There were significant differences between premature and term infants for T1 relaxation time (midbrain: P < .001; pons: P < .001; basis pontis: P = .005; tegmentum pontis: P < .001; medulla oblongata: P < .001), T2 relaxation time (midbrain: P < .001; tegmentum pontis: P < .001), and proton density (tegmentum pontis: P = .004). The post hoc Bonferroni test revealed that T1 relaxation time/T2 relaxation time in the midbrain differed significantly between extremely preterm and preterm (T1 relaxation time: P < .001/T2 relaxation time: P = .02), extremely preterm and term (T1 relaxation time/T2 relaxation time: P < .001), and preterm and term infants (T1 relaxation time: P < .001/T2 relaxation time: P = .006).CONCLUSIONS:Quantitative MR parameters allow preterm and term neonates to be differentiated. T1 and T2 relaxation time metrics of the midbrain allow differentiation between the different stages of prematurity. SyMRI allows for a quantitative assessment of incomplete brain maturation by providing tissue-specific properties while not exceeding a clinically acceptable imaging time.

The myelination process begins in the fetal period and proceeds in a stepwise manner.^1,2 Brain maturation progresses caudally to rostrally following a characteristic pattern.³ Hence, histologically, the maximum myelin deposition is detectable in the spinal cord and the brain stem at the time of birth.^1,3Based on the biochecture of the myelin sheath, neonatal brain development can be evaluated by MR imaging.^4,5 Thus, myelination visualized on conventional T1-weighted and T2-weighted MR contrasts serves as an imaging biomarker for the assessment of brain maturation in neonates.⁶Prematurity is associated with delayed myelination, which is considered a risk factor for impaired neurologic and cognitive development.^7,8 Furthermore, there is a correlation between gestational age (GA) at birth and developmental outcome, with lower GA associated with a higher risk for more severe cognitive impairment.^9,10 Therefore, the assessment of myelination is paramount, primarily in preterm born neonates, to predict potential mental and neurologic impairment. Despite being a highly sensitive tool for the detection of subtle cerebral pathologies in premature infants, the evaluation of myelination by brain MR imaging in this group of patients remains challenging in pediatric neuroimaging.^11-13Quantitative MR techniques enable the characterization of cerebral development and brain maturation based on tissue-specific relaxation parameters and proton density (PD).^14-16 Quantitative T1 and T2 mapping have proved beneficial when assessing neonatal brain myelination qualitatively.^6,17 However, quantitative MR data acquisition is a highly time-consuming process, even with modern methods and therefore is not applicable in the clinical routine.^15,17By acquiring a single multidynamic multiecho (MDME) sequence (acquisition time: 5 minutes, 24 seconds), the MR data postprocessing software SyMRI (Synthetic MR; version 11.1.5) generates a variety of conventional MR contrasts and quantitative MR maps.^18-20 Based on a single sequence, intrinsic physical parameters of the examined tissue, such as T1 relaxation time (T1R), T2 relaxation time (T2R), and PD, can be determined.²⁰ The software allows definition of TR, TE, and TI after data acquisition to generate and to modulate the preferred MR contrasts. Because the image postprocessing is performed in less than 1 minute, SyMRI provides qualitative as well as quantitative MR data in a clinically acceptable time.^21-23In neonates, the process of myelination leads to subtle MR signal changes because of alterations in relaxation parameters and spin density, detectable by quantitative MR techniques. The aim of this study was to investigate the impact of different stages of prematurity on the maturational characteristics of the neonatal brain stem, as measured by SyMRI-based T1, T2, and PD mapping. The study was designed to prove that certain stages of prematurity are linked to specific quantitative MR metrics.     

CT findings of hydatid cyst with unusual location: infratemporal fossa

Hydatid disease has a high incidence in the countries of the temperate zones such as Turkey. Only few cases in the head and neck region have been reported in the literature. Our case, an unusual localization of hydatidosis, i. e. hydatid disease of the infratemporal fossa of a 9-year-old male patient suffering from a swelling of the left maxillary region which was diagnosed by CT, is presented. The lesion visualized on CT images was compressing the neighbouring structures. The possible diagnosis was made based on the images obtained from CT examination. Received 17 November 1997; Revision received 28 January 1998; Accepted 2 March 1998     

Effects of Mobile Telephones on the Function of Implantable Cardioverter Defibrillators

