Ermelando V. Cosmi

Correlation between endometriosis and pelvic pain

STUDY OBJECTIVE To evaluate the relationship between prevalence and severity of chronic pelvic pain (CPP) and stage, site, and type of endometriosis. DESIGN Prospective, observational study (Canadian Task Force classification II-2). SETTING University Hospital. PATIENTS Of 90 consecutive women with biopsy-proved endometriosis, laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis. INTERVENTION Preoperatively, using a 10-point visual analog scale, the severity of dysmenorrhea, CPP, and deep dyspareunia was assessed. During laparoscopy all visible endometriotic lesions were recorded and treated. MEASUREMENTS AND MAIN RESULTS Ten women (11.1%) had no pain; 72 had dysmenorrhea (mild in 13, moderate in 37, severe in 22); 55 had CPP (mild in 11, moderate in 25, severe in 19); and 39 deep dyspareunia (mild in 5, moderate in 31, severe in 3). The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions (p = 0.004); the severity of CPP correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001) and extent of pelvic adhesions (p = 0.02); and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments (p = 0.04). Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001), peritoneal adhesions (p = 0.01), and extent of adnexal adhesions (p = 0.01). No significant correlation was found among revised American Fertility Society stage of endometriosis; presence and size of ovarian endometriomas; extent, type, and site of peritoneal lesions; and pain scores. By logistic regression analysis, the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis (p = 0.0001) and presence and extent of adnexal adhesions without cystic endometriosis (p = 0.01), and by the presence of ovarian endometrioma with periovarian adhesions (p = 0.03). Chronic pelvic pain was predicted by both deep endometriosis (p = 0.0001) and ovarian endometriomas with adnexal adhesions (p = 0.03). Deep dyspareunia was predicted simultaneously by deep endometriosis (p = 0.01) and an ovarian endometrioma with periovarian adhesions (p = 0. 008). Conclusion. Deep endometriosis, pelvic adhesions, and ovarian cystic endometriosis were independent predictors of pelvic pain. These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain.

Adrenomedullin, a New Vasoactive Peptide, Is Increased in Preeclampsia

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.

Immunoreactive adrenomedullin in human fetoplacental tissues

OBJECTIVE Adrenomedullin is increased in maternal plasma in pregnancy and has been found in very high concentrations in amniotic fluid and umbilical plasma. To identify adrenomedullin-producing tissue in pregnancy we measured adrenomedullin concentration and distribution in fetoplacental tissues. STUDY DESIGN By use of a specific radioimmunoassay we determined the concentrations of adrenomedullin and, by immunohistochemical studies, its localization and distribution in fetal membranes and placentas collected at elective cesarean section from 11 healthy pregnant women at term. RESULTS The content of adrenomedullin in placentas (117.7 +/- 7.8 pg/mg wet tissue) and fetal membranes (168.7 +/- 2.3 pg/mg wet tissue) was similar to the adrenomedullin concentration in adrenal medulla (157.3 +/- 4.4 pg/mg wet tissue). Adrenomedullin staining appears to be greater in fetal membranes than in placentas and was localized in amnion and trophoblast cells. In term placentas positive staining was detected predominantly in extravillous trophoblast cells, although a few syncytiotrophoblast cells and endothelial cells of primary villi stained for adrenomedullin. CONCLUSION This study provides evidence that is consistent with fetoplacental tissues as a site of synthesis or action of adrenomedullin during pregnancy.

Prenatal diagnosis of fetal cytomegalovirus infection after primary or recurrent maternal infection

OBJECTIVE To determine the reliability of prenatal diagnosis of cytomegalovirus infection in women with primary or recurrent infection. METHODS Amniotic fluid (AF) samples from 117 pregnant women were evaluated for cytomegalovirus culture and cytomegalovirus-DNA detection. Neonatal and postnatal samples also were examined to confirm or exclude transmission of maternal-fetal cytomegalovirus infection. RESULTS Of 25 women with primary cytomegalovirus infection, 13 (52%) had cytomegalovirus-positive AF samples by polymerase chain reaction (PCR), nine of which also were diagnosed by culture. All eight neonates born to mothers whose AF was cytomegalovirus-positive by PCR and culture were cytomegalovirus infected, and three were symptomatic. One aborted fetus had cytomegalovirus-DNAemia. Of four women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates and two aborted (one fetus had cytomegalovirus encephalopathy). Of 45 mothers with recurrent infection, two with AF cytomegalovirus-positive by PCR and culture, and another with cytomegalovirus-positive AF samples by PCR only, aborted cytomegalovirus-DNA-positive fetuses. Of the other seven women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates, two delivered neonates cytomegalovirus-positive by PCR only (one was symptomatic), and three delivered infants cytomegalovirus-negative by PCR and culture. All 47 mothers with nonactive cytomegalovirus infection and cytomegalovirus-negative AF samples had uninfected neonates. Polymerase chain reaction was superior to viral culture in sensitivity and negative predictive value (100% compared with 57% and 94%, respectively) but was lower in specificity and positive predictive value (97% and 83%, respectively, compared with 100%). CONCLUSION Prenatal diagnosis of fetal cytomegalovirus infection should include PCR in addition to viral culture, particularly for congenital cytomegalovirus infections following maternal recurrence.

