Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study

Background: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. Patients and methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m(2) each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. Results: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade >= 3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade >= 3 or treatment-related death did not occur. Conclusions: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed

Fractionated administration of irinotecan and cisplatin for treatment of lung cancer: a phase I study

A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m−2 and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m−2, and the dose was escalated by an increase of 10 mg m−2. The maximally tolerated dose of CPT-11 was determined as 60 mg m−2 because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m−2 and 60 mg m−2 respectively. © 1999 Cancer Research Campaig

Relative effects of furosemide and ethacrynic acid on ion transport and energy metabolism in slices of rat kidney-cortex

The effects of furosemide and ethacrynic acid have been studied using slices of rat kidney cortex incubated in a Ringer medium. At concentrations from 0.2–2.0 mM, furosemide had no significant effect on the tissue ATP content or on the metabolism-dependent net movements of intracellular Na + , K + and Ca 2+ . It did, however, induce an increase in the net, outward movement of Cl − ; we suggest that this may have srisen from inhibition of a Cl − accumulating mechanism. In contrast, ethacrynic acid in the same concentration range caused marked reduction of cell respiration and ATP content and virtually total inhibitition of several processes of ion transport (Na + , Cl − and Ca 2+ loss, and K + uptake). Concentrations of furosemide greater than 5 mM caused marked inhibition of energy metabolism and transport of ions, and 10 mM furosemide had quantitatively similar effects to 2 mM ethacrynic acid. Electron micrographs of kidney-cortex slices treated with the diuretics at 2 mM show that the ultrastructure was well maintained in the presence of furosemide but that ethacrynic acid caused severe structural disorganisation and necrosis. The mitochondria were generally in the orthodox configuration in the presence of furosemide, but swollen in ethacrynic acid in accord with the marked effects of 2 mM ethacrynate on mitochondrial energy metabolism. Of the effects we have detected, that of low concentrations of furosemide on Cl − movement appears to be rather specific. Higher concentrations of this agent (5 mM and above), and all concentrations of ethacrynic acid studied (0.1–5.0 mM), have several inhibitory effects which seem to result from primary inhibition of mitochondrial activities and are presumably manifestations of toxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46309/1/210_2004_Article_BF00506264.pd

Tremor in multiple sclerosis

Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide some relief, but published evidence of effectiveness is very limited. Most trials were of small size and of short duration. Cannabinoids appear ineffective. Tremor reduction can be obtained with stereotactic thalamotomy or thalamic stimulation. However, the studies were small and information on long-term functional outcome is scarce. Physiotherapy, tremor reducing orthoses, and limb cooling can achieve some functional improvement. Tremor in MS remains a significant challenge and unmet need, requiring further basic and clinical research

Effect of freezing and thawing process on mictobiological safety of human milk

Mleko kobiece uznawane jest za „złoty standard” żywienia dla noworodków ze względu na unikatowe właściwości odżywcze i immunologiczne oraz źródło mikroflory stanowiącej podstawę do kształtowania mikrobiomu człowieka. Działalność Banków Mleka przyczynia się do racjonalizacji dostępności mleka kobiecego. Metodą utrwalania mleka w celu jego przechowywania jest zamrażanie. W pracy podjęto próbę oceny jakości mikrobiologicznej mleka kobiecego nieutrwalonego oraz mleka poddanego zamraża- niu i rozmrażaniu z zastosowaniem metody w nawiewie powietrza o temp. 37 ºC. Analizy wykonano w kierunku: ogólnej liczby drobnoustrojów tlenowych mezofilnych (OLD), Escherichia coli, Staphylococ- cus aureus, Cronobacter sakazakii, Listeria monocytogenes, Salmonella spp. Na podstawie uzyskanych wyników stwierdzono, że w przypadku ogólnej liczby drobnoustrojów tlenowych mezofilnych 30 % pró- bek mleka kobiecego przed zamrożeniem przekraczało maksymalną akceptowaną liczbę drobnoustrojów, natomiast w przypadku mleka rozmrożonego było to 5 % prób. Liczba Staphylococcus aureus została przekroczona w 10 % próbek mleka przed zamrożeniem i w 5 % próbek mleka rozmrożonego. Stwierdzo- no, że proces zamrażania i prawidłowo przeprowadzony proces rozmrażania mogą stanowić istotny ele- ment kształtowania jakości mikrobiologicznej mleka kobiecego. W próbkach mleka kobiecego poddanych analizie nie wykryto bakterii patogennych: Listeria monocytogenes, Salmonella, Cronobacter sakazakii. Bakterie E. coli również były nieobecne, co świadczy o dobrym stanie higieny i przestrzeganiu instrukcji higieny postępowania z mlekiem

Investigation of improvement of protein and colloid resistance of beer using immobilized enzyme preparations

The article presents the results of studying the possibility of obtaining and using an immobilized complex stabilizer to enhance the colloidal resistance of beer. The pH zones of action and temperature range of the immobilized enzyme preparation have been experimentally established. The result of the experiment of hydrolysis of high molecular beer polypeptides with immobilized G 10x Protosubtilin is given. The physicochemical parameters of the beer sample under study are evaluated. Research results can be used to stabilize beer, wine, juices, etc