[Incidence of influenza episodes at a health care center].
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Biomedical subjects
Publications and source records attributed to P Mena.
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Although natural family planning (NFP) is a form of contraception without ostensible maternal risks (other than pregnancy), potential fetal risks could exist if aging gametes are involved in inadvertent fertilization. In the following report, we first review animal studies firmly establishing that aging sperm and aging oocytes (delayed fertilization) cause chromosomal abnormalities in mammals and other species. We next review human studies associating decreased coital frequency with trisomy and studies of NFP populations that generally show no increased frequency of anomalous offspring or spontaneous abortions. Our rationale for initiating an international cohort study is presented, along with the experimental design selected. Preliminary findings indicate that the experimental design chosen will indeed provide information allowing NFP safety to be assessed definitively.
In the isolated pancreatic islets incubated in vitro, carboxylmethylation increases following stimulation with 20 mM glucose. This increase is dependent on extracellular calcium concentration and is suppressed in the presence of trifluoperazine, a calmodulin inhibitor. In conclusion, the increase in carboxylmethylation induced by 20 mM glucose seems to be a calcium-dependent process and it is probably mediated by calmodulin.
In a randomized, double-blind study, 12 and 16 mg of metergoline and 5 mg of bromoergocriptine were given daily to three groups of 100 women each for ten consecutive days to prevent lactation. Excellent or good results were obtained in 86%, 90% and 83%, respectively. Serum prolactin (PRL) levels were evaluated in three settings. The first was after a single dose in four groups of patients (4, 6 and 8 mg of metergoline and 2.5 mg of bromoergocriptine were studied for ten hours). Second, for a study of the suckling reflex, PRL levels were measured 15, 30 and 60 minutes after breast stimulation in four groups of five patients each: two groups on the fourth postpartum day with and without metergoline treatment and two groups on the eighth postpartum day (the reflex was suppressed in the two groups treated with metergoline). Third, serum PRL levels rose after the intravenous administration of 200 mg of thyrotropin-releasing hormone (TRH) in another two groups of ten patients, one treated with metergoline and the other not so treated. TRH stimulation was not blocked in the treated groups.
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Thyrotropin releasing hormone (TRH) readily crosses the placenta and stimulates the fetal pituitary. We studied the response of the maternal and fetal pituitary-thyroid axes to TRH and the influence of prenatal exposure to TRH on the physiological postnatal increase in thyrotropin (TSH) and triiodothyronine (T3) in the neonate. Twenty-six pregnant women received TRH (400 or 600 micrograms) intravenous or saline (controls) either 2 or 12 h before elective cesarean section at term. Administration of 400 micrograms of TRH resulted in significant elevations of maternal TSH (15.7 +/- 2.9 versus 3.2 +/- 0.4 microU/ml, p less than 0.01) and prolactin (416 +/- 94 versus 223 +/- 41 ng/ml, p less than 0.05) 2 h later. Maternal T3 remained unchanged. A higher dose of TRH (600 micrograms) produced comparable results. Maternal administration of TRH (400 micrograms) 2 h before delivery resulted in significant increases in fetal TSH and T3 over controls (21.1 +/- 3.7 versus 4.8 +/- 1.0 microU/ml, and 132 +/- 12 versus 64 +/- 9 ng/dl, p less than 0.01, respectively). Cord blood hormone levels 12 hours after TRH administration were similar to controls. Higher doses of TRH did not produce further increases in fetal TSH or T3. Control and treated neonates demonstrated similar physiological postnatal increases in TSH and T3, suggesting that prior exposure to TRH did not blunt this response. These data suggest that maternal administration of TRH is an effective way of increasing fetal T3 levels, and that this treatment does not inhibit the postnatal surge in TSH and T3.
