Dimitrios Lolis

Association of estrogen receptor gene polymorphisms with endometriosis

OBJECTIVE To explore the association of the estrogen receptor two-allele (point) polymorphism and multiallele (microsatellite) polymorphism with endometriosis. DESIGN Case-control study. SETTING Genetics and Endoscopy Unit, Department of Obstetrics and Gynecology, Ioannina University HOSPITAL, Ioannina, Greece. PATIENT(S) Fifty-seven women with surgically and histologically diagnosed endometriosis of stages I-IV. INTERVENTION(S) Diagnostic laparoscopy. MAIN OUTCOME MEASURE(S) Frequency and distribution of the estrogen receptor gene polymorphisms. RESULT(S) There was a statistically significant difference between the patients and the controls in the frequency of the two-allele Pvu II polymorphism (0.72 vs. 0.49) and in the median repeats of the (TA)n multiallele polymorphism (15 vs. 20 repeats). In both groups, linkage was found between the fewer (TA)n repeats (range, 12-19) and the positive Pvu II polymorphism. CONCLUSION(S) The variability of the estrogen receptor gene likely contributes to the pathogenesis of endometriosis.

Interaction between the polymorphisms of the renin-angiotensin system in preeclampsia.

Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P<0.02). In addition, women with preeclampsia and TT genotype had more frequently the DD genotype or the 1166C allele than the control group showing a significant interaction between the genes. In conclusion, we found an association between the angiotensinogen variant 235T and preeclampsia as well as an interaction between the variant 235T and the two other genes studied.

Management and evolution of cervical intraepithelial neoplasia during pregnancy and postpartum.

OBJECTIVE To investigate the evolution of cervical intraepithelial neoplasia (CIN), and to evaluate the safety of cytological and colposcopical surveillance of women with CIN during pregnancy. STUDY DESIGN Ninety-eight women with antenatal cytological and/or colposcopical impression of CIN were followed up during pregnancy with cytology and colposcopy every 2 months. A cytological and colposcopical reevaluation 2 months postpartum was done, and large loop excision of the transformation zone (LLETZ) was performed if appropriate. Punch or loop biopsies were only taken if there was suspicion of microinvasion. RESULTS In 14 of 39 (35.9%) and in 25 of 52 (48.1%) women with antenatal impression of CIN I and CIN II-III, respectively, there was postnatal impression of regression. Seven women with findings suspicious of microinvasion underwent small loop biopsies during pregnancy, but early stromal invasion (< 1 mm) was seen in just one case. There was one more case of microinvasion (1.5 mm) diagnosed postnatally in which the antenatal impression was of CIN III. 84.6% of the women with regression compared to 67.3% of the women with stable disease or progression had a vaginal delivery (P = 0.057). CONCLUSION There is a considerable regression rate of CIN after pregnancy possibly attributable to the loss of the dysplastic cervical epithelium during cervical ripening and vaginal delivery. Frequent cytological and colposcopical evaluation seems to be safe. Small loop biopsies are recommended in cases of possible microinvasion.

Fetal loss following ultrasound diagnosis of a live fetus at 6–10 weeks of gestation

To examine prospectively the value of demographic characteristics and ultrasound findings in the prediction of subsequent fetal loss in pregnancies with live fetuses at 6–10 weeks of gestation.

Osteogenesis imperfecta and other skeletal dysplasias presenting with increased nuchal translucency in the first trimester

We present two case reports of osteogenesis imperfecta associated with increased nuchal translucency in the first trimester. We also review the literature of first trimester diagnosis of skeletal dysplasias and their association with increased nuchal translucency.

Vaginoscopic approach to outpatient hysteroscopy.

STUDY OBJECTIVE To evaluate a new method of outpatient hysteroscopy. DESIGN Prospective observational study. SETTING Departments of Obstetrics and Gynecology, Medical School of Ioannina, Greece, and Brooklyn Hospital Center, Brooklyn, New York. PATIENTS Three hundred twenty-four women, 316 of whom were symptomatic and 8 asymptomatic. INTERVENTIONS Hysteroscopic vaginoscopy with directed endometrial biopsies. MEASUREMENTS AND MAIN RESULTS The procedure was successful and well tolerated in 211 (65%) women. In 90 (27.9%) women, the procedure was successful but with significant pelvic pain, and in the remaining 23 (7.1%) it was complicated by either vagal reaction or complete intolerance. Hysteroscopic findings were in agreement with histopathologic results in 290 (89.5%) patients. In all 12 women with endometrial adenocarcinoma, hysteroscopic findings were identical with histopathologic results. CONCLUSION The vaginoscopic approach is effective for outpatient hysteroscopy.

