Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients.

Dasatinib (DAS) and interferon-α have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-α2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 µg/week and it increased to 25 µg/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR(4) was achieved by 46% and MR(4.5) by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS±PegIFN is warranted.

LAS degradability by marine biofilms derived from seawater in Spain and Sweden.

Marine biofilms were established on glass beads with or without deliberate pre-exposure to LAS (20 µg/L) in Spain (Cadiz) and Sweden (Kristineberg). The ability of each community to mineralize LAS (100 µg/L) was then assessed in biometers at four experimental temperatures (between 6 and 21°C). Genetic diversity and biomass of the biofilms were assessed by genetic fingerprinting (DGGE) and direct bacterial counts. With biofilms from Sweden, where LAS was not detected in seawater (n = 3), deliberate pre-exposure to LAS resulted in lower genetic diversity and higher mineralization rate constant; however, with biofilms from Spain, where 6.4 ± 3.9 µgLAS/L (n = 3) was measured during the colonization, pre-exposure did not affect the bacterial community. Bacterial acclimation therefore appeared to have been induced at environmental concentrations < 6 µgLAS/L. Environmental pre-exposure was not a pre-requisite for featuring the full consortia of LAS degraders in the biometers. The mineralization rate was described using an Arrhenius equation at experimental temperatures within the typical annual range; however, they departed from this model below this range.

A phylogenetic approach to detect selection on the target site of the antifouling compound irgarol in tolerant periphyton communities.

Using DNA sequence data for phylogenetic assessment of toxicant targets is a new and promising approach to study toxicant-induced selection in communities. Irgarol 1051 is a photosystem (PS) II inhibitor used in antifouling paint. It inhibits photosynthesis through binding to the D1 protein in PS II, which is encoded by the psbA gene found in genomes of chloroplasts, cyanobacteria and cyanophages. psbA mutations that alter the target protein can confer tolerance to PS II inhibitors. We have previously shown that irgarol induces community tolerance in natural marine periphyton communities and suggested a novel tolerance mechanism, involving the amino acid sequence of a turnover-regulating domain of D1, as contributive to this tolerance. Here we use a large number of psbA sequences of known identity to assess the taxonomic affinities of psbA sequences from these differentially tolerant communities, by performing phylogenetic analysis. We show that periphyton communities have high psbA diversity and that this diversity is adversely affected by irgarol. Moreover, we suggest that within tolerant periphyton the novel tolerance mechanism is present among diatoms only, whereas some groups of irgarol-tolerant cyanobacteria seem to have other tolerance mechanisms. However, it proved difficult to identify periphyton psbA haplotypes to the species or genus level, which indicates that the genomic pool of the attached, periphytic life forms is poorly studied and inadequately represented in international sequence databases.

Community-level analysis of psbA gene sequences and irgarol tolerance in marine periphyton.

This study analyzes psbA gene sequences, predicted D1 protein sequences, species relative abundance, and pollution-induced community tolerance in marine periphyton communities exposed to the antifouling compound Irgarol 1051. The mechanism of action of Irgarol is the inhibition of photosynthetic electron transport at photosystem II by binding to the D1 protein. The metagenome of the communities was used to produce clone libraries containing fragments of the psbA gene encoding the D1 protein. Community tolerance was quantified with a short-term test for the inhibition of photosynthesis. The communities were established in a continuous flow of natural seawater through microcosms with or without added Irgarol. The selection pressure from Irgarol resulted in an altered species composition and an inducted community tolerance to Irgarol. Moreover, there was a very high diversity in the psbA gene sequences in the periphyton, and the composition of psbA and D1 fragments within the communities was dramatically altered by increased Irgarol exposure. Even though tolerance to this type of compound in land plants often depends on a single amino acid substitution (Ser(264)-->Gly) in the D1 protein, this was not the case for marine periphyton species. Instead, the tolerance mechanism likely involves increased degradation of D1. When we compared sequences from low and high Irgarol exposure, differences in nonconserved amino acids were found only in the so-called PEST region of D1, which is involved in regulating its degradation. Our results suggest that environmental contamination with Irgarol has led to selection for high-turnover D1 proteins in marine periphyton communities at the west coast of Sweden.