Objective: We investigated whether mobile telephones affect the function of implantable cardioverter defibrillators (ICDs). Background: It is well known that electromagnetic fields can affect medical devices. Methods: The study included 43 patients with ventricular tachycardia and/or fibrillation treated with transvenous pectoral ICDs. Testing was done under continuous electrocardiograph monitoring under supervision of an ICD programmer. Initially, each patient was tested during spontaneous rhythm. Then the ICD was programmed to a pace rhythm higher than the patient's heart rate, and the tests were repeated at paced rhythm. In 7 patients, tests were performed during the implantation procedure as well. In 3 of the patients, only a single defibrillation zone was active. The other 40 patients had one or more active ventricular tachycardia zones. Two mobile phones (both GSM 900 MHz) were positioned 50 cm away from the implanted device in opposite directions and switched on. Communication was established between these phones, two investigators had a 20‐second conversation, and then the phones were switched off. The same procedure was repeated at 30, 20, and 10 cm away from the implantation site, respectively. Finally, the procedure was performed with the antennae of both phones touching the device pocket. In the above‐mentioned 7 cases where testing was done during implantation of the ICD, a call was made from one phone to the other, ringing occurred for 5 seconds, and then two investigators conversed while the device was implanted. Results: There was no change in the function of the ICDs during any of the phone testing procedures. In 5 cases, artifacts were noted on the surface electrocardiographic (ECG) screen of the programmer during the tests, but no such changes were observed on the simultaneous intracardiac ECGs. Conclusion: The results of the study suggest that mobile phones have no effects on ICD function.     

Treatment of closed femoral diaphyseal fractures with external fixators in children

From August 1992 to July 1996, 57 patients with closed femoral fractures were treated by external fixator in the Orthopaedic and Traumatology Clinics, School of Medicine, Dicle University. The technique was applied to children with closed femoral fractures. Their mean age was 6 (range 4–12) years old. The mean hospitalisation period was 8 (range 5–15) days. Fixators were removed on an average of 55 (range 38–79) days. The mean follow-up period was 18 (range 9–36) months. Pintract infection was observed in 3 and refracture in 1 patient. Infection was controlled with oral antibiotics and local dressing. An external fixator was applied to a patient in whom refracture developed. No patient had malunion, nonunion, or leg length discrepancy. We propose that external fixation in closed femoral shaft fractures of children could be a rational alternative mode of therapy, since it has some advantages and can be easily removed without undergoing a second round of anaesthesia. Received: 27 May 1997     

Comparison of Neoral and Sandimmun for induction and maintenance immunosuppression after kidney transplantation

We compared the mean trough level/dose (L/D) ratio, mean coefficient of variation (CV) of individual patients, and graft, patient, and rejection-free survival rates of 40 renal transplant recipients receiving Neoral (CyE) with 103 consecutive renal transplant recipients receiving Sandimmun (CyA). The mean L/D ratio on the 3rd post-transplant day (16.2 vs 11.8, P < 0.04), in the 1st week (24.6 vs 16.1; P < 0.03), and 1st month (39.1 vs 28.7; P < 0.05) were higher in the CyE group. In both groups the L/D ratio improved in proportion to the duration of time post-transplant and reached a maximum in the 3rd post-transplant month. In the early post-transplant period in particular, the number of patients achieving target levels was significantly higher, and the mean dose needed to achieve target levels lower, in the CyE group. The variation in trough levels, demonstrated by the CV, was lower in the CyE group (0.41 ± 0.14) than in the CyA group (0.62 ± 0.21; P < 0.005). Actuarial 1-year patient and graft survival rates in the CyE group were 100 % and 96 %, respectively; these were similar to the 100 % and 95 % in the CyA group. The 1-year rejection-free survival rate in the CyE group was 61 % compared to 43 % in the CyA group (P < 0.02). We conclude that it is possible to obtain higher blood trough levels at lower doses by administering CyE, particularly in the early post-transplant period. The lower variability of trough levels and the higher L/D ratio in the CyE group, which are related to improved bioavailability of CyE, may explain the lower rejection rate among these patients. In this study, the microemulsion formulation of cyclosporin (CyE) was found to be more beneficial and cost-effective as induction and maintenance immunosuppression than the conventional formulation (CyA). Received: 28 January 1997 Received after revision: 13 May 1997 Accepted: 15 May 1997     

Effect of treatment on established osteoporosis in young women with amenorrhoea

BACKGROUND AND OBJECTIVE Amenorrhoea in women of reproductive age causes loss of bone mineral. This study assessed the effect of treatment of amenorrhoea on bone mineral density. DESIGN Serial measurements of bone mineral density were obtained in women receiving treatment for amenorrhoea. PATIENTS Eighty-five women aged 17-40 with a past or current history of amenorrhoea, from various causes, with median duration of 46.5 months (range 8 months-21 years). MEASUREMENTS Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptlometry. RESULTS initial vertebral bone mineral density was low, mean 0·85 (SD 0·10) g/cm². After an interval of 19·6 (SD 7·5) months on treatment there was a highly significant increase to 0·89 (SD 0·10) g/cm² (P < 0·0005). This was equivalent to a gain in bone mass of 21% per year (95% confidence interval 1·5–2·8%). improvement was seen in ail diagnostic groups (except polycystic ovary syndrome) and with all types of therapy. We observed no difference in the response of previously untreated patients compared with those already on treatment, nor any change in response with increasing duration of treatment. No new fractures were reported during the study. CONCLUSIONS Bone mineral density in young women with amenorrhoea is improved by appropriate treatment, but recovery is not substantial. Hence early diagnosis and therapy is essentlal to prevent bone loss.