Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial

BACKGROUND: Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. METHODS: 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. CONCLUSIONS: Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01609543

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

Ciclosporin For Refractory Aplastic Anemia

Scopu

The effects of alternating magnetic field on the biomechanic parameters of streptozotocin-induced diabetic rat diaphragm muscles

2003 IEEE International Symposium on Electromagnetic Compatibility, EMC 2003 --11 May 2003 through 16 May 2003 -- --In the present study, totally 40 rats Wistar Albino weighing 271±12 gr were used. They were divided into four groups; control (n=10), control group exposed to AC magnetic field (n=10), diabetic groups(n=10) and diabetic group exposed to AC magnetic field (n=10), 20 rats were in the experimental group exposed to AC magnetic field, 10 of them (control) having magnetic field and the other ten were diabetic group. The rats in the experimental groups were exposed to a smooth Magnetic field with 5 mT force in 50 Hz frequency during four weeks 3 hours a day, and diaphragm and muscle strips (0.053 ±. 0,06 g.) were taken from the rats in the each group. Muscle twitch measured by isometric transducers was observed through digital storage oscilloscope, and put into computer in order for analysis. Of the isometric twitch tensions (Ps), contraction time (CT), one-half relaxation time (1/2RT) were determined. In conclusion, the data analysed revealed that there was a significant difference between the isometric twitch parameters CT, 1/2Rt and isometric contraction force Ps taken from muscle strips belonging to the four groups and mere were significant difference between the other parameters measured. © 2003 IEEE

The effect of bupivacaine on gastrocnemius muscle contractility in rats with diabetes

WOS: 000483394900007This study examined the changes in skeletal muscle contraction parameters after the injection of bupivacaine into the gastrocnemius muscle in diabetic rats. Forty male Wistar albino rats (230-270 g) were divided into four groups: Group I: Untreated healthy control; Group II: Healthy injected with Bupivacaine; Group III: Diabetic control; Group IV: Diabetic injected with bupivacaine. The diabetes was induced with streptozotocin in 0.1 M citrate buffer (pH 4.5) injection at 45 mg/kg in tail vein. On 7th day of streptozotocin injection, the rats in groups II and IV were injected with 0.25% bupivacaine at 8 mg/kg body weight into the gastrocnemius muscle. Three weeks post bupivacaine application, the animals were sacrificed and right leg gastrocnemius muscle was isolated for studying various parameters such as muscle twitch, tetanic force, contraction and relaxation time and maximum contraction and relaxation rates. The blood glucose estimation showed that the rats in group III and IV developed diabetes at two days after administration of streptozotocin. The administration of bupivacaine resulted in a significant (p<0.05) increase in the muscle twitch parameters both in Group II and Group IV. Thus, bupivacaine can increase muscle contractility in diabetic muscles also.Cukurova University Scientific Research FoundationCukurova University [TSA-2015-3600]The research was supported by Cukurova University Scientific Research Foundation (project No. TSA-2015-3600). No competing financial interests exist

Pulmonary involvement in adult Gaucher's disease: High resolution CT appearance

High resolution CT findings of pulmonary involvement are described in a patient with adult type Gaucher's disease. Although the reticular pattern on the chest radiograph was typical, appearance of pulmonary involvement on high resolution CT has not been demonstrated in the literature. High resolution CT demonstrated interlobular septal and intralobular interstitial thickening, irregular interfaces at the pleural surfaces and ground-glass appearance, corresponding to both the alveolar and the interstitial components of the pulmonary involvement

MRI of non-neoplastic cranial complications of malignant disorders

PubMed: 18553277Purpose: To depict the well-known and atypical magnetic resonance imaging (MRI) findings of neo-neoplastic central nervous system (CNS) complications of extra-CN5 tumors and portray additional information from advanced techniques, such as diffusion and perfusion MRI. Materials and Methods: MRI scans of 92 patients were retrospectively evaluated based on the non-neoplastic effects induced by treatment or the remote effects of the tumor itself. Patients with brain metastases and/or patients who had whole brain radiation therapy were excluded so as not to take the primary radiation effects into consideration. Results: Sixteen patients (9 females and 7 males; age range, 11-68 years; median age, 45 years) had positive findings other than brain metastases. Six patients had posterior reversible encephalopathies, 3 patients had chemotherapy toxicity to the white matter, and 2 patients had acute strokes involving the posterior fossa and bilateral anterior circulation territory. Three patients had bilateral radionecrosis of the temporal lobe due to radiotherapy given for the vicinal tumor (nasopharyngeal carcinoma). One patient had encephalitis in the bitemporal region and one patient had cerebellar degeneration, each of whom had a paraneoplastic syndrome. Conclusion: One of the major and noteworthy complications of malignancies directly affecting survival is brain metastasis, but non-neoplastic complications are infrequently encountered and are thus underestimated, either due to the absence of a true diagnosis or the lack of information pertaining to the clinical outcome. It is important for the radiologist to recognize these effects so as to help the clinician develop an optimal treatment strategy and avoid irreversible complications. © Turkish Society of Radiology 2008

The effects of extremely low-frequency pulsed electromagnetic fields on analgesia in the nitric oxide pathway

