A summability method in some strong laws of large numbers

This survey paper contains several results concerning applications of some summability methods in ergodic theory and in generalizations of some strong laws of large numbers

Comatose states caused by intoxication a twelve-year experience

U članku autori su prikazali 105 bolesnika u komi zbog otrovanja liječenih u dvanaestogodišnjem razdoblju. Lijekovima koji djeluju na CNS bilo je otrovano 66 bolesnika, 6 bolesnika bilo je otrova no lijekovima koji djeluju na ostale organske sustave, 18 bolesnika bilo je otrovano pesticidima a 15 bolesnika etilnim alkoholom. U 58 bolesnika zabilježena je višestruko otrovanje. U IV. stupnju kome bilo je 35 bolesnika, u III. stupnju 31 bolesnik, u II. stupnju 27 bolesnika, u I. stupnju 9 a u komi O. stupnja bila su 3 bolesnika. Ukupni letalitet u komatoznih bolesnika bio je 11,5%. Od 12 umrlih bolesnika 11 je bilo u komi IV. stupnja, a 1 u komi III. stupnja. Opisani su nalazi patoanatomske obdukcije u umrlih bolesnika. Metode ekstrakorporalnog odstranjenja otrova iz krvi (hemodijaliza, hemoperfuzija ih kombinacija obih metoda) primijenjene su u 32 teško otrova na bolesnika. U toj skupini letalitet je iznosio 9,4%, a sva 3 umrla bolesnika bila su u komi IV. stupnja. Rezultati upućuju na potencijalnu veliku djelotvornost ekstrakorporalnih metoda u odstranjenju otrova iz krvi. Autori se zalažu za primjenu tih metoda u bolesnika u dubokoj ili prolongiranoj komi zbog otrovanja, kao i u bolesnika s izraženom teškom kliničkom slikom nakon ingestije letalne doze otrovnih tvari.The study included a total of 105 patients in a state of coma caused by intoxication, who were treated at an intensive care unit over a period of twelve years. Sixty-six patients were intoxicated with drugs that affect the central nervous system, six with drugs that affect the other organs, 18 were intoxicated with pesticides and 15 with alcohol. Fifty-eight patients had taken two or more toxic agents simultaneously. Thirty-five patients were in a state of grade IV coma, 31 were in grade III, 27 in grade II, nine in grade I and three patients were in grade O coma. The overall mortality was 11.5%. Of 12 deceased patients, 11 were in grade IV coma and one was in grade III coma. The autopsy findings are described. Extracorporeal methods for the elimination of toxins from the blood (haemodialysis, haemoperfusion or a combination of the two methods) were applied in 32 heavisly intoxicated patients. The mortality in this group was 9.4%. The three deceased patients were in grade IV coma. The results indicate good applicability of these methods for toxin elimination. Their use in deep or prolonged comatose states caused by intoxication, and in cases of severe intoxication following ingestion of lethal doses of toxic agents is therefore recommended

Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)

Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide ( average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mgm(-2) (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mgm(-2). Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mgm(-2). The half-lives of both MAG-CPT and released CPT were prolonged (46 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development

A phase I study with MAG-camptothecin intravenously administered weekly for 3 weeks in a 4-week cycle in adult patients with solid tumours

In MAG-camptothecin (MAG-CPT), the topoisomerase inhibitor camptothecin is linked to a water-soluble polymer. Preclinical experiments showed enhanced antitumour efficacy and limited toxicity compared to camptothecin alone. Prior phase I trials guided the regimen used in this study. The objectives were to determine the maximum tolerated dose, dose-limiting toxicities, safety profile, and pharmacokinetics of weekly MAG-CPT. Patients with solid tumours received MAG-CPT intravenously administered weekly for 3 weeks in 4-week cycles. At the starting dose level ( 80 mg m(-2) week(-1)), no dose-limiting toxicities occurred during the first cycle (n = 3). Subsequently, three patients were enrolled at the second dose level ( 120 mg m(-2) week(-1)). Two of three patients at the 80 mg m(-2) week(-1) cohort developed haemorrhagic cystitis ( grade 1/3 dysuria and grade 2/3 haematuria) during the second and third cycles. Next, the 80 mg m(-2) week(-1) cohort was enlarged to a total of six patients. One other patient at this dose level experienced grade 1 haematuria. At 120 mg m(-2) week(-1), grade 1 bladder toxicity occurred in two of three patients. Dose escalation was stopped at 120 mg m(-2) week(-1). Cumulative bladder toxicity was dose-limiting toxicity at 80 mg m(-2) week(-1). Pharmacokinetics revealed highly variable urinary camptothecin excretion, associated with bladder toxicity. Due to cumulative bladder toxicity, weekly MAG-CPT is not a suitable regimen for treatment of patients with solid tumours

