Monte Carlo Optimization Method Based QSAR Modeling of Placental Barrier Permeability.

PURPOSE: In order to ensure that drug administration is safe during pregnancy, it is crucial to have the possibility to predict the placental permeability of drugs in humans. The experimental method which is most widely used for the said purpose is in vitro human placental perfusion, though the approach is highly expensive and time consuming. Quantitative structure-activity relationship (QSAR) modeling represents a powerful tool for the assessment of the drug placental transfer, and can be successfully employed to be an alternative in in vitro experiments. METHODS: The conformation-independent QSAR models covered in the present study were developed through the use of the SMILES notation descriptors and local molecular graph invariants. What is more, the Monte Carlo optimization method, was used in the test sets and the training sets as the model developer with three independent molecular splits. RESULTS: A range of different statistical parameters was used to validate the developed QSAR model, including the standard error of estimation, mean absolute error, root-mean-square error (RMSE), correlation coefficient, cross-validated correlation coefficient, Fisher ratio, MAE-based metrics and the correlation ideality index. Once the mentioned statistical methods were employed, an excellent predictive potential and robustness of the developed QSAR model was demonstrated. In addition, the molecular fragments, which are derived from the SMILES notation descriptors accounting for the decrease or increase in the investigated activity, were revealed. CONCLUSION: The presented QSAR modeling can be an invaluable tool for the high-throughput screening of the placental permeability of drugs.

Manifestation of an undifferentiated uterine sarcoma in a 51 years old patient and its prognosis: A case report.

INTRODUCTION: Undifferentiated uterine sarcoma is a rare histological subtype of uterine sarcoma. This study aimed to summarize the clinical and pathological presentation of this case. CASE REPORT: A 51-years-old patient was admitted to the clinic because of severe pain in the lower abdomen, and scanty bleeding from the genitals. Gynecological examination revealed an enlarged uterus. Conventional and Doppler transvaginal sonography detected a tumorously altered uterus with a maximum diameter of 20 cm a tumefaction with unclear borders and a diameter of 10 cm, with hyperechoic and hypoechoic fields within the tumefaction, presenting pathological vascularization and reduced values of the (Pulsatile index  ≤ 1) and (Resistance index  ≤ 0.40). Preoperatively, the chest, abdomen, and pelvis were examined. The patient underwent surgery and total abdominal hysterectomy with bilateral salpingo-oophorectomy, and partial omentectomy, with complete removal of the tumor. A pathohistological diagnosis, of undifferentiated uterine sarcoma, was made by excluding other types of uterine sarcomas. At the control examination after completion of chemotherapy, recurrence was ascertained. CONCLUSION: undifferentiated uterine sarcoma is an aggressive malignant tumor that in most cases shows rapid progression of the disease after complete resection of the tumor, with a poor prognosis.

Predictors of poor neonatal outcomes in fetuses diagnosed with congenital urinary tract anomalie.

OBJECTIVES: Urinary tract anomalies account for approximately one-quarter of all antenatally detected anomalies. The aim of this study was to identify factors associated with severe adverse neonatal outcomes of a prenatally diagnosed urinary tract anomaly. MATERIAL AND METHODS: A retrospective-prospective study included 101 pregnant women with prenatally diagnosed fetal urinary tract anomalies presented to the Council for Fetal Anomalies. Prenatal diagnoses were compared with autopsy findings in cases of terminated pregnancy or with clinical and operative findings of the infants. RESULTS: The mortality rate in the group of patients with fetal obstructive uropathy (60 patients) was 10% and in the group of patients with fetal multicystic dysplastic kidney (38 patients) 15.7%. Surgery was performed on 53.4% of the children, whereas more than half of the operations involved resolving associated urinary tract anomalies. Postoperative renal function deterioration occurred in 19% of the children. CONCLUSIONS: The prognosis of renal function in obstructive uropathies is excellent if oligoamnios does not develop prenatally and in case of timely provided surgical care is provided postnatally. The finding of the bilateral multicystic dysplastic kidney is associated with poor prognosis. The prognosis in fetal unilateral multicystic dysplastic kidney depends primarily on the condition of the contralateral kidney and the existence of associated anomalies.

Role of optical coherence tomography in the early detection of macular thinning in rheumatoid arthritis patients with chloroquine retinopathy.

