Relationship of Cholelithiasis and Urolithiasis with Methylenetetrahydrofolate Reductase Polymorphisms.

AIM: To investigate the relationship of cholelithiasis and urolithiasis with Methylenetetrehydrofolate Reductase (MTHFR) polymorphism(s) in patients with poor obstetric history to search whether they are risk factors for adverse pregnancy outcome. MATERIALS AND METHOD: This study is consisted of 94 patients with poor obstetric history. Patients were evaluated in terms of the presence of cholelithiasis and urolithiasis in association with MTHFR polymorphism(s). Additional laboratory tests including homocysteine measurements were also performed. ROC analysis for assessing the performance of blood homocysteine level in predicting the presence of cholelithiasis and urolithiasis were also performed. RESULTS: Patients were divided into three groups such as cholelithiasis group (n = 9, 9.6%), urolithiasis group (n = 18, 19.1%) and control group (n = 67, 71.3%). Groups did not differ in term of age and Beksac obstetrics index (BOI) which is "[living child+(π/10)]/gravidity." The rate of the presence of MTHFR polymorphisms were 88.9% (8/9), 88.9% (16/18) and 43.3% (29/67) in cholelithiasis, urolithiasis and control groups respectively. Median homocysteine levels were found to be 13.1, 11.6 and 7.2 micromol/lt for the groups respectively. Statistically significant differences were found for MTHFR polymorphism rates and homocysteine levels (<0.001 for both). According to ROC analysis, 10.9 mcmol/L (88.9% sensitivity, 89.6% specificity) and 9.25 mcmol/L (83.3% sensitivity, 73.1% specificity) were determined to be cutoff values of homocysteine for cholelithiasis and urolithiasis respectively. CONCLUSION: More frequent MTHFR polymorphisms are observed in women with a clinical history of gall or renal stones. Thus, screening of these patients may be benefical for the approprate management of their subsequent pregnancies.

PERINATAL OUTCOMES OF PREGNANT WOMEN WITH TYPE 1 DIABETES MELLITUS: COMPARISON OF MULTIDOSE INJECTION AND CONTINUOUS SUBCUTANEOUS INSULIN INFUSION.

OBJECTIVE: To evaluate obstetric and neonatal outcomes of patients with type 1 diabetes mellitus (T1DM) and compare multidose injection (MDI) and continuous subcutaneous insulin infusion (CSII). STUDY DESIGN: Retrospective study of 53 pregnant patients with T1DM reaching at least 24th gestational week. RESULTS: Fourteen patients (26.4%) hospitalized for insulin dose regulation. Ten patients had hypertensive diseases. Perinatal mortality occurred in 2 neonates owing to cardiac malformations. Neonatal hypoglycemia, small for gestational age, large for gestational age, and neonatal jaundice were demonstrated in 8, 4, 12 and 19 newborns, respectively. Sixteen newborns were admitted to the NICU for various reasons. Congenital malformations were detected in 7 newborns (6 cardiovascular and 1 central nervous system anomaly). Despite lack of statistical significance, total daily insulin doses were higher in the MDI group than in the CSII group with doses of 62 IU (18-166) and 51 IU (20-114), respectively (p=0.119). Gestational and perinatal outcomes also showed no statistical significance. However, all congenital abnormalities and perinatal deaths occurred in the MDI group. CONCLUSION: T1DM in pregnancy is a challenging problem in terms of having better obstetric and perinatal results. CSII may be used safely instead of MDI in appropriate patients.

Prenatal Diagnosis of Organic Acidemias at a Tertiary Center.

The aim of this study was to share our experience in the prenatal diagnosis (PND) of organic acidemias (OAs) in our clinic. This study consisted of 10 cases in whom an invasive prenatal diagnostic test (IPNDT) was performed by a single physician for the PND of OAs. Median maternal age, parity, gestational week of IPNDT, prenatal test indications, OA types, method of IPNDT, IPNDT results and gestational outcomes were evaluated. Targeted mutation analysis was performed in fetal DNA for the specific mutations by using polymerase chain reaction (PCR) and direct Sanger sequencing. The diagnosis was confirmed by genetic targeted mutation analysis after birth. Median maternal age, parity and gestational week of IPNDT values were 30 (range 21-35), one (range 0-4) and 11.5 (range 11-17), respectively. Indications for IPNDT were mother being a carrier of the disease for one case (10.0%) and at least one child with OA in the family for nine cases (90.0%). Organic acidemia types investigated were maple syrup urine disease (MSUD), methylmalonic acidemia (MMA) and isovaleric acidemia (IVA) in five (50.0%), three (30.0%) and two (20.0%) patients, respectively. Chorion villus sampling (CVS) was done in seven (70.0%) patients and amniocentesis was performed in three (30.0%) patients. Eight fetuses (80.0%) were found to be healthy and two fetuses (20.0%) were found to be affected (one case with IVA and one case with MMA). The two pregnancies (20.0%) with affected fetuses were terminated. Prenatal diagnosis of OAs is critical. Appropriate prenatal counseling should be given to families with known risk factors.