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For the prevention of lactation we administered metergoline, 12 to 16 mg per day for five to ten days, to six groups of 100 patients each with excellent or good results in 95% to 99% of the cases. In addition, metergoline was given to 100 patients in order to suppress previously established lactation, with excellent or good results in 100% of the cases. The decrease of prolactin during the first 21 days of metergoline administration was compared with that in a group given bromoergocriptine (5 mg per day) and with that in a breast-binding control group. Metergoline is effective and does not have secondary effects in the inhibition and suppression of lactation due to its antiserotonin and dopaminergic effects.
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We studied the methyl acceptor capacity of insulin and glucagon in vitro. The levels of carboxylmethylation of pancreatic hormones (dpm x 10(3], when incubated with S-adenosyl-L-(3H-methyl)-methionine as methyl donor and purified protein carboxylmethylase, were: insulin (n = 6) 8.1 +/- 0.2 and 11.1 +/- 1.5 (mean +/- SEM) for 0.25 and 1.0 mg/ml, respectively; glucagon (n = 6) 17.0 +/- 3.2 and 40.2 +/- 2.5 (mean +/- SEM) for 0.5 and 1.0 mg/ml, respectively. On a molar basis, the methyl acceptor capacity was 1.0 dpm/pmol for insulin and 9.5 dpm/pmol for glucagon. Polyacrylamide gel electrophoresis of carboxylmethylated hormones showed a radioactivity (3H-methyl) peak that co-migrated with the corresponding 125I-hormone. Glucagon, but not insulin, seems to be a relatively good substrate for carboxylmethylation.
OBJECTIVE: Various birth defects and untoward perinatal outcomes have been claimed to be associated with pregnancies conceived by gametes aged in vivo before fertilization. Thus, these outcomes were systematically assessed in pregnancies occurring in natural family planning (NFP) users. Our international multicenter cohort study of NFP pregnancies (n = 877) is by far the largest systematic study designed to assess pregnancy outcome and is of sufficient power to allow us to address the concern of low birth weight (< 2500 g) and preterm delivery (< 37 weeks gestation). STUDY DESIGN: In addition to gathering baseline medical data, evaluation was performed at 16 weeks, 32 weeks and at term. Data were collected in a systematic cohort fashion, verified by the five collaborating international recruiting centers, and analyzed by investigators in the US. Most recruiting center principal investigators are obstetrician-gynecologists and, if not, have integral relationships with such specialists. Standard criteria could thus be applied within and among centers. In our cohort, birth weight was recorded accurately at delivery. Almost all of the deliveries occurred in hospitals; thus, data should be quite reliable. Neonatal examination for anomalies was usually conducted immediately after delivery, when birth weight was recorded. RESULTS: Analysis of risk factors for low birth weight and preterm delivery showed that this population had a low risk profile. Low birth weight infants (< 2500 g) and preterm deliveries were increased among women with a history of either prior low birth weight or preeclampsia in the index pregnancy. However, mean birth weight was unaffected by the timing of conception vis à vis ovulation or pregnancy history. Mean birth weight for the 877 singleton NFP pregnancies was 3349.6 g. The risk of preterm delivery was increased among older women who drank alcohol, but there were no significant effects of timing of conception vis à vis ovulation on preterm delivery. Results held when analysis was stratified according to whether NFP was being used for contraception or to achieve pregnancy. CONCLUSIONS: Our data do not appear to show striking differences between 877 NFP pregnancies and the general obstetric population. The timing of conception vis à vis ovulation does not exert significant effects on the birth weight or preterm delivery of resulting pregnancies, a reassuring finding for NFP users.
Conceptions involving aging gametes are of relevance to natural family planning (NFP) because women using NFP to avoid pregnancy abstain from intercourse during the fertile time of the cycle. To help verify the safety of pregnancies occurring among NFP practitioners, our group has, since 1986, conducted a large cohort study involving six experienced NFP centers. Timing of conception was determined from NFP charts, in which women recorded days on which intercourse occurred. The number of days from the most probable conception intercourse to probable day of ovulation was first determined, and used as an estimate of the time gametes remained in the genital tract before fertilization. Several studies have already been completed, cohort as well as case-control in nature.