BACKGROUND: Chloroquine and hydroxychloroquine are drugs that are primarily used for the treatment of malaria and are also recommended for treating connective tissue disorders, autoimmune diseases, and some dermatological and inflammatory diseases. Treatment with these drugs has potential risk for the development of retinopathy, clinically characterized by bilateral pigment changes in the macula, as one serious ocular complication. The aim of this research was to evaluate the parafoveal and perifoveal macular retinal thickness, as central foveal thickness in adult patients with rheumatoid arthritis (RA) on chloroquine therapy using optical coherence tomography (OCT). MATERIALS AND METHODS: In this cross-sectional study, 56 RA patients (56 eyes) were included and examined. All patients were treated with chloroquine (tablets resochin or delagil) at a dose of 250 mg/day without treatment with steroids and other immunosuppressive drugs. Patients were divided into two groups, namely, Group I patients - no visible changes in the macula (26 patients) and Group II patients- with visible changes in the macula (30 patients). The central fovea thickness and parafoveal and perifoveal retinal thickness in all quadrants were measured by OCT and compared in both groups. RESULTS: There are a significantly higher number of eyes without thinning of the macula in Group I patients than in Group II (P < 0.001) patients. There are a higher number of patients with recorded parafoveal thinning in Group II patients, especially in the inferior, nasal, and temporal sectors, respectively (P < 0.05). CONCLUSION: Maculopathy is the main side effect of chloroquine therapy in RA patients that can be detected by OCT in the early stages of the macular involvement.

The role of magnetic resonance imaging in the evaluation of endometrial carcinoma.

PURPOSE: Gynecological cancers comprise about 19% of all cancers in women whereas the endometrial cancer is the most common malignant tumor of the female reproductive organs. The application of modern imaging tools plays an important role in the preoperative assessment of disease extent and allows the selection of a proper and adequate therapeutic approach for each patient. The purpose of this review was to show the role of magnetic resonance imaging (MRI) in the evaluation of endometrial carcinoma. MRI enables the display of zonal anatomy of the uterus, detection of the anomalies as well as the detection and characterization of pathological processess. Endometrial cancer is staged with the International Federation of Gynecology and Obstetrics (FIGO) classification, which was significantly revised in 2009. The FIGO classification incorporates two of the important prognostic parameters, the depth of myometrial invasion and histological grade. The depth of myometrial invasion can be accurately assessed by MRI. MRI is not officially included in the FIGO staging system. However, it is widely accepted as a suitable imaging technique for preoperative staging, treatment planning and monitoring of patients with endometrial cancer.

Flexible GnRH antagonist protocol vs. long GnRH agonist protocol in patients with polycystic ovary syndrome treated for IVF: comparison of clinical outcome and embryo quality.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, primarily affecting women of the reproductive age. The aim of the study was to assess the clinical efficacy and embryo quality in flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison to the long GnRH agonist protocol in PCOS women undergoing in vitro fertilization (IVF). MATERIAL AND METHODS: This prospective, randomized study was conducted at the Department of Gynecology and Obstetrics, Clinical Center Nis, Serbia, between 2013 and 2014. The treatment included either a flexible GnRH antagonist protocol (n = 45, antagonist group) or a long GnRH agonist protocol (n = 45, agonist group). RESULTS: The length of the stimulation, total amount of gonadotropins used, as well as the average number of the aspirated and mature oocytes were higher in the agonists group. The endometrial thickness was also greater in the agonists group. A higher number of Class I and Class IV embryos were obtained after the agonist treatment and higher number of Class II and Class III embryos were obtained after the antagonist treatment. Pregnancy, implantation, and miscarriage rates were comparable between the groups. CONCLUSIONS: The GnRH antagonist protocol in PCOS patients has a pregnancy rate comparable to that of the GnRH agonist protocol. Since this protocol has a lower rate of complications and is more convenient for patients, we believe that the GnRH antagonist protocol should be used as the first-line treatment for PCOS patients in an IVF program.

Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients.

Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image.

Metastatic malignant melanoma of the uterus diagnosed by colposcopy.

Introduction: Primary and metastatic malignant melanomas represent a rare diagnosis with a small number of described cases. The aggressive nature of the tumor, non-specific symptoms, difficult diagnosis, and no official protocol about the treatment result in poor disease prognosis. Case Outline: The authors presented a 41-year-old multigravida patient. She had an operation of malignant melanoma in the occipital area of the head. She went to her gynecologist because of increased pale pink vaginal secretion. Gynecological examination didn't show any significant abnormalities apart from a slightly enlarged uterus. Papanicolaou test and vaginal secretion examination were normal. Colposcopically, a significant dark brown hyperpigmented area around 1 cm in size was observed on the posterior lip of the cervix, near the orifice and cervical canal, suspicious of melanoma, which was proven on targeted biopsy of the hyperpigmented change on the cervix, and by magnetic resonance imaging of the lesser pelvis. Classic hysterectomy with adnexectomy and regional pelvic lymphadenectomy were performed. Conclusion: This case report pointed out the significance of applying colposcopy in diagnosing suspected metastatic melanoma of the uterine cervix, along with other diagnostic methods and anamnestic data.

INFLUENCE OF BODY MASS INDEX ON IN VITRO FERTILIZATION OUTCOME IN WOMEN WITH POLYCYSTIC OVARY SYNDROME.

