CYP1A1 and CYP2D6 gene polymorphisms in Israeli Jewish women with cervical cancer.

HYPOTHESIS: To assess the frequency distribution of the CYP1A1 and CYP2D6 gene polymorphisms in Israeli Jewish women with cervical cancer. METHODS: Forty-three Israeli Jewish women with cervical cancer and 123 healthy Israeli Jewish women were assessed. CYP1A1 (2 alleles) and CYP2D6 polymorphism was analyzed using an allele-specific, polymerase chain reaction-based method. RESULTS: The allele frequency and genotype distribution for the CYP1A1 (2 alleles) and CYP2D6 polymorphism did not reach a level of significance. Smoking was the only independent risk factor for cervical cancer (P = 0.0003). CONCLUSION: CYP1A1 and CYP2D6 mutations are not related to an increased risk for cervical cancer in the Jewish Israeli population.

Loeys-Dietz syndrome in pregnancy: a case description and report of a novel mutation.

Loeys-Dietz syndrome is a syndrome caused by heterozygous mutations in the genes encoding type 1 or 2 transforming growth factor-beta receptor (TGF-beta-R1/2). The obstetrical manifestations are risk of rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period, and damage to the vagina, perineum and the colon. We describe, for the first time, a new TGF-beta-R2 gene mutation in a family with several individuals who either had aortic rupture and dissection, sudden death or aortic root dilatation. The pregnancy was followed up and the baby was successfully delivered by a cesarean section at 34 weeks of gestation. The mother's recovery was uneventful and the baby was negative for the mutation on postnatal molecular testing. With appropriate supervision and early delivery by cesarean section, women with Loeys-Dietz syndrome can tolerate pregnancy and delivery without any adverse effect.

Recombinant luteinizing hormone induces increased production of ovarian follicular adiponectin in vivo: implications for enhanced insulin sensitivity.

OBJECTIVE: To determine in vivo whether LH supplementation during the late follicular phase induces increased production of ovarian follicle adiponectin in humans. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Twenty infertile, healthy women (aged 18-39 years) undergoing IVF. INTERVENTION(S): Administration of recombinant FSH after down-regulation and equal randomization of subjects to receive recombinant LH 75 IU/day or placebo when two or more follicles reached a mean diameter of 14 mm. MAIN OUTCOME MEASURE(S): Follicular fluid (FF) adiponectin levels were measured. RESULT(S): Adiponectin FF levels were significantly higher in the recombinant LH group compared with the placebo group, and these differences were unaltered after correction to estrogen (E) levels and number of follicles in each cycle. CONCLUSION(S): This is the first demonstration of in vivo induction of adiponectin by gonadotropins in the human ovary. The addition of recombinant LH during the late follicular phase may enhance follicular insulin sensitivity, resulting in decreased androgen levels through a cascade mediated by increased production of adiponectin.

Regulation of vascular endothelial growth factor-A and its soluble receptor sFlt-1 by luteinizing hormone in vivo: implication for ovarian follicle angiogenesis.

OBJECTIVE: To determine in vivo whether LH supplementation during the late follicular phase induces ovarian follicle angiogenesis in humans, as reflected by vascular endothelial growth factor (VEGF)-A, its soluble receptor sFlt-1, and placental growth factor (PlGF) expression. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Twenty infertile, healthy women (aged 18-39 years) undergoing IVF. INTERVENTION(S): Administration of recombinant FSH after down-regulation and equal randomization of subjects to receive recombinant LH 75 IU/day or placebo when two or more follicles reached a mean diameter of 14 mm. MAIN OUTCOME MEASURE(S): Serum and follicular fluid (FF) VEGF-A, sFlt-1, and PlGF protein levels were measured. RESULT(S): Recombinant LH increased both the FF VEGF-A/sFlt-1 ratio statistically significantly and PlGF/sFlt-1 insignificantly. Recombinant LH did not affect the serum VEGF/sFlt-1 ratio. Plasma levels of PlGF were undetectable. CONCLUSIONS: This in vivo study demonstrates for the first time in humans that LH induces ovarian follicular angiogenesis via modulation of VEGF-A and its soluble receptor sFlt-1 expression. A constant VEGF-A/sFlt-serum ratio may prevent adverse effects of VEGF-A. Because angiogenesis is essential during the periovulatory period, recombinant LH supplementation during the late follicular phase may improve ovulation induction outcome.

