Angiogenesis during implantation, and placental and early embryonic development.

Angiogenesis, the development of new capillaries from pre-existing vessels, is induced by inflammation, wound healing, immune reactions and neoplasia, and is required for tumour growth and progression. Angiogenesis participates in a wide range of ovulatory-related and non-ovulatory-related reproductive processes. We present a review of current data pertaining to angiogenesis of pregnancy, with specific emphasis on implantation and placental and embryonic development in both normal physiology processes and various pathological conditions. To this goal, MEDLINE, Current Contents and Index Medicus were searched for studies published between 1966 and August 1999. Pertinent studies (including human and animal models) pertaining to angiogenesis of implantation and placental and embryonic development were reviewed. Current literature supports that angiogenesis is an essential physiological component of implantation, and placental and embryonic development. Angiogenesis also actively participates in abnormal implantation, and various pathological processes of the placenta including those observed in association with pre-eclampsia, growth restriction, maternal anaemia in the first-trimester and other hypoxia-related conditions during pregnancy. Finally, administration of an angiogenesis inhibitor (AGM-1470) in mice has been shown to result in complete failure of embryonic growth due to interference with decidualization, placental and yolk sac formation, and embryonic vascular development.

Recurrent transient superior vena cava-like syndrome possibly associated with megestrol acetate.

BACKGROUND: Superior vena cava syndrome is a rare, life-threatening clinical entity associated with occlusion of venous outflow from the head, neck, and upper extremities; this syndrome produces facial edema, cyanosis, dyspnea, and prominent neck veins, and is usually caused by intrathoracic neoplasms. CASE: In this unusual case, a patient receiving megestrol acetate for stage IV endometrial carcinoma developed recurrent transient superior vena cava-like syndrome in the absence of venous obstruction. CONCLUSION: Superior vena cava-like syndrome may occur with megestrol acetate. This unusual complication should be considered in patients receiving this medication who present with symptomatology similar to that of superior vena cava syndrome.

Angiogenesis of the endometrium.

OBJECTIVE: To present current data pertaining to angiogenesis of the endometrium throughout the normal menstrual cycle and in benign and neoplastic diseases of the endometrium. SOURCES: We conducted a computerized search of MEDLINE, Current Contents, and Index Medicus for relevant studies in the English literature published between January 1966 and October 1998. STUDY SELECTION: We reviewed all studies that included human and animal models of angiogenesis of normal cyclic endometrium and benign and neoplastic endometrial diseases. TABULATION, INTEGRATION, AND RESULTS: Angiogenesis is important to cyclic, regenerating endometria and disease processes including dysfunctional uterine bleeding, response to exogenous hormonal treatment, bleeding associated with intrauterine contraceptive devices, uterine leiomyomata, endometriosis, complex endometrial hyperplasia, and endometrial carcinoma. CONCLUSION: In the future, knowledge of specific angiogenic patterns of various disease processes might improve application of antiangiogenic medications in therapies for benign and neoplastic diseases of the endometrium.

Prenatal ultrasonographic assessment of the ductus arteriosus: a review.

OBJECTIVE: To review current data pertaining to prenatal ultrasonography of the ductus arteriosus. DATA SOURCES: We reviewed manuscripts published in the English language regarding prenatal ultrasonography and the fetal ductus arteriosus obtained from a MEDLINE search for 1966 onward. Additional sources were identified through cross-referencing. METHODS OF STUDY SELECTION: Data regarding morphology, physiology, pathophysiology of fetal disease, and hemodynamic changes after administration of various maternal medications and structural congenital anomalies of the ductus arteriosus were selected. DATA EXTRACTION AND SYNTHESIS: Knowledge of the function of the ductus arteriosus in both normal and abnormal fetal conditions is enhanced by prenatal ultrasonographic findings. Detailed analyses of ductus arteriosus hemodynamics are indicated in well-defined medical conditions, including maternal medication and established structural or functional fetal cardiac disease. CONCLUSION: The fetal ductus arteriosus is a vascular structure of major functional importance. Knowledge of physiologic hemodynamic changes of blood flow in this vessel obtained by prenatal ultrasonography in conjunction with increasing gestational age, maternal medication, fetal growth restriction, as well as the detection of structural anomalies, may assist in clinical management of complicated pregnancies.