PubMedID: 31408675There is growing interest in the effects of extremely low-frequency electromagnetic fields on mechanisms in biological organisms. This study's goal is to determine the role of the Nitiric Oxide (NO) pathway for thermal pain by intentionally interfering with it using a pulsed electromagnetic field generated by an extremely low-frequency alternating current (ELF-PEMF) in combination with BAY41-2272 (sGC activator), NOS inhibitor L-NAME, and NO donor L-arginine. This study included 72 adult male Wistar albino rats (mean weight of 230 ± 12 g). The rats were kept at room temperature (22 ± 2 °C) in a 12-h light/dark cycle and in a room with sound insulation. PEMF (50 Hz, 5 mT) were applied four times a day for 30 min and at 15-min intervals for 15 days. Analgesic effects were assessed with tail-flick and hot-plate tests. Before the tests, NO donor L-arginine (300 mg/kg), sGC activator BAY41-2272 (10 mg/kg), and NOS inhibitor L-name (40 mg/kg) were injected intraperitoneally into rats in six randomly-selected groups. The maximum analgesic effect of a 5 mT electromagnetic field was on day 7. PEMF significantly increased the analgesia effect when the functioning of the NO pathway was ensured with L-arginine, which is a NO donor, and BAY41-2271, which is the intracellular receptor and sGC activator. However, there was no difference between rats treated with PEMF and the NOS inhibitor L-NAME as compared to rats only treated with PEMF. In conclusion, PEMF generate analgesia by activating the NO pain pathway. © 2019 Elsevier Inc.T-629This study was funded by Sivas Cumhuriyet University Scientific Research Project ( T-629 , CUBAP, Turkey)

Comparison of microscopic examination, rK39, and PCR for visceral leishmaniasis diagnosis in Turkey

PubMedID: 19859739The laboratory diagnosis of visceral leishmaniasis is based on microscopic examination, culture, serological tests, and molecular methods. In this study, we examined 50 blood specimens from suspected visceral leishmaniasis patients by microscopic examination, recombinant antigen dipstick test (rK39), and polymerase chain reaction (PCR) in the University of Cukurova, Faculty of Medicine, Parasitology Department in Turkey. We calculated the sensitivity-specificity and positive-negative predictive values for these diagnostic tests. We found that positive predictive value of microscopy examination, rK39 dipstick test, and PCR were 20%, 24%, and 58% for visceral leishmaniasis, respectively. When we compared polymerase chain reaction, recombinant antigen dipstick test, and microscopic examination for visceral leishmaniasis diagnosis, the polymerase chain reaction is more sensitive (100%) than recombinant antigen dipstick test and microscopy examination. © 2009 Springer-Verlag.TF.2005Acknowledgments This project was supported by the Cukurova University Research Grant TF.2005.D4

The acute effect of trimetazidine on the high frequency fatigue in the isolated rat diaphragm muscle

PubMedID: 15283468The objective of this study was to determine the acute effect of trimetazidine (TMZ) on the pre-fatigue, fatigue and post-fatigue contractile characteristics and tension-frequency relationships of isolated rat diaphragm muscle. Muscle strips were taken from the ventral-costal aspects of the diaphragm muscle of rats killed by decapitation. The muscle strips were suspended in organ baths containing Krebs solution, with a gas mixture of 95% O2 and 5% CO2 at 37°C and pH 7.35-7.45. After determining the thermoregulation and optimum muscle length the muscles were subjected to direct supramaximal stimulation with 0.05 Hz frequency square pulses for periods of 0.5 msec to obtain control values. After adding 5×10-6 and 5×10-5 M trimetazidine solution to the respective bath media, the contractile parameters of the muscles were recorded. The contractile parameters were also recorded for both the trimetazidine and trimetazidine-free media after application of the high frequency fatigue protocols. Later, the tension-frequency relationship was determined by applying stimulating pulses of 10, 20, 50 and 100 Hz to the muscle strips. Whilst the twitch tension obtained from the 5×10-6 and 5×10-5 M trimetazidine media showed numerical increases compared to that of the controls, these were not statistically significant (p&gt;0.05). The contraction time exhibited a dose dependent increase (p&lt;0.001), whilst the contraction and relaxation rates did not differ significantly. The isometric contraction forces obtained with the different stimulating frequencies showed a significant increase in the tetanic contraction only at 100 Hz (p&lt;0.05). A comparison of the pre- and postfatigue twitch tensions in the trimetazidine media showed the post- fatigue twitch tensions to be significantly higher than those of the pre-fatigue contraction forces (p&lt;0.05). In the 5×10-6 and 5×10-5 M trimetazidine media the increases in the post-fatigue contraction force were 22 and 30%, respectively. These results demonstrated that in isolated rat diaphragm muscle, TMZ significantly limited the mechanical performance decrease during fatigue. It is our opinion that trimetazidine contributed to the observed fatigue tolerance by eliminating the factors of fatigue, due to preservation of intracellular calcium homeostasis, provision of the ATP energy levels needed by ATPase dependent pumps and especially by keeping the intracellular pH within certain limits