The motility of human spermatozoa as influenced by prostasomes at various pH levels.

Human semen contains several components among which spermatozoa, membranous vesicles called ‘prostasomes’, secreted by the prostate gland and unorganized material. Prostasomes possess an unusual lipid composition, contain a number of proteins and small molecules and have been claimed to take a part in the immune response, in seminal fluid liquefaction and in sperm motility. Since sperm may come in contact with an acidic environment in the vagina, it may be of some interest to know whether prostasomes may affect spermatozoon motility or may protect spermatozoa upon the exposure to an acidic milieu. Human semen was supplied by donors. From whole semen we collected spermatozoa by centrifugation and used the supernatant to prepare prostasomes (centrifugation at 105000 g for 120 min, followed by purification step on Sephadex G 200); spermatozoa were then collected by a swim‐up procedure and exposed to an acidic pH medium (from 5 to 7) in the presence or absence of prostasomes. Spermatozoa motility was subsequently assessed with a superimposed image analysis system (SIAS). Results indicate that the motility of spermatozoa was affected by the pH value of the medium. Acidic media reduced the percentage of motile cells and decreased the straight line velocity of spermatozoa (VLS). Prostasomes had a protective effect and increased the percentage of motile cells. However, they did not change the characteristics of motility (curvilinear and straight). Prostasomes may be considered as a system for counteracting the negative effects of acidic pH values that may be present in the vagina after coitus.

Transvaginal sonography of the yolk sac in normal and abnormal pregnancy

A cross‐sectional study comprising 117 consecutive first trimester singleton pregnancies was performed using transvaginal sonography (TVS) to evaluate size abnormalities of the secondary yolk sac (YS) vis‐à‐vis pregnancy outcome. In normal pregnancy outcome (NPO) the YS diameter showed an increase from the 5th to the 11th week, menstrual age, followed by a decrease and its disappearance after 12 weeks. A YS of abnormal size was statistically significant (p < 0.001) in spontaneous abortion (SA) versus NPO, with a sensitivity of 68.7%, a specificity of 99%, a positive predictive value of 91.6% and a negative predictive value of 95.2%. These preliminary results indicate that a measurement of the YS very early in gestation may be a useful marker of pregnancy outcome.

Prostasome to sperm transfer of CD13/aminopeptidase N (EC 3.4.11.2)

Prostasomes are membranous vesicles (150-200 nm in diameter) that are present in human semen. They are secreted by the prostate gland and contain large amounts of cholesterol, sphingomyelin and Ca2+. In addition, some of their proteins are enzymes. Prostasomes enhance the motility of ejaculated spermatozoa and are involved in a number of additional biological functions. In previous papers, we demonstrated that lipid can be transferred from prostasomes to sperm by a fusion process occurring at slightly acidic pH. CD (cluster antigens) are ubiquitous proteins; in this paper, we demonstrate that CD13/aminopeptidase N is present is semen, where it is bound to prostasomes. Upon mixing prostasomes and sperm at slightly acidic pH (7 or less), aminopeptidase is transferred from prostasomes to sperm. This evidence comes from enzymatic activity determinations and from the use of the monoclonal antibody, anti-human CD13. The transfer was about 8% of total prostasomal activity at pH 5 and with a prostasome to sperm ratio of 2 (on a protein basis). The transfer did not occur at pH 8.0, but was measurable at pH 7. Therefore, this mechanism may represent a means of modifying the composition and the biological properties of ejaculated sperm.

Clinical manifestations and abnormal laboratory findings in pregnant women with primary cytomegalovirus infection

Objective To compare the clinical manifestations and laboratory abnormalities associated with primary cytomegalovirus (CMV) infection in pregnancy with recurrent and non‐active CMV infection (controls).

Amniotic fluid nitric oxide and uteroplacental blood flow in pregnancy complicated by intrauterine growth retardation

Objective To examine the correlation between placental nitric oxide production and uteroplacental blood flow.

Hyperimmunoglobulin therapy for a twin fetus with cytomegalovirus infection and growth restriction

OBJECTIVE Cytomegalovirus immunoglobulin was administered to a pregnant woman with primary cytomegalovirus infection and placental involvement of 1 twin fetus, in whom growth restriction had developed. STUDY DESIGN Inhibition of viral activity was attempted by administration of high-titer cytomegalovirus neutralizing antibodies for therapy of the involved fetoplacental unit and prevention of cytomegalovirus infection in the uninfected twin fetus. RESULTS After cytomegalovirus immunoglobulin infusions the placental edema decreased and the infected fetus started to grow once again, showing at birth only hepatosplenomegaly associated with viruria and cytomegalovirus deoxyribonucleic acidemia. Moreover, cytomegalovirus immunoglobulin G avidity increased and cell-mediated immunity improved. The other twin, who had negative results of cytomegalovirus culture and deoxyribonucleic acid detection at birth, was found to have cytomegalovirus deoxyribonucleic acid in the urine after 1 week. From the age of 9 months, however, both twins had persistent negative results of cytomegalovirus deoxyribonucleic acid detection. CONCLUSION Although large-scale studies are needed to establish the real efficacy and the best therapeutic regimen, cytomegalovirus immunoglobulin may be considered for treatment or prevention of fetal cytomegalovirus infection.