Transvaginal sonographic imaging of early second-trimester fetal anatomy assisted by uterine fundal pressure.

OBJECTIVE: To assess the advantage of applying uterine fundal pressure to assist transvaginal sonographic imaging of early second-trimester fetal anatomy. METHODS: One hundred consecutive patients with singleton fetuses underwent routine transvaginal sonographic assessment of fetal anatomy between 13 and 17 weeks' gestation. If the entire fetal anatomy including cardiac outflow tracts was not depicted, uterine fundal pressure was applied with the operator's nonscanning hand in a bimanual fashion, to facilitate transvaginal imaging. Transabdominal sonography was performed when visualization of the entire fetal anatomy was not obtainable with transvaginal or uterine fundal pressure-assisted transvaginal sonography. Observed fetal structures with and without fundal pressure were compared. Factors assessed that may have modified the value of fundal pressure included patient weight, gestational age, fetal presentation, previous abdominal surgery, and the presence of uterine fibroids. Statistical analysis included McNemar test, chi 2, Fisher exact test, and t test, with P < .05 considered significant. RESULTS: Visualization of lower limbs, head (including intracranial structures), upper limbs, kidneys, spine, gender, feet, hands (digits), face, four-chamber view, and cardiac outflow tracts was significantly enhanced by uterine fundal pressure-assisted versus nonassisted transvaginal sonography. Uterine fundal pressure improved transvaginal sonographic imaging in 91% of subjects, and in 51% of all subjects, a complete examination was thus obtained. In 20% of all subjects, transabdominal sonography was required to complete the examination. Complete fetal anatomic scanning was unobtainable despite uterine fundal pressure supplemented by transabdominal sonography in 29% of cases. Completion of the transvaginal sonographic fetal anatomic survey with uterine fundal pressure was related to gestational age (P < .02) and maternal weight (P < .05) yet not related to fetal presentation (P = .13), previous abdominal surgery (P = .06), or uterine fibroids (P = .26). CONCLUSION: Uterine fundal pressure applied during early second-trimester transvaginal sonographic evaluation of fetal anatomy significantly improves visualization of fetal structures otherwise located beyond the effective range of the transvaginal transducer.

Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix.

OBJECTIVE: To evaluate angiogenesis in squamous cell carcinoma in situ (CIS) and microinvasive squamous cell carcinoma of the uterine cervix and to investigate the relations among angiogenesis, stromal inflammation, and depth of invasion. METHODS: Three groups of women were studied: 22 controls who had undergone hysterectomy for benign conditions; 18 with squamous cell CIS of the cervix who underwent cone biopsy, hysterectomy, or both; and 14 with microinvasive squamous cell carcinoma who underwent conization of the cervix and subsequent surgical management according to depth of invasion. All specimens were stained immunohistochemically for factor VIII-related antigen. Areas below the basement membrane with the highest angiogenic density were selected. The degree of stromal inflammatory reaction was assessed. Statistical analyses included Kruskal-Wallis, analyses of variance and covariance, Scheffe and Bonferroni-Dunn post hoc procedures, and Pearson correlation analysis. P < .05 was considered statistically significant. RESULTS: Microvessel counts per high-power field (x 400) of microinvasive squamous cell carcinoma of the cervix differed significantly from those of controls and squamous cell CIS (median 34.5 per high-power field, range 9-76 versus median 17, range 7-47, and median 19, range 8-39, respectively; P < .005). Microvessel counts per high-power field in squamous cell CIS did not differ significantly from those of controls (P = .91). Among patients with microinvasive squamous cell carcinoma of the cervix, no significant correlation was found between microvessel counts per high-power field and the depth of invasion (r = 0.19, P = .51). Stromal inflammatory reaction (graded 0-3) differed significantly among controls, squamous cell CIS, and microinvasive carcinoma (mean 0.40, 0.83, and 1.64, respectively; P < .005). CONCLUSIONS: Microinvasive squamous cell carcinoma of the uterine cervix is angiogenic, but depth of invasion is not associated with increased angiogenicity. Squamous cell CIS is not angiogenic.

