ULTRAZVUČNA PROSUDBA MIGRACIJE PLACENTE PREVIJE U ODNOSU NA MAJČINE DEMOGRAFSKE ČIMBENIKE

Objective. To assess the association between maternal age, parity, history of prior cesarean delivery and placental location in evaluating the persistence and rate of placental migration in low-lying or complete placenta previas followed by serial ultrasound examination. Study design. This is a retrospective study of 92 cases of low-lying/placenta previa diagnosed at 28 weeks of gestation followed serially by transvaginal ultrasound. The patients were stratified into three groups depending on the placenta to internal cervical os distance: (1) an overlap of 0.0 cm and over the cervical os (complete previa), (2) 0.1 to 2.9 cm (marginal placenta previa), (3) 3.0 cm or above (normal placental location). The ¬prevalence of complete and marginal placenta previas, and the mean rate of placental »migration« (mm/week) were ¬obtained at 28 and 36 weeks of gestation, and compared with maternal age, parity, history of prior cesarean delivery and placental location. Results. At the time of delivery, 51 patients had placenta previa: 22 complete and 29 marginal placenta previas. In contrast, 41 patients had sufficient placental ’migration’ to be categorized into the normal placental location group. The prevalence of complete placenta of 3.3% and 6.5% at 28 weeks, and 3.3% and 5.4% at 36 weeks’ gestation, for patients who had parity more than 1, or history or prior cesarean delivery (CD), respectively, was not statistically significant. The rate of placental migration was significantly associated with maternal age (p=0.002), while did not differ when stratified by parity (p=0.672) or prior history of CD (p=0.805), or placental location (p=0.147). Conclusion. Maternal age significantly modifies the rate of placenta previa migration. A history of prior CD, maternal parity and placental location did not affect the rate of placental migration in our sample of patients with complete or marginal placenta previa diagnosed by ¬ultrasound at 28 weeks’ gestation.Cilj rada. Prosuditi povezanost dobi majke, pariteta, prethodnog carskog reza i smještaja posteljice, s perzistiranjem ili migracijom posteljice kod nisko nasjele ili predležeće placente previje, praćene serijskim ultrazvučnim pregledima. Način istraživanja. Retrospektivna studija 92 nisko nasjele posteljice ili placente previje, dijagnosticirane s 28 tjedana i serijski ultrazvučno praćene. Bolesnice su bile podijeljene u tri skupine, ovisno o udaljenosti posteljice od unutrašnjeg ušća cerviksa: 1) preraštanje više od 0,0 mm preko ušća cerviksa (kompletna previja); 2) 0,1 do 2,9 cm (marginalna previja); 3) 3,0 ili više cm od ušća cerviksa (normalni smještaj posteljice). Zastupljenost kompletnih i marginalnih placenta previja i srednja vrijednost »migracije« posteljice (mm/tjedan) su utvrđeni s 28 i 36 tjedana trudnoće te uspoređeni s dobi majke, paritetom, ranijim carskim rezom i smještajem posteljice. Rezultati. Od 92 trudnice s 28 tjedana, u vrijeme poroda 51 trudnica je imala placentu previju: 22 kompletnu i 29 marginalnu, dok je u 41 trudnice posteljica dovoljno »migrirala« da bi bila razvrstana u skupinu s normalnim smještajem. Zastupljenost kompletne previje za trudnice s više od jednog poroda od 3,3% s 28 i 3,3% s 36 tjedana, odnosno s prethodnim carskim rezom od 6,5% s 28 i 5,4% s 36 tjedana, nije statistički signifikantno različita. Stopa »migracije« posteljice je znakovito povezana s dobi trudnice (p=0,002), a nije s paritetom (p=0,672), ranijim carskim rezom (p=0,805) ili ležištem posteljice (p=0,147). Zaključak. Dob trudnice znakovito modificira stupanj migracije placente previje. U našem uzorku kompletnih i marginalnih posteljica otkrivenih ultrazvukom s 28 tjedana, raniji carski rez, paritet majke i ležište posteljice (sprijeda/straga) ne utječu na stupanj migracije posteljice

Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception

BACKGROUND: Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle. METHODS: Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant). The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1. RESULTS: The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining. CONCLUSION: The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants

Abnormal Uterine Bleeding during Progestin-Only Contraception May Result from Free Radical-Induced Alterations in Angiopoietin Expression

Abnormal uterine bleeding is the leading indication for discontinuation of long-term progestin-only contraceptives (LTPOCs). Histological sections of endometria from LTPOC-treated patients display abnormally enlarged blood vessels at bleeding sites. Paradoxically, a trend toward reduced endometrial perfusion in LTPOC users has been reported in these patients. We hypothesized that hypoxia/reperfusion-induced free radical production inhibits the expression of angiopoietin-1 (Ang-1), a vessel stabilizing factor, leaving unopposed the effects of endothelial Ang-2, a vessel-branching and permeability factor. Immunohistochemical studies confirmed selective decreases in stromal cell Ang-1 in LTPOC-exposed endometrium. To indirectly assess whether LTPOC enhances endometrial free radical production, immunostaining was conducted for the phosphorylated form of the stress-activated kinases SAPK/JNK and p38. These kinases were greatly increased in endometria from LTPOC-treated patients. Interestingly, the endothelial cells but not the stromal cells displayed enhanced immunostaining for the phosphorylated mitogen-activated kinase (pMAPK) after LTPOC treatment. To further examine the effects of progestin, hypoxia, and reactive oxygen species (ROS) on the regulation of Ang-1 and Ang-2 as well as the activation of MAPK, SAPK/JNK, and p38 by the relevant cell types, we conducted in vitro studies with cultured human endometrial stromal cells (HESCs) and human endometrial endothelial cells (HEECs). Cultures of HESCs were treated with vehicle control, estradiol (E(2)), or with medroxyprogesterone acetate ± E(2) under hypoxic and normoxic conditions. Although medroxyprogesterone acetate but not E(2) increased Ang-1 expression, hypoxia greatly decreased Ang-1 protein and mRNA expression. In contrast, HESCs did not appear to express Ang-2 protein or mRNA. Conversely, cultured HEECs did not appear to express Ang-1, but expressed Ang-2, the levels of which were significantly increased by hypoxia. Hypoxia also induced the phosphorylation of SAPK/JNK and p38 in both cultured HESCs and HEECs. Moreover, ROS such as that observed after hypoxia/reperfusion resulted in the activation of SAPK/JNK and p38 in HESCs and HEECs and inhibited Ang-1 in cultured HESCs. These effects could be blocked by oxygen radical scavengers. Consistent with the in vivo studies, MAPK was activated after ROS treatment in HEECs but not in HESCs. Our findings suggest that LTPOC-induced endometrial bleeding occurs as a result of hypoxia/reperfusion-induced free radicals that directly damage vessels and alter the balance of Ang-1 and Ang-2 to produce the characteristic enlarged and permeable vessels that are prone to bleeding

