Bibliographic record
Abstract
Preterm birth that occurs before 37 weeks gestation, complicates 5-10% of all pregnancies and represents a significant obstetrical challenge which imposes a large burden on the Canadian health care system. 70% of all neonatal deaths and up to 75% of neonatal morbidity is associated with preterm birth (1-8). Various tocolytic drugs have been employed in the treatment of preterm labour. However, currently there is no drug available on the market that can stop preterm labour and improve neonatal outcome. Although effective at blocking labour contractions, most tocolytic drugs were associated with significant maternal and fetal side effects. The purpose of this thesis was to test a new potential tocolytic drug, meloxicam, for the treatment of preterm labour and to examine the effects of meloxicam on the cyclooxygenase enzymes important for prostaglandin production involved in the labour process and uterine activity during induced preterm labour contractions. We investigated these effects in parallel experiments using an in vivo chronically catheterized pregnant sheep model, and an in vitro human amnion and placental cell culture model. We hypothesized that meloxicam would be an effective tocolytic, blocking preterm labour contractions without serious maternal or fetal side effects observed with other tocolytics. In our ovine model meloxciam successfully reversed induced preterm labour contractions to their pre-labour type for a 48 hour period, without affecting maternal or fetal physiological parameters, fetal lower-body regional blood flow, fetal urine production and osmolality and maternal and fetal blood osmolality. Furthermore meloxicam decreased prostaglandin concentration in maternal and fetal blood, and cyclooxygenase-2 protein levels in intrauterine tissues (Study 1) without affecting the cyclooxygenase-1 isoform (Study 1 and Study 2). This effect was dose and time dependant. In cell culture models meloxicam also decreased prostaglandin concentration and cyclooxygenase-2 protein levels but spared cyclooxygenase-1 protein. The results obtained in this thesis using meloxicam as a new potential tocolytic are very encouraging, as meloxicam was able to reverse uterine labour contractions without serious side effects. However, we suggest that in human clinical trials meloxicam should be administered for a short period of time to avoid potential side effects caused by downregulation of cyclooxygenase-2 synthesis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".