Acute transient thrombocytopenia associated with cocaine abuse in pregnancy.

A case is described of cocaine-induced severe transient thrombocytopenia associated with a hypertensive crisis at 21 weeks' gestation. Liver function tests and coagulation studies were all within normal ranges. Blood pressure was controlled with hydralazine. This clinical presentation, similar to severe preeclampsia, should be considered in the differential diagnosis of acute hypertension and low platelet count, especially in early gestations when preeclampsia is relatively rare. Unlike severe preeclampsia, for which active intervention and delivery are usually selected, cocaine-related hypertension-thrombocytopenia, especially in very premature gestations, may warrant conservative management.

Prevention of neonatal group B streptococcal infections: advances in maternal vaccine development.

OBJECTIVE: We describe the current state of prevention of neonatal group B streptococcal infections and present recent advances toward the development of a maternal vaccine for prevention of this disease. DATA SOURCES: We used a MEDLINE search of the Index Medicus from 1976-1992 for articles regarding group B streptococcus classification and immunology. Group B streptococcus was also cross-referenced with bacterial antigens, antibodies, and vaccines. Relevant textbooks were reviewed. METHODS OF STUDY SELECTION: Fifty-seven articles were selected as providing important background and new findings pertinent to this topic. DATA EXTRACTION AND SYNTHESIS: The literature supports prophylactic use of intrapartum antibiotics in mothers who are known carriers of group B streptococcus but highlights the need for more sensitive rapid screening techniques to identify this high-risk population. The promise of intravenous immunoglobulin for neonatal prophylaxis has not been borne out, although hyperimmune and monoclonal preparations offer renewed hope for prophylaxis and adjuvant therapy. Native bacterial polysaccharides, conjugated oligosaccharides and polysaccharides, and C proteins have been investigated as antigens for candidate vaccines. Antibodies elicited in human and animal studies provide protection against bacterial strains possessing these determinants. The theoretical existence of a "universal antigen" is significant because polysaccharide and C protein formulations are required to be polyvalent. CONCLUSIONS: The development of a vaccine for prevention of neonatal group B streptococcal sepsis is an attainable goal. Further study of the immunogenic properties of bacterial-cell-wall polysaccharides and their conjugates, C proteins, and the potential universal antigen is required.

Prenatal ultrasonographic assessment of the ductus venosus: a review.

OBJECTIVE: To review current data pertaining to prenatal ultrasonography of the ductus venosus. DATA SOURCES: We identified English-language studies regarding prenatal ultrasonography and the fetal ductus venosus. The studies were obtained from a MEDLINE search for the period 1966 through March 1996. Additional sources were identified through cross-referencing. METHODS OF STUDY SELECTION: We reviewed all published reports, case studies, and articles regarding ultrasonographic morphology, physiology, and pathophysiology of the fetal ductus venosus. TABULATION, INTEGRATION, AND RESULTS: Knowledge of the function of the fetal ductus venosus in both normal and abnormal fetal conditions is increased by prenatal ultrasonographic data. Altered ductus venosus hemodynamics may be noted in various medical conditions that include fetal growth restriction, twin-twin transfusion, invasive diagnostic procedures (chorionic villus sampling and fetal blood sampling), fetal anemia and transfusion, complex cardiac structural anomalies, and cardiac arrhythmias. CONCLUSION: Blood flow velocity in the fetal ductus venosus reflects the pressure gradient between the umbilical vein and the cardiac atria. Knowledge of pathophysiologic hemodynamic changes of blood flow in this vessel obtainable by prenatal ultrasonography in conjunction with fetal disease may assist diagnosis and management.