Use of the copper intrauterine device in the management of secondary amenorrhea.

OBJECTIVE: To determine whether the insertion of a copper intrauterine device can restore regular menses in patients with functional secondary amenorrhea. DESIGN: Prospective, observational study. SETTING: Clinical practices. PATIENT(S): Forty-eight volunteers with functional secondary amenorrhea. INTERVENTION(S): Insertion of a copper intrauterine device. MAIN OUTCOME MEASURE(S): Restoration of menses. RESULT(S): In 40 patients, regular menses were restored within a few weeks after insertion of the device. Normal menses were maintained as long as the copper intrauterine device remained in place. After removal of the device, normal menses persisted for 1 year. CONCLUSION(S): Insertion of a copper intrauterine device restores regular menses in women with functional secondary amenorrhea. The mechanism of action of the device probably is related to the release of prostaglandins from the endometrium.

Characterization of FR 172357, a new non-peptide bradykinin B(2) receptor antagonist, in human, pig and rabbit preparations.

FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of bradykinin. The displacements were parallel to the controls without reduction of the maximum effect in the human umbilical vein and in the rabbit jugular vein, but not in the pig coronary artery. Schild plots confirmed that FR 172357 acts as a competitive antagonist in the human umbilical vein (pA(2) 8.65) and in the rabbit jugular vein (pA(2) 9. 07), and as a non-competitive antagonist in the pig coronary artery (pK(B) 10.14). FR 172357 is selective for the kinin B(2) receptor since it does not influence the effects of Lys-des-Arg(9)-bradykinin in the human umbilical vein, in the rabbit aorta, and in the pig renal vein. It is specific because it does not affect the contractions induced by angiotensin II, noradrenaline, 5-hydroxytryptamine, or endothelin-1 in the human umbilical vein. It, however, interacts with the tachykinin NK(1) receptor of the rabbit jugular vein and pig coronary artery. Compared to other bradykinin B(2) receptor antagonists, FR 172357 emerges as a very potent compound, which may represent a choice for experimental (and clinical?) applications.

Evaluation of intrauterine growth pattern of twins by linear discriminant analysis of the values of biparietal diameter, femur length and abdominal circumference1.

In a cross-sectional study, the intrauterine growth pattern of 32 twins was compared to that of 205 singletons by analysis of the coefficients of the equations of biparietal diameter (BPD), femur length (FL) and abdominal circumference (AC). Lower values were observed in twins from the 20th week. BPD and AC curves showed a progressively diverging pattern, and yielded different coefficients of equations. AC showed the highest discriminant capacity followed by BPD and FL. Combined values of the two series solved by discriminant function output produced an overlapping of 58%. Based on our data, nomograms of growth of singletons should not be used for twins.

Inhibition of amniotic prostaglandin E release by ampicillin.

OBJECTIVE: The effect of antibiotics in the prevention of preterm labor needs to be further investigated. The aim of this study was to determine the effect of ampicillin on prostaglandin E release from amnion as a possible explanation for its ability to retard preterm labor. STUDY DESIGN: The effect of the beta-lactam antibiotic ampicillin on prostaglandin E release from human amnion was tested under basal and stimulated conditions. RESULTS: Ampicillin dose dependently inhibits basal prostaglandin E release from amnion in both static and dynamic conditions. In our experiments, 10(-7) mol/L ampicillin (a concentration able to significantly inhibit prostaglandin E output) leaves the microbiologic features of the medium substantially unmodified up to 5 hours of incubation. Moreover, the drug reversibly counteracts the prostaglandin E elevation induced by arachidonic acid or oxytocin. CONCLUSION: This finding (i.e., that ampicillin inhibits prostaglandin E release from amnion) may offer an explanation for a beneficial response to ampicillin therapy in the case of preterm labor even in the absence of bacterial infection.

Increased incidence of preeclampsia in pregnancies complicated by fetal malformation.

There seems to be a correlation between preeclampsia and congenital abnormalities, but whether it is positive or negative is a matter of controversy. Since it has been demonstrated that reduced perfusion of the trophoblast, which is an early feature of preeclampsia, can also represent a cause of fetal malformation, a positive correlation between the two conditions should be found. In the search for such a correlation we retrospectively examined 8,894 cases collected until 1994 by the IMER group (Indagine Malformazioni Emilia-Romagna). In the presence of malformation a higher incidence of preeclampsia was found (4.60 versus 3.47) with an odds ratio of 1.34 (95% CI = 1.08-1.67). Furthermore multivariate analysis showed that malformations of the male genital apparatus and those named 'multiple congenital abnormalities' can be considered as risk factors for preeclampsia. Since it is known that the development of male genitalia occurs under the influence of androgens, it can be hypothesized that hypoxia could act by favoring low end organ responsiveness. In our opinion the positive correlation with fetal malformations should be interpreted as clinical evidence of the early onset of the physiopathologic mechanism of preeclampsia.

Human vascular kinin receptors of the B2 type characterized by radioligand binding.

1. The human umbilical vein responds to bradykinin (BK) with contractions that are mediated by B2 receptors. In the present study, the corresponding vascular smooth muscle B2 binding sites have been investigated. 2. [3H]-BK, a full agonist labelled ligand, was used to demonstrate a single binding site giving a Kd value of 0.51+/-0.02 nM and a Bmax of 24+/-1 fmol mg(-1) protein. Scatchard plots were linear (r=0.98) in the 0.05-5 nM range of concentrations. Non-specific binding was found to be 30% of total binding. 3. Competition binding curves gave the following order of potency for various B2 receptor agonists: BK-[Hyp3]-BK > or = Lys-BK >> [Aib7]-BK >>> [desArg9]-BK, which is typical of B2 receptors. There was no binding to B1 receptors since the selective B1 receptor ligand, Lys-[desArg9]BK was inactive up to 10 microM (n=4). 4. Characterization of the binding site with antagonists, performed with three chemically distinct series of peptide and non-peptide compounds, revealed a high affinity of Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK) (Ki 0.17 nM; n=4) which was more potent that FR 173657 ([(E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinol inyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl] acrylamide]) (Ki 1.94 nM; n=4), D-Arg-[Hyp3,D-Phe7,Leu8]-BK (Ki 256 nM; n=4) and Win 64338 (phosphonium, [[4[[2[[bis(cyclohexylamino)methylene]amino]-3-(2-naphthalenyl)-1-oxopro pyl]amino]phenyl]methyl]tributyl, chloride, monohydrochloride) (Ki 1,450 nM; n=4). 5. The present study describes and characterises B2 receptor binding sites in the vascular smooth muscle of the human umbilical vein. The binding assay appears to be suitable for studying new agonists or antagonists designed to activate or block the B2 receptor class that mediate the majority of the physiopathological effects of kinins in man.

Raised level of amniotic endothelin in pregnancies with fetal aneuploidy.

Amniotic fluid endothelin-1 (ET-1) levels were measured in 38 euploid and in 15 aneuploid pregnancies in the 17th gestational week. Varying distribution of the peptide levels was found in the two groups, with higher values in the pathological cases. Should this finding be confirmed in maternal blood, ET-1 could represent a further analyte to be used in prenatal screening for aneuploidy.