Reduced Fitness of <Emphasis Type="Italic">Daphnia magna</Emphasis> Fed a Bt-Transgenic Maize Variety

Genetically modified (GM) maize expressing the Bt-toxin Cry1Ab (Bt-maize) was tested for effects on survival, growth, and reproduction of the water flea Daphnia magna, a crustacean arthropod commonly used as a model organism in ecotoxicological studies. In three repeated experiments, D. magna were fed 100% ground maize in suspension, using either GM or isogenic unmodified (UM) maize. D. magna fed GM-maize showed a significantly reduced fitness performance: The mortality was higher, a lower proportion of females reached sexual maturation, and the overall egg production was lower compared to D. magna fed UM isogenic maize. We conclude that the tested variety of Bt-maize and its UM counterpart do not have the same quality as food sources for this widely used model organism. The combination of a reduced fitness performance combined with earlier onset of reproduction of D. magna fed Bt-maize indicates a toxic effect rather than a lower nutritional value of the GM-maize.     

First-trimester maternal alcohol consumption and the risk of infant oral clefts in Norway: a population-based case-control study

Although alcohol is a recognized teratogen, evidence is limited on alcohol intake and oral cleft risk. The authors examined the association between maternal alcohol consumption and oral clefts in a national, population-based case-control study of infants born in 1996-2001 in Norway. Participants were 377 infants with cleft lip with or without cleft palate, 196 with cleft palate only, and 763 controls. Mothers reported first-trimester alcohol consumption in self-administered questionnaires completed within a few months after delivery. Logistic regression was used to calculate odds ratios and 95% confidence intervals, adjusting for confounders. Compared with nondrinkers, women who reported binge-level drinking (>or=5 drinks per sitting) were more likely to have an infant with cleft lip with or without cleft palate (odds ratio = 2.2, 95% confidence interval: 1.1, 4.2) and cleft palate only (odds ratio = 2.6, 95% confidence interval: 1.2, 5.6). Odds ratios were higher among women who binged on three or more occasions: odds ratio = 3.2 for cleft lip with or without cleft palate (95% confidence interval: 1.0, 10.2) and odds ratio = 3.0 for cleft palate only (95% confidence interval: 0.7, 13.0). Maternal binge-level drinking may increase the risk of infant clefts.     

Familial patterns of preterm delivery: maternal and fetal contributions

Women who deliver preterm (<37 completed weeks' gestation) are at high risk for recurrence. This has prompted exploration of candidate genes (both maternal and fetal) associated with preterm delivery. Epidemiologists can use recurrence patterns of preterm delivery across generations to assess the relative contributions of maternal and fetal genes. The authors used data from the Medical Birth Registry of Norway (1967-2004) to identify 191,282 mothers and 127,830 fathers who subsequently had at least one singleton offspring. The authors stratified parents according to whether or not they had been born preterm and calculated the risk of preterm delivery among their firstborn. Mothers born preterm had a relative risk for preterm delivery of 1.54 (95% confidence interval (CI): 1.42, 1.67). This association was weaker for fathers born preterm (relative risk (RR) = 1.12, 95% CI: 1.01, 1.25). Among early preterm births (<35 weeks), the effect became stronger for mothers (RR = 1.85, 95% CI: 1.52, 2.27) and weaker for fathers (RR = 1.06, 95% CI: 0.77, 1.44). These data suggest that paternal genes have little, if any, effect on preterm delivery risk. This argues against major contributions of fetal genes inherited from either parent. The increased risk of preterm delivery among mothers born preterm is consistent with heritable maternal phenotypes that confer a propensity to deliver preterm.     

Weekly one-hour paclitaxel as first-line chemotherapy for metastatic breast cancer

In this first reported study of weekly paclitaxel administered as first-line chemotherapy for metastatic breast cancer, paclitaxel 100 mg/m² was administered in a 1-h infusion on a weekly basis to 35 patients who may previously have received adjuvant chemotherapy (but not taxane-containing regimens), but not for advanced or metastatic disease. A median of 14 infusions per patient was given at a mean delivered dose intensity of 94 mg/m² per week. In 33 assessable patients, a complete response (CR) was observed in 1 patient and partial responses (PRs) in 12 patients, producing an overall response rate of 40%. Stable disease (SD) was observed in 17 patients, of whom 9 were stabilized for more than 24 weeks. Thus, clinical benefit (CR+PR+SD_{≥24 weeks}) was observed in 67% of the patients. Time to progression was 189 days, the duration of response 180 days and overall survival 544 days. Five patients developed grade 3 neutropenia and five patients grade 3 neurotoxicity. Thus, this study has shown that weekly paclitaxel as first-line therapy for metastatic or advanced breast cancer produces comparable response rates and less toxicity than when the drug is given every three weeks.     

Autosomal dominant retinitis pigmentosa in Norway: a 20-year clinical follow-up study with molecular genetic analysis. Two novel rhodopsin mutations: 1003delG and I179F

PURPOSE: To examine the clinical picture and molecular genetics of 12 Norwegian families with autosomal dominant retinitis pigmentosa (adRP) in order to achieve a genotype-phenotype correlation. METHODS: In addition to a clinical ophthalmological examination, fundus photography, dark adaptometry and electroretinography were performed. Four genes were analysed: rhodopsin (RHO); retinitis pigmentosa 1 (RP1); retinal degeneration slow/peripherin (RDS/peripherin), and inosine monophosphate dehydrogenase 1 (IMPDH1). Seven of the families had been examined about 20 years previously. A total of 63 patients or first-degree relatives (aged 18-79 years) were examined. RESULTS: Mutations were found only in the RHO gene. Seven families were given a diagnosis of classical RP. Two of them had novel mutation 1003delG, and one family had the mutation V345M. Four families had pericentral retinal dystrophy (PRD), two families with the mutation A164V and one with novel mutation I179F. One family was given a diagnosis of central and pericentral retinal dystrophy (CPRD), a special type of cone/rod dystrophy, and no mutation was found. CONCLUSIONS: Six of 12 families had an RHO mutation. The mutation V345M and the novel mutation 1003delG both caused classical RP, the former indicating the most unfavourable prognosis. Two of the families with PRD had the A164V mutation with a favourable prognosis, whereas the novel mutation I179F caused PRD with extremely variable expressivity.     

Treatment needs and acknowledgement of illness – importance for satisfaction with psychiatric inpatient treatment

Background  

Patient satisfaction is an important, but controversial part of health service evaluation. This study dealt with how acknowledgement of illness and treatment needs effected the distribution of positive, neutral and negative evaluations in a group of first time admitted patients to a psychiatric hospital.     

Monoclonal antibodies and superantigens: A novel therapeutic approach

We have developed a monoclonai antibody (mAb) based therapy intended forthe treatment ofsolid tumors utilizing both main arms of the immune system by incorporating the colon carcinoma recognizing mAb C215 and the T cell activating bacterial staphylococcal enterotoxin A (SEA) in a single hybrid molecule. The recombinant tumor specific superantigen C215-SEA retained excellent antigen binding properties while the binding to MHC class II was markedly reduced and should allow targeting of a large fraction of T cells to tumorsin vivo. C215-SEA mediated T cell killing of C215 expressing tumor cells irrespective of their expression of MHC class [I antigens and induced levels of IFN-y and TNF in mononuclear cells sufficient to completely suppress the growth of colon carcinoma cellsin vitro. In initial studies of anti-tumor effects, C215Fab-SEA was found to markedly inhibit the growth of colon carcinoma cells transplanted to Scid mice adoptively transferred with human mononulear cells.