Second-Trimester Pregnancy Loss at an Urban Hospital

Objectives: Second-trimester spontaneous pregnancy losses are less common than first-trimester losses, and are often associated with ascending infection and/or acute chorioamnionitis. A Medline search revealed only two large studies published in the recent literature, reporting incidences of chorioamnionitis of 39.3% and 58.2%, respectively. These studies did not address the use of histopathology for the identification of organisms. Since ascending infection is likely to be a significant cause of second-trimester loss in the inner-city population at the University Hospital in Newark, New Jersey, we sought to evaluate the usefulness of stains for microorganisms, which are rarely utilized on these specimens. Methods: Retrospective review of the medical records and pathologic material for cases of spontaneous abortions seen at the University Hospital in Newark between January 1999 and March 2001 was undertaken. Stains for microorganisms were performed on archival placental tissue for cases with histologic acute chorioamnionitis. Results: A total of 67 cases were available for review, of which 38 cases (56.7%) showed histologic acute chorioamnionitis, similar to the rates in one previous study, but significantly higher than those in the other (p = 0.01). Of 25 cases with histological chorioamnionitis for which appropriate fetal material was available, 13 cases (52%) showed polymorphonuclear leukocytes (PMNs) in the fetal lungs, one case (4%) showed PMNs in the fetal stomach, and seven cases (28%) showed PMNs in both the lung and the stomach. Of the 38 cases with chorioamnionitis, Gram stains showed Gram-positive cocci in six cases, two of which were culture positive for group B streptococcus. Warthin–Starry stains showed filamentous organisms consistent with Fusobacterium sp. in the placenta in three cases. Conclusions: Acute chorioamnionitis is associated with second-trimester pregnancy loss at this inner-city hospital, and may be related to the high incidence of risk factors in this population. A small proportion of cases can be further characterized by the inclusion of Gram and Warthin–Starry stains in the evaluation. Selection of cases with histologic acute chorioamnionitis for further study with special stains may provide additional information on the causative organism

Pathology of the Human Placenta

XVIII, 941 p. 704 illus., 164 illus. in color.onl

Tumor Suppressor Gene, Cell Surface Adhesion Molecule, and Multidrug Resistance in Müllerian Serous Carcinomas: Clinical Divergence without Immunophenotypic Differences

Objectives. We hypothesize that differences in the expression of selected tumor suppressor genes, cell surface adhesion molecules, and multidrug resistance glycoproteins could account for some of the reported differences between uterine serous carcinoma (USC) and extrauterine serous carcinomas (ESC), including ovarian and primary peritoneal carcinoma (OSC and PSC, respectively). Methods. We studied the expression of the following antigens in 20 USCs, 20 OSCs, and 10 PSCs: p53 and mdm-2 (tumor suppressor genes), CD44 and CD44v6 (cell surface adhesion molecules), and the p-glycoprotein (a multidrug resistance protein recognized by two antibodies, C494 and JSB1). We further studied chemotherapeutic drug resistance by examining reports prepared using the Oncotech Extreme Drug Resistance Assay from 24 of the 50 study patients. Clinical data were obtained from medical record review. Results. USC, OSC, and PSC patients were similar with respect to mean age at diagnosis, mean gravidity, mean parity, personal history of breast cancer, percentage treated with chemotherapy, and survival at 3 and 5 years postdiagnosis. Significant clinical differences included a high prevalence of nulliparity in OSC (P = 0.05), a low prevalence of Caucasian race in USC (P = 0.008), a paucity of stage I patients in OSC and PSC (P = 0.03), a high prevalence of familial breast cancer in OSC (P = 0.06), and superior 2-year survival in OSC (P = 0.02). Seventy-five percent of USCs, 52% of OSCs, and 60% of PSCs expressed p53. Five percent of USCs, 19% of OSCs, and 0% of PSCs expressed mdm-2. Forty percent of USCs, 33% of OSCs, and 10% of PSCs expressed CD44. None of the USCs, OSCs, or PSCs expressed CD44v6. Sixty-one percent of USCs and OSCs and 82% of PSCs expressed C494 while 17% of USCs, 19% of OSCs, and 20% of PSCs expressed JSB1. None of these apparent differences was statistically significant. USC, OSC, and PSCs patients did not demonstrate significant differences with respect to extreme drug resistance. However, the following trends were noted (P = 0.06): more prevalent low drug resistance for cyclophosphamide in OSC compared with USC and more prevalent extreme drug resistance for etoposide in OSC compared with USC. Conclusions. Therefore, despite significant clincial differences, the USCs and ESCs in our series do not differ significantly with respect to the expression of the tumor suppressor genes, cell surface adhesion molecules, and drug resistance proteins studied. It is premature, however, to recommend that USCs and ESCs should be treated identically