Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.

To describe gene expression patterns of the apoptotic regulatory genes Bcl and Bax in human uterine leiomyoma tissue. To investigate the relationship between alterations of gene expression patterns and several relevant clinical parameters. We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for gene expression analysis of the Bcl-2 and Bax genes. Gene expression was quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was significantly overexpressed compared with the control group although there was no such difference in the gene expression of Bax. Gene activity of Bcl-2 positively correlated with the tumor number in individual uterine leiomyoma cases. Although there was no significant correlation between the length of the cumulative lactation period before the development of uterine leiomyoma and Bcl-2 gene expression in the leiomyoma tissue, we observed a trend for a shorter cumulative lactation period to be associated with overexpression of the Bcl-2 gene. Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax gene did not seem to play a role in the process.

[Epigenetic background of the most common non-oncologic gynecological diseases]. / A leggyakoribb nem onkológiai eredetu nogyógyászati kórképek epigenetikai háttere.

Epigenetic effects influence the function of genes regulating the main physiological mechanisms. Some of these environmental factors may reduce or inhibit the function of these genes. The environmental effects on gene function may result in a change of the DNA structure leading to non-heritable phenotype changes. Epigenetic factors play an important etiological role in the development of numerous diseases in obstetrics and gynecology. Uterine fibroids probably have a complex etiological background including epigenetic mechanisms. The multifactorial aetiology of endometriosis suggests key roles for immunological and hormonal factors in the development of the diseases. These mechanisms are influenced by epigenetic factors, which may serve as therapeutic targets in the future. The possible in utero origin of polycystic ovary syndrome determines the main directions of research concerning epigenetic factors in the etiological background, with the hope of eventual prevention and/or treatment in the preconceptional period as well as during pregnancy care.

The role of the alcohol dehydrogenase-1 (ADH1) gene in the pathomechanism of uterine leiomyoma.

OBJECTIVE: To describe alterations of gene expression patterns of the alcohol dehydrogenase-1 (ADH1) gene in human leiomyoma tissue. We correlated changes in ADH1 gene activity with several clinical and demographic variables. STUDY DESIGN: We compared gene expression patterns of ADH1 in leiomyoma tissue samples obtained from 101 hysterectomy cases to 110 cases of hysterectomy performed for non-oncological indications. Gene expression was determined by standard PCR technique. Clinical and epidemiological data were extracted from the computerized database of the 1st Department of Obstetrics and Gynecology of Semmelweis University and from patient questionnaires. RESULTS: Median age in the leiomyoma group was significantly lower than in the control group (47.5 ± 12.1 vs. 54.7 ± 10.2 years). The incidence of uterine leiomyoma was highest (48%) in the 41-50 year age group. In the obstetric history, cumulative gestational age in the leiomyoma group was significantly lower (105.1 ± 8.2 weeks) than in the control group (127.2 ± 9.1 weeks) and cumulative lactation length was also significantly shorter (2.4 ± 1.2 months vs. 5.1 ± 2.2 months). Surgical treatment of the fibroid was myomectomy in 39.6% of the cases and hysterectomy in 60.4%. The ADH1 gene was significantly underexpressed in the leiomyoma group compared to the control group. There was no significant association between ADH1 gene expression and family history. Within the leiomyoma group, there was no significant difference in ADH1 gene expression between subgroups of cases with different number of fibroid tumors found in the hysterectomy sample, but individual tumor number did correlate with the degree of underexpression of the ADH1 gene. There was no significant association between ADH1 gene expression and cumulative history of lactation. CONCLUSIONS: Underexpression of the ADH1 gene, which influences the transformation of the extracellular matrix, plays a probable role in the etiology of uterine fibroid. Although significant differences in ADH1 gene activity were not seen, a negative correlation between tumor number and degree of ADH1 underexpression was found. Neither family history nor cumulative lactation length was a significant predictor of uterine leiomyoma.

Gene expression patterns of insulin-like growth factor 2 in human uterine fibroid tissues: a genetic study with clinical correlations.

BACKGROUND/AIMS: We investigated insulin-like growth factor 2 (IGF-2) gene activity in human uterine fibroid tissue. Results of the genetic testing were correlated with clinical data. METHODS: We obtained samples from patients treated for uterine fibroid and from patients undergoing hysterectomy due to other indications (control group). The examined group (with fibroid) contained 101 cases, while the control group was similar with 110 patients. Gene expression values were determined using the standard PCR technique. Clinical data were available from the computer database of the department. RESULTS: IGF-2 gene expression was significantly higher in the fibroid group. There was no correlation between increase in gene activity and the number of tumors. History of previous uterine fibroid did not seem to predict IGF-2 gene activity in the current fibroid tumor tissue. IGF-2 gene expression did not correlate with cumulative duration of lactation following prior pregnancies. CONCLUSION: IGF-2 gene activity is significantly increased in leiomyoma tissue compared to normal myometrium. Familial aggregation of uterine fibroids is not significantly associated with increased IGF-2 gene activity; other genes may have a stronger etiological role. It appears that the genetic factors potentially important in the development of familiar uterine leiomyoma are not related to the IGF-2 gene.

Fetopathological investigations after induced abortions performed in mid-term gemini pregnancies.