INTRODUCTION: The purpose of this study was to investigate the influence of the body mass index on the outcome of in vitro fertilization in patients with polycystic ovary syndrome. MATERIAL AND METHODS: The study sample consisted of 123 patients with polycystic ovary syndrome who completed their in vitro fertilization treatment at the Department of Gynecology and Obstetrics, Clinical Center Nis. Republic of Serbia, and they were retrospectively analyzed. The patients were divided by body mass index into two groups for the comparison of the findings. One group (normal weight) consi- sted ofwomenwithbodymass index ≤25 kg/in² (mean22.O8±1.90), and the other group (overweight) included women with body mass index>25 kg/in² (mean 27.65±1.47). The patients underwent either the standard long gonadotrophin-releasing hormone agonist protocol or flexible multidose gonadotrophin-releasing hormone antagonist protocol. RESULTS: The normal-weight patients had a higher number of mature oncytes, significantly higher fertilization rate (p

Retinal hemorrhages as one of complications of optic disc drusen during pregnancy.

INTRODUCTION: Drusen of the optic nerve head are relatively benign and asymptomatic. They represent retinal hyaline corpuscles resulting from impaired axoplasmic transport of the retinal ganglion cells of optic nerve in front of the lamina cribrosa. They are usually detected accidentally, during a routine ophthalmologic examination. Most patients with optic disc drusen are not aware of the deterioration of their eyesight because of the slow progression of visual field defects. Damage in visual acuity due to optic disc drusen is rare. CASE REPORT: A 27-year-old female patient in the sixth month of pregnancy visited an ophthalmologist because of a visual impairment described as the appearance of mist and shadows over her right eye. When first examined, her visual acuity in both eyes was 20/20. The retinal hemorrhages framing the bottom half of the optic nerve were seen. Complete laboratory and clinical testing as well as specific ophthalmic examinations (photofundus, computerized visual field, optical coherence tomography, and ultrasound) were performed to exclude systemic causes and they presented no risk for the pregnancy. Echosonographic examination confirmed the presence of bilateral optic nerve head drusen. CONCLUSION: Hemodynamic changes during pregnancy are possible factors for the development of optical disc and retinal hemorrhages. Since treatment of optic disc drusen is limited, recognition of optic nerve drusen as a cause of hemorrhage during pregnancy prevents unnecessary diagnostic and therapeutic interventions.

Comparative analysis of autodermal graft and polypropylene mesh use in large incisional hernia defects reconstruction.

BACKGROUND: Large defects of the abdominal wall caused by incisional hernia still represent a challenging problem in plastic, reconstructive, and abdominal surgery. For their successful tension-free repair a proper selection of reconstructive material is essential. In the last decades, the use of synthetic meshes was dominant while biological autodermal grafts were rarely used. The aim of the study was to comparatively analyse efficacy and safety of autodermal graft and polypropylene mesh in surgical treatment of large abdominal wall defects. METHODS: This prospective comparative clinical study enroled 40 patients surgically treated for large incisional hernia repair in a 10-year period. The patients were divided into two equal groups consisting of 20 subjects and treated either by biological autodermal graft or by synthetic polypropylene mesh. The surgical techniques of reconstruction, duration of surgery, the occurrence of early, minor, and major (severe) and delyed complications and hospital stay were analysed. The average follow-up took 2 years. RESULTS: Statistically significant differences in demographic characteristics of patients and in size of defects were not found. The surgical technique of reconstruction with an autodermal graft was more complicated. The duration of surgery in patients treated with autodermal grafts was significantly longer. There was no statistically significant difference regarding occurrence of early, minor postoperative complications and hospital stay in our study. Two severe complications were registered in the synthetic mesh group: intestinal obstruction and enterocutaneous fistula. The recurrence rate was 10% in the autodermal graft group and 15% in the group with a synthetic mesh. CONCLUSION: Tension-free repair of large incisional hernia with autodermal grafts was unjustly neglected despite the fact that it is safe and effective. It can be applied in all cases where synthetic mesh are not indicated (presence of infection, immunodeficient patients, after radiotherapy). They are especially important in war surgery and in lack of funds when commercial grafts cannot be purchased.

Postpartum HELLP syndrome--the case of lost battle.

Unexpected rapid maternal death after delivery due to HELLP syndrome is rarely encountered and may become the subject of forensic expertise. Unexpectedness, suddenness, and fulminant course of this syndrome as well as absence of classical signs of pre-eclampsia can confuse physicians and lead to diagnostic delay. A definitive post-mortem diagnosis of HELLP syndrome in questionable cases of maternal death should be based on accepted laboratory criteria and characteristic histopathological alterations. We present a case of acute postpartum HELLP syndrome complicated by disseminated intravascular coagulation and acute renal failure which caused rapid maternal death only 20 hours after a caesarean section following an uncomplicated pregnancy.

