[Determination of blood cystatin C in pregnant women during labor and in their newborns]. / Determinazione della cistatina C sierica in gestanti al momento del parto e nei loro neonati.

INTRODUCTION: Human cystatin C is a basic low molecular mass protein (M(r) = 13,359) freely filtered by the glomerulus and almost completely reabsorbed and catabolized by the proximal tubular cells. In this study, we determined maternal and neonatal serum cystatin C levels both in a group of healthy pregnant women and in their newborns over the first five days of life. PATIENTS AND METHODS: Fifty healthy pregnant women, aged from 19 to 40 years, were selected. Newborns (31 males, 19 females) demonstrated the 1-min Apgar score ranging between 8 and 10, and the 5-min between 9 and 10. Their gestational age (GA) ranged between 37 and 43 weeks. Cystatin C was determined by using the cystatin C PET kit (Dako, Milano, Italy). We also determined serum creatinine and urea in all patients by using the Ektachem enzymatic assay (Ortho Diagnostic Division, Milano, Italy). RESULTS: In pregnant women, serum cystatin C was 1.52 +/- 0.39 mg/L, ranging from 0.69 to 2.30 mg/L. Serum creatinine was 58.9 +/- 11.5 mumol/L, and serum urea was 3.117 +/- 0.729 mmol/L. In newborns, serum cystatin C was at birth 2.29 +/- 0.52 mg/L, ranging from 1.17 to 4.84 mg/L. Subsequently, cystatin C significantly decreased over the first five days of life. Serum creatinine was at birth 80.08 +/- 14.26 mumol/L. By using analysis of variance (ANOVA) we found a statistically significant difference between maternal and neonatal cystatin C (p < 0.001) as well as between maternal and neonatal creatinine (p +/- 0.001). However, no correlation has been demonstrated by simple linear regression between maternal and neonatal cystatin C (r = 0.05), while maternal and neonatal creatinine significantly correlated (r = 0.45). CONCLUSIONS: Our preliminary findings suggest that cystatin C does not cross the placental barrier. Thus, in the neonate cystatin C serum levels may solely derived from himself.

[Prophylactic use of cefotetan in gynecologic surgery]. / Profilassi con cefotetan in chirurgia ginecologica.

The efficacy of prophylactic treatment with systemic antibiotics in laparotomic gynecologic surgery is well established. Lately, short-term schemes have been preferred in surgical prophylaxis for different reasons. First of all, experimental data demonstrated that the efficacy of an antibiotic is maximal when it reaches active tissue concentrations at the time of bacterial contamination. In addition with the availability of new, long-acting antibiotics, a long period of time around the operations was possibly covered. The effectiveness of a single preoperative 2 gm dose of Cefotetan was compared with a traditional treatment of 3 gm daily of Cefazolin for one week following surgery in 86 women undergoing laparotomic gynecologic surgery for benign pathology. Our results confirm that preoperative treatment with Cefotetan is able to prevent infectious disease such as 3 gm of Cefazolin per day for one week. Thus, Cefotetan can be used for this type of prophylaxis considering its broad spectrum of action and pharmacokinetic properties.

Radioreceptor assay for the measurement of endogenous digitalis-like factors using membrane particulate fraction of human placenta and 125I-digoxin: comparison with RIA method.

We measured purified extracts of serum (plasma) or urine samples of newborns, pregnant women, normal adults, and uremic patients by a radioreceptor assay (RRA), which uses particulate membrane fractions from human placenta as a binding system, and 125I-digoxin as a tracer. We also measured the digoxin-like immunoreactivity by a sensitive RIA, and results were compared with those found by the RRA. Specific 125I-digoxin binding to placental receptors was competitively inhibited by purified plasma and/or urine extracts of newborns, adult subjects, pregnant women and uremic patients. A linear relationship was found between inhibition of binding and volume of plasma and urine assayed. Moreover, a significant correlation was found between the values obtained by RRA and those found by RIA (n = 17, r = 0.699, p = 0.0012). Our data confirm that increased circulating and/or urinary levels of substances with biological and immunological activity similar to cardiac glycoside drugs are present in newborns, pregnant women and uremic patients compared to healthy adult subjects. In addition, our preliminary study indicates that these endogenous factors are able to bind to the specific receptor of digitalis drugs on the placental membranes.

Evaluation of the central dopaminergic activity in gestational hyperprolactinaemia by means of the electroretinographic technique.

Electroretinography, a simple, bloodless technique commonly used in ophthalmological diagnostic practice, seems to give important informations on the level of activity of the retinal and/or other central dopaminergic systems. The Authors have employed this technique in a group of 30 normal pregnant women in the ninth month of gestation, in order to evaluate the dopaminergic activity in a condition of physiological hyperprolactinemia, such as pregnancy, and in a group of 25 normal nonpregnant control women. The b wave amplitude of the electroretinographic traces was significantly higher in pregnant women than in controls, suggesting an over-activity of dopaminergic systems in late pregnancy. The possible interpretations of these data are discussed.

Dilemmas in intrauterine fetal growth retardation. The significance of anticomplement and heparin-like activities of placenta at term and the prognostic value of HCS and E3 maternal plasma concentrations during pregnancy.