Heparanase expression increases throughout the endometrial hyperplasia-cancer sequence.

OBJECTIVE: To assess the expression of heparanase in the different stages leading to endometrial cancer. METHODS: The 38 examined specimens included adenocarcinoma, hyperplasia, and normal endometrium specimens. Heparanase, estrogen, and progesterone receptor expressions were analyzed immunohistochemically and the intensity was scored. RESULTS: Secretory normal endometrium and simple hyperplasia specimens expressed the lowest mean values of expression (1.00 and 0.63, respectively); the complex hyperplasia specimens and G2 endometrioid adenocarcinoma showed the highest values of expression (2.33 and 2.71, respectively). A linear trend (P=0.005) of heparanase expression was observed when comparing the normal endometrium and simple hyperplasia group with the complex hyperplasia+G1 carcinoma group and the G2+G3 carcinoma group. Evaluation of atrophic and inactive endometrium compared with papillary serous carcinomas yielded no significant differences. We found no significant correlation between heparanase expression and estrogen receptor or progesterone receptor expression. CONCLUSION: Heparanase expression was tightly regulated in endometrial tumorigenesis.

[Long-term health consequences of polycystic ovaries syndrome: metabolic, cardiovascular and oncological aspects].

The polycystic ovary syndrome (PCOS), then called the Stein-Leventhal syndrome, was first described in 1935. Originally, diagnosis required pathognomonic ovarian findings and the clinical triad of hirsutism, amenorrhea, and obesity. During fertility years, women with PCOS are often seen for immediate concerns such as infertility, menstrual irregularity, and symptoms of androgen excess. During the past two decades, however, such patients have been observed to have increased risk of cardiovascular disease, dyslipidaemia, hypertension and diabetes and increased risk for endometrial cancer. The management of polycystic ovary syndrome is now complex and includes life style modifications, dietary-induced weight loss, oral contraceptives, clomiphene citrate, gonadotropins, antiandrogens and insulin-sensitising agents. These observations have led to a unique clinical perspective about PCOS--one that recognizes the need to address the immediate issues of irregular bleeding, hirsutism, and infertility, but also emphasizes the long-term goals of preventing diabetes, heart disease, and cancer.

Prediction of cervical involvement in endometrial cancer by hysteroscopy.

OBJECTIVE: This study evaluated the ability of hysteroscopy to preoperatively predict cervical involvement in endometrial cancer. METHODS: The records of 110 surgically staged consecutive endometrial cancer patients treated at our institution from 1997 to 2003 were retrospectively analyzed. Data on demographics, preoperative staging procedures, surgical pathology reports, and adjuvant treatments were retrieved. RESULTS: Fourteen (12.7%) patients had cervical involvement (stage II) according to the surgical pathology report, of whom nine (8.1%) had stage IIA and five (4.6%) had stage IIB. Clinical evaluation by speculoscopy and palpation had failed to reveal any indication of cervical involvement. Preoperative diagnostic hysteroscopy procedures were included. None of the hysteroscopy procedures revealed any suspicious lesion in the cervical canal. CONCLUSION: Hysteroscopy and clinical examination fail to adequately predict cervical involvement in endometrial carcinoma. Fractional D&C appears to be the best method until a more effective alternative becomes available.

[The male's role in the etiology of preeclampsia].