[Fetal multicystic kidney disease--outcome and follow up].

INTRODUCTION: Congenital fetal anomalies are the great problem and one of the main causes of increased perinatal mortality and morbidity. The aim of this study is to determine the outcome of prenataly detected multicystic dysplastic kidney and to point to the necessity of postnatal diagnostic procedures. MATERIAL AND METHODS: The retrospective-prospective study encompasses 38 cases of the prenatally diagnosed unilateral fetal multicystic dysplastic kidney. The associated anomalies were revealed either by autopsy findings when the pregnancy was terminated, or when the pregnancy continued, by clinical and operative findings the newborns. RESULTS: The autopsy finding revealed bilateral multicystic displastic kidney or unilateral mylticystic displastic kidney and the agenesis of the contralateral kidney. The postnatal evaluation of the newborns with unilateral multicistic disease revealed that 84.3% of them had some concomitant anomaly of the urinary tract, most of them had an anomaly of the contralateral kidney (31.4%). The surgery was performed in 73.6% of children, in 17% of children the kidney function deteriorated after the surgery. CONCLUSION: The findings of bilateral multicystic kidney disease and unilateral multicystic kidney disease and amnion are the indication to terminate the pregnancy. The finding of an isolated unilateral multicystic dysplastic kidney require thorough examination, both prenatally and postnatally. We propose obligatory serial prenatal ultrasound examinations, followed by postnatal ultrasound, isotope scan, and urinary cystourethography.

[Association of fetal unilateral multicystic kidney disease with other urinary tract anomalies]. / Udruzenost unilateralne multicisticne displazije bubrega fetusa sa drugim anomalijama urinarnog sistema.

BACKGROUND/AIM: Multicystic dysplastic kidney represents a disorder in the fetus development presented prenatally of postnatally, this deserving special attention due to a risk of additional anomalies in children with this disorder. The aim of this study was to determine the incidence and type of common anomalies of the urinary system in the prenatal diagnosis of unilateral multicystic dysplastic kidney, and point out the necessity of postnatal diagnostic procedures in order to evaluate the state of the urinary system. METHODS: This retrospective-prospective study encompassed 38 cases of prenatally diagnosed unilateral fetal multicystic dysplastic kidney, presented to the Council for Fetal Anomalies from the Institute for Gynecology and Obstetrics of the Clinical Centre of Serbia and the University Children's Clinic within a three-year period. Associated anomalies were revealed by autopsy findings when pregnancy was terminated, ie resumed with clinical and operative findings of born children. RESULTS: In every case of terminated pregnancy and death after birth the autopsy revealed additional renal or exstrarenal anomaly which were not prenataly detected. Postnatal evaluation of survived children with unilateral multicistic disease revealed that 31.4% of them have an anomaly of the contralateral kidney, 26.3% anomaly of the ipsilateral side, 13.2% anomaly of the lower portions of the urinary system and the same percent an additional extrarenal anomaly. The surgery was performed in 73.6% of children, more than half of the interventions were related to extrarenal anomaly. In 17% of children the kidney function was deteriorated after surgery. CONCLUSION: Children suffering from unilateral multicystic dysplastic kidney have a greater chance of exhibiting an anomaly of the contralateral kidney and the urinary system in general. Therefore, they require thorough examination, both prenatally and postnatally. We propose obligatory serial professional prenatal ultrasound examinations, followed by postnatal ultrasound, isotope scan, and we especially emphasize the need for performing urinary cystouretherography, bearing in mind the high incidence of the vesicoureteral reflux of the contralateral kidney. In addition to nephrectomy, cytoscopy and colposcopy also need to be performed for the purpose of discovering possible hidden anomalies of the urogenital system.

Immunohistohemical evidences of pregnancy in uterine curettage tissue by the use of a double immunocytochemical staining technique using cytokeratin 7 and vimentin antibodies.

BACKGROUND/AIM: Usual histopatological diagnosis of intrauterine pregnancy is made by demonstration of chorionic villi, but in the curettage tissue from intrauterine miscarriage they may not be present in all cases. The use of monoclonal antibody against cytokeratin as a sensitive and reliable marker for the morphologic discrimination between invasive trophoblastic (IT) cells and decidual cells has been well established. The aim of this study was to determine the presence of pregnancy in endometrial curettings when chorionic villi are absent from patients suspected of intrauterine pregnancy. METHODS: Twenty cases of endometrial tissue specimens were investigated for cytokeratin and vimentin expression by a double immunostaining for detection of IT cells. RESULTS: Out of the total number of cases (20) 17 cases expressed cytokeratin 7 positive IT cells, that are an evidence of pregnancy. CONCLUSION: The obtained results indicated, that double immunohistochemical demonstration of cytokeratin and vimentin is useful for identifying pregnancy in all chorionic villi-negative cases.