Use of hormonal contraceptives and occurrence of pregnancy-related pelvic pain: a prospective cohort study in Norway

Background  

Pregnancy-related pelvic pain is a common condition, and use of hormonal contraceptives before pregnancy has been proposed as a risk factor. We used data from a sub-sample of women participating in the "Norwegian Women and Cancer study" (NOWAC) to assess the association between hormonal contraceptive use and pelvic pain in pregnancy.     

Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo

The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.     

Escitalopram versus citalopram: the surprising role of the <Emphasis Type="Italic">R</Emphasis>-enantiomer

Rationale Citalopram is a racemate consisting of a 1:1 mixture of the R(–)- and S(+)-enantiomers. Non-clinical studies show that the serotonin reuptake inhibitory activity of citalopram is attributable to the S-enantiomer, escitalopram. A series of recent non-clinical and clinical studies comparing escitalopram and citalopram to placebo found that equivalent doses of these two drugs, i.e. containing the same amount of the S-enantiomer, showed better effect for escitalopram. These results suggested that the R-citalopram in citalopram inhibits the effect of the S-enantiomer.Objective To review the pharmacological and non-clinical literature that describes the inhibition of escitalopram by R-citalopram, as well as the implications of this inhibition for the clinical efficacy of escitalopram compared to citalopram.Methods The information in this review was gathered from published articles and abstracts.Results In appropriate neurochemical, functional, and behavioural non-clinical experiments, escitalopram shows greater efficacy and faster onset of action than comparable doses of citalopram. The lower efficacy of citalopram in these studies is apparently due to the inhibition of the effect of the S-enantiomer by the R-enantiomer, possibly via an allosteric interaction with the serotonin transporter. Data from randomised clinical trials consistently show better efficacy with escitalopram than with citalopram, including higher rates of response and remission, and faster time to symptom relief.Conclusion The R-enantiomer present in citalopram counteracts the activity of the S-enantiomer, thereby providing a possible basis for the pharmacological and clinical differences observed between citalopram and escitalopram.     

Incorporation of an ERA attachment for obturator framework design: a clinical report

Swinglock framework designs have been used to retain obturators for some time. One of the problems with Swinglock designs has been loss of retention due to wear of the metal latch assembly. This clinical report describes the incorporation of an ERA attachment as the latch assembly of a Swinglock framework for an obturator. The premise behind this design was that wear would be at the expense of the nylon retention male component, which is easily interchangeable, rather than the metal component of the assembly. The life of the latch assembly, framework, and prosthesis would thereby be prolonged.     

Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2

Deletion of a part of the short arm of chromosome 1 is one of the most common chromosomal rearrangements observed in neuroblastoma (NBL) tumors and it is associated with a poor prognosis. No NBL tumor suppressor gene has yet been identified in the region. Our shortest region of overlap of deletions, ranging from marker D1S80 to D1S244, was shown to partly overlap a 500 kb region that was homozygously deleted in a NBL cell line. We have screened seven genes known to reside in or very close to this overlap consensus region, UBE4B/UFD2, KIF1B, DFFA, PGD, CORT, PEX14, and ICAT, for coding mutations in NBL tumor DNA. A few deviations from the reference sequences were identified; most interestingly being a splice site mutation that was detected in UBE4B/UFD2 in a stage 3 NBL with a fatal outcome. This mutation was neither present in the patients constitutional DNA nor in any of 192 control chromosomes analysed. Also, the expression of UBE4B/UFD2 was markedly diminished in the high-stage/poor-outcome tumors as compared to the low-stage/favorable-outcome tumors. Overall, the number of amino-acid changes in the genes of the region was low, which shows that mutations in these genes are rare events in NBL development. Given the data presented here, UBE4B/UFD2 stands out as the strongest candidate NBL tumor suppressor gene in the region at this stage.     

Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study

The aim of our study was to examine the risk of breast cancer according to specific types of estrogens and progestagens in oral contraceptives (OCs) based on the prospective Norwegian Women and Cancer study (NOWAC). Between 1991-97 women aged 30-70 years were drawn at random from the central person register and mailed an invitation and a questionnaire. Women (102,443) were enrolled with follow-up information collected throughout 1999 by linkage with national registries of cancer, mortality and emigration based on the unique national identification number. Among the 96,362 women included in the present analysis 851 invasive breast cancer were diagnosed. The adjusted risk of breast cancer increased with 25% for ever use of OCs and the risk increased with increasing duration of use (test for trend: p = 0.007). No association between time since last use and breast cancer risk was found after stratification on duration of use. Positive trend was still found for total duration of use among women who used OCs more than 5 years ago. Second generation of OCs had an increased risk with increasing duration of use. Classifying progestagens according to chemical groups, the relative risk increased significantly with increasing cumulative dose of levonorgestrel progestagen. It was difficult to conclude for the other groups due to lack of power. In a multivariate analysis the cumulative dose for all progestagen groups were non-significant, although we observed a significant increased risk with increasing milligram-months of estrogen exposure (p = 0.002). In conclusion, the increased risk of breast cancer related with OC formulations could be due mostly to estrogen component.