The Authors studied the behaviour of anticomplement and heparin-like activities in human term placentas in relation to intrauterine fetal growth retardation. These two biological activities might be involved in regulatory mechanisms of great importance for the fetal growth. The anticomplement activity was significantly lower in IUGR placentas than in controls, while no change was found in heparin-like activity. The decrease of anticomplement activity might be associated to immunological mechanisms, possibly related to a placental microcirculation damage, with consequent fetal growth retardation. For what concerns HCS and E3 plasma levels during pregnancy, a significant reduction of HCS in IUGR subjects was observed, confirming a decreased functional activity of placenta. The E3 levels, on the contrary, were slightly, but not significantly lower in IUGR patients.

Placental transfer of pinazepam and its metabolite N-desmethyldiazepam in women at term.

Placental transfer of pinazepam and its metabolite N-desmethyldiazepam was investigated in 25 pregnant women at term. Pinazepam was administered orally as a single (10 mg) dose to 13 women, or in multiple doses of 5 mg daily to 12 women. The dose-delivery interval ranged between 1 and 26 h for the single dose, and the period between the last of the multiple doses and delivery was 1.4 to 24 h. Pinazepam and N-desmethyldiazepam were measured in plasma obtained from the umbilical vein and from the mother, at delivery. Pinazepam was only detectable in plasma after the 10 mg dose. The drug did not reach an apparent equilibrium between fetal and maternal plasma. The average (+/- SEM) cord/maternal ratio of plasma pinazepam concentrations was 0.64 +/- 0.07. N-desmethyldiazepam was detectable on each occasion. Its concentration in the plasma from the cord vein became higher than that in the maternal specimens 1-2 h after administration of the parent drug. Little N-desmethyldiazepam was excreted in breast milk.

Normoprolactinemic galactorrhea in a fertile woman with a copper intra-uterine device (copper IUD).

We report a case of galactorrhea in a normoprolactinemic fertile woman (30 years old) wearing a copper intra-uterine device (Gravigard). The Gravigard was first inserted in July 1977. In February 1979 our patient noted spontaneous galactorrhea, mainly on the left, but it was also present on the right, after breast pressure. X-ray film of the sella turcica, visual-field examination, thyroid function and basal prolactin levels were all within normal limits. In May 1979 the Gravigard was withdrawn and milk loss stopped finally in December 1979. In March 1980 the IUD was replaced; after only 3 days, mild spontaneous lactation again ensued, on the right side. The patient never took drugs which might have occasioned a prolactin rise. Possible explanations for this unusual phenomenon are discussed.

PIP: The authors report a case of galactorrhea in a normoprolactinemic fertile woman age 30 wearing a copper IUD (Gravigard). The Gravigard was 1st inserted in July 1977; in February 1979, the patient noted spontaneous galactorrhea, mainly on the left side, but also present on the right, after breast pressure. X-rays of the sella turcica, visual field examination, thyroid function, and basal prolactin levels were all within normal limits. In May 1979, the Gravigard was withdrawn and milk loss stopped finally in December 1979. In March 1980, the IUD was replaced; after only 3 days, mild spontaneous lactation again ensued, on the right side. The patient never took drugs that might have occasioned a prolactin rise. Possible explanations for this unusual phenomenon are discussed.

Bromocryptine-cyclofenil associated therapy: an effective and safe mode of treatment of female normoprolactinemic infertility.

In 51 infertile normoprolactinemic women, aged 19 to 44 years, with anovulatory menstrual cycles and with no endocrine disorders, who had never conceived after the currently employed drugs for female sterility (human chorionic gonadotropin, human menopausal gonadotropin, clomiphene, cyclofenil, bromocryptine itself) a new therapeutic approach was tried: cyclofenil and bromocryptine in association. Before the treatment, a standard luteinizing hormone (LH)-releasing hormone (LHRH) test (100 micrograms intravenously) was performed for each woman to evaluate serum gonadotropin and prolactin response; furthermore, the urinary estrogen excretion or the serum 17-beta-estradiol concentration had been evaluated in all women. The schedule of treatment was as follows: cyclofenil, 600 mg/day, from the 5th to the 12th day of the cycle and bromocryptine, 2.5 mg/day, from the 5th to the 26th day. This scheme was employed for three successive trials at the most. Forty pregnancies (80%) were achieved with the associated therapy, almost all (37) within the second treatment cycle. Thirty-one women delivered a vital baby, five are now pregnant, four aborted spontaneously. All seven women who had been unsuccessfully treated with bromocryptine alone, conceived after the associated regimen. In view of the excellent therapeutic results achieved in our hands, it is justified to consider our proposed scheme cyclofenil-bromocryptine an effective therapy for the management of infertile normo-prolactinemic women.

Unusual prolactin response to luteinizing hormone-releasing hormone in some anovulatory women.

We studied PRL, FSH, and LH response to LRH in 82 anovulatory and 4 normally ovulating women. Ten anovulatory patients who were basally hyperprolactinemic showed no significant change in PRL concentration after LRH. Of the remaining 72 anovulatory patients with basal PRL levels in the normal range, 59 showed no PRL modification after LRH (as in normals) whereas in 13 patients, a prompt and significant rise of PRL concentration above basal levels in response to LRH was observed. In these 13 patients, the basal PRL levels were significantly higher than those of the other 59 normoprolactinemic women. No significant differences in gonadotropin concentrations were detected among the three groups. The unusual rise in PRL levels after LRH in these 13 patients can be interpreted as a paradoxical response of the pituitary to a specific stimulus, as seen in other clinical conditions. It is suggested that this phasic hyperprolactinemia might represent an intermediate phase between true normoprolactinemia and chronic hyperprolactinemia.