Smoking habits among pregnant women in Norway 1994-95.

AIMS: To investigate the smoking prevalence the last three months before pregnancy and at 18 weeks of gestation among women in Norway and to evaluate the impact of pre-pregnancy smoking habits, maternal age, level of education, civil status and parity on smoking cessation. MATERIAL AND METHODS: A prospective, multicenter survey. The study population included 4 766 pregnant women who attended a routine ultrasound examination at 18 weeks of pregnancy in six Norwegian hospitals during the period from September 1994 to March 1995. Smoking habits before and during pregnancy were recorded. RESULTS: The point prevalence of self-reported daily smoking among the women three months before the pregnancy was 34%. At 18 weeks of pregnancy, 21% of the women reported smoking daily (p<0.001). A multiple logistic regression analysis revealed that a low number of cigarettes smoked per day during the last three months before pregnancy was the best predictor for smoking cessation. Educational level, maternal age, parity and civil status were also statistically significant contributors to smoking cessation. Eighty percent of the women who were unable to stop smoking, reported a reduction in cigarette consumption. The mean number of cigarettes per day was reduced from 13.9 before pregnancy to 7.3 at 18 weeks of pregnancy (p<0.001). CONCLUSION: In a national survey, 21% of the pregnant women reported smoking daily in the second trimester. Thirty-eight percent of the women who were daily smokers before the pregnancy stopped smoking in early pregnancy. A low cigarette consumption prior to the pregnancy was the best predictor for smoking cessation.

Nutrition and acute leukemia in adults: relation between nutritional status and infectious complications during remission induction.

BACKGROUND: The purpose of this study was to determine whether nutritional state was related to infectious complications in adult patients with acute leukemia. METHODS: During first-remission induction therapy (mean, 71 days), the duration of neutropenia, various infections, and fevers were related to changes in body weight and serum albumin concentrations as well as total parenteral nutrition (TPN) in 52 patients receiving standardized anti-infectious treatment. RESULTS: Severe neutropenia prevailed for 27% and fever for 28% of the induction period. A mean weight loss of 5.1 kg, corresponding to a reduction of body mass index from 23.5 to 21.7, was correlated with the number of days that patients had fever (P = 0.026). Despite a normal serum albumin value at the time of admission, patients had severe hypoalbuminemia (<25 g/L) during 16% of the induction period. The drop in serum albumin was independently related to the weight loss (r = 0.37, P = 0.03). Moreover, the incidence and duration of hypoalbuminemia were significantly correlated with duration of fever (P < 0.0001), diarrhea (P = 0.03), and TPN administration (P = 0.00002). CONCLUSIONS: Weight loss and severe hypoalbuminemia were common during remission induction for these adult patients with acute leukemia and were closely related to the patients' infections.

Smoking habits among pregnant women in a Norwegian county 1987-1994.

BACKGROUND: The aim of the study was to investigate changes in smoking habits among pregnant women in the city of Trondheim and its surroundings. We also wanted to register the effect of a national campaign against smoking in pregnancy introduced in December 1989. MATERIAL AND METHODS: From 1987-1994 midwives interviewed 21 348 women in a non-selected population during a routine ultrasound examination at 18 weeks of pregnancy. Smoking habits and cigarette consumption were recorded. RESULTS: The point prevalence smoking rate among pregnant women decreased from 34% in 1987 to 22% in 1994 (p<0.001). A stratified analysis indicated that the reduction was not confounded by changes in age and parity over time. The mean number of cigarettes per pregnant smoker decreased from 8.6 cigarettes per day to 7.0 cigarettes per day during the study period (p<0.001). In 1987, 49% of the pregnant smokers consumed > or = 10 cigarettes compared with 35% in 1994 (p<0.001). The national campaign may have reinforced the on-going decline in smoking rate, but no significant effect was observed. CONCLUSIONS: The study demonstrated a statistically significant reduction in smoking prevalence among pregnant women in the study area. A similar decrease was not observed among women in the general population. No significant effect of the national campaign against smoking during pregnancy was observed.