Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing

Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies.     

Electric discharge patterns of ankle muscles during the normal gait cycle

EMG patterns in ankle muscles were examined during normal gait cycles in 147 healthy asymptomatic adults. In all subjects, the tibialis anterior (Ta) showed marked activities around the toe-off and before the heel-strike, and the gastrocnemius lateral head (Gl) showed marked activity during the midstance phase but no activity in the early part of the swing phase. The Ta activity contributed to ground clearance, prevention of foot-drop, and shock absorption at the heel-strike. The Gl activity contributed to push-off from the ground and prevention of foot-drop. The Ta activity consisted of double bursts with (15% of subjects) or without (44%) electric silence in the midswing phase, continuous discharge (33%), and triple discharge patterns (8%). The Gl activity consisted of a single-peak (95%) pattern or double-peak (5%) patterns.     

Pregnancy and neonatal screening in Austria

In Austria neonatal mortality remains higher than in comparable industrial countries. For this reason the Austrian Academy of Sciences published a study (K?ck Ch., Kytir J., Münz R.: Risiko Süglingstod, Pl?doyer für eine gesundheitspolitische Reform, Franz Deuticke, Wien 1988) comprising a historical review, an analysis of the present situation and proposals for improvement of the public health care programmes for pregnant women, mothers and neonates. Furthermore, current Austrian health policy is criticized on the basis of two concrete examples (the neonatal mass screening programme for inherited metabolic diseases and compulsory ultrasound screening in pregnancy). However, the authors reach their conclusions from incompletely cited and subjectively (partly falsely) interpreted scientific literature, with misleading consequences. Reviewing the literature in a more complete way, we wish to point out the superficial character of the research carried out by the authors. This kind of work should not serve as a basis for decisions in public health policy.     

Mechanisms for the serum lipid-lowering effect of n-3 fatty acids

Both epidemiological and experimental studies have demonstrated that a high content of n-3 fatty acids in the diet lowers serum lipid concentration. However, the mechanism for this effect is unclear. In this present study it has been shown that labelled linolenic acid (18:3, n-3) is oxidized to a larger extent than linoleic acid (18:2,n-6) in isolated rat hepatocytes. Conversely, the incorporation of linolenic acid and the desaturated/chain-elongated products in VLDL-triacylglycerol is decreased compared with linoleic acid. Dietary n-3 fatty acids have probably a depressing effect on both hepatic triacylglycerol synthesis and on secretion of VLDL. The finding that n-3 fatty acids are transported from the liver as ketone bodies to a larger extent than n-6 fatty acids may thus explain that a high intake of n-3 fatty acids is not accompanied with hepatic steatosis.     

Multiresistant Staphylococcus epidermidis as a pathogen

The purpose of this study was to examine the occurrence and the present clinical significance of multiresistant strains of Staphylococcus epidermidis (MSE) at the departments of internal medicine, general surgery, neurology and lung diseases of an university hospital. All those 178 consecutive in-patients from whom, during a half-year investigation period, a strain of MSE was isolated, were immediately enrolled in the study. A strain was defined as multiresistant if it was resistant to 3 or more antimicrobial agents. The clinical course of the patients was followed prospectively daily for any sign of infection. The multiresistant strains amounted to 57.9% of all recovered Staph. epidermidis strains. The mean age of the patients was 50.3 years. A chronic underlying disease was present in 97%. There was a clinical infection in 155 patients, and in 115 of these (65% of the total) the MSE very probably was the true pathogen. The distribution of these infections was as follows: wound infection in 49 (43%), urinary tract infection in 43 (37%), local soft tissue infection in 13 (11%) and septicaemia in 10 (9%) patients. In 40 patients (22% of the total) the role of the MSE in the infection remained uncertain and in 23 patients (13%) the finding obviously was an accidental skin contamination.     

Plasma lipid changes in the female in aging and the menopause. Results from three population studies.

Postabsorbtive plasma lipid levels have been analyzed in studies of the female population in the Swedish city of Gothenburg. The population samples cover the ages 15, 23, 30, 38, 40, 45, 46, 50, 54, 60 and 70. In some groups data are available from both cross-sectional and prospective longitudinal studies. Cross-sectional studies showed a successive increase in total plasma cholesterol from 15 to 54 years of age. Longitudinal studies showed a further increase at least up to 60 years of age. The triglyceride level remained rather constant between 15 and 30 years of age, then increased but was again rather similar in the 40--50-year olds and reached the highest level in the 60- and 70-year samples. The total phospholipid curve was approximately parallel with the cholesterol curve at younger ages but nearer the cholesterol curve at higher ages. The composition of the plasma phospholipid fraction apparently changed at the ages around the menopause, mainly due to an increase in the proportions of lecithin and lysolecithin. Data available allowed considerations concerning possible influences on plasma lipids by age, by changes in dietary habits and body composition, as well as by gonadal steroid hormones.