Gestational outcomes of patients with multiple sclerosis: A tertiary centre experience

Background. Multiple sclerosis (MS) is a disease that predominantly affects the young female population. It is important for an obstetrician to know the effects of pregnancy on MS, and vice versa. Objective. To demonstrate the impact of MS on pregnancy outcomes. Methods. We retrospectively evaluated demographic features, clinical characteristics, and obstetric outcomes of 47 pregnancies in 24 patients with MS, between January 2007 and December 2016. Results. Patients were divided into three groups: (i) 35 pregnancies in patients with MS who were in remission at the beginning of pregnancy; (ii) 10 pregnancies in patients with MS whose disease was exacerbated at the beginning of pregnancy; and (iii) 2 pregnancies in patients with active MS whose symptoms were relieved after becoming pregnant. The overall early pregnancy loss rate was 36.2%, whereas it was 60% and 31.4% in the exacerbation and remission groups, respectively; and the overall preterm delivery rate was 30%, while it was 29.1% and 50% in the remission and exacerbation groups, respectively. Conclusion. Miscarriage and preterm delivery seem to be significant obstetric complications in pregnant women with MS

A severely mentally and motor retarded girl with monosomy 3pter-->p25 and trisomy 8q24-->qter due to a familial reciprocal translocation t(3;8)(p25;q24).

A severely mentally and motor retarded girl with monosomy 3pter--p25 and trisomy 8q24-qter due to a familial reciprocal translocation t(3;8) (p25;q24): We report a familial translocation t(3;8) in a three generation family that includes a severely retarded 9-year-old girl with intrauterine and postnatal growth retardation, microcephaly, capillary hemangiomas of the forehead and perioral region, synophrys, ptosis, long philtrum, high arched palate, micrognathia, malformed ears, clinodactyly, hypotonia, mental and motor retardation. The pedigree was highly suggestive ofa familial rearrangement. Cytogenetics and fluorescent in situ hybridization (FISH) showed an unbalanced translocation of chromosomes 3p25 and 8q24 of maternal origin, karyotype 46,XX,der(3)t(3;8)(p25q24)mat. Using FISH the breakpoint at 8q24 was located distal of TRPS1, the gene for trichorhinophalangeal syndrome. The balanced translocation was found in the mother, maternal grandmother and prenatally diagnosed brother. Ten individuals (seven miscarriages, niece, two nephews) probably also had an unbalanced translocation. Genetic counseling was given to the family. Because of the hemizygous deletion of the VHL gene at chromosome 3p25.3, the patient is at risk for von Hippel-Lindau (VHL) syndrome, predisposing to retinal, cerebellar, spinal haemangioblastomas, renal cell carcinoma, phaeochromocytoma and pancreatic tumors. Therefore, for early detection and treatment of VHL syndrome, we performed periodic screening beginning at age 5 years. A familial translocation t(3;8) is very rare and there are no previous reports on terminal monosomy 3p (pter-->p25) and terminal trisomy 8q (q24-->qter).

Ring chromosome 4 and Wolf-Hirschhorn syndrome (WHS) in a child with multiple anomalies.

We report on a 16-month-old male patient with ring chromosome 4 and deletion of Wolf-Hirschhorn syndrome (WHS) region with multiple congenital anomalies including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices. Peripheral chromosome analysis of the patient showed 46,XY,r(4)(p16.3q35) de novo. Multicolor fluorescence in situ hybridization (FISH) study was also performed and according to multicolor banding (MCB) a r(4)(::p16.3 --> q34.3 approximately 35.1::) was found in all metaphases. Subtelomeric 4p region, subtelomeric 4q region, as well as, Wolf-Hirschhorn critical region were deleted in ring chromosome 4. Genomic microarray analysis was also performed to delineate the size of deletion. Cranial magnetic resonance imaging (MRI) showed hypoplastic corpus callosum, delayed myelinization, and frontal and occipital lobe atrophies. Both maternal and paternal chromosomal analyses were normal. We compare the phenotypic appearance of our patient with the previously reported 16 cases of ring chromosome 4 in the medical literature.

Association between trichomoniasis and bacterial vaginosis: examination of 600 cervicovaginal smears.