Preeclampsia is a major cause of morbidity and mortality in mothers, fetuses, and neonates worldwide, with 5%-10% of human births being affected. The cause is still uncertain, and many controversies exist concerning its management. Preeclampsia-eclampsia is due to the failure of extra-villous cytotrophoblast to invade the maternal uterine spiral arteries to a sufficient depth, inducing poor vascular exchanges between the mother and the placenta. This physiological endovascular trophoblast invasion represents a remarkable immunological placental-maternal interaction. Recent data strongly indicate an important role for the male partner in the causation of this common pregnancy disorder. This review aims to discuss the relevant literature and to explain how paternal, relational and sexual factors play an important role in the etiology of preeclampsia.

Chorioamnionitis associated with Crohn's disease and azathioprine treatment: a case report.

This paper reports a case of S. constellatus chorioamnionitis in a pregnant Crohn's disease patient who was taking azathioprine. Chorioamnionitis is a major cause of perinatal morbidity. Azathioprine, an immunosuppressive antimetabolite, is widely used to treat inflammatory bowel disease. Streptococcus constellatus is a Gram-positive bacterium that has not previously been associated with chorioamnionitis. A high index of suspicion for chorioamnionitis and unusual pathogens should be maintained in the management of obstetric patients on immunosuppressive agents.

Interleukin-18 is high in the serum of IVF pregnancies with ovarian hyperstimulation syndrome.

PROBLEM: The presence of interleukin-18 (IL-18) in serum and pre-ovulatory follicular fluid (FF) and its possible correlation to in-vitro fertilization/embryo transfer (IVF/ET) outcome and ovarian hyperstimulation syndrome (OHSS) development. METHOD OF STUDY: A prospective study was carried out. Assays for serum and pooled pre-ovulatory FF levels of IL-18 were performed on 30 patients who underwent oocyte retrieval for IVF/ET. RESULTS: Mean serum and FF levels of IL-18 were 370.4 +/- 224 and 228.9 +/- 208 pg/mL, respectively (r = 0.77, P < 0.0001). Levels of FF IL-18 were comparable between the two ovaries (right = 221 +/- 166.8 pg/mL, left = 237 +/- 171.9 pg/mL; r = 0.7550, P = 0.49). A positive correlation was found between IL-18 FF levels and number of retrieved oocytes (r = 0.45; P = 0.019). In three patients (10%) who developed OHSS, the mean serum level of IL-18 at day of ovum pickup was significantly higher compared with patients without OHSS (620 +/- 196 pg/mL versus 345 +/- 251 pg/mL, respectively, P = 0.04). CONCLUSIONS: Both pre-ovulatory FF and serum levels of IL-18 correlate with the number of retrieved oocytes. The serum IL-18 level at day of ovum pickup may predict consequent development of OHSS. Further investigations are warranted to determine the role of IL-18 in the folliculogenesis and OHSS pathogenesis.

The significance of clinical signs and blood indices for the diagnosis of appendicitis during pregnancy.

OBJECTIVE: To evaluate the significance of clinical signs and blood indices for the diagnosis of appendicitis during pregnancy. SAMPLE: Of the 40,112 women delivering at our institution (January 1995 to June 2002), 38 women (0.094%) were operated due to the suspicion of appendicitis during pregnancy. METHODS: Body temperature, clinical examination, white blood cell counts and lag time from arrival to operation were obtained for each patient. All women were operated with the clinical diagnosis of appendicitis, and their appendices were removed and examined by a pathologist. RESULTS: Inflammatory appendix was discovered in 19 (0.047%) of the pregnancies with subsequent deliveries while a normal appendix was found in 19 of the 38 (50%) appendices removed. The group with normal appendix did not significantly differ from women with inflamed appendix with regard to gestational age at presentation, signs of peritoneal irritation, body temperature, leukocyte count, time elapsed between arrival and surgery, gestational age at delivery and birth weight. CONCLUSIONS: The accurate diagnosis of appendicitis during pregnancy is a difficult task requiring a very high level of suspicion and clinical skills and not merely relying upon laboratory and classic signs.