Novel Mutation in the COL11A1 Gene Causing Marshall-Stickler Syndrome in Three Generations of a Bulgarian Family.

Here we report the first familial case spread through at least three generations, genetically verified cases of Marshall-Stickler syndrome in Bulgaria. The proband, a 2-year-old girl, has craniofacial dysplasia, ocular hypertelorism, small saddle nose with a flat bridge and midface hypoplasia. The pedigree of the proband's family showed that her father has the same clinical manifestations of the disease. In addition, her father presented with a tall, thin stature and mild hearing loss, manifested with aging. The same dysmorphological symptoms were presented by the paternal grandfather. Both patients, the 2-year-old girl and her father, have been diagnosed to carry Marshall-Stickler syndrome. The COL2A1 gene tested negative in the family. Based on the higher percentage of mutations in the COL2A1 gene, we analyzed this gene as the first target in the family. The COL2A1 gene tested negative, and we sequenced the gene further. A novel splice site mutation c.3474+1G>A was found in intron 44. This variant is related to the clinical presentation in the patient and her father. The c.3474+1G>A mutation results in altered splicing affects at the donor splice site of intron 44, which most probably gives a nonfunctional protein. The variant affects the major triple-helical domain that represents a mutation hot-spot for the gene.

[ANTENATAL APPLICATION OF CORTICOSTEROIDS IN LATE PRETERM BIRTHS].

The aim of the following study is to present the current evidence of antenatal use of corticoids in premature birth. The benefits of antenatal use of corticosteroids after 34 week of gestation is still a process of discussion.

[CALCIUM LEVELS IN URINE SAMPLE IN PREGNANT WOMEN WITH PREECLAPMSIA].

Hypertensive disorders during pregnancy are still leading cause for maternal and perinatal death. Calcium metabolism is impaired significantly in women with preeclampsia. Measurement of calcium levels in 24 hours urine sample is easy, modern, fast and not expensive predictive test to reveal women in high risk of developing preeclampsia in late pregnancy. The severity of condition strongly correlates with decrease level of calcium excretion in urine.

[The role of insulin resistace in preeclampsia].

INTRODUCTION: Contemporary data show that there is a link between insulin resistance and preeclampsia (PE) due to many common features. MATERIAL AND METHODS: We examined 90 pregnant women at the clinic of Obstetrics and Gynecology at the University Hospital "St.George". 35 of them were preeclamptic and 55 normotensive. Glucose levels were measured at 0, 1, 2 h after OGTT (after 75 g. oral glucose administration). Insulin levels were also measured and HOMA IR was evaluated. RESULTS: Fasting glucose and insulin levels were similar in both groups and showed no statistical significance. HOMA IR was higher in the preeclamptic group 2.89 vs 2.09 for normotensive group no statistical significance was shown. CONCLUSION: Our results indicate that PE is not associated with insulin resistance.

[The effect of vitamin D on pregnancy].

Vitamin D is a steroid hormone which plays an essential role in regulation of calcium metabolism. Many recent studies suggest that vitamin D is taking part in regulation of numerous physiological processes-glucose and neural metabolism, cardiovascular and sexual systems. Normal plasma levels of Vitamin D3 are needed for physiological development of pregnancy, normal skeletal mineralization of the fetal skeleton and lactation. Deficiency of vitamin D during pregnancy is associated with increased risk of serious complications like gestational diabetes and preeclampsia.

[The role of Dianatal Obstetric Gel in normal labor].

In the following study we present Dianatal Obstetric Gel and its role in normal labor. We would like to determine the effect of the Obstetric gel on first and second stage of labor as well as prevention of perineal trauma.

[Anti-Mullerian hormone- its role in the pathogenesis of the polycystic ovary syndrome].

Anti-Mullerian hormone (AMH) is a glycoprotein produced by the granulosa ovarian cells with respect to the regulation of the follicular growth and development. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disturbances affecting 6-7 of women in reproductive age. Women with PCOS exhibit a number of metabolic and endocrine disturbances some of which are paramount in the pathogenesis of PCOS. The studies examining the connection between AMH and PCOS are few and quite controversial. Women with PCOS are considered to have significantly lower levels of AMH as compared with controls which is interpreted as resulting from the greater number of pre-antral follicles, or a result of the specific synthesis of AMH by granulose cells causing follicular arrest in PCOS.

[The use of carboprost tromethamole for prevention and treatment of postpartal haemorrhage].

All around the world as well as in Bulgaria postpartal haemorrhage is a main reason of maternal death. The treatment of postpartal haemorrhage of which approximately 70% is caused by hypotony of the uterus is still a challenge for physician-obstetrician. In the following study we have used prostaglandin-Carboprost tromethamole (Prostin 15M) for treatment of this important obstetric pathology. One year investigation which includes 82 patients with hypotony during vaginal delivery or cesarian section. Results showed that the use of Carboprost tromethamole (Prostin 15M) in treatment of hypotony leads to fast and extended contraction of the uterus as well as significantly decreases blood loss and the necessity of haemotrasfusion.

[The use of Dinoproston for induction of delivery].

For the past decades induction of delivery is more often put in practice of modern obstetric. During the last couple of years it exceeds 20% of the vaginal deliveries. In the following study we have use Dinoprostone (Prepidil gel) as a remedy which stimulates labor. In 6 months 92 patients were selected. A 92 deliveries were stimulated with Prepidil gel. The results were satisfactory. Dinoprostone represents to be effective, safe and easy to use for induction of delivery.

[Insulin resistance in preeclampsia].

Contemporary scientific data show that there is a link between insulin resistance and preeclampsia. Many features of the insulin resistance syndrome are common with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity and lipid abnormalities. The women with preeclampsia are more insulin resistant than those with normal pregnancy. The surrogate markers of insulin resistance like leptin, TNF-alpha, tissue plasminogen activator, SHBG etc are also changed in preeclampsia. Whether these changes are connected with etiology or with the pathogenesis of preeclampsia is still not clear.

[Cornual heterotopic pregnancy: a case report].

Heterotopic pregnancy is the simultaneous development of an intrauterine pregnancy and ectopic pregnancy. We report a rare case of corneal heterotopic pregnancy at 9 weeks of amenorrhoea in a 30-year-old woman, after IVF. Because of the massive intraabdominal hemorrhage laparotomy was performed. Cornual resection and suture was performed and intrauterine pregnancy was evacuated. Doctors must be alert to the fact that confirming an intrauterine pregnancy does not exclude the coexistence of an ectopic pregnancy, particularly after IVF.

The appropriateness and use of focus group methodology across international mental health communities.

The ability to interpret collected data across international mental health communities often proves to be difficult. The following paper reports on the use and appropriateness of focus group methodology in helping to clarify issues that could help substantiate data collection and comparison across different cultures and regions. Field tests of the focus group methodology were undertaken in different regions and this paper describes an overview of the final field test in Sofia, Bulgaria. The findings and experiences with utilizing this methodology were incorporated in subsequent data collections.