To determine whether there is a relationship between trichomoniasis and bacterial vaginosis (BV), cervicovaginal smears obtained from 600 women were stained with the Papanicolaou technique and examined cytologically. Thirty-six (6%) of 600 women were diagnosed as having Trichomonas vaginalis [TV(+)]. Sixteen (44.4%) of 36 TV(+) cases were observed as having BV [BV(+)]. Thirty-one of 564 TV(-) vaginal smears were also positive for BV (5.5%). There was a statistically significant correlation between trichomoniasis and bacterial vaginosis (p < 0.05). It is possible that TV might create an anaerobic environment, thereby changing the vaginal flora. This flora becomes a more suitable milieu for growing of anaerobic microorganisms. It can be postulated that TV might be the most important protozoan that contributes to the overgrowth of BV-related microorganisms.

The association of Candida infection with intrauterine contraceptive device.

In order to analyse the relationship between intrauterine contraceptive device (IUCD) usage and Candida infection, we planned to examine cytologically the cervico-vaginal smears of 600 patients stained with Papanicolou method. Among 56 IUCD users 8 women had Candida infection (14%) while 44 of 544 non-users (8%) were infected by this fungus. Our detailed analyses indicated that the prolonged usage of Cu-IUCD may predispose the cervico-vaginal flora for Candida especially for the infectious "hyphae" form although statistically the correlation between IUCD usage and candidiasis was not significant (p>0.05). These findings imply the importance of controlled IUCD usage against Candida infection and its removal for treatment if necessary. Because retained IUCD may cause serious clinical complications especially in pregnant women such as "fetal candidiasis" which may lead to miscarriage, premature labor or ectopic pregnancy. For these reasons, the possibility of candidiasis should be considered in patients wearing IUCD for a long period.

Balanced de novo translocation t(6;7)(p25;q31) and cleft palate as an isolated finding.

We report a prenatally diagnosed balanced de novo translocation t(6;7)(p25;q31). Physical examination of the baby born at term revealed only a posterior cleft palate. Laboratory examinations and radiologic investigations were found normal. Two years follow-up of the patient showed her mental and motor development was appropriate with her age. Our report is the first observation on balanced de novo translocation t(6;7)(p25;q31) and cleft palate. Association of this translocation and cleft palate has not been reported previously.

Early prenatal diagnosis of familial intestinal polyatresia (FIPA) in a 19 weeks old fetus with sonographic and postmortem findings.

Familial intestinal polyatresia (FIPA) is a rare autosomal recessive disorder. In this article we present a new prenatally diagnosed case with FIPA from consanguineous parents with two affected daughters. The fourth pregnancy was diagnosed prenatally with FIPA at 18 weeks sonographically and these findings were confirmed by postmortem examination.

Prenatal diagnosis in three cases of iniencephaly with unusual postmortem findings.

Iniencephaly is a rare and lethal congenital malformation of the neural tube characterized by occipital bone defect, cervical dysraphism, fixed retroflexion of the fetal head and severe lordosis of the cervicothoracic spine. The etiology is unknown. Prenatally diagnosed cases of iniencephaly are rare because careful and early ultrasonographic evaluation is necessary. We present three cases of iniencephaly prenatally diagnosed by sonography at 20-22 weeks' gestation in which therapeutic abortion was induced. The sonographic findings were compatible with the postmortem findings. The present cases of iniencephaly were found to carry unusual associated malformations such as two lobes in the right lung and chorangiosis of the placenta. Only hypoplastic lungs have been reported by previous authors. We also studied the 677C-->T mutation on the methylenetetrahydrofolate reductase gene in the parents in one of the present cases. The mother was found to be heterozygous for the 677CT polymorphism.

Mitral balloon valvuloplasty during pregnancy in developing countries.

Two women presented with severe mitral stenosis at 28th and 23rd weeks of gestation, respectively. Both did not respond to medical therapy and percutaneous balloon valvuloplasty was performed during pregnancy successfully. While one of the women gave no history of cardiac disease the other had already underwent balloon valvuloplasty twice due to restenosis of the mitral valve. The rest of their pregnancies were both uncomplicated. They discontinued their medication. Both were able to deliver vaginally at term. Percutaneous balloon valvuloplasty is a promising approach to the treatment of patients with rheumatic mitral stenosis if medical management is unsuccessful.

In vitro differentiation of human endometrial stromal cells: effect of transforming growth factor beta 1 on prolactin secretion.

