Late Rescue Research Articles

Intoxicación aguda con metotrexato usado con fines abortivos: descripción de 2 casos

Acute intoxication with methotrexate, used as an abortive, has not been described in Chile. We report two female patients, aged 15 and 24 years old, who presented with mucositis, erythrodermia, pancytopenia, and elevation of hepatic enzymes. Plasma methotrexate levels confirmed the clinical diagnosis and both patients were treated with high leucovorin doses and management of associated complications. In one patient, pregnancy continued, giving birth to a newborn with cranial, face and limb malformations. The second patient had a late rescue with leucovorin and was discharged with a persistent sensory motor neuropathy. Considering the severity of complications and that patients may deny its use, when there is reasonable clinical suspicion of methotrexate intoxication, leucovorin treatment should be started.

Late luteal rescue in the baboon (Papio cynocephalus).

Numerous studies have used human chorionic gonadotrophin (HCG) administration to study the response of the primate ovary to gonadotrophin stimulation. These studies are generally performed in the luteal phase with very few studies of the follicular phase. We have studied the effect of both HCG and gonadotrophin releasing hormone (GnRH) agonist administered at the early follicular phase in normally cycling baboons (Papio cynocephalus). Five baboons were treated with increasing doses of HCG for 5 consecutive days starting on day 1 of the cycle and three untreated baboons served as controls. Follicular and luteal phase lengths were determined and serum samples were assayed for progesterone, oestradiol and 17alpha-OH progesterone. In a separate study, six baboons were treated with GnRH agonist (WY-40972) on days 2-6 of the cycle and saline-treated baboons served as controls (n = 5). Mean peak progesterone concentrations (+/- SE) during the treatment interval were 3.88+/-0.56 ng/ml in HCG-treated baboons compared to 0.19+/-0.07 ng/ml in controls (P < 0.001). A similar significant increase (P < 0.001) in serum 17alpha-OH progesterone concentrations was also observed (6.13+/-1.12 ng/ml versus 1.13+/-0.49 ng/ml). In association with the increase in luteal steroids there was also a significant prolongation of menstrual cycle length from 32.7+/-1.2 days in controls to 46.8+/-4.9 days in HCG-treated baboons (P < 0.05), which involved prolongation of the follicular phase (16.7+/-1.2 days to 29.0+/-4.6 days; P < 0.05) with no difference in luteal phase length or progesterone concentrations. In GnRH agonist-treated baboons, mean (+/- SE) cycle length was prolonged to 46.3+/-1.6 days and in saline-treated controls was 32.8+/-0.8 days (P < 0.001), again this was completely represented by the change in follicular phase length, from 13.4+/-0.7 days in controls to 27.2+/-2.1 days in agonist-treated baboons (P < 0.001). In contrast, there was no significant difference in luteal phase length between these two groups (19.4+/-0.7 versus 19.2+/-1.0 days). The prolongation of the follicular phase was accompanied by significant increases in both progesterone (P < 0.01) and oestradiol (P < 0.01) during GnRH agonist treatment above control concentrations. Luteal phase concentrations of these hormones were not different from controls. These results demonstrate the previously unreported finding that gonadotropin stimulation will rescue the corpus luteum in the next follicular phase.

Reinsemination by intracytoplasmic sperm injection of 1-day-old oocytes after complete conventional fertilization failure

Objective: To analyze the efficacy of intracytoplasmic sperm injection (ICSI) for “rescue” of failed conventional insemination cycles. Design: Retrospective clinical study. Setting: Private infertility clinic. Patient(s): Fifty-four couples with non-male factor infertility undergoing routine IVF within our clinic. Intervention(s): Twenty- to 24-hour-old unfertilized mature oocytes from conventional IVF cycles in which fertilization failure was complete were reinseminated by ICSI to attempt late fertilization and rescue of the otherwise failed IVF cycle. Main Outcome Measure(s): Late fertilization, pregnancy, and embryonic implantation. Result(s): Intracytoplasmic sperm injection reinsemination of 489 unfertilized mature oocytes caused degeneration in 50 (10.2%) oocytes, gave rise to normal fertilization in 215 (44.0%) of the injected oocytes, and allowed ET in 48 of the 54 cycles in which initial complete fertilization failure had occurred. One hundred sixty-four (76.3%) of 215 late-fertilized oocytes either were used for fresh transfer or were frozen-stored. Eight viable pregnancies resulted, yielding a 14.8% pregnancy rate per initiated cycle. Conclusion(s): Barring potential concerns regarding the chromosomal normality of embryos arising from reinsemination, our results suggest that ICSI is a relatively successful means of rescuing conventional IVF cycles in which fertilization fails completely.

Primary amines and chloroquine inhibit cytotoxic responses to Shigella toxin and permit late antibody rescue of toxin treated cells

The effect of lysosomotropic agents and primary amine inhibitors of transglutaminase on Shigella toxin activity in HeLa cells was determined by measuring cytotoxicity and late antibody rescue. All agents tested resulted in significant antibody rescue, but only ammonium chloride, dansylcadaverine, putrescine, bacitracin, serine/borate buffer, and chloroquine were inhibitory in the absence of added antibody. These compounds appear to be acting within the endocytic vacuole and/or inhibiting translocation of toxin from the cell surface to the cytosol. These data are consistent with a mechanism of translocation of ST from the cell surface to the cytosol by the process of receptor mediated endocytosis.