Multiple pregnancies present a special obstetric condition whose importance has increased due to the spread of assisted reproductive techniques. We have processed the fetopathological data of 43 abortions induced in mid-term gemini pregnancies, owing to malformations affecting one or both fetuses. 67.4% of the gemini pregnancies were conceived naturally and 32.6% by assisted reproduction techniques. The most commonly occurring malformations affected the fetuses' cardiovascular and central nervous systems. Positive histories could be detected in 23% of the cases. The male-to-female ratio was found to be 1.14. In the majority of the cases with central nervous system malformation, fetus "A" was affected (85.7%). In 29.4% of the cases, monochorionic placentation was established. Ultrasonography and fetopatological findings yielded perfectly matching results in 78.9% of the cases. The incidence of fetal malformations is probably not higher among fetuses conceived by assisted reproduction techniques compared to the ones conceived naturally. Fetal central nervous system malformations usually affect fetus "A". Based on the results of the fetopathological examinations, ultrasonography is a reliable method in the diagnostics of malformations affecting twin fetuses. Fetal echocardiography is indicated simply because of the pregnancy being a multiple one.

Successful operative management of an intact second trimester abdominal pregnancy with additional preoperative selective catheter embolization and postoperative methotrexate therapy.

BACKGROUND: Abdominal pregnancy is a rare condition that may lead to severe complications. CASE REPORT: The authors report the case of a 17-week intact abdominal pregnancy diagnosed in the course of an investigation of lower abdominal pain. Ultrasonography and MR examination revealed an intact abdominal pregnancy. Subsequent angiography was performed to occlude the supportive artery of the pregnancy by selective embolization. The pregnancy was terminated safely by laparotomy a day later. The placenta was left in the abdominal cavity because of the high risk of massive and often uncontrollable bleeding, and treatment with methotrexate was applied postoperatively. CONCLUSIONS: Preoperative embolization and the postoperative methotrexate therapy facilitate the safe surgical treatment of abdominal pregnancy.

Positive predictive value of prenatal ultrasonography confirmed by post-mortem investigations.

OBJECTIVE: To analyse the positive predictive value of ultrasonography based on the results of post-mortem investigations in respect of the most common malformations. STUDY DESIGN: We processed the details of 683 cases affecting the nervous, cardiovascular, urinary and skeletal systems, and the abdominal/thoracic walls. RESULTS: In four of the investigated groups of malformations, the proportion of sonographic diagnoses completely coinciding with the post mortem results was found to be approximately 70%, but it was found to be much lower (32%) in urinary malformations. The cumulative proportion of coinciding sonographic and post mortem diagnoses was 63%, while completely incorrect ultrasonographic diagnoses amounted to 17%. CONCLUSIONS: Sonography is an essential method for the diagnosis of the majority of fetal malformations, but post-mortem examinations yield an indispensable quality control as well as additional information to ultrasound examinations.

Non-syndromic malformations of the central nervous system in twin pregnancies: diagnostic and other clinical features of importance.

OBJECTIVE: The incidence of central nervous system malformations is higher among twins. Our aim was to summarize information about these malformations in twin pregnancies. STUDY DESIGN: Based on a sample originating from the biggest genetic centre in Hungary between January 1990 and December 2008, we examined the data of 42 twin pregnancies associated with non-syndromic malformations of the central nervous system. RESULTS: The involvement of monozygotic fetuses and dizygotic ones of the same gender was found to be 62.5%. Usually only one of the fetuses was affected (57.1%), while the other one was healthy. The male-to-female ratio was 0.75. Identical and fraternal twins were found in 68.4% and 31.6% of the cases, respectively. In the pregnancies of our study the malformation was diagnosed before the 24th gestational week in 90% of the cases. Polyhydramnios (54.8%) was the most commonly associated non-central nervous system malformation. CONCLUSION: Our findings suggest that, in addition to placentation and gestational age, the position of the affected fetus with relation to the uterine orifice is of great importance in determining whether selective abortion is an option in deciding about the outcome of pregnancies affected by craniospinal malformation.

Abdominal wall malformations in a 15-year fetopathological study: accuracy of prenatal ultrasonography diagnosis.

OBJECTIVE: The aim of this study was to evaluate the characteristics and diagnostic accuracy of prenatal ultrasonography in the diagnosis of abdominal wall malformations. METHOD: The characteristics of 113 pregnancies terminated due to abdominal wall malformations were analyzed. RESULTS: In cases of gastroschisis and omphalocele, similar female dominance was observed. Among the associated malformations, those affecting the cardiovascular system and the extremities were especially common. Regarding the diagnostic accuracy of prenatal sonography, autopsy confirmed sonographic diagnoses in 91% of omphalocele cases and 79% of gastroschisis. CONCLUSION: Prenatal sonographic diagnosis is more accurate in omphaloceles than in gastroschisis.

[Uterine leiomyoma]. / A méh leiomyomája.

Uterine fibroids, benign tumors of the human uterus, are the most common indication for hysterectomy. They are clinically apparent in 20-25% of women and cause significant complaints, like prolonged and heavy menstruation, pelvic pressure or pain, sometimes reproductive dysfunction. Though surgery has been the mainstay of fibroid treatment, various minimally invasive procedures have been developed in addition to hysterectomy and abdominal myomectomy. Formation of new leiomyomas after these conservative therapies remains a substantial problem. Also drug-therapy methods are available, but the possible side-effects limit their long-term use. Authors attempt to give an overview of this common gynecological disease, yielding a new insight into the basic biology and genetics of fibroids, with the hope of new and effective methods of therapy in the future.