OBJECTIVE: To investigate the role of Transforming Growth Factor beta 1 on differentiation of human endometrial stromal cells. STUDY DESIGN: A prospective study. MATERIAL AND METHODS: Human endometrial cells obtained from 9 women were cultured in DMEM-HAMs F12 media to adequate cell confluence and then the flasks were cultured in the presence and absence of TGF b 1. The influence of TGF beta 1 were measured by prolactin production expressed as nanograms of prolactin/mg of total DNA in cells measured by diphenylamine reaction. RESULTS: The levels of prolactin in the culture medium with and without TGF beta 1 were 0.16 +/- 0.27 ng/microgram DNA/day and 0.24 +/- 0.41 ng/microgram DNA/day respectively. There was no significant difference between groups. CONCLUSION: There is no direct effect of TGF beta 1 on differentiation of human endometrial stromal cells. However it may involve in more complex relationship in this process.

Vasculogenesis in early human placental villi: an ultrastructural study.

In this study we examined the chorionic villi of 5 normal human placentas at 12-14 weeks of gestation ultrastructurally with regard to differentiation of the vascular components. The aim of the present report is to discuss the factors influencing vasculogenesis (in situ formation of blood vessels) at the ultrastructural level. Our observations have led us to think that the cytotrophoblast influences vasculogenesis in human chorionic villi. Mesenchymal-preendothelial cell groups were always found in very close association with the cytotrophoblast at the periphery of the villi, forming blood vessels. The cytotrophoblast probably attracts mesenchymal cells towards the margin of the villi by secreting vascular endothelial growth factor (VEGF). Once cells attach to the trophoblastic basement membrane they begin to differentiate into endothelial cells. This close structural relation between two cell types (cytotrophoblast and mesenchymal cells) may not be the only mechanism controlling vasculogenesis, but it seems to be one of the factors influencing the differentiation of mesenchymal cells into the endothelial cells of blood vessels in early human chorionic villi.

An artificial intelligent diagnostic system on differential recognition of hematopoietic cells from microscopic images.

Despite their advantages, none of the automated white blood cell differentiated counters have replaced the conventional microscopic evaluations of blood and bone marrow slides by hematologists. We have analyzed the smears of 39 patients and 8 control subjects to develop an artificial expert system that recognizes 16 different types of nucleated hematopoietic cells during the stages of differentiation. A charge coupled television camera and a special frame grabber were used for data acquisition, and 247 nucleated cell images were transferred from a microscope to an IBM 386 computer to be processed. One hundred sixty-five and 82 of these images were used for training and testing, respectively. Our system is composed of image processing and analysis (enhancement, thresholding/smoothing, edge detection), pattern recognition (feature extraction and classification with supervised artificial neural network), and expert system development. Image processing and analysis were used to obtain 13 cellular features to be used as the input parameters (neurons) of the artificial neural network. A supervised artificial neural network (back-propagation learning algorithm) was used in the classification of 16 different cells (output neurons of the neural network), which is the second step of pattern recognition. A confusion matrix has been developed to compare the similarities and dissimilarities between the differential recognitions of the hematologist and the expert system. The discriminatory power of the procedure is statistically significant: Q = (N - n.K)2/N.(K - 1) = 28.2. The sensitivity and the specificity of the expert system were 71.4% and 90.9%, respectively.

Feature discovery and classification of Doppler umbilical artery blood flow velocity waveforms.

Doppler umbilical artery blood flow velocity waveform measurements are used in perinatal surveillance for the evaluation of fetal condition. There is an ongoing debate on the predictive value of Doppler measurements concerning the critical effect of the selection of parameters for the interpretation of Doppler waveforms. In this paper, we describe how neural network methods can be used both to discover relevant classification features and subsequently to classify Doppler umbilical artery blood flow velocity waveforms. Results obtained from 199 normal and high risk patients' umbilical artery waveforms highlighted a classification concordance varying from 90 to 98% accuracy.

An automated intelligent diagnostic system for the interpretation of umbilical artery Doppler velocimetry.

The objective is to develop an automated intelligent diagnostic system for the interpretation of umbilical artery velocity waveforms. An ultrasound instrument with pulsed-wave Doppler is connected to a microcomputer by means of a frame grabber. After data acquisition, umbilical Doppler velocimetry is handled as a pattern recognition (feature extraction and classification) and decision-making problem. Automated image processing (enhancement, smoothing/ thresholding and edge detection) and analysis are used for feature extraction. Six waveform indices obtained by feature extraction are used as input layer to vector quantization which classifies waveforms into six groups. A clinical decision is assigned to each group by the medical expert. Our system is trained by 278 and 380 waveform images of 94 normal and 157 high risk pregnancies, respectively. The system was tested with 193 and 61 images of normal and risky pregnancies; it was demonstrated that sensitivity and specificity of the system are 54.1% and 80.3%, respectively.