Comparison of tamoxifen with danazol for treatment of cyclical mastalgia

This study evaluates the benefits and side-effects of two drugs (tamoxifen or danazol) used randomly in women with severe cyclical mastalgia. Ninety-three patients with severe cyclical mastalgia of more than 6 months duration were randomly selected for treatment with tamoxifen (32 women), danazol (32 women) or placebo (29 women) for six consecutive cycles. A standard protocol was used, which included pain relief as measured by linear analog, side-effects and cost. Statistical analysis was performed using the non-parametric Mann-Whitney U or Kruskall-Wallis tests and Students t-test. As measured by linear analog scoring, pain relief was achieved in 23/32 (72%) of those receiving tamoxifen, 21/32 (65%) of those taking danazol (p < or = 0.001) and 11/29 (38%) of those taking placebo. Twelve months after the end of treatment, 17 (53%) women who received tamoxifen were still free of symptoms, as compared with 12 (37%) of the danazol-treated patients (p < 0.001) and none of the placebo-treated patients. These results suggest that tamoxifen is highly efficaceous and cost effective for the management of severe cyclical mastalgia.

Routine obstetrical ultrasound at 18–22 weeks: Our experience on 7,236 fetuses

OBJECTIVE This study aimed at examining the detection rate of congenital abnormalities by using routine ultrasonography at 18-22 weeks of gestation. METHODS The sample included 7,236 fetuses. A detailed sonographic examination was performed in each fetus and a neonatal evaluation or pathology examination was made to confirm the prenatal findings. RESULTS The total prevalence of fetal abnormalities in our sample was 2.24% (162/7,236). There were 29/162 (17.9%) fetuses with CNS abnormalities, 27/162 (16.7%) fetuses with gastrointestinal abnormalities, and 28/162 (17.3%) fetuses with urinary tract abnormalities. There were also 31/162 (19.1%) fetuses with cardiovascular abnormalities, 26/162 (16.0%) with malformation of the limbs and musculoskeletal system, and 21/162 (13%) fetuses with other various abnormalities. The overall sensitivity in detecting fetuses with congenital abnormalities was 80.25% (130/162). The sensitivity per system was 93.1% (27/29) for CNS, 45.2% (14/31) for cardiovascular system, 85.2% (23/27) for gastrointestinal system, 85.7% (24/28) for urinary system, 84.6% (22/26) for musculoskeletal system, and 95.2% (20/21) for the rest of the abnormalities detected. We performed 40 pregnancy terminations in the group of malformed fetuses. Among the fetuses considered as normal, 1.7% had chromosomal abnormalities. CONCLUSIONS The results indicate that routine sonographic examination at 18-22 weeks of gestation can detect the majority of congenital abnormalities. More experience is needed for the examination of the cardiovascular system, where the sensitivity was particularly low (14/31 or 45.2%).

GENOTYPES OF N-ACETYLTRANSFERASE-2 AND RISK OF BLADDER CANCER: A CASE-CONTROL STUDY

PURPOSE This study was conducted to examine whether certain slow N-acetylation genotypes could be risk factors for bladder cancer, and the possible association between specific genotypes and the severity of the disease at first diagnosis. MATERIALS AND METHODS This case-control study included 89 patients with transitional cell bladder cancer (diagnosed over a period of 21 months) and 147 controls. N-acetyltransferase-2 (NAT-2) genotypes were identified by allele specific polymerase chain reaction (PCR) on peripheral blood DNA samples. The x2 test was used for statistical evaluation to compare the differences observed between patients and controls and the different genotypes with tumor grading and local staging at presentation. Relative, attributable and population attributable risks were estimated for the genotypes found to present a significantly increased frequency for bladder cancer. RESULTS A statistically significant difference in the frequency of genotypes was found between the two groups. The patient group had the higher frequency of slow acetylation genotypes (p = 0.0016). Among slow acetylators, homozygotes 341C/341C and compound heterozygotes 341C/857A had the most excessive risk for bladder cancer (p = 0.0041 and 0.0031, respectively). The 341C/341C genotype was found to be associated with more aggressive disease, in terms of tumor grading at presentation (p <0.05). CONCLUSIONS According to our data, slow acetylators with 341C/341C and 341C/857A genotypes carry a substantially higher odds ratio (3.73 and 12.46, respectively) for bladder carcinogenesis. Additionally, among the slow acetylators, 341C/341C homozygotes are likely to have a higher risk for more aggressive disease.

Treatment of Premenstrual Mastalgia with Tamoxifen

Thirty‐four women with normal menstrual cycles but suffering from severe premenstrual mastalgia were randomly treated with either tamoxifen (10 mg daily) (18 women) or placebo (16 women) from cycle day 5 to 24 for six consecutive cycles. At the end of the treatment, 89% of the tamoxifen‐treated patients were free from the symptoms and the remainder experienced partial alleviation. In contrast, six patients treated with placebo showed only partial alleviation (38%)(p < 0.001). Twelve months after the end of tamoxifen treatment, 53% of the medicated women were still free of symptoms as compared with none of the placebo‐treated patients. These results suggest that tamoxifen is highly effective for the management of severe premenstrual mastalgia and should be useful for the treatment of this disorder.