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment

Miłość jako teologiczne i filozoficzne pojęcie w koncepcji Jana Pawła II

Humankind has been asking the questin about love during the ages. John Paul II took up the theme of Christian love in depth and based it on the theology of body. Pope brought back its real significance by relating this meaning to the betrothal love between woman and man. In his philosophy person is not a means to an end but an end in itself. This love is marked by the common aim, which biases couple in favour of marriage

A summability method in some strong laws of large numbers

This survey paper contains several results concerning applications of some summability methods in ergodic theory and in generalizations of some strong laws of large numbers

Comatose states caused by intoxication a twelve-year experience

U članku autori su prikazali 105 bolesnika u komi zbog otrovanja liječenih u dvanaestogodišnjem razdoblju. Lijekovima koji djeluju na CNS bilo je otrovano 66 bolesnika, 6 bolesnika bilo je otrova no lijekovima koji djeluju na ostale organske sustave, 18 bolesnika bilo je otrovano pesticidima a 15 bolesnika etilnim alkoholom. U 58 bolesnika zabilježena je višestruko otrovanje. U IV. stupnju kome bilo je 35 bolesnika, u III. stupnju 31 bolesnik, u II. stupnju 27 bolesnika, u I. stupnju 9 a u komi O. stupnja bila su 3 bolesnika. Ukupni letalitet u komatoznih bolesnika bio je 11,5%. Od 12 umrlih bolesnika 11 je bilo u komi IV. stupnja, a 1 u komi III. stupnja. Opisani su nalazi patoanatomske obdukcije u umrlih bolesnika. Metode ekstrakorporalnog odstranjenja otrova iz krvi (hemodijaliza, hemoperfuzija ih kombinacija obih metoda) primijenjene su u 32 teško otrova na bolesnika. U toj skupini letalitet je iznosio 9,4%, a sva 3 umrla bolesnika bila su u komi IV. stupnja. Rezultati upućuju na potencijalnu veliku djelotvornost ekstrakorporalnih metoda u odstranjenju otrova iz krvi. Autori se zalažu za primjenu tih metoda u bolesnika u dubokoj ili prolongiranoj komi zbog otrovanja, kao i u bolesnika s izraženom teškom kliničkom slikom nakon ingestije letalne doze otrovnih tvari.The study included a total of 105 patients in a state of coma caused by intoxication, who were treated at an intensive care unit over a period of twelve years. Sixty-six patients were intoxicated with drugs that affect the central nervous system, six with drugs that affect the other organs, 18 were intoxicated with pesticides and 15 with alcohol. Fifty-eight patients had taken two or more toxic agents simultaneously. Thirty-five patients were in a state of grade IV coma, 31 were in grade III, 27 in grade II, nine in grade I and three patients were in grade O coma. The overall mortality was 11.5%. Of 12 deceased patients, 11 were in grade IV coma and one was in grade III coma. The autopsy findings are described. Extracorporeal methods for the elimination of toxins from the blood (haemodialysis, haemoperfusion or a combination of the two methods) were applied in 32 heavisly intoxicated patients. The mortality in this group was 9.4%. The three deceased patients were in grade IV coma. The results indicate good applicability of these methods for toxin elimination. Their use in deep or prolonged comatose states caused by intoxication, and in cases of severe intoxication following ingestion of lethal doses of toxic agents is therefore recommended